Adiposis Dolorosa Pain Management

Article Type
Changed
Wed, 11/06/2019 - 14:32
While current approaches to treatment focus on surgery, opiates, and other medications, health care providers may also consider ketamine infusion, electrostimulation, and perineural injections.

Adiposis dolorosa (AD), or Dercum disease, is a rare disorder that was first described in 1888 and characterized by the National Organization of Rare Disorders (NORD) as a chronic pain condition of the adipose tissue generally found in patients who are overweight or obese.1,2 AD is more common in females aged 35 to 50 years and proposed to be a disease of postmenopausal women, though no prevalence studies exist.2 The etiology remains unclear.2 Several theories have been proposed, including endocrine and nervous system dysfunction, adipose tissue dysregulation, or pressure on peripheral nerves and chronic inflammation.2-4 Genetic, autoimmune, and trauma also have been proposed as a mechanism for developing the disease. Treatment modalities focusing on narcotic analgesics have been ineffective in long-term management.3

The objective of the case presentation is to report a variety of approaches for AD and their relative successes at pain control in order to assist other medical professionals who may come across patients with this rare condition.

Case Presentation

A 53-year-old male with a history of blast exposure-related traumatic brain injury, subsequent stroke with residual left hemiparesis, and seizure disorder presented with a 10-year history of nodule formation in his lower extremities causing restriction of motion and pain. The patient had previously undergone lower extremity fasciotomies for compartment syndrome with minimal pain relief. In addition, nodules over his abdomen and chest wall had been increasing over the past 5 years. He also experienced worsening fatigue, cramping, tightness, and paresthesias of the affected areas during this time. Erythema and temperature allodynia were noted in addition to an 80-pound weight gain. From the above symptoms and nodule excision showing histologic signs of lipomatous growth, a diagnosis of AD was made.

The following constitutes the approximate timetable of his treatments for 9 years. He was first diagnosed incidentally at the beginning of this period with AD during an electrodiagnostic examination. He had noticed the lipomas when he was in his 30s, but initially they were not painful. He was referred for treatment of pain to the physical medicine and rehabilitation department.

For the next 3 years, he was treated with prolotherapy. Five percent dextrose in water was injected around many of the painful lipomas in the upper extremities. He noted after the second round of neural prolotherapy that he had reduced swelling of his upper extremities and the lipomas decreased in size. He experienced mild improvement in pain and functional usage of his arms.

He continued to receive neural prolotherapy into the nodules in the arms, legs, abdomen, and chest wall. The number of painful nodules continued to increase, and the patient was started on hydrocodone 10 mg/acetaminophen 325 mg (1 tablet every 6 hours as needed) and methadone for pain relief. He was initially started on 5 mg per day of methadone and then was increased in a stepwise, gradual fashion to 10 mg in the morning and 15 mg in the evening. He transitioned to morphine sulfate, which was increased to a maximum dose of 45 mg twice daily. This medication was slowly tapered due to adverse effects (AEs), including sedation.

After weaning off morphine sulfate, the patient was started on lidocaine infusions every 3 months. Each infusion provided at least 50% pain reduction for 6 to 8 weeks. He was approved by the US Department of Veterans Affairs (VA) to have Vaser (Bausch Health, Laval, Canada) minimally invasive ultrasound liposuction treatment, performed at an outside facility. The patient was satisfied with the pain relief that he received and noted that the number of lipomas greatly diminished. However, due to funding issues, this treatment was discontinued after several months.

The patient had moderately good pain relief with methadone 5 mg in the morning, and 15 mg in the evening. However, the patient reported significant somnolence during the daytime with the regimen. Attempts to wean the patient off methadone was met with uncontrollable daytime pain. With suboptimal oral pain regimen, difficulty obtaining Vaser treatments, and limitation in frequency of neural prolotherapy, the decision was made to initiate 12 treatments of Calmare (Fairfield, CT) cutaneous electrostimulation.

During his first treatment, he had the electrodes placed on his lower extremities. The pre- and posttreatment 10-point visual analog scale (VAS) scores were 9 and 0, respectively, after the first visit. The position of the electrodes varied, depending on the location of his pain, including upper extremities and abdominal wall. During the treatment course, the patient experienced an improvement in subjective functional status. He was able to sleep in the same bed as his wife, shake hands without severe pain, and walk .25 mile, all of which he was unable to do before the electrostimulative treatment. He also reported overall improvement in emotional well-being, resumption of his hobbies (eg, playing the guitar), and social engagement. Methadone was successfully weaned off during this trial without breakthrough pain. This improvement in pain and functional status continued for several weeks; however, he had an exacerbation of his pain following a long plane flight. Due to uncertain reliability of pain relief with the procedure, the pain management service initiated a regimen of methadone 10 mg twice daily to be initiated when a procedure does not provide the desired duration of pain relief and gradually discontinued following the next interventional procedure.

The patient continued a regimen that included lidocaine infusions, neural prolotherapy, Calmare electrostimulative therapy, as well as lymphedema massage. Additionally, he began receiving weekly acupuncture treatments. He started with traditional full body acupuncture and then transitioned to battlefield acupuncture (BFA). Each acupuncture treatment provided about 50% improvement in pain on the VAS, and improved sleep for 3 days posttreatment.

However, after 18 months of the above treatment protocol, the patient experienced a general tonic-clonic seizure at home. Due to concern for the lowered seizure threshold, lidocaine infusions and methadone were discontinued. Long-acting oral morphine was initiated. The patient continued Calmare treatments and neural prolotherapy after a seizure-free interval. This regimen provided the patient with temporary pain relief but for a shorter duration than prior interventions.

Ketamine infusions were eventually initiated about 5 years after the diagnosis of AD was made, with postprocedure pain as 0/10 on the VAS. Pain relief was sustained for 3 months, with the notable AEs of hallucinations in the immediate postinfusion period. Administration consisted of the following: 500 mg of ketamine in a 500 mL bag of 0.9% NaCl. A 60-mg slow IV push was given followed by 60 mg/h increased every 15 min by 10 mg/h for a maximum dose of 150 mg/h. In a single visit the maximum total dose of ketamine administered was 500 mg. The protocol, which usually delivered 200 mg in a visit but was increased to 500 mg because the 200-mg dose was ineffective, was based on protocols at other institutions to accommodate the level of monitoring available in the Interventional Pain Clinic. The clinic also developed an infusion protocol with at least 1 month between treatments. The patient continues to undergo scheduled ketamine infusions every 14 weeks in addition to monthly BFA. The patient reported near total pain relief for about a month following ketamine infusion, with about 3 months of sustained pain relief. Each BFA session continues to provide 3 days of relief from insomnia. Calmare treatments and the neural prolotherapy regimen continue to provide effective but temporary relief from pain.

 

 

Discussion

Currently there is no curative treatment for AD. The majority of the literature is composed of case reports without summaries of potential interventions and their efficacies. AD therapies focus on symptom relief and mainly include pharmacologic and surgical intervention. In this case report several novel treatment modalities have been shown to be partially effective.

Surgical Intervention

Liposuction and lipoma resection have been described as effective only in the short term for AD.2,4-6 Hansson and colleagues suggested liposuction avulsion for sensory nerves and a portion of the proposed abnormal nerve connections between the peripheral nervous system and sensory nerves as a potential therapy for pain improvement.5 But the clinical significance of pain relief from liposuction is unclear and is contraindicated in recurrent lipomas.5

Pharmaceutical Approach

Although relief with nonsteroidal anti-inflammatory drugs and narcotic analgesics have been unpredictable, Herbst and Asare-Bediako described significant pain relief in a subset of patients with AD with a variety of oral analgesics.7,8 However, the duration of this relief was not clearly stated, and the types or medications or combinations were not discussed. Other pharmacologic agents trialed in the treatment of AD include methotrexate, infliximab, Interferon α-2b, and calcium channel modulators (pregabalin and oxcarbazepine).2,9-11 However, the mechanism and significance of pain relief from these medications remain unclear.

Subanesthesia Therapy

Lidocaine has been used as both a topical agent and an IV infusion in the treatment of chronic pain due to AD for decades. Desai and colleagues described 60% sustained pain reduction in a patient using lidocaine 5% transdermal patches.4 IV infusion of lidocaine has been described in various dosages, though the mechanism of pain relief is ambiguous, and the duration of effect is longer than the biologic half-life.2-4,9 Kosseifi and colleagues describe a patient treated with local injections of lidocaine 1% and obtained symptomatic relief for 3 weeks.9 Animal studies suggest the action of lidocaine involves the sodium channels in peripheral nerves, while another study suggested there may be an increase in sympathetic nervous system activity after the infusion of lidocaine.2,9

Ketamine infusions not previously described in the treatment of AD have long been used to treat other chronic pain syndromes (chronic cancer pain, complex regional pain syndrome [CRPS], fibromyalgia, migraine, ischemic pain, and neuropathic pain).9,12,13 Ketamine has been shown to decrease pain intensity and reduce the amount of opioid analgesic necessary to achieve pain relief, likely through the antagonism of N-methyl-D-aspartate receptors.12 A retrospective review by Patil and Anitescu described subanesthetic ketamine infusions used as a last-line therapy in refractory pain syndromes. They found ketamine reduced VAS scores from mean 8.5 prior to infusion to 0.8 after infusion in patients with CRPS and from 7.0 prior to infusion to 1.0 in patient with non-CRPS refractory pain syndromes.13 Hypertension and sedation were the most frequent AEs of ketamine infusion, though a higher incidence of hallucination and confusion were noted in non-CRPS patients. Hocking and Cousins suggest that psychotomimetic AEs of ketamine infusion may be more likely in patients with anxiety.14 However, it is important to note that ketamine infusion studies have been heterogeneous in their protocol, and only recently have standardization guidelines been proposed.15

 

 

Physical Modalities

Manual lymphatic massage has been described in multiple reports for symptom relief in patients with cancer with malignant growth causing outflow lymphatic obstruction. This technique also has been used to treat the obstructive symptoms seen with the lipomatous growths of AD. Lange and colleagues described a case as providing reduction in pain and the diameter of extremities with twice weekly massage.14 Herbst and colleagues noted that patients had an equivocal response to massage, with some patients finding that it worsened the progression of lipomatous growths.7

Electrocutaneous Stimulation

In a case study by Martinenghi and colleagues, a patient with AD improved following transcutaneous frequency rhythmic electrical modulation system (FREMS) treatment.16 The treatment involved 4 cycles of 30 minutes each for 6 months. The patient had an improvement of pain on the VAS from 6.4 to 1.7 and an increase from 12 to 18 on the 100-point Barthel index scale for performance in activities of daily living, suggesting an improvement of functional independence as well.16

The MC5-A Calmare is another cutaneous electrostimulation modality that previously has been used for chronic cancer pain management. This FDA-cleared device is indicated for the treatment of various chronic pain syndromes. The device is proposed to stimulate 5 separate pain areas via cutaneous electrodes applied beyond and above the painful areas in order to “scramble” pain information and reduce perception of chronic pain intensity. Ricci and colleagues included cancer and noncancer subjects in their study and observed reduction in pain intensity by 74% (on numeric rating scale) in the entire subject group after 10 days of treatments. Further, no AEs were reported in either group, and most of the subjects were willing to continue treatment.17 However, this modality was limited by concerns with insurance coverage, access to a Calmare machine, operator training, and reproducibility of electrode placement to achieve “zero pain” as is the determinant of device treatment cycle output by the manufacturer.

Perineural Injection/Prolotherapy

Perineural injection therapy (PIT) involves the injection of dextrose solution into tissues surrounding an inflamed nerve to reduce neuropathic inflammation. The proposed source of this inflammation is the stimulation of the superficial branches of peptidergic peripheral nerves. Injections are SC and target the affected superficial nerve pathway. Pain relief is usually immediate but requires several treatments to ensure a lasting benefit. There have been no research studies or case reports on the use of PIT or prolotherapy and AD. Although there is a paucity of published literature on the efficacy of PIT, it remains an alternative modality for treatment of chronic pain syndromes. In a systematic review of prolotherapy for chronic musculoskeletal pain, Hauser and colleagues supported the use of dextrose prolotherapy to treat chronic tendinopathies, osteoarthritis of finger and knee joints, spinal and pelvic pain if conservative measures had failed. However, the efficacy on acute musculoskeletal pain was uncertain.18 In addition to the paucity of published literature, prolotherapy is not available to many patients due to lack of insurance coverage or lack of providers able to perform the procedure.

 

 

Hypobaric Pressure Therapy

Hypobaric pressure therapy has been offered as an alternative “touch-free” method for treatment of pain associated with edema. Herbst and Rutledge describe a pilot study focusing on hypobaric pressure therapy in patients with AD using a cyclic altitude conditioning system, which significantly decreased the Pain Catastrophizing Scale (tendency to catastrophize pain symptoms) in patients with AD after 5 days of therapy. VAS scores also demonstrated a linear decrease over 5 days.8

Acupuncture

There have been no research studies or case reports regarding the use of either traditional full body acupuncture or BFA in management of AD. However, prior studies have been performed that suggest that acupuncture can be beneficial in chronic pain relief. For examples, a Cochrane review by Manheimer and colleagues showed that acupuncture had a significant benefit in pain relief in subjects with peripheral joint arthritis.19 In another Cochrane review there was low-to-moderate level evidence compared with no treatment in pain relief, but moderate-level evidence that the effect of acupuncture does not differ from sham (placebo) acupuncture.20,21

Conclusion

Current therapeutic approaches to AD focus on invasive surgical intervention, chronic opiate and oral medication management. However, we have detailed several additional approaches to AD treatment. Ketamine infusions, which have long been a treatment in other chronic pain syndromes may present a viable alternative to lidocaine infusions in patients with AD. Electrocutaneous stimulation is a validated treatment of chronic pain syndromes, including chronic neuropathic pain and offers an alternative to surgical or pharmacologic management. Further, PIT offers another approach to neuropathic pain management, which has yet to be fully explored. As no standard treatment approach exists for patients with AD, multimodal therapies should be considered to optimize pain management and reduce dependency on opiate mediations.

Acknowledgments
Hunter Holmes McGuire Research Institute and the Physical Medicine and Rehabilitation Department provided the resources and facilities to make this work possible.

References

1. Dercum FX. A subcutaneous dystrophy. In: University of Pennsylvania. University of Pennsylvania Medical Bulletin. Vol 1. Philadelphia, PA; University of Pennsylvania Press; 1888:140-150. Accessed October 4, 2019.

2. Hansson E, Svensson H, Brorson H. Review of Dercum’s disease and proposal of diagnositc criteria, diagnositic methods, classification and management. Orphanet J Rare Dis. 2012;7:1-15.

3. Amine B, Leguilchard F, Benhamou CL. Dercum’s disease (adiposis dolorosa): a new case-report. Joint Bone Spine. 2004;71(2):147-149.

4. Desai MJ, Siriki R, Wang D. Treatment of pain in Dercum’s disease with lidoderm (lidocaine 5% patch): a case report. Pain Med. 2008;9(8):1224-1226.

5. Hansson E, Svensson H, Brorson H. Liposuction may reduce pain in Dercum’s disease (adiposis dolorosa). Pain Med. 2011;12:942-952.

6. Kosseifi S, Anaya E, Dronovalli G, Leicht S. Dercum’s disease: an unusual presentation. Pain Med. 2010;11(9):1430-1434.

7. Herbst KL, Asare-Bediako S. Adiposis dolorasa is more than painful fat. Endocrinologist. 2007;17(6):326-334.

8. Herbst KL, Rutledge T. Pilot study: rapidly cycling hypobaric pressure improves pain after 5 days in adiposis dolorosa. J Pain Res. 2010;3:147-153.

9. Lange U, Oelzner P, Uhlemann C. Dercum’s disease (lipomatosis dolorosa): successful therapy with pregabalin and manual lymphatic drainage and a current overview. Rheumatol Int. 2008;29(1):17-22

10. Schaffer PR, Hale CS, Meehan SA, Shupack JL, Ramachandran S. Adoposis dolorosa. Dermatol Online J. 2014;20(12):1-3.

11. Singal A, Janiga JJ, Bossenbroek NM, Lim HW. Dercum’s disease (adiposis dolorosa): a report of improvement with infliximab and methotrexate. J Eur Acad Dermatol Venerol. 2007;21(5):717.

12. Loftus RW, Yeager MP, Clark JA, et al. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology. 2010;113(3):639-646.

13. Patil S, Anitescu M. Efficacy of outpatient ketamine infusions in refractory chronic pain syndromes: a 5-year retrospective analysis. Pain Med. 2012;13(2):263-269.

14. Hocking G, Cousins MJ. Ketamine in chronic pain management: an evidence-based review. Anesth Analg. 2003;97(6):1730-1739.

15. Cohen SP, Bhatia A, Buvanendran A, et al. Consensus guidelines on the use of intravenous ketamine infusions for chronic pain from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018;43(5):521-546.

16. Martinenghi S, Caretto A, Losio C, Scavini M, Bosi E. Successful treatment of Dercum’s disease by transcutaneous electrical stimulation: a case report. Medicine (Baltimore). 2015;94(24):e950.

17. Ricci M, Pirotti S, Scarpi E, et al. Managing chronic pain: results from an open-label study using MC5-A Calmare device. Support Care Cancer. 2012;20(2):405-412.

18. Hauser RA, Lackner JB, Steilen-Matias D, Harris DK. A systematic review of dextrose prolotherapy for chronic musculoskeletal pain. Clin Med Insights Arthritis Musculoskelet Disord. 2016;9:139-159.

19. Manheimer E, Cheng K, Linde K, et al. Acupuncture for peripheral joint osteoarthritis. Cochrane Database Syst Rev. 2010;(1):CD001977.

20. Deare JC, Zheng Z, Xue CC, et al. Acupuncture for treating fibromyalgia. Cochrane Database Syst Rev. 2013;(5):CD007070.

21. Chan MWC, Wu XY, Wu JCY, Wong SYS, Chung VCH. Safety of acupuncture: overview of systematic reviews. Sci Rep. 2017;7(1):3369.

Article PDF
Author and Disclosure Information

Anne Eliason is a Physiatrist at Kaiser Permanente in Jonesboro, Georgia. Young IL Seo is a Physiatrist at CNY Spine and Pain in Syracuse, New York. Douglas Murphy is the Regional Amputation Center Medical Director at Hunter Holmes Medical Center in Richmond, Virginia. Christopher Beal is a Pain Management Physician at Lexington Medical Center in West Columbia, South Carolina. At the time the article was written Young Il Seo was a Fellow in the Department of Physical Medicine and Rehabilitation (PM&R) at Hunter Holmes McGuire VA Medical Center, and Anne Eliason was a Resident in the Department of PM&R at Virginia Commonwealth University in Richmond.
Correspondence: Douglas Murphy ([email protected])

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Issue
Federal Practitioner - 36(11)a
Publications
Topics
Page Number
530-533
Sections
Author and Disclosure Information

Anne Eliason is a Physiatrist at Kaiser Permanente in Jonesboro, Georgia. Young IL Seo is a Physiatrist at CNY Spine and Pain in Syracuse, New York. Douglas Murphy is the Regional Amputation Center Medical Director at Hunter Holmes Medical Center in Richmond, Virginia. Christopher Beal is a Pain Management Physician at Lexington Medical Center in West Columbia, South Carolina. At the time the article was written Young Il Seo was a Fellow in the Department of Physical Medicine and Rehabilitation (PM&R) at Hunter Holmes McGuire VA Medical Center, and Anne Eliason was a Resident in the Department of PM&R at Virginia Commonwealth University in Richmond.
Correspondence: Douglas Murphy ([email protected])

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Author and Disclosure Information

Anne Eliason is a Physiatrist at Kaiser Permanente in Jonesboro, Georgia. Young IL Seo is a Physiatrist at CNY Spine and Pain in Syracuse, New York. Douglas Murphy is the Regional Amputation Center Medical Director at Hunter Holmes Medical Center in Richmond, Virginia. Christopher Beal is a Pain Management Physician at Lexington Medical Center in West Columbia, South Carolina. At the time the article was written Young Il Seo was a Fellow in the Department of Physical Medicine and Rehabilitation (PM&R) at Hunter Holmes McGuire VA Medical Center, and Anne Eliason was a Resident in the Department of PM&R at Virginia Commonwealth University in Richmond.
Correspondence: Douglas Murphy ([email protected])

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Article PDF
Article PDF
Related Articles
While current approaches to treatment focus on surgery, opiates, and other medications, health care providers may also consider ketamine infusion, electrostimulation, and perineural injections.
While current approaches to treatment focus on surgery, opiates, and other medications, health care providers may also consider ketamine infusion, electrostimulation, and perineural injections.

Adiposis dolorosa (AD), or Dercum disease, is a rare disorder that was first described in 1888 and characterized by the National Organization of Rare Disorders (NORD) as a chronic pain condition of the adipose tissue generally found in patients who are overweight or obese.1,2 AD is more common in females aged 35 to 50 years and proposed to be a disease of postmenopausal women, though no prevalence studies exist.2 The etiology remains unclear.2 Several theories have been proposed, including endocrine and nervous system dysfunction, adipose tissue dysregulation, or pressure on peripheral nerves and chronic inflammation.2-4 Genetic, autoimmune, and trauma also have been proposed as a mechanism for developing the disease. Treatment modalities focusing on narcotic analgesics have been ineffective in long-term management.3

The objective of the case presentation is to report a variety of approaches for AD and their relative successes at pain control in order to assist other medical professionals who may come across patients with this rare condition.

Case Presentation

A 53-year-old male with a history of blast exposure-related traumatic brain injury, subsequent stroke with residual left hemiparesis, and seizure disorder presented with a 10-year history of nodule formation in his lower extremities causing restriction of motion and pain. The patient had previously undergone lower extremity fasciotomies for compartment syndrome with minimal pain relief. In addition, nodules over his abdomen and chest wall had been increasing over the past 5 years. He also experienced worsening fatigue, cramping, tightness, and paresthesias of the affected areas during this time. Erythema and temperature allodynia were noted in addition to an 80-pound weight gain. From the above symptoms and nodule excision showing histologic signs of lipomatous growth, a diagnosis of AD was made.

The following constitutes the approximate timetable of his treatments for 9 years. He was first diagnosed incidentally at the beginning of this period with AD during an electrodiagnostic examination. He had noticed the lipomas when he was in his 30s, but initially they were not painful. He was referred for treatment of pain to the physical medicine and rehabilitation department.

For the next 3 years, he was treated with prolotherapy. Five percent dextrose in water was injected around many of the painful lipomas in the upper extremities. He noted after the second round of neural prolotherapy that he had reduced swelling of his upper extremities and the lipomas decreased in size. He experienced mild improvement in pain and functional usage of his arms.

He continued to receive neural prolotherapy into the nodules in the arms, legs, abdomen, and chest wall. The number of painful nodules continued to increase, and the patient was started on hydrocodone 10 mg/acetaminophen 325 mg (1 tablet every 6 hours as needed) and methadone for pain relief. He was initially started on 5 mg per day of methadone and then was increased in a stepwise, gradual fashion to 10 mg in the morning and 15 mg in the evening. He transitioned to morphine sulfate, which was increased to a maximum dose of 45 mg twice daily. This medication was slowly tapered due to adverse effects (AEs), including sedation.

After weaning off morphine sulfate, the patient was started on lidocaine infusions every 3 months. Each infusion provided at least 50% pain reduction for 6 to 8 weeks. He was approved by the US Department of Veterans Affairs (VA) to have Vaser (Bausch Health, Laval, Canada) minimally invasive ultrasound liposuction treatment, performed at an outside facility. The patient was satisfied with the pain relief that he received and noted that the number of lipomas greatly diminished. However, due to funding issues, this treatment was discontinued after several months.

The patient had moderately good pain relief with methadone 5 mg in the morning, and 15 mg in the evening. However, the patient reported significant somnolence during the daytime with the regimen. Attempts to wean the patient off methadone was met with uncontrollable daytime pain. With suboptimal oral pain regimen, difficulty obtaining Vaser treatments, and limitation in frequency of neural prolotherapy, the decision was made to initiate 12 treatments of Calmare (Fairfield, CT) cutaneous electrostimulation.

During his first treatment, he had the electrodes placed on his lower extremities. The pre- and posttreatment 10-point visual analog scale (VAS) scores were 9 and 0, respectively, after the first visit. The position of the electrodes varied, depending on the location of his pain, including upper extremities and abdominal wall. During the treatment course, the patient experienced an improvement in subjective functional status. He was able to sleep in the same bed as his wife, shake hands without severe pain, and walk .25 mile, all of which he was unable to do before the electrostimulative treatment. He also reported overall improvement in emotional well-being, resumption of his hobbies (eg, playing the guitar), and social engagement. Methadone was successfully weaned off during this trial without breakthrough pain. This improvement in pain and functional status continued for several weeks; however, he had an exacerbation of his pain following a long plane flight. Due to uncertain reliability of pain relief with the procedure, the pain management service initiated a regimen of methadone 10 mg twice daily to be initiated when a procedure does not provide the desired duration of pain relief and gradually discontinued following the next interventional procedure.

The patient continued a regimen that included lidocaine infusions, neural prolotherapy, Calmare electrostimulative therapy, as well as lymphedema massage. Additionally, he began receiving weekly acupuncture treatments. He started with traditional full body acupuncture and then transitioned to battlefield acupuncture (BFA). Each acupuncture treatment provided about 50% improvement in pain on the VAS, and improved sleep for 3 days posttreatment.

However, after 18 months of the above treatment protocol, the patient experienced a general tonic-clonic seizure at home. Due to concern for the lowered seizure threshold, lidocaine infusions and methadone were discontinued. Long-acting oral morphine was initiated. The patient continued Calmare treatments and neural prolotherapy after a seizure-free interval. This regimen provided the patient with temporary pain relief but for a shorter duration than prior interventions.

Ketamine infusions were eventually initiated about 5 years after the diagnosis of AD was made, with postprocedure pain as 0/10 on the VAS. Pain relief was sustained for 3 months, with the notable AEs of hallucinations in the immediate postinfusion period. Administration consisted of the following: 500 mg of ketamine in a 500 mL bag of 0.9% NaCl. A 60-mg slow IV push was given followed by 60 mg/h increased every 15 min by 10 mg/h for a maximum dose of 150 mg/h. In a single visit the maximum total dose of ketamine administered was 500 mg. The protocol, which usually delivered 200 mg in a visit but was increased to 500 mg because the 200-mg dose was ineffective, was based on protocols at other institutions to accommodate the level of monitoring available in the Interventional Pain Clinic. The clinic also developed an infusion protocol with at least 1 month between treatments. The patient continues to undergo scheduled ketamine infusions every 14 weeks in addition to monthly BFA. The patient reported near total pain relief for about a month following ketamine infusion, with about 3 months of sustained pain relief. Each BFA session continues to provide 3 days of relief from insomnia. Calmare treatments and the neural prolotherapy regimen continue to provide effective but temporary relief from pain.

 

 

Discussion

Currently there is no curative treatment for AD. The majority of the literature is composed of case reports without summaries of potential interventions and their efficacies. AD therapies focus on symptom relief and mainly include pharmacologic and surgical intervention. In this case report several novel treatment modalities have been shown to be partially effective.

Surgical Intervention

Liposuction and lipoma resection have been described as effective only in the short term for AD.2,4-6 Hansson and colleagues suggested liposuction avulsion for sensory nerves and a portion of the proposed abnormal nerve connections between the peripheral nervous system and sensory nerves as a potential therapy for pain improvement.5 But the clinical significance of pain relief from liposuction is unclear and is contraindicated in recurrent lipomas.5

Pharmaceutical Approach

Although relief with nonsteroidal anti-inflammatory drugs and narcotic analgesics have been unpredictable, Herbst and Asare-Bediako described significant pain relief in a subset of patients with AD with a variety of oral analgesics.7,8 However, the duration of this relief was not clearly stated, and the types or medications or combinations were not discussed. Other pharmacologic agents trialed in the treatment of AD include methotrexate, infliximab, Interferon α-2b, and calcium channel modulators (pregabalin and oxcarbazepine).2,9-11 However, the mechanism and significance of pain relief from these medications remain unclear.

Subanesthesia Therapy

Lidocaine has been used as both a topical agent and an IV infusion in the treatment of chronic pain due to AD for decades. Desai and colleagues described 60% sustained pain reduction in a patient using lidocaine 5% transdermal patches.4 IV infusion of lidocaine has been described in various dosages, though the mechanism of pain relief is ambiguous, and the duration of effect is longer than the biologic half-life.2-4,9 Kosseifi and colleagues describe a patient treated with local injections of lidocaine 1% and obtained symptomatic relief for 3 weeks.9 Animal studies suggest the action of lidocaine involves the sodium channels in peripheral nerves, while another study suggested there may be an increase in sympathetic nervous system activity after the infusion of lidocaine.2,9

Ketamine infusions not previously described in the treatment of AD have long been used to treat other chronic pain syndromes (chronic cancer pain, complex regional pain syndrome [CRPS], fibromyalgia, migraine, ischemic pain, and neuropathic pain).9,12,13 Ketamine has been shown to decrease pain intensity and reduce the amount of opioid analgesic necessary to achieve pain relief, likely through the antagonism of N-methyl-D-aspartate receptors.12 A retrospective review by Patil and Anitescu described subanesthetic ketamine infusions used as a last-line therapy in refractory pain syndromes. They found ketamine reduced VAS scores from mean 8.5 prior to infusion to 0.8 after infusion in patients with CRPS and from 7.0 prior to infusion to 1.0 in patient with non-CRPS refractory pain syndromes.13 Hypertension and sedation were the most frequent AEs of ketamine infusion, though a higher incidence of hallucination and confusion were noted in non-CRPS patients. Hocking and Cousins suggest that psychotomimetic AEs of ketamine infusion may be more likely in patients with anxiety.14 However, it is important to note that ketamine infusion studies have been heterogeneous in their protocol, and only recently have standardization guidelines been proposed.15

 

 

Physical Modalities

Manual lymphatic massage has been described in multiple reports for symptom relief in patients with cancer with malignant growth causing outflow lymphatic obstruction. This technique also has been used to treat the obstructive symptoms seen with the lipomatous growths of AD. Lange and colleagues described a case as providing reduction in pain and the diameter of extremities with twice weekly massage.14 Herbst and colleagues noted that patients had an equivocal response to massage, with some patients finding that it worsened the progression of lipomatous growths.7

Electrocutaneous Stimulation

In a case study by Martinenghi and colleagues, a patient with AD improved following transcutaneous frequency rhythmic electrical modulation system (FREMS) treatment.16 The treatment involved 4 cycles of 30 minutes each for 6 months. The patient had an improvement of pain on the VAS from 6.4 to 1.7 and an increase from 12 to 18 on the 100-point Barthel index scale for performance in activities of daily living, suggesting an improvement of functional independence as well.16

The MC5-A Calmare is another cutaneous electrostimulation modality that previously has been used for chronic cancer pain management. This FDA-cleared device is indicated for the treatment of various chronic pain syndromes. The device is proposed to stimulate 5 separate pain areas via cutaneous electrodes applied beyond and above the painful areas in order to “scramble” pain information and reduce perception of chronic pain intensity. Ricci and colleagues included cancer and noncancer subjects in their study and observed reduction in pain intensity by 74% (on numeric rating scale) in the entire subject group after 10 days of treatments. Further, no AEs were reported in either group, and most of the subjects were willing to continue treatment.17 However, this modality was limited by concerns with insurance coverage, access to a Calmare machine, operator training, and reproducibility of electrode placement to achieve “zero pain” as is the determinant of device treatment cycle output by the manufacturer.

Perineural Injection/Prolotherapy

Perineural injection therapy (PIT) involves the injection of dextrose solution into tissues surrounding an inflamed nerve to reduce neuropathic inflammation. The proposed source of this inflammation is the stimulation of the superficial branches of peptidergic peripheral nerves. Injections are SC and target the affected superficial nerve pathway. Pain relief is usually immediate but requires several treatments to ensure a lasting benefit. There have been no research studies or case reports on the use of PIT or prolotherapy and AD. Although there is a paucity of published literature on the efficacy of PIT, it remains an alternative modality for treatment of chronic pain syndromes. In a systematic review of prolotherapy for chronic musculoskeletal pain, Hauser and colleagues supported the use of dextrose prolotherapy to treat chronic tendinopathies, osteoarthritis of finger and knee joints, spinal and pelvic pain if conservative measures had failed. However, the efficacy on acute musculoskeletal pain was uncertain.18 In addition to the paucity of published literature, prolotherapy is not available to many patients due to lack of insurance coverage or lack of providers able to perform the procedure.

 

 

Hypobaric Pressure Therapy

Hypobaric pressure therapy has been offered as an alternative “touch-free” method for treatment of pain associated with edema. Herbst and Rutledge describe a pilot study focusing on hypobaric pressure therapy in patients with AD using a cyclic altitude conditioning system, which significantly decreased the Pain Catastrophizing Scale (tendency to catastrophize pain symptoms) in patients with AD after 5 days of therapy. VAS scores also demonstrated a linear decrease over 5 days.8

Acupuncture

There have been no research studies or case reports regarding the use of either traditional full body acupuncture or BFA in management of AD. However, prior studies have been performed that suggest that acupuncture can be beneficial in chronic pain relief. For examples, a Cochrane review by Manheimer and colleagues showed that acupuncture had a significant benefit in pain relief in subjects with peripheral joint arthritis.19 In another Cochrane review there was low-to-moderate level evidence compared with no treatment in pain relief, but moderate-level evidence that the effect of acupuncture does not differ from sham (placebo) acupuncture.20,21

Conclusion

Current therapeutic approaches to AD focus on invasive surgical intervention, chronic opiate and oral medication management. However, we have detailed several additional approaches to AD treatment. Ketamine infusions, which have long been a treatment in other chronic pain syndromes may present a viable alternative to lidocaine infusions in patients with AD. Electrocutaneous stimulation is a validated treatment of chronic pain syndromes, including chronic neuropathic pain and offers an alternative to surgical or pharmacologic management. Further, PIT offers another approach to neuropathic pain management, which has yet to be fully explored. As no standard treatment approach exists for patients with AD, multimodal therapies should be considered to optimize pain management and reduce dependency on opiate mediations.

Acknowledgments
Hunter Holmes McGuire Research Institute and the Physical Medicine and Rehabilitation Department provided the resources and facilities to make this work possible.

Adiposis dolorosa (AD), or Dercum disease, is a rare disorder that was first described in 1888 and characterized by the National Organization of Rare Disorders (NORD) as a chronic pain condition of the adipose tissue generally found in patients who are overweight or obese.1,2 AD is more common in females aged 35 to 50 years and proposed to be a disease of postmenopausal women, though no prevalence studies exist.2 The etiology remains unclear.2 Several theories have been proposed, including endocrine and nervous system dysfunction, adipose tissue dysregulation, or pressure on peripheral nerves and chronic inflammation.2-4 Genetic, autoimmune, and trauma also have been proposed as a mechanism for developing the disease. Treatment modalities focusing on narcotic analgesics have been ineffective in long-term management.3

The objective of the case presentation is to report a variety of approaches for AD and their relative successes at pain control in order to assist other medical professionals who may come across patients with this rare condition.

Case Presentation

A 53-year-old male with a history of blast exposure-related traumatic brain injury, subsequent stroke with residual left hemiparesis, and seizure disorder presented with a 10-year history of nodule formation in his lower extremities causing restriction of motion and pain. The patient had previously undergone lower extremity fasciotomies for compartment syndrome with minimal pain relief. In addition, nodules over his abdomen and chest wall had been increasing over the past 5 years. He also experienced worsening fatigue, cramping, tightness, and paresthesias of the affected areas during this time. Erythema and temperature allodynia were noted in addition to an 80-pound weight gain. From the above symptoms and nodule excision showing histologic signs of lipomatous growth, a diagnosis of AD was made.

The following constitutes the approximate timetable of his treatments for 9 years. He was first diagnosed incidentally at the beginning of this period with AD during an electrodiagnostic examination. He had noticed the lipomas when he was in his 30s, but initially they were not painful. He was referred for treatment of pain to the physical medicine and rehabilitation department.

For the next 3 years, he was treated with prolotherapy. Five percent dextrose in water was injected around many of the painful lipomas in the upper extremities. He noted after the second round of neural prolotherapy that he had reduced swelling of his upper extremities and the lipomas decreased in size. He experienced mild improvement in pain and functional usage of his arms.

He continued to receive neural prolotherapy into the nodules in the arms, legs, abdomen, and chest wall. The number of painful nodules continued to increase, and the patient was started on hydrocodone 10 mg/acetaminophen 325 mg (1 tablet every 6 hours as needed) and methadone for pain relief. He was initially started on 5 mg per day of methadone and then was increased in a stepwise, gradual fashion to 10 mg in the morning and 15 mg in the evening. He transitioned to morphine sulfate, which was increased to a maximum dose of 45 mg twice daily. This medication was slowly tapered due to adverse effects (AEs), including sedation.

After weaning off morphine sulfate, the patient was started on lidocaine infusions every 3 months. Each infusion provided at least 50% pain reduction for 6 to 8 weeks. He was approved by the US Department of Veterans Affairs (VA) to have Vaser (Bausch Health, Laval, Canada) minimally invasive ultrasound liposuction treatment, performed at an outside facility. The patient was satisfied with the pain relief that he received and noted that the number of lipomas greatly diminished. However, due to funding issues, this treatment was discontinued after several months.

The patient had moderately good pain relief with methadone 5 mg in the morning, and 15 mg in the evening. However, the patient reported significant somnolence during the daytime with the regimen. Attempts to wean the patient off methadone was met with uncontrollable daytime pain. With suboptimal oral pain regimen, difficulty obtaining Vaser treatments, and limitation in frequency of neural prolotherapy, the decision was made to initiate 12 treatments of Calmare (Fairfield, CT) cutaneous electrostimulation.

During his first treatment, he had the electrodes placed on his lower extremities. The pre- and posttreatment 10-point visual analog scale (VAS) scores were 9 and 0, respectively, after the first visit. The position of the electrodes varied, depending on the location of his pain, including upper extremities and abdominal wall. During the treatment course, the patient experienced an improvement in subjective functional status. He was able to sleep in the same bed as his wife, shake hands without severe pain, and walk .25 mile, all of which he was unable to do before the electrostimulative treatment. He also reported overall improvement in emotional well-being, resumption of his hobbies (eg, playing the guitar), and social engagement. Methadone was successfully weaned off during this trial without breakthrough pain. This improvement in pain and functional status continued for several weeks; however, he had an exacerbation of his pain following a long plane flight. Due to uncertain reliability of pain relief with the procedure, the pain management service initiated a regimen of methadone 10 mg twice daily to be initiated when a procedure does not provide the desired duration of pain relief and gradually discontinued following the next interventional procedure.

The patient continued a regimen that included lidocaine infusions, neural prolotherapy, Calmare electrostimulative therapy, as well as lymphedema massage. Additionally, he began receiving weekly acupuncture treatments. He started with traditional full body acupuncture and then transitioned to battlefield acupuncture (BFA). Each acupuncture treatment provided about 50% improvement in pain on the VAS, and improved sleep for 3 days posttreatment.

However, after 18 months of the above treatment protocol, the patient experienced a general tonic-clonic seizure at home. Due to concern for the lowered seizure threshold, lidocaine infusions and methadone were discontinued. Long-acting oral morphine was initiated. The patient continued Calmare treatments and neural prolotherapy after a seizure-free interval. This regimen provided the patient with temporary pain relief but for a shorter duration than prior interventions.

Ketamine infusions were eventually initiated about 5 years after the diagnosis of AD was made, with postprocedure pain as 0/10 on the VAS. Pain relief was sustained for 3 months, with the notable AEs of hallucinations in the immediate postinfusion period. Administration consisted of the following: 500 mg of ketamine in a 500 mL bag of 0.9% NaCl. A 60-mg slow IV push was given followed by 60 mg/h increased every 15 min by 10 mg/h for a maximum dose of 150 mg/h. In a single visit the maximum total dose of ketamine administered was 500 mg. The protocol, which usually delivered 200 mg in a visit but was increased to 500 mg because the 200-mg dose was ineffective, was based on protocols at other institutions to accommodate the level of monitoring available in the Interventional Pain Clinic. The clinic also developed an infusion protocol with at least 1 month between treatments. The patient continues to undergo scheduled ketamine infusions every 14 weeks in addition to monthly BFA. The patient reported near total pain relief for about a month following ketamine infusion, with about 3 months of sustained pain relief. Each BFA session continues to provide 3 days of relief from insomnia. Calmare treatments and the neural prolotherapy regimen continue to provide effective but temporary relief from pain.

 

 

Discussion

Currently there is no curative treatment for AD. The majority of the literature is composed of case reports without summaries of potential interventions and their efficacies. AD therapies focus on symptom relief and mainly include pharmacologic and surgical intervention. In this case report several novel treatment modalities have been shown to be partially effective.

Surgical Intervention

Liposuction and lipoma resection have been described as effective only in the short term for AD.2,4-6 Hansson and colleagues suggested liposuction avulsion for sensory nerves and a portion of the proposed abnormal nerve connections between the peripheral nervous system and sensory nerves as a potential therapy for pain improvement.5 But the clinical significance of pain relief from liposuction is unclear and is contraindicated in recurrent lipomas.5

Pharmaceutical Approach

Although relief with nonsteroidal anti-inflammatory drugs and narcotic analgesics have been unpredictable, Herbst and Asare-Bediako described significant pain relief in a subset of patients with AD with a variety of oral analgesics.7,8 However, the duration of this relief was not clearly stated, and the types or medications or combinations were not discussed. Other pharmacologic agents trialed in the treatment of AD include methotrexate, infliximab, Interferon α-2b, and calcium channel modulators (pregabalin and oxcarbazepine).2,9-11 However, the mechanism and significance of pain relief from these medications remain unclear.

Subanesthesia Therapy

Lidocaine has been used as both a topical agent and an IV infusion in the treatment of chronic pain due to AD for decades. Desai and colleagues described 60% sustained pain reduction in a patient using lidocaine 5% transdermal patches.4 IV infusion of lidocaine has been described in various dosages, though the mechanism of pain relief is ambiguous, and the duration of effect is longer than the biologic half-life.2-4,9 Kosseifi and colleagues describe a patient treated with local injections of lidocaine 1% and obtained symptomatic relief for 3 weeks.9 Animal studies suggest the action of lidocaine involves the sodium channels in peripheral nerves, while another study suggested there may be an increase in sympathetic nervous system activity after the infusion of lidocaine.2,9

Ketamine infusions not previously described in the treatment of AD have long been used to treat other chronic pain syndromes (chronic cancer pain, complex regional pain syndrome [CRPS], fibromyalgia, migraine, ischemic pain, and neuropathic pain).9,12,13 Ketamine has been shown to decrease pain intensity and reduce the amount of opioid analgesic necessary to achieve pain relief, likely through the antagonism of N-methyl-D-aspartate receptors.12 A retrospective review by Patil and Anitescu described subanesthetic ketamine infusions used as a last-line therapy in refractory pain syndromes. They found ketamine reduced VAS scores from mean 8.5 prior to infusion to 0.8 after infusion in patients with CRPS and from 7.0 prior to infusion to 1.0 in patient with non-CRPS refractory pain syndromes.13 Hypertension and sedation were the most frequent AEs of ketamine infusion, though a higher incidence of hallucination and confusion were noted in non-CRPS patients. Hocking and Cousins suggest that psychotomimetic AEs of ketamine infusion may be more likely in patients with anxiety.14 However, it is important to note that ketamine infusion studies have been heterogeneous in their protocol, and only recently have standardization guidelines been proposed.15

 

 

Physical Modalities

Manual lymphatic massage has been described in multiple reports for symptom relief in patients with cancer with malignant growth causing outflow lymphatic obstruction. This technique also has been used to treat the obstructive symptoms seen with the lipomatous growths of AD. Lange and colleagues described a case as providing reduction in pain and the diameter of extremities with twice weekly massage.14 Herbst and colleagues noted that patients had an equivocal response to massage, with some patients finding that it worsened the progression of lipomatous growths.7

Electrocutaneous Stimulation

In a case study by Martinenghi and colleagues, a patient with AD improved following transcutaneous frequency rhythmic electrical modulation system (FREMS) treatment.16 The treatment involved 4 cycles of 30 minutes each for 6 months. The patient had an improvement of pain on the VAS from 6.4 to 1.7 and an increase from 12 to 18 on the 100-point Barthel index scale for performance in activities of daily living, suggesting an improvement of functional independence as well.16

The MC5-A Calmare is another cutaneous electrostimulation modality that previously has been used for chronic cancer pain management. This FDA-cleared device is indicated for the treatment of various chronic pain syndromes. The device is proposed to stimulate 5 separate pain areas via cutaneous electrodes applied beyond and above the painful areas in order to “scramble” pain information and reduce perception of chronic pain intensity. Ricci and colleagues included cancer and noncancer subjects in their study and observed reduction in pain intensity by 74% (on numeric rating scale) in the entire subject group after 10 days of treatments. Further, no AEs were reported in either group, and most of the subjects were willing to continue treatment.17 However, this modality was limited by concerns with insurance coverage, access to a Calmare machine, operator training, and reproducibility of electrode placement to achieve “zero pain” as is the determinant of device treatment cycle output by the manufacturer.

Perineural Injection/Prolotherapy

Perineural injection therapy (PIT) involves the injection of dextrose solution into tissues surrounding an inflamed nerve to reduce neuropathic inflammation. The proposed source of this inflammation is the stimulation of the superficial branches of peptidergic peripheral nerves. Injections are SC and target the affected superficial nerve pathway. Pain relief is usually immediate but requires several treatments to ensure a lasting benefit. There have been no research studies or case reports on the use of PIT or prolotherapy and AD. Although there is a paucity of published literature on the efficacy of PIT, it remains an alternative modality for treatment of chronic pain syndromes. In a systematic review of prolotherapy for chronic musculoskeletal pain, Hauser and colleagues supported the use of dextrose prolotherapy to treat chronic tendinopathies, osteoarthritis of finger and knee joints, spinal and pelvic pain if conservative measures had failed. However, the efficacy on acute musculoskeletal pain was uncertain.18 In addition to the paucity of published literature, prolotherapy is not available to many patients due to lack of insurance coverage or lack of providers able to perform the procedure.

 

 

Hypobaric Pressure Therapy

Hypobaric pressure therapy has been offered as an alternative “touch-free” method for treatment of pain associated with edema. Herbst and Rutledge describe a pilot study focusing on hypobaric pressure therapy in patients with AD using a cyclic altitude conditioning system, which significantly decreased the Pain Catastrophizing Scale (tendency to catastrophize pain symptoms) in patients with AD after 5 days of therapy. VAS scores also demonstrated a linear decrease over 5 days.8

Acupuncture

There have been no research studies or case reports regarding the use of either traditional full body acupuncture or BFA in management of AD. However, prior studies have been performed that suggest that acupuncture can be beneficial in chronic pain relief. For examples, a Cochrane review by Manheimer and colleagues showed that acupuncture had a significant benefit in pain relief in subjects with peripheral joint arthritis.19 In another Cochrane review there was low-to-moderate level evidence compared with no treatment in pain relief, but moderate-level evidence that the effect of acupuncture does not differ from sham (placebo) acupuncture.20,21

Conclusion

Current therapeutic approaches to AD focus on invasive surgical intervention, chronic opiate and oral medication management. However, we have detailed several additional approaches to AD treatment. Ketamine infusions, which have long been a treatment in other chronic pain syndromes may present a viable alternative to lidocaine infusions in patients with AD. Electrocutaneous stimulation is a validated treatment of chronic pain syndromes, including chronic neuropathic pain and offers an alternative to surgical or pharmacologic management. Further, PIT offers another approach to neuropathic pain management, which has yet to be fully explored. As no standard treatment approach exists for patients with AD, multimodal therapies should be considered to optimize pain management and reduce dependency on opiate mediations.

Acknowledgments
Hunter Holmes McGuire Research Institute and the Physical Medicine and Rehabilitation Department provided the resources and facilities to make this work possible.

References

1. Dercum FX. A subcutaneous dystrophy. In: University of Pennsylvania. University of Pennsylvania Medical Bulletin. Vol 1. Philadelphia, PA; University of Pennsylvania Press; 1888:140-150. Accessed October 4, 2019.

2. Hansson E, Svensson H, Brorson H. Review of Dercum’s disease and proposal of diagnositc criteria, diagnositic methods, classification and management. Orphanet J Rare Dis. 2012;7:1-15.

3. Amine B, Leguilchard F, Benhamou CL. Dercum’s disease (adiposis dolorosa): a new case-report. Joint Bone Spine. 2004;71(2):147-149.

4. Desai MJ, Siriki R, Wang D. Treatment of pain in Dercum’s disease with lidoderm (lidocaine 5% patch): a case report. Pain Med. 2008;9(8):1224-1226.

5. Hansson E, Svensson H, Brorson H. Liposuction may reduce pain in Dercum’s disease (adiposis dolorosa). Pain Med. 2011;12:942-952.

6. Kosseifi S, Anaya E, Dronovalli G, Leicht S. Dercum’s disease: an unusual presentation. Pain Med. 2010;11(9):1430-1434.

7. Herbst KL, Asare-Bediako S. Adiposis dolorasa is more than painful fat. Endocrinologist. 2007;17(6):326-334.

8. Herbst KL, Rutledge T. Pilot study: rapidly cycling hypobaric pressure improves pain after 5 days in adiposis dolorosa. J Pain Res. 2010;3:147-153.

9. Lange U, Oelzner P, Uhlemann C. Dercum’s disease (lipomatosis dolorosa): successful therapy with pregabalin and manual lymphatic drainage and a current overview. Rheumatol Int. 2008;29(1):17-22

10. Schaffer PR, Hale CS, Meehan SA, Shupack JL, Ramachandran S. Adoposis dolorosa. Dermatol Online J. 2014;20(12):1-3.

11. Singal A, Janiga JJ, Bossenbroek NM, Lim HW. Dercum’s disease (adiposis dolorosa): a report of improvement with infliximab and methotrexate. J Eur Acad Dermatol Venerol. 2007;21(5):717.

12. Loftus RW, Yeager MP, Clark JA, et al. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology. 2010;113(3):639-646.

13. Patil S, Anitescu M. Efficacy of outpatient ketamine infusions in refractory chronic pain syndromes: a 5-year retrospective analysis. Pain Med. 2012;13(2):263-269.

14. Hocking G, Cousins MJ. Ketamine in chronic pain management: an evidence-based review. Anesth Analg. 2003;97(6):1730-1739.

15. Cohen SP, Bhatia A, Buvanendran A, et al. Consensus guidelines on the use of intravenous ketamine infusions for chronic pain from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018;43(5):521-546.

16. Martinenghi S, Caretto A, Losio C, Scavini M, Bosi E. Successful treatment of Dercum’s disease by transcutaneous electrical stimulation: a case report. Medicine (Baltimore). 2015;94(24):e950.

17. Ricci M, Pirotti S, Scarpi E, et al. Managing chronic pain: results from an open-label study using MC5-A Calmare device. Support Care Cancer. 2012;20(2):405-412.

18. Hauser RA, Lackner JB, Steilen-Matias D, Harris DK. A systematic review of dextrose prolotherapy for chronic musculoskeletal pain. Clin Med Insights Arthritis Musculoskelet Disord. 2016;9:139-159.

19. Manheimer E, Cheng K, Linde K, et al. Acupuncture for peripheral joint osteoarthritis. Cochrane Database Syst Rev. 2010;(1):CD001977.

20. Deare JC, Zheng Z, Xue CC, et al. Acupuncture for treating fibromyalgia. Cochrane Database Syst Rev. 2013;(5):CD007070.

21. Chan MWC, Wu XY, Wu JCY, Wong SYS, Chung VCH. Safety of acupuncture: overview of systematic reviews. Sci Rep. 2017;7(1):3369.

References

1. Dercum FX. A subcutaneous dystrophy. In: University of Pennsylvania. University of Pennsylvania Medical Bulletin. Vol 1. Philadelphia, PA; University of Pennsylvania Press; 1888:140-150. Accessed October 4, 2019.

2. Hansson E, Svensson H, Brorson H. Review of Dercum’s disease and proposal of diagnositc criteria, diagnositic methods, classification and management. Orphanet J Rare Dis. 2012;7:1-15.

3. Amine B, Leguilchard F, Benhamou CL. Dercum’s disease (adiposis dolorosa): a new case-report. Joint Bone Spine. 2004;71(2):147-149.

4. Desai MJ, Siriki R, Wang D. Treatment of pain in Dercum’s disease with lidoderm (lidocaine 5% patch): a case report. Pain Med. 2008;9(8):1224-1226.

5. Hansson E, Svensson H, Brorson H. Liposuction may reduce pain in Dercum’s disease (adiposis dolorosa). Pain Med. 2011;12:942-952.

6. Kosseifi S, Anaya E, Dronovalli G, Leicht S. Dercum’s disease: an unusual presentation. Pain Med. 2010;11(9):1430-1434.

7. Herbst KL, Asare-Bediako S. Adiposis dolorasa is more than painful fat. Endocrinologist. 2007;17(6):326-334.

8. Herbst KL, Rutledge T. Pilot study: rapidly cycling hypobaric pressure improves pain after 5 days in adiposis dolorosa. J Pain Res. 2010;3:147-153.

9. Lange U, Oelzner P, Uhlemann C. Dercum’s disease (lipomatosis dolorosa): successful therapy with pregabalin and manual lymphatic drainage and a current overview. Rheumatol Int. 2008;29(1):17-22

10. Schaffer PR, Hale CS, Meehan SA, Shupack JL, Ramachandran S. Adoposis dolorosa. Dermatol Online J. 2014;20(12):1-3.

11. Singal A, Janiga JJ, Bossenbroek NM, Lim HW. Dercum’s disease (adiposis dolorosa): a report of improvement with infliximab and methotrexate. J Eur Acad Dermatol Venerol. 2007;21(5):717.

12. Loftus RW, Yeager MP, Clark JA, et al. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology. 2010;113(3):639-646.

13. Patil S, Anitescu M. Efficacy of outpatient ketamine infusions in refractory chronic pain syndromes: a 5-year retrospective analysis. Pain Med. 2012;13(2):263-269.

14. Hocking G, Cousins MJ. Ketamine in chronic pain management: an evidence-based review. Anesth Analg. 2003;97(6):1730-1739.

15. Cohen SP, Bhatia A, Buvanendran A, et al. Consensus guidelines on the use of intravenous ketamine infusions for chronic pain from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018;43(5):521-546.

16. Martinenghi S, Caretto A, Losio C, Scavini M, Bosi E. Successful treatment of Dercum’s disease by transcutaneous electrical stimulation: a case report. Medicine (Baltimore). 2015;94(24):e950.

17. Ricci M, Pirotti S, Scarpi E, et al. Managing chronic pain: results from an open-label study using MC5-A Calmare device. Support Care Cancer. 2012;20(2):405-412.

18. Hauser RA, Lackner JB, Steilen-Matias D, Harris DK. A systematic review of dextrose prolotherapy for chronic musculoskeletal pain. Clin Med Insights Arthritis Musculoskelet Disord. 2016;9:139-159.

19. Manheimer E, Cheng K, Linde K, et al. Acupuncture for peripheral joint osteoarthritis. Cochrane Database Syst Rev. 2010;(1):CD001977.

20. Deare JC, Zheng Z, Xue CC, et al. Acupuncture for treating fibromyalgia. Cochrane Database Syst Rev. 2013;(5):CD007070.

21. Chan MWC, Wu XY, Wu JCY, Wong SYS, Chung VCH. Safety of acupuncture: overview of systematic reviews. Sci Rep. 2017;7(1):3369.

Issue
Federal Practitioner - 36(11)a
Issue
Federal Practitioner - 36(11)a
Page Number
530-533
Page Number
530-533
Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Eyebrow Default
Case In Point
Use ProPublica
Hide sidebar & use full width
render the right sidebar.
Article PDF Media

SEEDS for success: Lifestyle management in migraine

Article Type
Changed
Fri, 11/08/2019 - 09:22
Display Headline
SEEDS for success: Lifestyle management in migraine

Migraine is the second leading cause of years of life lived with a disability globally.1 It affects people of all ages, but particularly during the years associated with the highest productivity in terms of work and family life.

Migraine is a genetic neurologic disease that can be influenced or triggered by environmental factors. However, triggers do not cause migraine. For example, stress does not cause migraine, but it can exacerbate it.

Primary care physicians can help patients reduce the likelihood of a migraine attack, the severity of symptoms, or both by offering lifestyle counseling centered around the mnemonic SEEDS: sleep, exercise, eat, diary, and stress. In this article, each factor is discussed individually for its current support in the literature along with best-practice recommendations.

S IS FOR SLEEP

Advice to patients with migraine: SEEDS for success
Multiple sleep comorbidities are associated with migraine, including sleep apnea and insomnia.2 Poor sleep itself has been described as a migraine trigger. Those with both migraine and poor sleep report having lower quality of life, more mood disorders, lower socioeconomic status, higher stress, and higher tendency for poor lifestyle habits.3 The number needed to treat by initiating routine lifestyle behaviors including sleep, diet, and exercise is 2, indicating that every other person could benefit from this type of intervention.4

Before optimizing sleep hygiene, screen for sleep apnea, especially in those who have chronic daily headache upon awakening. An excellent tool is the STOP-Bang screening questionnaire5 (www.stopbang.ca/osa/screening.php). Patients respond “yes” or “no” to the following questions:

  • Snoring: Do you snore loudly (louder than talking or loud enough to be heard through closed doors)?
  • Tired: Do you often feel tired, fatigued, or sleepy during the daytime?
  • Observed: Has anyone observed you stop breathing during your sleep?
  • Pressure: Do you have or are you being treated for high blood pressure?
  • Body mass index greater than 35 kg/m2?
  • Age over 50?
  • Neck circumference larger than 40 cm (females) or  42 cm (males)?
  • Gender—male?

Each “yes” answer is scored as 1 point. A score less than 3 indicates low risk of obstructive sleep apnea; 3 to 4 indicates moderate risk; and 5 or more indicates high risk. Optimization of sleep apnea with continuous positive airway pressure therapy can improve sleep apnea headache.6 The improved sleep from reduced arousals may also mitigate migraine symptoms.

Sleep hygiene and behavior modification

Behavioral modification for sleep hygiene can convert chronic migraine to episodic migraine.7 One such program is stimulus control therapy, which focuses on using cues to initiate sleep (Table 1). Patients are encouraged to keep the bedroom quiet, dark, and cool, and to go to sleep at the same time every night. Importantly, the bed should be associated only with sleep. If patients are unable to fall asleep within 20 to 30 minutes, they should leave the room so they do not associate the bed with frustration and anxiety. Use of phones, tablets, and television in the bedroom is discouraged as these devices may make it more difficult to fall asleep.8

The next option is sleep restriction, which is useful for comorbid insomnia. Patients keep a sleep diary to better understand their sleep-wake cycle. The goal is 90% sleep efficiency, meaning that 90% of the time in bed (TIB) is spent asleep. For example, if the patient is in bed 8 hours but asleep only 4 hours, sleep efficiency is 50%. The goal is to reduce TIB to match the time asleep and to agree on a prescribed daily wake-up time. When the patient is consistently sleeping 90% of the TIB, add 30-minute increments until he or she is appropriately sleeping 7 to 8 hours at night.9 Naps are not recommended.

Let patients know that their migraine may worsen until a new routine sleep pattern emerges. This method is not recommended for patients with untreated sleep apnea.

E IS FOR EXERCISE

Exercise is broadly recommended for a healthy lifestyle; some evidence suggests that it can also be useful in the management of migraine.10 Low levels of physical activity and a sedentary lifestyle are associated with migraine.11 It is unclear if patients with migraine are less likely to exercise because they want to avoid triggering a migraine or if a sedentary lifestyle increases their risk.

Exercise has been studied for its prophylactic benefits in migraine, and one hypothesis relates to beta-endorphins. Levels of beta-endorphins are reduced in the cerebrospinal fluid of patients with migraine.12 Exercise programs may increase levels while reducing headache frequency and duration.13 One study showed that pain thresholds do not change with exercise programs, suggesting that it is avoidance behavior that is positively altered rather than the underlying pain pathways.14

A systematic review and meta-analysis based on 5 randomized controlled trials and 1 nonrandomized controlled clinical trial showed that exercise reduced monthly migraine days by only 0.6 (± 0.3) days, but the data also suggested that as the exercise intensity increased, so did the positive effects.10

Some data suggest that exercise may also reduce migraine duration and severity as well as the need for abortive medication.10 Two studies in this systematic review15,16 showed that exercise benefits were equivalent to those of migraine preventives such as amitriptyline and topiramate; the combination of amitriptyline and exercise was more beneficial than exercise alone. Multiple types of exercise were beneficial, including walking, jogging, cross-training, and cycling when done for least 6 weeks and for 30 to 50 minutes 3 to 5 times a week.

These findings are in line with the current recommendations for general health from the American College of Sports Medicine, ie, moderate to vigorous cardio­respiratory exercise for 30 to 60 minutes 3 to 5 times a week (or 150 minutes per week). The daily exercise can be continuous or done in intervals of less than 20 minutes. For those with a sedentary lifestyle, as is seen in a significant proportion of the migraine population, light to moderate exercise for less than 20 minutes is still beneficial.17

Based on this evidence, the best current recommendation for patients with migraine is to engage in graded moderate cardiorespiratory exercise, although any exercise is better than none. If a patient is sedentary or has poor exercise tolerance, or both, exercising once a week for shorter time periods may be a manageable place to start.

Some patients may identify exercise as a trigger or exacerbating factor in migraine. These patients may need appropriate prophylactic and abortive therapies before starting an exercise regimen.

 

 

THE SECOND E IS FOR EAT (FOOD AND DRINK)

Many patients believe that some foods trigger migraine attacks, but further study is needed. The most consistent food triggers appear to be red wine and caffeine (withdrawal).18,19 Interestingly, patients with migraine report low levels of alcohol consumption,20 but it is unclear if that is because alcohol has a protective effect or if patients avoid it.

Some patients may crave certain foods in the prodromal phase of an attack, eat the food, experience the attack, and falsely conclude that the food caused the attack.21 Premonitory symptoms include fatigue, cognitive changes, homeostatic changes, sensory hyperresponsiveness, and food cravings.21 It is difficult to distinguish between premonitory phase food cravings and true triggers because premonitory symptoms can precede headache by 48 to 72 hours, and the timing for a trigger to be considered causal is not known.22

Chocolate is often thought to be a migraine trigger, but the evidence argues against this and even suggests that sweet cravings are a part of the premonitory phase.23 Monosodium glutamate is often identified as a trigger as well, but the literature is inconsistent and does not support a causal relationship.24 Identifying true food triggers in migraine is difficult, and patients with migraine may have poor quality diets, with some foods acting as true triggers for certain patients.25 These possibilities have led to the development of many “migraine diets,” including elimination diets.

Elimination diets

Elimination diets involve avoiding specific food items over a period of time and then adding them back in one at a time to gauge whether they cause a reaction in the body. A number of these diets have been studied for their effects on headache and migraine:

Gluten-free diets restrict foods that contain wheat, rye, and barley. A systematic review of gluten-free diets in patients with celiac disease found that headache or migraine frequency decreased by 51.6% to 100% based on multiple cohort studies (N = 42,388).26 There are no studies on the use of a gluten-free diet for migraine in patients without celiac disease.

Immunoglobulin G-elimination diets restrict foods that serve as antigens for IgG. However, data supporting these diets are inconsistent. Two small randomized controlled trials found that the diets improved migraine symptoms, but a larger study found no improvement in the number of migraine days at 12 weeks, although there was an initially significant effect at 4 weeks.27–29

Antihistamine diets restrict foods that have high levels of histamines, including fermented dairy, vegetables, soy products,  wine, beer, alcohol, and those that cause histamine release regardless of IgE testing results. A prospective single-arm study of antihistamine diets in patients with chronic headache reported symptom improvement, which could be applied to certain comorbidities such as  mast cell activation syndrome.30 Another prospective nonrandomized controlled study eliminated foods based on positive IgE skin-prick testing for allergy in patients with recurrent migraine and found that it reduced headache frequency.31

Tyramine-free diets are often recommended due to the presumption that tyramine-containing foods (eg, aged cheese, cured or smoked meats and fish, and beer) are triggers. However, multiple studies have reviewed this theory with inconsistent results,32 and the only study of a tyramine-free diet was negative.33 In addition, commonly purported high-tyramine foods have lower tyramine levels than previously thought.34

Low-fat diets in migraine are supported by 2 small randomized controlled trials and a prospective study showing a decrease in symptom severity; the results for frequency are inconsistent.35–37

Low-glycemic index diets are supported in migraine by 1 randomized controlled trial that showed improvement in migraine frequency in a diet group and in a control group of patients who took a standard migraine-preventive medication to manage their symptoms.38

 

 

Other migraine diets

Diets high in certain foods or ingredient ratios, as opposed to elimination diets, have also been studied in patients with migraine. One promising diet containing high levels of omega-3 fatty acids and low levels of omega-6 fatty acids was shown in a systematic review to reduce the duration of migraine but not the frequency or severity.39 A more recent randomized controlled trial of this diet in chronic migraine also showed that it decreased migraine frequency.40

The ketogenic diet (high fat, low carbohydrate) had promising results in a randomized controlled trial in overweight women with migraine and in a prospective study.41,42 However, a prospective study of the Atkins diet in teenagers with chronic daily headaches showed no benefit.43 The ketogenic diet is difficult to follow and may work in part due to weight loss alone, although ketogenesis itself may also play a role.41,44

Sodium levels have been shown to be higher in the cerebrospinal fluid of patients with migraine than in controls, particularly during an attack.45 For a prehypertensive population or an elderly population, a low-sodium diet may be beneficial based on 2 prospective trials.46,47 However, a younger female population without hypertension and low-to-normal body mass index had a reduced probability of migraine while consuming a high-sodium diet.48

Counseling about sodium intake should be tailored to specific patient populations. For example, a diet low in sodium may be appropriate for patients with vascular risk factors such as hypertension, whereas a high-sodium diet may be appropriate in patients with comorbidities like postural tachycardia syndrome or in those with a propensity for low blood pressure or low body mass index.

Encourage routine meals and hydration

The standard advice for patients with migraine is to consume regular meals. Headaches have been associated with fasting, and those with migraine are predisposed to attacks in the setting of fasting.49,50 Migraine is more common when meals are skipped, particularly breakfast.51

It is unclear how fasting lowers the migraine threshold. Nutritional studies show that skipping meals, particularly breakfast, increases low-grade inflammation and impairs  glucose metabolism by affecting insulin and fat oxidation metabolism.52 However, hypoglycemia itself is not a consistent cause of headache or migraine attacks.53 As described above, a randomized controlled trial of a low-glycemic index diet actually decreased migraine frequency and severity.38 Skipping meals also reduces energy and is associated with reduced physical activity, perhaps leading to multiple compounding triggers that further lower the migraine threshold.54,55

When counseling patients about the need to eat breakfast, consider what they normally consume (eg, is breakfast just a cup of coffee?). Replacing simple carbohydrates with protein, fats, and fiber may be beneficial for general health, but the effects on migraine are not known, nor is the optimal composition of breakfast foods.55

The optimal timing of breakfast relative to awakening is also unclear, but in general, it should be eaten within 30 to 60 minutes of rising. Also consider patients’ work hours—delayed-phase or shift workers have altered sleep cycles.

Recommendations vary in regard to hydration. Headache is associated with fluid restriction and dehydration,56,57 but only a few studies suggest that rehydration and increased hydration status can improve migraine.58 In fact, a single post hoc analysis of a metoclopramide study showed that intravenous fluid alone for patients with migraine in the emergency room did not improve pain outcomes.59

The amount of water patients should drink daily in the setting of migraine is also unknown, but a study showed benefit with 4 L, which equates to a daily intake of 16 eight-ounce glasses.60 One review on general health that could be extrapolated given the low risk of the intervention indicated that 1.8 L daily (7 to 8 eight-ounce glasses) promoted a euhydration status in most people, although many factors contribute to hydration status.61

Caffeine intake is also a major consideration. Caffeine is a nonspecific adenosine receptor antagonist that modulates adenosine receptors like the pronociceptive 2A receptor, leading to changes integral to the neuropathophysiology of migraine.62 Caffeine has analgesic properties at doses greater than 65 to 200 mg and augments the effects of analgesics such as acetaminophen and aspirin. Chronic caffeine use can lead to withdrawal symptoms when intake is stopped abruptly; this is thought to be due to upregulation of adenosine receptors, but the effect varies based on genetic predisposition.19

The risk of chronic daily headache may relate to high use of caffeine preceding the onset of chronification, and caffeine abstinence may improve response to acute migraine treatment.19,63 There is a dose-dependent risk of headache.64,65 Current recommendations suggest limiting caffeine consumption to less than 200 mg per day or stopping caffeine consumption altogether based on the quantity required for caffeine-withdrawal headache.66 Varying  the caffeine dose from day to day may also trigger headache due to the high sensitivity to caffeine withdrawal.

While many diets have shown potential benefit in patients with migraine, more studies are needed before any one “migraine diet” can be recommended. Caution should be taken, as there is risk of adverse effects from nutrient deficiencies or excess levels, especially if the patient is not under the care of a healthcare professional who is familiar with the diet.

Whether it is beneficial to avoid specific food triggers at this time is unclear and still controversial even within the migraine community because some of these foods may be misattributed as triggers instead of premonitory cravings driven by the hypothalamus. It is important to counsel patients with migraine to eat a healthy diet with consistent meals, to maintain adequate hydration, and to keep their caffeine intake low or at least consistent, although these teachings are predominantly based on limited studies with extrapolation from nutrition research.

 

 

D IS FOR DIARY

A headache diary is a recommended part of headache management and may enhance the accuracy of diagnosis and assist in treatment modifications. Paper and electronic diaries have been used. Electronic diaries may be more accurate for real-time use, but patients may be more likely to complete a paper one.67 Patients prefer electronic diaries over long paper forms,68 but a practical issue to consider is easy electronic access.

Patients can start keeping a headache diary before the initial consultation to assist with diagnosis, or early in their management. A first-appointment diary mailed with instructions is a feasible option.69 These types of diaries ask detailed questions to help diagnose all major primary headache types including menstrual migraine and to identify concomitant medication-overuse headache. Physicians and patients generally report improved communication with use of a diary.70

Some providers distinguish between a headache diary and a calendar. In standard practice, a headache diary is the general term referring to both, but the literature differentiates between the two. Both should at least include headache frequency, with possible inclusion of other factors such as headache duration, headache intensity, analgesic use, headache impact on function, and absenteeism. Potential triggers including menses can also be tracked. The calendar version can fit on a single page and can be used for simple tracking of headache frequency and analgesia use.

One of the simplest calendars to use is the “stoplight” calendar. Red days are when a patient is completely debilitated in bed. On a yellow day, function at work, school, or daily activities is significantly reduced by migraine, but the patient is not bedbound. A green day is when headache is present but function is not affected. No color is placed if the patient is 100% headache-free.

Acute treatment use can be written in or, to improve compliance, a checkmark can be placed on days of treatment. Patients who are tracking menses circle the days of menstruation. The calendar-diary should be brought to every appointment to track treatment response and medication use.

THE SECOND S IS FOR STRESS

Techniques for stress management in migraine
Stress and anxiety are associated with migraine. Either may lead to avoidance and hypervigilance of perceived triggers, and this association may affect migraines.71,72 High stress and chronic migraine are associated with lifestyle factors such as medication overuse, smoking, sedentary habits, and obesity.73 Fortunately, many evidence-based techniques used for management of stress and mood disorders can also be used in migraine, including cognitive behavioral therapy, biofeedback, mindfulness, and relaxation techniques (Table 2).

Behavioral management such as cognitive behavioral therapy in migraine has been shown to decrease catastrophizing, migraine disability, and headache severity and frequency.74 Both depression and anxiety can improve along with migraine.75 Cognitive behavioral therapy can be provided in individualized sessions or group sessions, either in person or online.74,76,77 The effects become more prominent about 5 weeks into treatment.78

Biofeedback, which uses behavioral techniques paired with physiologic autonomic measures, has been extensively studied, and shows benefit in migraine, including in meta-analysis.79 The types of biofeedback measurements used include electromyography, electroencephalography, temperature, sweat sensors, heart rate, blood volume pulse feedback, and respiration bands. While biofeedback is generally done under the guidance of a therapist, it can still be useful with minimal therapist contact and supplemental audio.80

Mindfulness, or the awareness of thoughts, feelings, and sensations in the present moment without judgment, is a behavioral technique that can be done alone or paired with another technique. It is often taught through a mindfulness-based stress-reduction  program, which relies on a standardized approach. A meta-analysis showed that mindfulness improves pain intensity, headache frequency, disability, self-efficacy, and quality of life.81 It may work by encouraging pain acceptance.82

Relaxation techniques are also employed in migraine management, either alone or in conjunction with techniques mentioned  above, such as mindfulness. They include progressive muscle relaxation and deep breathing. Relaxation has been shown to be effective when done by professional trainers as well as lay trainers in both individual and group settings.83,84

In patients with intractable headache, more-intensive inpatient and outpatient programs have been tried. Inpatient admissions with multidisciplinary programs that include a focus on behavioral techniques often paired with lifestyle education and sometimes pharmacologic management can be beneficial.85,86 These programs have also been successfully conducted as multiple outpatient sessions.86–88

Stress management is an important aspect of migraine management. These treatments often involve homework and require active participation.

LIFESTYLE FOR ALL

All patients with migraine should initiate lifestyle modifications (see Advice to patients with migraine: SEEDS for success). Modifications with the highest level of evidence, specifically behavioral techniques, have had the most reproducible results. A headache diary is an essential tool to identify patterns and needs for optimization of acute or preventive treatment regimens. The strongest evidence is for the behavioral management techniques for stress reduction.

References
  1. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390(10100):1211–1259. doi:10.1016/S0140-6736(17)32154-2
  2. Vgontzas A, Pavlovic JM. Sleep diorders and migraine: review of literature and potential pathophysiology mechanisms. Headache 2018; 58(7):1030–1039. doi:10.1111/head.13358
  3. Lund N, Westergaard ML, Barloese M, Glumer C, Jensen RH. Epidemiology of concurrent headache and sleep problems in Denmark. Cephalalgia 2014; 34(10):833–845. doi:10.1177/0333102414543332
  4. Woldeamanuel YW, Cowan RP. The impact of regular lifestyle behavior in migraine: a prevalence case-referent study. J Neurol 2016; 263(4):669–676. doi:10.1007/s00415-016-8031-5
  5. Chung F, Abdullah HR, Liao P. STOP-Bang questionnaire: a practical approach to screen for obstructive sleep apnea. Chest 2016; 149(3):631–638. doi:10.1378/chest.15-0903
  6. Johnson KG, Ziemba AM, Garb JL. Improvement in headaches with continuous positive airway pressure for obstructive sleep apnea: a retrospective analysis. Headache 2013; 53(2):333–343. doi:10.1111/j.1526-4610.2012.02251.x
  7. Calhoun AH, Ford S. Behavioral sleep modification may revert transformed migraine to episodic migraine. Headache 2007; 47(8):1178–1183. doi:10.1111/j.1526-4610.2007.00780.x
  8. Calhoun AH, Ford S, Finkel AG, Kahn KA, Mann JD. The prevalence and spectrum of sleep problems in women with transformed migraine. Headache 2006; 46(4):604–610. doi:10.1111/j.1526-4610.2006.00410.x
  9. Rains JC. Optimizing circadian cycles and behavioral insomnia treatment in migraine. Curr Pain Headache Rep 2008; 12(3):213–219. pmid:18796272
  10. Lemmens J, De Pauw J, Van Soom T, et al. The effect of aerobic exercise on the number of migraine days, duration and pain intensity in migraine: a systematic literature review and meta-analysis. J Headache Pain 2019; 20(1):16. doi:10.1186/s10194-019-0961-8
  11. Amin FM, Aristeidou S, Baraldi C, et al; European Headache Federation School of Advanced Studies (EHF-SAS). The association between migraine and physical exercise. J Headache Pain 2018; 19(1):83. doi:10.1186/s10194-018-0902-y
  12. Genazzani AR, Nappi G, Facchinetti F, et al. Progressive impairment of CSF beta-EP levels in migraine sufferers. Pain 1984; 18:127-133. pmid:6324056
  13. Hindiyeh NA, Krusz JC, Cowan RP. Does exercise make migraines worse and tension type headaches better? Curr Pain Headache Rep 2013;17:380. pmid:24234818
  14. Kroll LS, Sjodahl Hammarlund C, Gard G, Jensen RH, Bendtsen L. Has aerobic exercise effect on pain perception in persons with migraine and coexisting tension-type headache and neck pain? A randomized, controlled, clinical trial. Eur J Pain 2018; 10:10. pmid:29635806
  15. Santiago MD, Carvalho Dde S, Gabbai AA, Pinto MM, Moutran AR, Villa TR. Amitriptyline and aerobic exercise or amitriptyline alone in the treatment of chronic migraine: a randomized comparative study. Arq Neuropsiquiatr 2014; 72(11):851-855. pmid:25410451
  16. Varkey E, Cider A, Carlsson J, Linde M. Exercise as migraine prophylaxis: a randomized study using relaxation and topiramate as controls. Cephalalgia 2011; 31(14):1428-1438. pmid:21890526
  17. Garber CE, Blissmer B, Deschenes MR, et al. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc 2011; 43(7):1334-1359. pmid:21694556
  18. Guarnieri P, Radnitz CL, Blanchard EB. Assessment of dietary risk factors in chronic headache. Biofeedback Self Regul 1990; 15(1):15–25. pmid:2361144
  19. Shapiro RE. Caffeine and headaches. Curr Pain Headache Rep 2008; 12(4):311–315. pmid:18625110
  20. Yokoyama M, Yokoyama T, Funazu K, et al. Associations between headache and stress, alcohol drinking, exercise, sleep, and comorbid health conditions in a Japanese population. J Headache Pain 2009; 10(3):177–185. doi:10.1007/s10194-009-0113-7
  21. Karsan N, Bose P, Goadsby PJ. The migraine premonitory phase. Continuum (Minneap Minn) 2018; 24(4, Headache):996–1008. doi:10.1212/CON.0000000000000624
  22. Pavlovic JM, Buse DC, Sollars CM, Haut S, Lipton RB. Trigger factors and premonitory features of migraine attacks: summary of studies. Headache 2014; 54(10):1670–1679. doi:10.1111/head.12468
  23. Marcus DA, Scharff L, Turk D, Gourley LM. A double-blind provocative study of chocolate as a trigger of headache. Cephalalgia 1997; 17(8):855–862. doi:10.1046/j.1468-2982.1997.1708855.x
  24. Obayashi Y, Nagamura Y. Does monosodium glutamate really cause headache? A systematic review of human studies. J Headache Pain 2016; 17:54. doi:10.1186/s10194-016-0639-4
  25. Evans EW, Lipton RB, Peterlin BL, et al. Dietary intake patterns and diet quality in a nationally representative sample of women with and without severe headache or migraine. Headache 2015; 55(4):550–561. doi:10.1111/head.12527
  26. Zis P, Julian T, Hadjivassiliou M. Headache associated with coeliac disease: a systematic review and meta-analysis. Nutrients 2018; 10(10). doi:10.3390/nu10101445
  27. Alpay K, Ertas M, Orhan EK, Ustay DK, Lieners C, Baykan B. Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Cephalalgia 2010; 30(7):829–837. doi:10.1177/0333102410361404
  28. Aydinlar EI, Dikmen PY, Tiftikci A, et al. IgG-based elimination diet in migraine plus irritable bowel syndrome. Headache 2013; 53(3):514–525. doi:10.1111/j.1526-4610.2012.02296.x
  29. Mitchell N, Hewitt CE, Jayakody S, et al. Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches. Nutr J 2011; 10:85. doi:10.1186/1475-2891-10-85
  30. Wantke F, Gotz M, Jarisch R. Histamine-free diet: treatment of choice for histamine-induced food intolerance and supporting treatment for chronic headaches. Clin Exp Allergy 1993; 23(12):982–985. pmid:10779289
  31. Mansfield LE, Vaughan TR, Waller SF, Haverly RW, Ting S. Food allergy and adult migraine: double-blind and mediator confirmation of an allergic etiology. Ann Allergy 1985; 55(2):126–129. pmid:4025956
  32. Kohlenberg RJ. Tyramine sensitivity in dietary migraine: a critical review. Headache 1982; 22(1):30–34. pmid:17152742
  33. Medina JL, Diamond S. The role of diet in migraine. Headache 1978; 18(1):31–34. pmid:649377
  34. Mosnaim AD, Freitag F, Ignacio R, et al. Apparent lack of correlation between tyramine and phenylethylamine content and the occurrence of food-precipitated migraine. Reexamination of a variety of food products frequently consumed in the United States and commonly restricted in tyramine-free diets. Headache Quarterly. Current Treatment and Research 1996; 7(3):239–249.
  35. Ferrara LA, Pacioni D, Di Fronzo V, et al. Low-lipid diet reduces frequency and severity of acute migraine attacks. Nutr Metab Cardiovasc Dis 2015; 25(4):370–375. doi:10.1016/j.numecd.2014.12.006
  36. Bic Z, Blix GG, Hopp HP, Leslie FM, Schell MJ. The influence of a low-fat diet on incidence and severity of migraine headaches. J Womens Health Gend Based Med 1999; 8(5):623–630. doi:10.1089/jwh.1.1999.8.623
  37. Bunner AE, Agarwal U, Gonzales JF, Valente F, Barnard ND. Nutrition intervention for migraine: a randomized crossover trial. J Headache Pain 2014; 15:69. doi:10.1186/1129-2377-15-69
  38. Evcili G, Utku U, Ogun MN, Ozdemir G. Early and long period follow-up results of low glycemic index diet for migraine prophylaxis. Agri 2018; 30(1):8–11. doi:10.5505/agri.2017.62443
  39. Maghsoumi-Norouzabad L, Mansoori A, Abed R, Shishehbor F. Effects of omega-3 fatty acids on the frequency, severity, and duration of migraine attacks: a systematic review and meta-analysis of randomized controlled trials. Nutr Neurosci 2018; 21(9):614–623. doi:10.1080/1028415X.2017.1344371
  40. Soares AA, Loucana PMC, Nasi EP, Sousa KMH, Sa OMS, Silva-Neto RP. A double- blind, randomized, and placebo-controlled clinical trial with omega-3 polyunsaturated fatty acids (OPFA Ω-3) for the prevention of migraine in chronic migraine patients using amitriptyline. Nutr Neurosci 2018; 21(3):219–223. doi:10.1080/1028415X.2016.1266133
  41. Di Lorenzo C, Coppola G, Sirianni G, et al. Migraine improvement during short lasting ketogenesis: a proof-of-concept study. Eur J Neurol 2015; 22(1):170–177. doi:10.1111/ene.12550
  42. Di Lorenzo C, Coppola G, Bracaglia M, et al. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study. J Headache Pain 2016; 17:58. doi:10.1186/s10194-016-0650-9
  43. Kossoff EH, Huffman J, Turner Z, Gladstein J. Use of the modified Atkins diet for adolescents with chronic daily headache. Cephalalgia 2010; 30(8):1014–1016. https://journals.sagepub.com/doi/full/10.1111/j.1468-2982.2009.02016.x
  44. Slavin M, Ailani J. A clinical approach to addressing diet with migraine patients. Curr Neurol Neurosci Rep 2017; 17(2):17. doi:10.1007/s11910-017-0721-6
  45. Amer M, Woodward M, Appel LJ. Effects of dietary sodium and the DASH diet on the occurrence of headaches: results from randomised multicentre DASH-sodium clinical trial. BMJ Open 2014; 4(12):e006671. doi:10.1136/bmjopen-2014-006671
  46. Chen L, Zhang Z, Chen W, Whelton PK, Appel LJ. Lower sodium intake and risk of headaches: results from the trial of nonpharmacologic interventions in the elderly. Am J Public Health 2016; 106(7):1270–1275. doi:10.2105/AJPH.2016.303143
  47. Pogoda JM, Gross NB, Arakaki X, Fonteh AN, Cowan RP, Harrington MG. Severe headache or migraine history is inversely correlated with dietary sodium intake: NHANES 1999–2004. Headache 2016; 56(4):688–698. doi:10.1111/head.12792
  48. Awada A, al Jumah M. The first-of-Ramadan headache. Headache 1999; 39(7):490–493. pmid:11279933
  49. Abu-Salameh I, Plakht Y, Ifergane G. Migraine exacerbation during Ramadan fasting. J Headache Pain 2010; 11(6):513–517. doi:10.1007/s10194-010-0242-z
  50. Nazari F, Safavi M, Mahmudi M. Migraine and its relation with lifestyle in women. Pain Pract 2010; 10(3):228–234. doi:10.1111/j.1533-2500.2009.00343.x
  51. Nas A, Mirza N, Hagele F, et al. Impact of breakfast skipping compared with dinner skipping on regulation of energy balance and metabolic risk. Am J Clin Nutr 2017; 105(6):1351–1361. doi:10.3945/ajcn.116.151332
  52. Torelli P, Manzoni GC. Fasting headache. Curr Pain Headache Rep 2010; 14(4):284–291. doi:10.1007/s11916-010-0119-5
  53. Yoshimura E, Hatamoto Y, Yonekura S, Tanaka H. Skipping breakfast reduces energy intake and physical activity in healthy women who are habitual breakfast eaters: a randomized crossover trial. Physiol Behav 2017; 174:89–94. doi:10.1016/j.physbeh.2017.03.008
  54. Pendergast FJ, Livingstone KM, Worsley A, McNaughton SA. Correlates of meal skipping in young adults: a systematic review. Int J Behav Nutr Phys Act 2016; 13(1):125. doi:10.1186/s12966-016-0451-1
  55. Maki KC, Phillips-Eakley AK, Smith KN. The effects of breakfast consumption and composition on metabolic wellness with a focus on carbohydrate metabolism. Adv Nutr 2016; 7(3):613S–621S. doi:10.3945/an.115.010314
  56. Shirreffs SM, Merson SJ, Fraser SM, Archer DT. The effects of fluid restriction on hydration status and subjective feelings in man. Br J Nutr 2004; 91(6):951–958. doi:10.1079/BJN20041149
  57. Blau JN. Water deprivation: a new migraine precipitant. Headache 2005; 45(6):757–759. doi:10.1111/j.1526-4610.2005.05143_3.x
  58. Price A, Burls A. Increased water intake to reduce headache: learning from a critical appraisal. J Eval Clin Pract 2015; 21(6):1212–1218. doi:10.1111/jep.12413
  59. Balbin JE, Nerenberg R, Baratloo A, Friedman BW. Intravenous fluids for migraine: a post hoc analysis of clinical trial data. Am J Emerg Med 2016; 34(4):713–716. doi:10.1016/j.ajem.2015.12.080
  60. Spigt M, Weerkamp N, Troost J, van Schayck CP, Knottnerus JA. A randomized trial on the effects of regular water intake in patients with recurrent headaches. Fam Pract 2012; 29(4):370–375. doi:10.1093/fampra/cmr112
  61. Armstrong LE, Johnson EC. Water intake, water balance, and the elusive daily water requirement. Nutrients 2018; 10(12). doi:10.3390/nu10121928
  62. Fried NT, Elliott MB, Oshinsky ML. The role of adenosine signaling in headache: a review. Brain Sci 2017; 7(3). doi:10.3390/brainsci7030030
  63. Lee MJ, Choi HA, Choi H, Chung CS. Caffeine discontinuation improves acute migraine treatment: a prospective clinic-based study. J Headache Pain 2016; 17(1):71. doi:10.1186/s10194-016-0662-5
  64. Shirlow MJ, Mathers CD. A study of caffeine consumption and symptoms; indigestion, palpitations, tremor, headache and insomnia. Int J Epidemiol 1985; 14(2):239–248. doi:10.1093/ije/14.2.239
  65. Silverman K, Evans SM, Strain EC, Griffiths RR. Withdrawal syndrome after the double-blind cessation of caffeine consumption. N Engl J Med 1992; 327(16):1109–1114. doi:10.1056/NEJM199210153271601
  66. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018; 38(1):1–211. doi:10.1177/0333102417738202
  67. Krogh AB, Larsson B, Salvesen O, Linde M. A comparison between prospective Internet-based and paper diary recordings of headache among adolescents in the general population. Cephalalgia 2016; 36(4):335–345. doi:10.1177/0333102415591506
  68. Bandarian-Balooch S, Martin PR, McNally B, Brunelli A, Mackenzie S. Electronic-diary for recording headaches, triggers, and medication use: development and evaluation. Headache 2017; 57(10):1551–1569. doi:10.1111/head.13184
  69. Tassorelli C, Sances G, Allena M, et al. The usefulness and applicability of a basic headache diary before first consultation: results of a pilot study conducted in two centres. Cephalalgia 2008; 28(10):1023–1030. doi:10.1111/j.1468-2982.2008.01639.x
  70. Baos V, Ester F, Castellanos A, et al. Use of a structured migraine diary improves patient and physician communication about migraine disability and treatment outcomes. Int J Clin Pract 2005; 59(3):281–286. doi:10.1111/j.1742-1241.2005.00469.x
  71. Martin PR, MacLeod C. Behavioral management of headache triggers: avoidance of triggers is an inadequate strategy. Clin Psychol Rev 2009; 29(6):483–495. doi:10.1016/j.cpr.2009.05.002
  72. Giannini G, Zanigni S, Grimaldi D, et al. Cephalalgiaphobia as a feature of high-frequency migraine: a pilot study. J Headache Pain 2013; 14:49. doi:10.1186/1129-2377-14-49
  73. Westergaard ML, Glumer C, Hansen EH, Jensen RH. Medication overuse, healthy lifestyle behaviour and stress in chronic headache: results from a population-based representative survey. Cephalalgia 2016; 36(1):15–28. doi:10.1177/0333102415578430
  74. Christiansen S, Jurgens TP, Klinger R. Outpatient combined group and individual cognitive-behavioral treatment for patients with migraine and tension-type headache in a routine clinical setting. Headache 2015; 55(8):1072–1091. doi:10.1111/head.12626
  75. Martin PR, Aiello R, Gilson K, Meadows G, Milgrom J, Reece J. Cognitive behavior therapy for comorbid migraine and/or tension-type headache and major depressive disorder: an exploratory randomized controlled trial. Behav Res Ther 2015; 73:8–18. doi:10.1016/j.brat.2015.07.005
  76. Nash JM, Park ER, Walker BB, Gordon N, Nicholson RA. Cognitive-behavioral group treatment for disabling headache. Pain Med 2004; 5(2):178–186. doi:10.1111/j.1526-4637.2004.04031.x
  77. Sorbi MJ, Balk Y, Kleiboer AM, Couturier EG. Follow-up over 20 months confirms gains of online behavioural training in frequent episodic migraine. Cephalalgia 2017; 37(3):236–250. doi:10.1177/0333102416657145
  78. Thorn BE, Pence LB, Ward LC, et al. A randomized clinical trial of targeted cognitive behavioral treatment to reduce catastrophizing in chronic headache sufferers. J Pain 2007; 8(12):938–949. doi:10.1016/j.jpain.2007.06.010
  79. Nestoriuc Y, Martin A. Efficacy of biofeedback for migraine: a meta-analysis. Pain 2007; 128(1–2):111–127. doi:10.1016/j.pain.2006.09.007
  80. Blanchard EB, Appelbaum KA, Nicholson NL, et al. A controlled evaluation of the addition of cognitive therapy to a home-based biofeedback and relaxation treatment of vascular headache. Headache 1990; 30(6):371–376. pmid:2196240
  81. Gu Q, Hou JC, Fang XM. Mindfulness meditation for primary headache pain: a meta-analysis. Chin Med J (Engl) 2018; 131(7):829–838. doi:10.4103/0366-6999.228242
  82. Day MA, Thorn BE. The mediating role of pain acceptance during mindfulness-based cognitive therapy for headache. Complement Ther Med 2016; 25:51–54. doi:10.1016/j.ctim.2016.01.002
  83. Williamson DA, Monguillot JE, Jarrell MP, Cohen RA, Pratt JM, Blouin DC. Relaxation for the treatment of headache. Controlled evaluation of two group programs. Behav Modif 1984; 8(3):407–424. doi:10.1177/01454455840083007
  84. Merelle SY, Sorbi MJ, Duivenvoorden HJ, Passchier J. Qualities and health of lay trainers with migraine for behavioral attack prevention. Headache 2010; 50(4):613–625. doi:10.1111/j.1526-4610.2008.01241.x
  85. Gaul C, van Doorn C, Webering N, et al. Clinical outcome of a headache-specific multidisciplinary treatment program and adherence to treatment recommendations in a tertiary headache center: an observational study. J Headache Pain 2011; 12(4):475–483. doi:10.1007/s10194-011-0348-y
  86. Wallasch TM, Kropp P. Multidisciplinary integrated headache care: a prospective 12-month follow-up observational study. J Headache Pain 2012; 13(7):521–529. doi:10.1007/s10194-012-0469-y
  87. Lemstra M, Stewart B, Olszynski WP. Effectiveness of multidisciplinary intervention in the treatment of migraine: a randomized clinical trial. Headache 2002; 42(9):845–854. pmid:12390609
  88. Krause SJ, Stillman MJ, Tepper DE, Zajac D. A prospective cohort study of outpatient interdisciplinary rehabilitation of chronic headache patients. Headache 2017; 57(3):428–440. doi:10.1111/head.13020
Article PDF
Author and Disclosure Information

Jennifer Robblee, MD, MSc
Headache Fellow, Department of Neurology, Mayo Clinic Arizona, Scottsdale, AZ

Amaal J. Starling, MD
Assistant Professor, Department of Neurology, Mayo Clinic Arizona, Scottsdale, AZ

Address: Amaal J. Starling, MD, Department of Neurology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259; [email protected]

Issue
Cleveland Clinic Journal of Medicine - 86(11)
Publications
Topics
Page Number
741-749
Legacy Keywords
migraine, headache, lifestyle, SEEDS, sleep, exercise, eat, diary, stress, sleep hygiene, STOP-Bang, behavioral modification, elimination diet, gluten-free diet, immunoglobulin G-elimination diet, antihistamine diet, tyramine-free diet, low-fat diet, low-glycemic index diet, ketogenic diet, hydration, caffeine, headache diary, biofeedback, mindfulness, relaxation, Jennifer Robblee, Amaal Starling
Sections
Author and Disclosure Information

Jennifer Robblee, MD, MSc
Headache Fellow, Department of Neurology, Mayo Clinic Arizona, Scottsdale, AZ

Amaal J. Starling, MD
Assistant Professor, Department of Neurology, Mayo Clinic Arizona, Scottsdale, AZ

Address: Amaal J. Starling, MD, Department of Neurology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259; [email protected]

Author and Disclosure Information

Jennifer Robblee, MD, MSc
Headache Fellow, Department of Neurology, Mayo Clinic Arizona, Scottsdale, AZ

Amaal J. Starling, MD
Assistant Professor, Department of Neurology, Mayo Clinic Arizona, Scottsdale, AZ

Address: Amaal J. Starling, MD, Department of Neurology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259; [email protected]

Article PDF
Article PDF
Related Articles

Migraine is the second leading cause of years of life lived with a disability globally.1 It affects people of all ages, but particularly during the years associated with the highest productivity in terms of work and family life.

Migraine is a genetic neurologic disease that can be influenced or triggered by environmental factors. However, triggers do not cause migraine. For example, stress does not cause migraine, but it can exacerbate it.

Primary care physicians can help patients reduce the likelihood of a migraine attack, the severity of symptoms, or both by offering lifestyle counseling centered around the mnemonic SEEDS: sleep, exercise, eat, diary, and stress. In this article, each factor is discussed individually for its current support in the literature along with best-practice recommendations.

S IS FOR SLEEP

Advice to patients with migraine: SEEDS for success
Multiple sleep comorbidities are associated with migraine, including sleep apnea and insomnia.2 Poor sleep itself has been described as a migraine trigger. Those with both migraine and poor sleep report having lower quality of life, more mood disorders, lower socioeconomic status, higher stress, and higher tendency for poor lifestyle habits.3 The number needed to treat by initiating routine lifestyle behaviors including sleep, diet, and exercise is 2, indicating that every other person could benefit from this type of intervention.4

Before optimizing sleep hygiene, screen for sleep apnea, especially in those who have chronic daily headache upon awakening. An excellent tool is the STOP-Bang screening questionnaire5 (www.stopbang.ca/osa/screening.php). Patients respond “yes” or “no” to the following questions:

  • Snoring: Do you snore loudly (louder than talking or loud enough to be heard through closed doors)?
  • Tired: Do you often feel tired, fatigued, or sleepy during the daytime?
  • Observed: Has anyone observed you stop breathing during your sleep?
  • Pressure: Do you have or are you being treated for high blood pressure?
  • Body mass index greater than 35 kg/m2?
  • Age over 50?
  • Neck circumference larger than 40 cm (females) or  42 cm (males)?
  • Gender—male?

Each “yes” answer is scored as 1 point. A score less than 3 indicates low risk of obstructive sleep apnea; 3 to 4 indicates moderate risk; and 5 or more indicates high risk. Optimization of sleep apnea with continuous positive airway pressure therapy can improve sleep apnea headache.6 The improved sleep from reduced arousals may also mitigate migraine symptoms.

Sleep hygiene and behavior modification

Behavioral modification for sleep hygiene can convert chronic migraine to episodic migraine.7 One such program is stimulus control therapy, which focuses on using cues to initiate sleep (Table 1). Patients are encouraged to keep the bedroom quiet, dark, and cool, and to go to sleep at the same time every night. Importantly, the bed should be associated only with sleep. If patients are unable to fall asleep within 20 to 30 minutes, they should leave the room so they do not associate the bed with frustration and anxiety. Use of phones, tablets, and television in the bedroom is discouraged as these devices may make it more difficult to fall asleep.8

The next option is sleep restriction, which is useful for comorbid insomnia. Patients keep a sleep diary to better understand their sleep-wake cycle. The goal is 90% sleep efficiency, meaning that 90% of the time in bed (TIB) is spent asleep. For example, if the patient is in bed 8 hours but asleep only 4 hours, sleep efficiency is 50%. The goal is to reduce TIB to match the time asleep and to agree on a prescribed daily wake-up time. When the patient is consistently sleeping 90% of the TIB, add 30-minute increments until he or she is appropriately sleeping 7 to 8 hours at night.9 Naps are not recommended.

Let patients know that their migraine may worsen until a new routine sleep pattern emerges. This method is not recommended for patients with untreated sleep apnea.

E IS FOR EXERCISE

Exercise is broadly recommended for a healthy lifestyle; some evidence suggests that it can also be useful in the management of migraine.10 Low levels of physical activity and a sedentary lifestyle are associated with migraine.11 It is unclear if patients with migraine are less likely to exercise because they want to avoid triggering a migraine or if a sedentary lifestyle increases their risk.

Exercise has been studied for its prophylactic benefits in migraine, and one hypothesis relates to beta-endorphins. Levels of beta-endorphins are reduced in the cerebrospinal fluid of patients with migraine.12 Exercise programs may increase levels while reducing headache frequency and duration.13 One study showed that pain thresholds do not change with exercise programs, suggesting that it is avoidance behavior that is positively altered rather than the underlying pain pathways.14

A systematic review and meta-analysis based on 5 randomized controlled trials and 1 nonrandomized controlled clinical trial showed that exercise reduced monthly migraine days by only 0.6 (± 0.3) days, but the data also suggested that as the exercise intensity increased, so did the positive effects.10

Some data suggest that exercise may also reduce migraine duration and severity as well as the need for abortive medication.10 Two studies in this systematic review15,16 showed that exercise benefits were equivalent to those of migraine preventives such as amitriptyline and topiramate; the combination of amitriptyline and exercise was more beneficial than exercise alone. Multiple types of exercise were beneficial, including walking, jogging, cross-training, and cycling when done for least 6 weeks and for 30 to 50 minutes 3 to 5 times a week.

These findings are in line with the current recommendations for general health from the American College of Sports Medicine, ie, moderate to vigorous cardio­respiratory exercise for 30 to 60 minutes 3 to 5 times a week (or 150 minutes per week). The daily exercise can be continuous or done in intervals of less than 20 minutes. For those with a sedentary lifestyle, as is seen in a significant proportion of the migraine population, light to moderate exercise for less than 20 minutes is still beneficial.17

Based on this evidence, the best current recommendation for patients with migraine is to engage in graded moderate cardiorespiratory exercise, although any exercise is better than none. If a patient is sedentary or has poor exercise tolerance, or both, exercising once a week for shorter time periods may be a manageable place to start.

Some patients may identify exercise as a trigger or exacerbating factor in migraine. These patients may need appropriate prophylactic and abortive therapies before starting an exercise regimen.

 

 

THE SECOND E IS FOR EAT (FOOD AND DRINK)

Many patients believe that some foods trigger migraine attacks, but further study is needed. The most consistent food triggers appear to be red wine and caffeine (withdrawal).18,19 Interestingly, patients with migraine report low levels of alcohol consumption,20 but it is unclear if that is because alcohol has a protective effect or if patients avoid it.

Some patients may crave certain foods in the prodromal phase of an attack, eat the food, experience the attack, and falsely conclude that the food caused the attack.21 Premonitory symptoms include fatigue, cognitive changes, homeostatic changes, sensory hyperresponsiveness, and food cravings.21 It is difficult to distinguish between premonitory phase food cravings and true triggers because premonitory symptoms can precede headache by 48 to 72 hours, and the timing for a trigger to be considered causal is not known.22

Chocolate is often thought to be a migraine trigger, but the evidence argues against this and even suggests that sweet cravings are a part of the premonitory phase.23 Monosodium glutamate is often identified as a trigger as well, but the literature is inconsistent and does not support a causal relationship.24 Identifying true food triggers in migraine is difficult, and patients with migraine may have poor quality diets, with some foods acting as true triggers for certain patients.25 These possibilities have led to the development of many “migraine diets,” including elimination diets.

Elimination diets

Elimination diets involve avoiding specific food items over a period of time and then adding them back in one at a time to gauge whether they cause a reaction in the body. A number of these diets have been studied for their effects on headache and migraine:

Gluten-free diets restrict foods that contain wheat, rye, and barley. A systematic review of gluten-free diets in patients with celiac disease found that headache or migraine frequency decreased by 51.6% to 100% based on multiple cohort studies (N = 42,388).26 There are no studies on the use of a gluten-free diet for migraine in patients without celiac disease.

Immunoglobulin G-elimination diets restrict foods that serve as antigens for IgG. However, data supporting these diets are inconsistent. Two small randomized controlled trials found that the diets improved migraine symptoms, but a larger study found no improvement in the number of migraine days at 12 weeks, although there was an initially significant effect at 4 weeks.27–29

Antihistamine diets restrict foods that have high levels of histamines, including fermented dairy, vegetables, soy products,  wine, beer, alcohol, and those that cause histamine release regardless of IgE testing results. A prospective single-arm study of antihistamine diets in patients with chronic headache reported symptom improvement, which could be applied to certain comorbidities such as  mast cell activation syndrome.30 Another prospective nonrandomized controlled study eliminated foods based on positive IgE skin-prick testing for allergy in patients with recurrent migraine and found that it reduced headache frequency.31

Tyramine-free diets are often recommended due to the presumption that tyramine-containing foods (eg, aged cheese, cured or smoked meats and fish, and beer) are triggers. However, multiple studies have reviewed this theory with inconsistent results,32 and the only study of a tyramine-free diet was negative.33 In addition, commonly purported high-tyramine foods have lower tyramine levels than previously thought.34

Low-fat diets in migraine are supported by 2 small randomized controlled trials and a prospective study showing a decrease in symptom severity; the results for frequency are inconsistent.35–37

Low-glycemic index diets are supported in migraine by 1 randomized controlled trial that showed improvement in migraine frequency in a diet group and in a control group of patients who took a standard migraine-preventive medication to manage their symptoms.38

 

 

Other migraine diets

Diets high in certain foods or ingredient ratios, as opposed to elimination diets, have also been studied in patients with migraine. One promising diet containing high levels of omega-3 fatty acids and low levels of omega-6 fatty acids was shown in a systematic review to reduce the duration of migraine but not the frequency or severity.39 A more recent randomized controlled trial of this diet in chronic migraine also showed that it decreased migraine frequency.40

The ketogenic diet (high fat, low carbohydrate) had promising results in a randomized controlled trial in overweight women with migraine and in a prospective study.41,42 However, a prospective study of the Atkins diet in teenagers with chronic daily headaches showed no benefit.43 The ketogenic diet is difficult to follow and may work in part due to weight loss alone, although ketogenesis itself may also play a role.41,44

Sodium levels have been shown to be higher in the cerebrospinal fluid of patients with migraine than in controls, particularly during an attack.45 For a prehypertensive population or an elderly population, a low-sodium diet may be beneficial based on 2 prospective trials.46,47 However, a younger female population without hypertension and low-to-normal body mass index had a reduced probability of migraine while consuming a high-sodium diet.48

Counseling about sodium intake should be tailored to specific patient populations. For example, a diet low in sodium may be appropriate for patients with vascular risk factors such as hypertension, whereas a high-sodium diet may be appropriate in patients with comorbidities like postural tachycardia syndrome or in those with a propensity for low blood pressure or low body mass index.

Encourage routine meals and hydration

The standard advice for patients with migraine is to consume regular meals. Headaches have been associated with fasting, and those with migraine are predisposed to attacks in the setting of fasting.49,50 Migraine is more common when meals are skipped, particularly breakfast.51

It is unclear how fasting lowers the migraine threshold. Nutritional studies show that skipping meals, particularly breakfast, increases low-grade inflammation and impairs  glucose metabolism by affecting insulin and fat oxidation metabolism.52 However, hypoglycemia itself is not a consistent cause of headache or migraine attacks.53 As described above, a randomized controlled trial of a low-glycemic index diet actually decreased migraine frequency and severity.38 Skipping meals also reduces energy and is associated with reduced physical activity, perhaps leading to multiple compounding triggers that further lower the migraine threshold.54,55

When counseling patients about the need to eat breakfast, consider what they normally consume (eg, is breakfast just a cup of coffee?). Replacing simple carbohydrates with protein, fats, and fiber may be beneficial for general health, but the effects on migraine are not known, nor is the optimal composition of breakfast foods.55

The optimal timing of breakfast relative to awakening is also unclear, but in general, it should be eaten within 30 to 60 minutes of rising. Also consider patients’ work hours—delayed-phase or shift workers have altered sleep cycles.

Recommendations vary in regard to hydration. Headache is associated with fluid restriction and dehydration,56,57 but only a few studies suggest that rehydration and increased hydration status can improve migraine.58 In fact, a single post hoc analysis of a metoclopramide study showed that intravenous fluid alone for patients with migraine in the emergency room did not improve pain outcomes.59

The amount of water patients should drink daily in the setting of migraine is also unknown, but a study showed benefit with 4 L, which equates to a daily intake of 16 eight-ounce glasses.60 One review on general health that could be extrapolated given the low risk of the intervention indicated that 1.8 L daily (7 to 8 eight-ounce glasses) promoted a euhydration status in most people, although many factors contribute to hydration status.61

Caffeine intake is also a major consideration. Caffeine is a nonspecific adenosine receptor antagonist that modulates adenosine receptors like the pronociceptive 2A receptor, leading to changes integral to the neuropathophysiology of migraine.62 Caffeine has analgesic properties at doses greater than 65 to 200 mg and augments the effects of analgesics such as acetaminophen and aspirin. Chronic caffeine use can lead to withdrawal symptoms when intake is stopped abruptly; this is thought to be due to upregulation of adenosine receptors, but the effect varies based on genetic predisposition.19

The risk of chronic daily headache may relate to high use of caffeine preceding the onset of chronification, and caffeine abstinence may improve response to acute migraine treatment.19,63 There is a dose-dependent risk of headache.64,65 Current recommendations suggest limiting caffeine consumption to less than 200 mg per day or stopping caffeine consumption altogether based on the quantity required for caffeine-withdrawal headache.66 Varying  the caffeine dose from day to day may also trigger headache due to the high sensitivity to caffeine withdrawal.

While many diets have shown potential benefit in patients with migraine, more studies are needed before any one “migraine diet” can be recommended. Caution should be taken, as there is risk of adverse effects from nutrient deficiencies or excess levels, especially if the patient is not under the care of a healthcare professional who is familiar with the diet.

Whether it is beneficial to avoid specific food triggers at this time is unclear and still controversial even within the migraine community because some of these foods may be misattributed as triggers instead of premonitory cravings driven by the hypothalamus. It is important to counsel patients with migraine to eat a healthy diet with consistent meals, to maintain adequate hydration, and to keep their caffeine intake low or at least consistent, although these teachings are predominantly based on limited studies with extrapolation from nutrition research.

 

 

D IS FOR DIARY

A headache diary is a recommended part of headache management and may enhance the accuracy of diagnosis and assist in treatment modifications. Paper and electronic diaries have been used. Electronic diaries may be more accurate for real-time use, but patients may be more likely to complete a paper one.67 Patients prefer electronic diaries over long paper forms,68 but a practical issue to consider is easy electronic access.

Patients can start keeping a headache diary before the initial consultation to assist with diagnosis, or early in their management. A first-appointment diary mailed with instructions is a feasible option.69 These types of diaries ask detailed questions to help diagnose all major primary headache types including menstrual migraine and to identify concomitant medication-overuse headache. Physicians and patients generally report improved communication with use of a diary.70

Some providers distinguish between a headache diary and a calendar. In standard practice, a headache diary is the general term referring to both, but the literature differentiates between the two. Both should at least include headache frequency, with possible inclusion of other factors such as headache duration, headache intensity, analgesic use, headache impact on function, and absenteeism. Potential triggers including menses can also be tracked. The calendar version can fit on a single page and can be used for simple tracking of headache frequency and analgesia use.

One of the simplest calendars to use is the “stoplight” calendar. Red days are when a patient is completely debilitated in bed. On a yellow day, function at work, school, or daily activities is significantly reduced by migraine, but the patient is not bedbound. A green day is when headache is present but function is not affected. No color is placed if the patient is 100% headache-free.

Acute treatment use can be written in or, to improve compliance, a checkmark can be placed on days of treatment. Patients who are tracking menses circle the days of menstruation. The calendar-diary should be brought to every appointment to track treatment response and medication use.

THE SECOND S IS FOR STRESS

Techniques for stress management in migraine
Stress and anxiety are associated with migraine. Either may lead to avoidance and hypervigilance of perceived triggers, and this association may affect migraines.71,72 High stress and chronic migraine are associated with lifestyle factors such as medication overuse, smoking, sedentary habits, and obesity.73 Fortunately, many evidence-based techniques used for management of stress and mood disorders can also be used in migraine, including cognitive behavioral therapy, biofeedback, mindfulness, and relaxation techniques (Table 2).

Behavioral management such as cognitive behavioral therapy in migraine has been shown to decrease catastrophizing, migraine disability, and headache severity and frequency.74 Both depression and anxiety can improve along with migraine.75 Cognitive behavioral therapy can be provided in individualized sessions or group sessions, either in person or online.74,76,77 The effects become more prominent about 5 weeks into treatment.78

Biofeedback, which uses behavioral techniques paired with physiologic autonomic measures, has been extensively studied, and shows benefit in migraine, including in meta-analysis.79 The types of biofeedback measurements used include electromyography, electroencephalography, temperature, sweat sensors, heart rate, blood volume pulse feedback, and respiration bands. While biofeedback is generally done under the guidance of a therapist, it can still be useful with minimal therapist contact and supplemental audio.80

Mindfulness, or the awareness of thoughts, feelings, and sensations in the present moment without judgment, is a behavioral technique that can be done alone or paired with another technique. It is often taught through a mindfulness-based stress-reduction  program, which relies on a standardized approach. A meta-analysis showed that mindfulness improves pain intensity, headache frequency, disability, self-efficacy, and quality of life.81 It may work by encouraging pain acceptance.82

Relaxation techniques are also employed in migraine management, either alone or in conjunction with techniques mentioned  above, such as mindfulness. They include progressive muscle relaxation and deep breathing. Relaxation has been shown to be effective when done by professional trainers as well as lay trainers in both individual and group settings.83,84

In patients with intractable headache, more-intensive inpatient and outpatient programs have been tried. Inpatient admissions with multidisciplinary programs that include a focus on behavioral techniques often paired with lifestyle education and sometimes pharmacologic management can be beneficial.85,86 These programs have also been successfully conducted as multiple outpatient sessions.86–88

Stress management is an important aspect of migraine management. These treatments often involve homework and require active participation.

LIFESTYLE FOR ALL

All patients with migraine should initiate lifestyle modifications (see Advice to patients with migraine: SEEDS for success). Modifications with the highest level of evidence, specifically behavioral techniques, have had the most reproducible results. A headache diary is an essential tool to identify patterns and needs for optimization of acute or preventive treatment regimens. The strongest evidence is for the behavioral management techniques for stress reduction.

Migraine is the second leading cause of years of life lived with a disability globally.1 It affects people of all ages, but particularly during the years associated with the highest productivity in terms of work and family life.

Migraine is a genetic neurologic disease that can be influenced or triggered by environmental factors. However, triggers do not cause migraine. For example, stress does not cause migraine, but it can exacerbate it.

Primary care physicians can help patients reduce the likelihood of a migraine attack, the severity of symptoms, or both by offering lifestyle counseling centered around the mnemonic SEEDS: sleep, exercise, eat, diary, and stress. In this article, each factor is discussed individually for its current support in the literature along with best-practice recommendations.

S IS FOR SLEEP

Advice to patients with migraine: SEEDS for success
Multiple sleep comorbidities are associated with migraine, including sleep apnea and insomnia.2 Poor sleep itself has been described as a migraine trigger. Those with both migraine and poor sleep report having lower quality of life, more mood disorders, lower socioeconomic status, higher stress, and higher tendency for poor lifestyle habits.3 The number needed to treat by initiating routine lifestyle behaviors including sleep, diet, and exercise is 2, indicating that every other person could benefit from this type of intervention.4

Before optimizing sleep hygiene, screen for sleep apnea, especially in those who have chronic daily headache upon awakening. An excellent tool is the STOP-Bang screening questionnaire5 (www.stopbang.ca/osa/screening.php). Patients respond “yes” or “no” to the following questions:

  • Snoring: Do you snore loudly (louder than talking or loud enough to be heard through closed doors)?
  • Tired: Do you often feel tired, fatigued, or sleepy during the daytime?
  • Observed: Has anyone observed you stop breathing during your sleep?
  • Pressure: Do you have or are you being treated for high blood pressure?
  • Body mass index greater than 35 kg/m2?
  • Age over 50?
  • Neck circumference larger than 40 cm (females) or  42 cm (males)?
  • Gender—male?

Each “yes” answer is scored as 1 point. A score less than 3 indicates low risk of obstructive sleep apnea; 3 to 4 indicates moderate risk; and 5 or more indicates high risk. Optimization of sleep apnea with continuous positive airway pressure therapy can improve sleep apnea headache.6 The improved sleep from reduced arousals may also mitigate migraine symptoms.

Sleep hygiene and behavior modification

Behavioral modification for sleep hygiene can convert chronic migraine to episodic migraine.7 One such program is stimulus control therapy, which focuses on using cues to initiate sleep (Table 1). Patients are encouraged to keep the bedroom quiet, dark, and cool, and to go to sleep at the same time every night. Importantly, the bed should be associated only with sleep. If patients are unable to fall asleep within 20 to 30 minutes, they should leave the room so they do not associate the bed with frustration and anxiety. Use of phones, tablets, and television in the bedroom is discouraged as these devices may make it more difficult to fall asleep.8

The next option is sleep restriction, which is useful for comorbid insomnia. Patients keep a sleep diary to better understand their sleep-wake cycle. The goal is 90% sleep efficiency, meaning that 90% of the time in bed (TIB) is spent asleep. For example, if the patient is in bed 8 hours but asleep only 4 hours, sleep efficiency is 50%. The goal is to reduce TIB to match the time asleep and to agree on a prescribed daily wake-up time. When the patient is consistently sleeping 90% of the TIB, add 30-minute increments until he or she is appropriately sleeping 7 to 8 hours at night.9 Naps are not recommended.

Let patients know that their migraine may worsen until a new routine sleep pattern emerges. This method is not recommended for patients with untreated sleep apnea.

E IS FOR EXERCISE

Exercise is broadly recommended for a healthy lifestyle; some evidence suggests that it can also be useful in the management of migraine.10 Low levels of physical activity and a sedentary lifestyle are associated with migraine.11 It is unclear if patients with migraine are less likely to exercise because they want to avoid triggering a migraine or if a sedentary lifestyle increases their risk.

Exercise has been studied for its prophylactic benefits in migraine, and one hypothesis relates to beta-endorphins. Levels of beta-endorphins are reduced in the cerebrospinal fluid of patients with migraine.12 Exercise programs may increase levels while reducing headache frequency and duration.13 One study showed that pain thresholds do not change with exercise programs, suggesting that it is avoidance behavior that is positively altered rather than the underlying pain pathways.14

A systematic review and meta-analysis based on 5 randomized controlled trials and 1 nonrandomized controlled clinical trial showed that exercise reduced monthly migraine days by only 0.6 (± 0.3) days, but the data also suggested that as the exercise intensity increased, so did the positive effects.10

Some data suggest that exercise may also reduce migraine duration and severity as well as the need for abortive medication.10 Two studies in this systematic review15,16 showed that exercise benefits were equivalent to those of migraine preventives such as amitriptyline and topiramate; the combination of amitriptyline and exercise was more beneficial than exercise alone. Multiple types of exercise were beneficial, including walking, jogging, cross-training, and cycling when done for least 6 weeks and for 30 to 50 minutes 3 to 5 times a week.

These findings are in line with the current recommendations for general health from the American College of Sports Medicine, ie, moderate to vigorous cardio­respiratory exercise for 30 to 60 minutes 3 to 5 times a week (or 150 minutes per week). The daily exercise can be continuous or done in intervals of less than 20 minutes. For those with a sedentary lifestyle, as is seen in a significant proportion of the migraine population, light to moderate exercise for less than 20 minutes is still beneficial.17

Based on this evidence, the best current recommendation for patients with migraine is to engage in graded moderate cardiorespiratory exercise, although any exercise is better than none. If a patient is sedentary or has poor exercise tolerance, or both, exercising once a week for shorter time periods may be a manageable place to start.

Some patients may identify exercise as a trigger or exacerbating factor in migraine. These patients may need appropriate prophylactic and abortive therapies before starting an exercise regimen.

 

 

THE SECOND E IS FOR EAT (FOOD AND DRINK)

Many patients believe that some foods trigger migraine attacks, but further study is needed. The most consistent food triggers appear to be red wine and caffeine (withdrawal).18,19 Interestingly, patients with migraine report low levels of alcohol consumption,20 but it is unclear if that is because alcohol has a protective effect or if patients avoid it.

Some patients may crave certain foods in the prodromal phase of an attack, eat the food, experience the attack, and falsely conclude that the food caused the attack.21 Premonitory symptoms include fatigue, cognitive changes, homeostatic changes, sensory hyperresponsiveness, and food cravings.21 It is difficult to distinguish between premonitory phase food cravings and true triggers because premonitory symptoms can precede headache by 48 to 72 hours, and the timing for a trigger to be considered causal is not known.22

Chocolate is often thought to be a migraine trigger, but the evidence argues against this and even suggests that sweet cravings are a part of the premonitory phase.23 Monosodium glutamate is often identified as a trigger as well, but the literature is inconsistent and does not support a causal relationship.24 Identifying true food triggers in migraine is difficult, and patients with migraine may have poor quality diets, with some foods acting as true triggers for certain patients.25 These possibilities have led to the development of many “migraine diets,” including elimination diets.

Elimination diets

Elimination diets involve avoiding specific food items over a period of time and then adding them back in one at a time to gauge whether they cause a reaction in the body. A number of these diets have been studied for their effects on headache and migraine:

Gluten-free diets restrict foods that contain wheat, rye, and barley. A systematic review of gluten-free diets in patients with celiac disease found that headache or migraine frequency decreased by 51.6% to 100% based on multiple cohort studies (N = 42,388).26 There are no studies on the use of a gluten-free diet for migraine in patients without celiac disease.

Immunoglobulin G-elimination diets restrict foods that serve as antigens for IgG. However, data supporting these diets are inconsistent. Two small randomized controlled trials found that the diets improved migraine symptoms, but a larger study found no improvement in the number of migraine days at 12 weeks, although there was an initially significant effect at 4 weeks.27–29

Antihistamine diets restrict foods that have high levels of histamines, including fermented dairy, vegetables, soy products,  wine, beer, alcohol, and those that cause histamine release regardless of IgE testing results. A prospective single-arm study of antihistamine diets in patients with chronic headache reported symptom improvement, which could be applied to certain comorbidities such as  mast cell activation syndrome.30 Another prospective nonrandomized controlled study eliminated foods based on positive IgE skin-prick testing for allergy in patients with recurrent migraine and found that it reduced headache frequency.31

Tyramine-free diets are often recommended due to the presumption that tyramine-containing foods (eg, aged cheese, cured or smoked meats and fish, and beer) are triggers. However, multiple studies have reviewed this theory with inconsistent results,32 and the only study of a tyramine-free diet was negative.33 In addition, commonly purported high-tyramine foods have lower tyramine levels than previously thought.34

Low-fat diets in migraine are supported by 2 small randomized controlled trials and a prospective study showing a decrease in symptom severity; the results for frequency are inconsistent.35–37

Low-glycemic index diets are supported in migraine by 1 randomized controlled trial that showed improvement in migraine frequency in a diet group and in a control group of patients who took a standard migraine-preventive medication to manage their symptoms.38

 

 

Other migraine diets

Diets high in certain foods or ingredient ratios, as opposed to elimination diets, have also been studied in patients with migraine. One promising diet containing high levels of omega-3 fatty acids and low levels of omega-6 fatty acids was shown in a systematic review to reduce the duration of migraine but not the frequency or severity.39 A more recent randomized controlled trial of this diet in chronic migraine also showed that it decreased migraine frequency.40

The ketogenic diet (high fat, low carbohydrate) had promising results in a randomized controlled trial in overweight women with migraine and in a prospective study.41,42 However, a prospective study of the Atkins diet in teenagers with chronic daily headaches showed no benefit.43 The ketogenic diet is difficult to follow and may work in part due to weight loss alone, although ketogenesis itself may also play a role.41,44

Sodium levels have been shown to be higher in the cerebrospinal fluid of patients with migraine than in controls, particularly during an attack.45 For a prehypertensive population or an elderly population, a low-sodium diet may be beneficial based on 2 prospective trials.46,47 However, a younger female population without hypertension and low-to-normal body mass index had a reduced probability of migraine while consuming a high-sodium diet.48

Counseling about sodium intake should be tailored to specific patient populations. For example, a diet low in sodium may be appropriate for patients with vascular risk factors such as hypertension, whereas a high-sodium diet may be appropriate in patients with comorbidities like postural tachycardia syndrome or in those with a propensity for low blood pressure or low body mass index.

Encourage routine meals and hydration

The standard advice for patients with migraine is to consume regular meals. Headaches have been associated with fasting, and those with migraine are predisposed to attacks in the setting of fasting.49,50 Migraine is more common when meals are skipped, particularly breakfast.51

It is unclear how fasting lowers the migraine threshold. Nutritional studies show that skipping meals, particularly breakfast, increases low-grade inflammation and impairs  glucose metabolism by affecting insulin and fat oxidation metabolism.52 However, hypoglycemia itself is not a consistent cause of headache or migraine attacks.53 As described above, a randomized controlled trial of a low-glycemic index diet actually decreased migraine frequency and severity.38 Skipping meals also reduces energy and is associated with reduced physical activity, perhaps leading to multiple compounding triggers that further lower the migraine threshold.54,55

When counseling patients about the need to eat breakfast, consider what they normally consume (eg, is breakfast just a cup of coffee?). Replacing simple carbohydrates with protein, fats, and fiber may be beneficial for general health, but the effects on migraine are not known, nor is the optimal composition of breakfast foods.55

The optimal timing of breakfast relative to awakening is also unclear, but in general, it should be eaten within 30 to 60 minutes of rising. Also consider patients’ work hours—delayed-phase or shift workers have altered sleep cycles.

Recommendations vary in regard to hydration. Headache is associated with fluid restriction and dehydration,56,57 but only a few studies suggest that rehydration and increased hydration status can improve migraine.58 In fact, a single post hoc analysis of a metoclopramide study showed that intravenous fluid alone for patients with migraine in the emergency room did not improve pain outcomes.59

The amount of water patients should drink daily in the setting of migraine is also unknown, but a study showed benefit with 4 L, which equates to a daily intake of 16 eight-ounce glasses.60 One review on general health that could be extrapolated given the low risk of the intervention indicated that 1.8 L daily (7 to 8 eight-ounce glasses) promoted a euhydration status in most people, although many factors contribute to hydration status.61

Caffeine intake is also a major consideration. Caffeine is a nonspecific adenosine receptor antagonist that modulates adenosine receptors like the pronociceptive 2A receptor, leading to changes integral to the neuropathophysiology of migraine.62 Caffeine has analgesic properties at doses greater than 65 to 200 mg and augments the effects of analgesics such as acetaminophen and aspirin. Chronic caffeine use can lead to withdrawal symptoms when intake is stopped abruptly; this is thought to be due to upregulation of adenosine receptors, but the effect varies based on genetic predisposition.19

The risk of chronic daily headache may relate to high use of caffeine preceding the onset of chronification, and caffeine abstinence may improve response to acute migraine treatment.19,63 There is a dose-dependent risk of headache.64,65 Current recommendations suggest limiting caffeine consumption to less than 200 mg per day or stopping caffeine consumption altogether based on the quantity required for caffeine-withdrawal headache.66 Varying  the caffeine dose from day to day may also trigger headache due to the high sensitivity to caffeine withdrawal.

While many diets have shown potential benefit in patients with migraine, more studies are needed before any one “migraine diet” can be recommended. Caution should be taken, as there is risk of adverse effects from nutrient deficiencies or excess levels, especially if the patient is not under the care of a healthcare professional who is familiar with the diet.

Whether it is beneficial to avoid specific food triggers at this time is unclear and still controversial even within the migraine community because some of these foods may be misattributed as triggers instead of premonitory cravings driven by the hypothalamus. It is important to counsel patients with migraine to eat a healthy diet with consistent meals, to maintain adequate hydration, and to keep their caffeine intake low or at least consistent, although these teachings are predominantly based on limited studies with extrapolation from nutrition research.

 

 

D IS FOR DIARY

A headache diary is a recommended part of headache management and may enhance the accuracy of diagnosis and assist in treatment modifications. Paper and electronic diaries have been used. Electronic diaries may be more accurate for real-time use, but patients may be more likely to complete a paper one.67 Patients prefer electronic diaries over long paper forms,68 but a practical issue to consider is easy electronic access.

Patients can start keeping a headache diary before the initial consultation to assist with diagnosis, or early in their management. A first-appointment diary mailed with instructions is a feasible option.69 These types of diaries ask detailed questions to help diagnose all major primary headache types including menstrual migraine and to identify concomitant medication-overuse headache. Physicians and patients generally report improved communication with use of a diary.70

Some providers distinguish between a headache diary and a calendar. In standard practice, a headache diary is the general term referring to both, but the literature differentiates between the two. Both should at least include headache frequency, with possible inclusion of other factors such as headache duration, headache intensity, analgesic use, headache impact on function, and absenteeism. Potential triggers including menses can also be tracked. The calendar version can fit on a single page and can be used for simple tracking of headache frequency and analgesia use.

One of the simplest calendars to use is the “stoplight” calendar. Red days are when a patient is completely debilitated in bed. On a yellow day, function at work, school, or daily activities is significantly reduced by migraine, but the patient is not bedbound. A green day is when headache is present but function is not affected. No color is placed if the patient is 100% headache-free.

Acute treatment use can be written in or, to improve compliance, a checkmark can be placed on days of treatment. Patients who are tracking menses circle the days of menstruation. The calendar-diary should be brought to every appointment to track treatment response and medication use.

THE SECOND S IS FOR STRESS

Techniques for stress management in migraine
Stress and anxiety are associated with migraine. Either may lead to avoidance and hypervigilance of perceived triggers, and this association may affect migraines.71,72 High stress and chronic migraine are associated with lifestyle factors such as medication overuse, smoking, sedentary habits, and obesity.73 Fortunately, many evidence-based techniques used for management of stress and mood disorders can also be used in migraine, including cognitive behavioral therapy, biofeedback, mindfulness, and relaxation techniques (Table 2).

Behavioral management such as cognitive behavioral therapy in migraine has been shown to decrease catastrophizing, migraine disability, and headache severity and frequency.74 Both depression and anxiety can improve along with migraine.75 Cognitive behavioral therapy can be provided in individualized sessions or group sessions, either in person or online.74,76,77 The effects become more prominent about 5 weeks into treatment.78

Biofeedback, which uses behavioral techniques paired with physiologic autonomic measures, has been extensively studied, and shows benefit in migraine, including in meta-analysis.79 The types of biofeedback measurements used include electromyography, electroencephalography, temperature, sweat sensors, heart rate, blood volume pulse feedback, and respiration bands. While biofeedback is generally done under the guidance of a therapist, it can still be useful with minimal therapist contact and supplemental audio.80

Mindfulness, or the awareness of thoughts, feelings, and sensations in the present moment without judgment, is a behavioral technique that can be done alone or paired with another technique. It is often taught through a mindfulness-based stress-reduction  program, which relies on a standardized approach. A meta-analysis showed that mindfulness improves pain intensity, headache frequency, disability, self-efficacy, and quality of life.81 It may work by encouraging pain acceptance.82

Relaxation techniques are also employed in migraine management, either alone or in conjunction with techniques mentioned  above, such as mindfulness. They include progressive muscle relaxation and deep breathing. Relaxation has been shown to be effective when done by professional trainers as well as lay trainers in both individual and group settings.83,84

In patients with intractable headache, more-intensive inpatient and outpatient programs have been tried. Inpatient admissions with multidisciplinary programs that include a focus on behavioral techniques often paired with lifestyle education and sometimes pharmacologic management can be beneficial.85,86 These programs have also been successfully conducted as multiple outpatient sessions.86–88

Stress management is an important aspect of migraine management. These treatments often involve homework and require active participation.

LIFESTYLE FOR ALL

All patients with migraine should initiate lifestyle modifications (see Advice to patients with migraine: SEEDS for success). Modifications with the highest level of evidence, specifically behavioral techniques, have had the most reproducible results. A headache diary is an essential tool to identify patterns and needs for optimization of acute or preventive treatment regimens. The strongest evidence is for the behavioral management techniques for stress reduction.

References
  1. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390(10100):1211–1259. doi:10.1016/S0140-6736(17)32154-2
  2. Vgontzas A, Pavlovic JM. Sleep diorders and migraine: review of literature and potential pathophysiology mechanisms. Headache 2018; 58(7):1030–1039. doi:10.1111/head.13358
  3. Lund N, Westergaard ML, Barloese M, Glumer C, Jensen RH. Epidemiology of concurrent headache and sleep problems in Denmark. Cephalalgia 2014; 34(10):833–845. doi:10.1177/0333102414543332
  4. Woldeamanuel YW, Cowan RP. The impact of regular lifestyle behavior in migraine: a prevalence case-referent study. J Neurol 2016; 263(4):669–676. doi:10.1007/s00415-016-8031-5
  5. Chung F, Abdullah HR, Liao P. STOP-Bang questionnaire: a practical approach to screen for obstructive sleep apnea. Chest 2016; 149(3):631–638. doi:10.1378/chest.15-0903
  6. Johnson KG, Ziemba AM, Garb JL. Improvement in headaches with continuous positive airway pressure for obstructive sleep apnea: a retrospective analysis. Headache 2013; 53(2):333–343. doi:10.1111/j.1526-4610.2012.02251.x
  7. Calhoun AH, Ford S. Behavioral sleep modification may revert transformed migraine to episodic migraine. Headache 2007; 47(8):1178–1183. doi:10.1111/j.1526-4610.2007.00780.x
  8. Calhoun AH, Ford S, Finkel AG, Kahn KA, Mann JD. The prevalence and spectrum of sleep problems in women with transformed migraine. Headache 2006; 46(4):604–610. doi:10.1111/j.1526-4610.2006.00410.x
  9. Rains JC. Optimizing circadian cycles and behavioral insomnia treatment in migraine. Curr Pain Headache Rep 2008; 12(3):213–219. pmid:18796272
  10. Lemmens J, De Pauw J, Van Soom T, et al. The effect of aerobic exercise on the number of migraine days, duration and pain intensity in migraine: a systematic literature review and meta-analysis. J Headache Pain 2019; 20(1):16. doi:10.1186/s10194-019-0961-8
  11. Amin FM, Aristeidou S, Baraldi C, et al; European Headache Federation School of Advanced Studies (EHF-SAS). The association between migraine and physical exercise. J Headache Pain 2018; 19(1):83. doi:10.1186/s10194-018-0902-y
  12. Genazzani AR, Nappi G, Facchinetti F, et al. Progressive impairment of CSF beta-EP levels in migraine sufferers. Pain 1984; 18:127-133. pmid:6324056
  13. Hindiyeh NA, Krusz JC, Cowan RP. Does exercise make migraines worse and tension type headaches better? Curr Pain Headache Rep 2013;17:380. pmid:24234818
  14. Kroll LS, Sjodahl Hammarlund C, Gard G, Jensen RH, Bendtsen L. Has aerobic exercise effect on pain perception in persons with migraine and coexisting tension-type headache and neck pain? A randomized, controlled, clinical trial. Eur J Pain 2018; 10:10. pmid:29635806
  15. Santiago MD, Carvalho Dde S, Gabbai AA, Pinto MM, Moutran AR, Villa TR. Amitriptyline and aerobic exercise or amitriptyline alone in the treatment of chronic migraine: a randomized comparative study. Arq Neuropsiquiatr 2014; 72(11):851-855. pmid:25410451
  16. Varkey E, Cider A, Carlsson J, Linde M. Exercise as migraine prophylaxis: a randomized study using relaxation and topiramate as controls. Cephalalgia 2011; 31(14):1428-1438. pmid:21890526
  17. Garber CE, Blissmer B, Deschenes MR, et al. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc 2011; 43(7):1334-1359. pmid:21694556
  18. Guarnieri P, Radnitz CL, Blanchard EB. Assessment of dietary risk factors in chronic headache. Biofeedback Self Regul 1990; 15(1):15–25. pmid:2361144
  19. Shapiro RE. Caffeine and headaches. Curr Pain Headache Rep 2008; 12(4):311–315. pmid:18625110
  20. Yokoyama M, Yokoyama T, Funazu K, et al. Associations between headache and stress, alcohol drinking, exercise, sleep, and comorbid health conditions in a Japanese population. J Headache Pain 2009; 10(3):177–185. doi:10.1007/s10194-009-0113-7
  21. Karsan N, Bose P, Goadsby PJ. The migraine premonitory phase. Continuum (Minneap Minn) 2018; 24(4, Headache):996–1008. doi:10.1212/CON.0000000000000624
  22. Pavlovic JM, Buse DC, Sollars CM, Haut S, Lipton RB. Trigger factors and premonitory features of migraine attacks: summary of studies. Headache 2014; 54(10):1670–1679. doi:10.1111/head.12468
  23. Marcus DA, Scharff L, Turk D, Gourley LM. A double-blind provocative study of chocolate as a trigger of headache. Cephalalgia 1997; 17(8):855–862. doi:10.1046/j.1468-2982.1997.1708855.x
  24. Obayashi Y, Nagamura Y. Does monosodium glutamate really cause headache? A systematic review of human studies. J Headache Pain 2016; 17:54. doi:10.1186/s10194-016-0639-4
  25. Evans EW, Lipton RB, Peterlin BL, et al. Dietary intake patterns and diet quality in a nationally representative sample of women with and without severe headache or migraine. Headache 2015; 55(4):550–561. doi:10.1111/head.12527
  26. Zis P, Julian T, Hadjivassiliou M. Headache associated with coeliac disease: a systematic review and meta-analysis. Nutrients 2018; 10(10). doi:10.3390/nu10101445
  27. Alpay K, Ertas M, Orhan EK, Ustay DK, Lieners C, Baykan B. Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Cephalalgia 2010; 30(7):829–837. doi:10.1177/0333102410361404
  28. Aydinlar EI, Dikmen PY, Tiftikci A, et al. IgG-based elimination diet in migraine plus irritable bowel syndrome. Headache 2013; 53(3):514–525. doi:10.1111/j.1526-4610.2012.02296.x
  29. Mitchell N, Hewitt CE, Jayakody S, et al. Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches. Nutr J 2011; 10:85. doi:10.1186/1475-2891-10-85
  30. Wantke F, Gotz M, Jarisch R. Histamine-free diet: treatment of choice for histamine-induced food intolerance and supporting treatment for chronic headaches. Clin Exp Allergy 1993; 23(12):982–985. pmid:10779289
  31. Mansfield LE, Vaughan TR, Waller SF, Haverly RW, Ting S. Food allergy and adult migraine: double-blind and mediator confirmation of an allergic etiology. Ann Allergy 1985; 55(2):126–129. pmid:4025956
  32. Kohlenberg RJ. Tyramine sensitivity in dietary migraine: a critical review. Headache 1982; 22(1):30–34. pmid:17152742
  33. Medina JL, Diamond S. The role of diet in migraine. Headache 1978; 18(1):31–34. pmid:649377
  34. Mosnaim AD, Freitag F, Ignacio R, et al. Apparent lack of correlation between tyramine and phenylethylamine content and the occurrence of food-precipitated migraine. Reexamination of a variety of food products frequently consumed in the United States and commonly restricted in tyramine-free diets. Headache Quarterly. Current Treatment and Research 1996; 7(3):239–249.
  35. Ferrara LA, Pacioni D, Di Fronzo V, et al. Low-lipid diet reduces frequency and severity of acute migraine attacks. Nutr Metab Cardiovasc Dis 2015; 25(4):370–375. doi:10.1016/j.numecd.2014.12.006
  36. Bic Z, Blix GG, Hopp HP, Leslie FM, Schell MJ. The influence of a low-fat diet on incidence and severity of migraine headaches. J Womens Health Gend Based Med 1999; 8(5):623–630. doi:10.1089/jwh.1.1999.8.623
  37. Bunner AE, Agarwal U, Gonzales JF, Valente F, Barnard ND. Nutrition intervention for migraine: a randomized crossover trial. J Headache Pain 2014; 15:69. doi:10.1186/1129-2377-15-69
  38. Evcili G, Utku U, Ogun MN, Ozdemir G. Early and long period follow-up results of low glycemic index diet for migraine prophylaxis. Agri 2018; 30(1):8–11. doi:10.5505/agri.2017.62443
  39. Maghsoumi-Norouzabad L, Mansoori A, Abed R, Shishehbor F. Effects of omega-3 fatty acids on the frequency, severity, and duration of migraine attacks: a systematic review and meta-analysis of randomized controlled trials. Nutr Neurosci 2018; 21(9):614–623. doi:10.1080/1028415X.2017.1344371
  40. Soares AA, Loucana PMC, Nasi EP, Sousa KMH, Sa OMS, Silva-Neto RP. A double- blind, randomized, and placebo-controlled clinical trial with omega-3 polyunsaturated fatty acids (OPFA Ω-3) for the prevention of migraine in chronic migraine patients using amitriptyline. Nutr Neurosci 2018; 21(3):219–223. doi:10.1080/1028415X.2016.1266133
  41. Di Lorenzo C, Coppola G, Sirianni G, et al. Migraine improvement during short lasting ketogenesis: a proof-of-concept study. Eur J Neurol 2015; 22(1):170–177. doi:10.1111/ene.12550
  42. Di Lorenzo C, Coppola G, Bracaglia M, et al. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study. J Headache Pain 2016; 17:58. doi:10.1186/s10194-016-0650-9
  43. Kossoff EH, Huffman J, Turner Z, Gladstein J. Use of the modified Atkins diet for adolescents with chronic daily headache. Cephalalgia 2010; 30(8):1014–1016. https://journals.sagepub.com/doi/full/10.1111/j.1468-2982.2009.02016.x
  44. Slavin M, Ailani J. A clinical approach to addressing diet with migraine patients. Curr Neurol Neurosci Rep 2017; 17(2):17. doi:10.1007/s11910-017-0721-6
  45. Amer M, Woodward M, Appel LJ. Effects of dietary sodium and the DASH diet on the occurrence of headaches: results from randomised multicentre DASH-sodium clinical trial. BMJ Open 2014; 4(12):e006671. doi:10.1136/bmjopen-2014-006671
  46. Chen L, Zhang Z, Chen W, Whelton PK, Appel LJ. Lower sodium intake and risk of headaches: results from the trial of nonpharmacologic interventions in the elderly. Am J Public Health 2016; 106(7):1270–1275. doi:10.2105/AJPH.2016.303143
  47. Pogoda JM, Gross NB, Arakaki X, Fonteh AN, Cowan RP, Harrington MG. Severe headache or migraine history is inversely correlated with dietary sodium intake: NHANES 1999–2004. Headache 2016; 56(4):688–698. doi:10.1111/head.12792
  48. Awada A, al Jumah M. The first-of-Ramadan headache. Headache 1999; 39(7):490–493. pmid:11279933
  49. Abu-Salameh I, Plakht Y, Ifergane G. Migraine exacerbation during Ramadan fasting. J Headache Pain 2010; 11(6):513–517. doi:10.1007/s10194-010-0242-z
  50. Nazari F, Safavi M, Mahmudi M. Migraine and its relation with lifestyle in women. Pain Pract 2010; 10(3):228–234. doi:10.1111/j.1533-2500.2009.00343.x
  51. Nas A, Mirza N, Hagele F, et al. Impact of breakfast skipping compared with dinner skipping on regulation of energy balance and metabolic risk. Am J Clin Nutr 2017; 105(6):1351–1361. doi:10.3945/ajcn.116.151332
  52. Torelli P, Manzoni GC. Fasting headache. Curr Pain Headache Rep 2010; 14(4):284–291. doi:10.1007/s11916-010-0119-5
  53. Yoshimura E, Hatamoto Y, Yonekura S, Tanaka H. Skipping breakfast reduces energy intake and physical activity in healthy women who are habitual breakfast eaters: a randomized crossover trial. Physiol Behav 2017; 174:89–94. doi:10.1016/j.physbeh.2017.03.008
  54. Pendergast FJ, Livingstone KM, Worsley A, McNaughton SA. Correlates of meal skipping in young adults: a systematic review. Int J Behav Nutr Phys Act 2016; 13(1):125. doi:10.1186/s12966-016-0451-1
  55. Maki KC, Phillips-Eakley AK, Smith KN. The effects of breakfast consumption and composition on metabolic wellness with a focus on carbohydrate metabolism. Adv Nutr 2016; 7(3):613S–621S. doi:10.3945/an.115.010314
  56. Shirreffs SM, Merson SJ, Fraser SM, Archer DT. The effects of fluid restriction on hydration status and subjective feelings in man. Br J Nutr 2004; 91(6):951–958. doi:10.1079/BJN20041149
  57. Blau JN. Water deprivation: a new migraine precipitant. Headache 2005; 45(6):757–759. doi:10.1111/j.1526-4610.2005.05143_3.x
  58. Price A, Burls A. Increased water intake to reduce headache: learning from a critical appraisal. J Eval Clin Pract 2015; 21(6):1212–1218. doi:10.1111/jep.12413
  59. Balbin JE, Nerenberg R, Baratloo A, Friedman BW. Intravenous fluids for migraine: a post hoc analysis of clinical trial data. Am J Emerg Med 2016; 34(4):713–716. doi:10.1016/j.ajem.2015.12.080
  60. Spigt M, Weerkamp N, Troost J, van Schayck CP, Knottnerus JA. A randomized trial on the effects of regular water intake in patients with recurrent headaches. Fam Pract 2012; 29(4):370–375. doi:10.1093/fampra/cmr112
  61. Armstrong LE, Johnson EC. Water intake, water balance, and the elusive daily water requirement. Nutrients 2018; 10(12). doi:10.3390/nu10121928
  62. Fried NT, Elliott MB, Oshinsky ML. The role of adenosine signaling in headache: a review. Brain Sci 2017; 7(3). doi:10.3390/brainsci7030030
  63. Lee MJ, Choi HA, Choi H, Chung CS. Caffeine discontinuation improves acute migraine treatment: a prospective clinic-based study. J Headache Pain 2016; 17(1):71. doi:10.1186/s10194-016-0662-5
  64. Shirlow MJ, Mathers CD. A study of caffeine consumption and symptoms; indigestion, palpitations, tremor, headache and insomnia. Int J Epidemiol 1985; 14(2):239–248. doi:10.1093/ije/14.2.239
  65. Silverman K, Evans SM, Strain EC, Griffiths RR. Withdrawal syndrome after the double-blind cessation of caffeine consumption. N Engl J Med 1992; 327(16):1109–1114. doi:10.1056/NEJM199210153271601
  66. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018; 38(1):1–211. doi:10.1177/0333102417738202
  67. Krogh AB, Larsson B, Salvesen O, Linde M. A comparison between prospective Internet-based and paper diary recordings of headache among adolescents in the general population. Cephalalgia 2016; 36(4):335–345. doi:10.1177/0333102415591506
  68. Bandarian-Balooch S, Martin PR, McNally B, Brunelli A, Mackenzie S. Electronic-diary for recording headaches, triggers, and medication use: development and evaluation. Headache 2017; 57(10):1551–1569. doi:10.1111/head.13184
  69. Tassorelli C, Sances G, Allena M, et al. The usefulness and applicability of a basic headache diary before first consultation: results of a pilot study conducted in two centres. Cephalalgia 2008; 28(10):1023–1030. doi:10.1111/j.1468-2982.2008.01639.x
  70. Baos V, Ester F, Castellanos A, et al. Use of a structured migraine diary improves patient and physician communication about migraine disability and treatment outcomes. Int J Clin Pract 2005; 59(3):281–286. doi:10.1111/j.1742-1241.2005.00469.x
  71. Martin PR, MacLeod C. Behavioral management of headache triggers: avoidance of triggers is an inadequate strategy. Clin Psychol Rev 2009; 29(6):483–495. doi:10.1016/j.cpr.2009.05.002
  72. Giannini G, Zanigni S, Grimaldi D, et al. Cephalalgiaphobia as a feature of high-frequency migraine: a pilot study. J Headache Pain 2013; 14:49. doi:10.1186/1129-2377-14-49
  73. Westergaard ML, Glumer C, Hansen EH, Jensen RH. Medication overuse, healthy lifestyle behaviour and stress in chronic headache: results from a population-based representative survey. Cephalalgia 2016; 36(1):15–28. doi:10.1177/0333102415578430
  74. Christiansen S, Jurgens TP, Klinger R. Outpatient combined group and individual cognitive-behavioral treatment for patients with migraine and tension-type headache in a routine clinical setting. Headache 2015; 55(8):1072–1091. doi:10.1111/head.12626
  75. Martin PR, Aiello R, Gilson K, Meadows G, Milgrom J, Reece J. Cognitive behavior therapy for comorbid migraine and/or tension-type headache and major depressive disorder: an exploratory randomized controlled trial. Behav Res Ther 2015; 73:8–18. doi:10.1016/j.brat.2015.07.005
  76. Nash JM, Park ER, Walker BB, Gordon N, Nicholson RA. Cognitive-behavioral group treatment for disabling headache. Pain Med 2004; 5(2):178–186. doi:10.1111/j.1526-4637.2004.04031.x
  77. Sorbi MJ, Balk Y, Kleiboer AM, Couturier EG. Follow-up over 20 months confirms gains of online behavioural training in frequent episodic migraine. Cephalalgia 2017; 37(3):236–250. doi:10.1177/0333102416657145
  78. Thorn BE, Pence LB, Ward LC, et al. A randomized clinical trial of targeted cognitive behavioral treatment to reduce catastrophizing in chronic headache sufferers. J Pain 2007; 8(12):938–949. doi:10.1016/j.jpain.2007.06.010
  79. Nestoriuc Y, Martin A. Efficacy of biofeedback for migraine: a meta-analysis. Pain 2007; 128(1–2):111–127. doi:10.1016/j.pain.2006.09.007
  80. Blanchard EB, Appelbaum KA, Nicholson NL, et al. A controlled evaluation of the addition of cognitive therapy to a home-based biofeedback and relaxation treatment of vascular headache. Headache 1990; 30(6):371–376. pmid:2196240
  81. Gu Q, Hou JC, Fang XM. Mindfulness meditation for primary headache pain: a meta-analysis. Chin Med J (Engl) 2018; 131(7):829–838. doi:10.4103/0366-6999.228242
  82. Day MA, Thorn BE. The mediating role of pain acceptance during mindfulness-based cognitive therapy for headache. Complement Ther Med 2016; 25:51–54. doi:10.1016/j.ctim.2016.01.002
  83. Williamson DA, Monguillot JE, Jarrell MP, Cohen RA, Pratt JM, Blouin DC. Relaxation for the treatment of headache. Controlled evaluation of two group programs. Behav Modif 1984; 8(3):407–424. doi:10.1177/01454455840083007
  84. Merelle SY, Sorbi MJ, Duivenvoorden HJ, Passchier J. Qualities and health of lay trainers with migraine for behavioral attack prevention. Headache 2010; 50(4):613–625. doi:10.1111/j.1526-4610.2008.01241.x
  85. Gaul C, van Doorn C, Webering N, et al. Clinical outcome of a headache-specific multidisciplinary treatment program and adherence to treatment recommendations in a tertiary headache center: an observational study. J Headache Pain 2011; 12(4):475–483. doi:10.1007/s10194-011-0348-y
  86. Wallasch TM, Kropp P. Multidisciplinary integrated headache care: a prospective 12-month follow-up observational study. J Headache Pain 2012; 13(7):521–529. doi:10.1007/s10194-012-0469-y
  87. Lemstra M, Stewart B, Olszynski WP. Effectiveness of multidisciplinary intervention in the treatment of migraine: a randomized clinical trial. Headache 2002; 42(9):845–854. pmid:12390609
  88. Krause SJ, Stillman MJ, Tepper DE, Zajac D. A prospective cohort study of outpatient interdisciplinary rehabilitation of chronic headache patients. Headache 2017; 57(3):428–440. doi:10.1111/head.13020
References
  1. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390(10100):1211–1259. doi:10.1016/S0140-6736(17)32154-2
  2. Vgontzas A, Pavlovic JM. Sleep diorders and migraine: review of literature and potential pathophysiology mechanisms. Headache 2018; 58(7):1030–1039. doi:10.1111/head.13358
  3. Lund N, Westergaard ML, Barloese M, Glumer C, Jensen RH. Epidemiology of concurrent headache and sleep problems in Denmark. Cephalalgia 2014; 34(10):833–845. doi:10.1177/0333102414543332
  4. Woldeamanuel YW, Cowan RP. The impact of regular lifestyle behavior in migraine: a prevalence case-referent study. J Neurol 2016; 263(4):669–676. doi:10.1007/s00415-016-8031-5
  5. Chung F, Abdullah HR, Liao P. STOP-Bang questionnaire: a practical approach to screen for obstructive sleep apnea. Chest 2016; 149(3):631–638. doi:10.1378/chest.15-0903
  6. Johnson KG, Ziemba AM, Garb JL. Improvement in headaches with continuous positive airway pressure for obstructive sleep apnea: a retrospective analysis. Headache 2013; 53(2):333–343. doi:10.1111/j.1526-4610.2012.02251.x
  7. Calhoun AH, Ford S. Behavioral sleep modification may revert transformed migraine to episodic migraine. Headache 2007; 47(8):1178–1183. doi:10.1111/j.1526-4610.2007.00780.x
  8. Calhoun AH, Ford S, Finkel AG, Kahn KA, Mann JD. The prevalence and spectrum of sleep problems in women with transformed migraine. Headache 2006; 46(4):604–610. doi:10.1111/j.1526-4610.2006.00410.x
  9. Rains JC. Optimizing circadian cycles and behavioral insomnia treatment in migraine. Curr Pain Headache Rep 2008; 12(3):213–219. pmid:18796272
  10. Lemmens J, De Pauw J, Van Soom T, et al. The effect of aerobic exercise on the number of migraine days, duration and pain intensity in migraine: a systematic literature review and meta-analysis. J Headache Pain 2019; 20(1):16. doi:10.1186/s10194-019-0961-8
  11. Amin FM, Aristeidou S, Baraldi C, et al; European Headache Federation School of Advanced Studies (EHF-SAS). The association between migraine and physical exercise. J Headache Pain 2018; 19(1):83. doi:10.1186/s10194-018-0902-y
  12. Genazzani AR, Nappi G, Facchinetti F, et al. Progressive impairment of CSF beta-EP levels in migraine sufferers. Pain 1984; 18:127-133. pmid:6324056
  13. Hindiyeh NA, Krusz JC, Cowan RP. Does exercise make migraines worse and tension type headaches better? Curr Pain Headache Rep 2013;17:380. pmid:24234818
  14. Kroll LS, Sjodahl Hammarlund C, Gard G, Jensen RH, Bendtsen L. Has aerobic exercise effect on pain perception in persons with migraine and coexisting tension-type headache and neck pain? A randomized, controlled, clinical trial. Eur J Pain 2018; 10:10. pmid:29635806
  15. Santiago MD, Carvalho Dde S, Gabbai AA, Pinto MM, Moutran AR, Villa TR. Amitriptyline and aerobic exercise or amitriptyline alone in the treatment of chronic migraine: a randomized comparative study. Arq Neuropsiquiatr 2014; 72(11):851-855. pmid:25410451
  16. Varkey E, Cider A, Carlsson J, Linde M. Exercise as migraine prophylaxis: a randomized study using relaxation and topiramate as controls. Cephalalgia 2011; 31(14):1428-1438. pmid:21890526
  17. Garber CE, Blissmer B, Deschenes MR, et al. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc 2011; 43(7):1334-1359. pmid:21694556
  18. Guarnieri P, Radnitz CL, Blanchard EB. Assessment of dietary risk factors in chronic headache. Biofeedback Self Regul 1990; 15(1):15–25. pmid:2361144
  19. Shapiro RE. Caffeine and headaches. Curr Pain Headache Rep 2008; 12(4):311–315. pmid:18625110
  20. Yokoyama M, Yokoyama T, Funazu K, et al. Associations between headache and stress, alcohol drinking, exercise, sleep, and comorbid health conditions in a Japanese population. J Headache Pain 2009; 10(3):177–185. doi:10.1007/s10194-009-0113-7
  21. Karsan N, Bose P, Goadsby PJ. The migraine premonitory phase. Continuum (Minneap Minn) 2018; 24(4, Headache):996–1008. doi:10.1212/CON.0000000000000624
  22. Pavlovic JM, Buse DC, Sollars CM, Haut S, Lipton RB. Trigger factors and premonitory features of migraine attacks: summary of studies. Headache 2014; 54(10):1670–1679. doi:10.1111/head.12468
  23. Marcus DA, Scharff L, Turk D, Gourley LM. A double-blind provocative study of chocolate as a trigger of headache. Cephalalgia 1997; 17(8):855–862. doi:10.1046/j.1468-2982.1997.1708855.x
  24. Obayashi Y, Nagamura Y. Does monosodium glutamate really cause headache? A systematic review of human studies. J Headache Pain 2016; 17:54. doi:10.1186/s10194-016-0639-4
  25. Evans EW, Lipton RB, Peterlin BL, et al. Dietary intake patterns and diet quality in a nationally representative sample of women with and without severe headache or migraine. Headache 2015; 55(4):550–561. doi:10.1111/head.12527
  26. Zis P, Julian T, Hadjivassiliou M. Headache associated with coeliac disease: a systematic review and meta-analysis. Nutrients 2018; 10(10). doi:10.3390/nu10101445
  27. Alpay K, Ertas M, Orhan EK, Ustay DK, Lieners C, Baykan B. Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Cephalalgia 2010; 30(7):829–837. doi:10.1177/0333102410361404
  28. Aydinlar EI, Dikmen PY, Tiftikci A, et al. IgG-based elimination diet in migraine plus irritable bowel syndrome. Headache 2013; 53(3):514–525. doi:10.1111/j.1526-4610.2012.02296.x
  29. Mitchell N, Hewitt CE, Jayakody S, et al. Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches. Nutr J 2011; 10:85. doi:10.1186/1475-2891-10-85
  30. Wantke F, Gotz M, Jarisch R. Histamine-free diet: treatment of choice for histamine-induced food intolerance and supporting treatment for chronic headaches. Clin Exp Allergy 1993; 23(12):982–985. pmid:10779289
  31. Mansfield LE, Vaughan TR, Waller SF, Haverly RW, Ting S. Food allergy and adult migraine: double-blind and mediator confirmation of an allergic etiology. Ann Allergy 1985; 55(2):126–129. pmid:4025956
  32. Kohlenberg RJ. Tyramine sensitivity in dietary migraine: a critical review. Headache 1982; 22(1):30–34. pmid:17152742
  33. Medina JL, Diamond S. The role of diet in migraine. Headache 1978; 18(1):31–34. pmid:649377
  34. Mosnaim AD, Freitag F, Ignacio R, et al. Apparent lack of correlation between tyramine and phenylethylamine content and the occurrence of food-precipitated migraine. Reexamination of a variety of food products frequently consumed in the United States and commonly restricted in tyramine-free diets. Headache Quarterly. Current Treatment and Research 1996; 7(3):239–249.
  35. Ferrara LA, Pacioni D, Di Fronzo V, et al. Low-lipid diet reduces frequency and severity of acute migraine attacks. Nutr Metab Cardiovasc Dis 2015; 25(4):370–375. doi:10.1016/j.numecd.2014.12.006
  36. Bic Z, Blix GG, Hopp HP, Leslie FM, Schell MJ. The influence of a low-fat diet on incidence and severity of migraine headaches. J Womens Health Gend Based Med 1999; 8(5):623–630. doi:10.1089/jwh.1.1999.8.623
  37. Bunner AE, Agarwal U, Gonzales JF, Valente F, Barnard ND. Nutrition intervention for migraine: a randomized crossover trial. J Headache Pain 2014; 15:69. doi:10.1186/1129-2377-15-69
  38. Evcili G, Utku U, Ogun MN, Ozdemir G. Early and long period follow-up results of low glycemic index diet for migraine prophylaxis. Agri 2018; 30(1):8–11. doi:10.5505/agri.2017.62443
  39. Maghsoumi-Norouzabad L, Mansoori A, Abed R, Shishehbor F. Effects of omega-3 fatty acids on the frequency, severity, and duration of migraine attacks: a systematic review and meta-analysis of randomized controlled trials. Nutr Neurosci 2018; 21(9):614–623. doi:10.1080/1028415X.2017.1344371
  40. Soares AA, Loucana PMC, Nasi EP, Sousa KMH, Sa OMS, Silva-Neto RP. A double- blind, randomized, and placebo-controlled clinical trial with omega-3 polyunsaturated fatty acids (OPFA Ω-3) for the prevention of migraine in chronic migraine patients using amitriptyline. Nutr Neurosci 2018; 21(3):219–223. doi:10.1080/1028415X.2016.1266133
  41. Di Lorenzo C, Coppola G, Sirianni G, et al. Migraine improvement during short lasting ketogenesis: a proof-of-concept study. Eur J Neurol 2015; 22(1):170–177. doi:10.1111/ene.12550
  42. Di Lorenzo C, Coppola G, Bracaglia M, et al. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study. J Headache Pain 2016; 17:58. doi:10.1186/s10194-016-0650-9
  43. Kossoff EH, Huffman J, Turner Z, Gladstein J. Use of the modified Atkins diet for adolescents with chronic daily headache. Cephalalgia 2010; 30(8):1014–1016. https://journals.sagepub.com/doi/full/10.1111/j.1468-2982.2009.02016.x
  44. Slavin M, Ailani J. A clinical approach to addressing diet with migraine patients. Curr Neurol Neurosci Rep 2017; 17(2):17. doi:10.1007/s11910-017-0721-6
  45. Amer M, Woodward M, Appel LJ. Effects of dietary sodium and the DASH diet on the occurrence of headaches: results from randomised multicentre DASH-sodium clinical trial. BMJ Open 2014; 4(12):e006671. doi:10.1136/bmjopen-2014-006671
  46. Chen L, Zhang Z, Chen W, Whelton PK, Appel LJ. Lower sodium intake and risk of headaches: results from the trial of nonpharmacologic interventions in the elderly. Am J Public Health 2016; 106(7):1270–1275. doi:10.2105/AJPH.2016.303143
  47. Pogoda JM, Gross NB, Arakaki X, Fonteh AN, Cowan RP, Harrington MG. Severe headache or migraine history is inversely correlated with dietary sodium intake: NHANES 1999–2004. Headache 2016; 56(4):688–698. doi:10.1111/head.12792
  48. Awada A, al Jumah M. The first-of-Ramadan headache. Headache 1999; 39(7):490–493. pmid:11279933
  49. Abu-Salameh I, Plakht Y, Ifergane G. Migraine exacerbation during Ramadan fasting. J Headache Pain 2010; 11(6):513–517. doi:10.1007/s10194-010-0242-z
  50. Nazari F, Safavi M, Mahmudi M. Migraine and its relation with lifestyle in women. Pain Pract 2010; 10(3):228–234. doi:10.1111/j.1533-2500.2009.00343.x
  51. Nas A, Mirza N, Hagele F, et al. Impact of breakfast skipping compared with dinner skipping on regulation of energy balance and metabolic risk. Am J Clin Nutr 2017; 105(6):1351–1361. doi:10.3945/ajcn.116.151332
  52. Torelli P, Manzoni GC. Fasting headache. Curr Pain Headache Rep 2010; 14(4):284–291. doi:10.1007/s11916-010-0119-5
  53. Yoshimura E, Hatamoto Y, Yonekura S, Tanaka H. Skipping breakfast reduces energy intake and physical activity in healthy women who are habitual breakfast eaters: a randomized crossover trial. Physiol Behav 2017; 174:89–94. doi:10.1016/j.physbeh.2017.03.008
  54. Pendergast FJ, Livingstone KM, Worsley A, McNaughton SA. Correlates of meal skipping in young adults: a systematic review. Int J Behav Nutr Phys Act 2016; 13(1):125. doi:10.1186/s12966-016-0451-1
  55. Maki KC, Phillips-Eakley AK, Smith KN. The effects of breakfast consumption and composition on metabolic wellness with a focus on carbohydrate metabolism. Adv Nutr 2016; 7(3):613S–621S. doi:10.3945/an.115.010314
  56. Shirreffs SM, Merson SJ, Fraser SM, Archer DT. The effects of fluid restriction on hydration status and subjective feelings in man. Br J Nutr 2004; 91(6):951–958. doi:10.1079/BJN20041149
  57. Blau JN. Water deprivation: a new migraine precipitant. Headache 2005; 45(6):757–759. doi:10.1111/j.1526-4610.2005.05143_3.x
  58. Price A, Burls A. Increased water intake to reduce headache: learning from a critical appraisal. J Eval Clin Pract 2015; 21(6):1212–1218. doi:10.1111/jep.12413
  59. Balbin JE, Nerenberg R, Baratloo A, Friedman BW. Intravenous fluids for migraine: a post hoc analysis of clinical trial data. Am J Emerg Med 2016; 34(4):713–716. doi:10.1016/j.ajem.2015.12.080
  60. Spigt M, Weerkamp N, Troost J, van Schayck CP, Knottnerus JA. A randomized trial on the effects of regular water intake in patients with recurrent headaches. Fam Pract 2012; 29(4):370–375. doi:10.1093/fampra/cmr112
  61. Armstrong LE, Johnson EC. Water intake, water balance, and the elusive daily water requirement. Nutrients 2018; 10(12). doi:10.3390/nu10121928
  62. Fried NT, Elliott MB, Oshinsky ML. The role of adenosine signaling in headache: a review. Brain Sci 2017; 7(3). doi:10.3390/brainsci7030030
  63. Lee MJ, Choi HA, Choi H, Chung CS. Caffeine discontinuation improves acute migraine treatment: a prospective clinic-based study. J Headache Pain 2016; 17(1):71. doi:10.1186/s10194-016-0662-5
  64. Shirlow MJ, Mathers CD. A study of caffeine consumption and symptoms; indigestion, palpitations, tremor, headache and insomnia. Int J Epidemiol 1985; 14(2):239–248. doi:10.1093/ije/14.2.239
  65. Silverman K, Evans SM, Strain EC, Griffiths RR. Withdrawal syndrome after the double-blind cessation of caffeine consumption. N Engl J Med 1992; 327(16):1109–1114. doi:10.1056/NEJM199210153271601
  66. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018; 38(1):1–211. doi:10.1177/0333102417738202
  67. Krogh AB, Larsson B, Salvesen O, Linde M. A comparison between prospective Internet-based and paper diary recordings of headache among adolescents in the general population. Cephalalgia 2016; 36(4):335–345. doi:10.1177/0333102415591506
  68. Bandarian-Balooch S, Martin PR, McNally B, Brunelli A, Mackenzie S. Electronic-diary for recording headaches, triggers, and medication use: development and evaluation. Headache 2017; 57(10):1551–1569. doi:10.1111/head.13184
  69. Tassorelli C, Sances G, Allena M, et al. The usefulness and applicability of a basic headache diary before first consultation: results of a pilot study conducted in two centres. Cephalalgia 2008; 28(10):1023–1030. doi:10.1111/j.1468-2982.2008.01639.x
  70. Baos V, Ester F, Castellanos A, et al. Use of a structured migraine diary improves patient and physician communication about migraine disability and treatment outcomes. Int J Clin Pract 2005; 59(3):281–286. doi:10.1111/j.1742-1241.2005.00469.x
  71. Martin PR, MacLeod C. Behavioral management of headache triggers: avoidance of triggers is an inadequate strategy. Clin Psychol Rev 2009; 29(6):483–495. doi:10.1016/j.cpr.2009.05.002
  72. Giannini G, Zanigni S, Grimaldi D, et al. Cephalalgiaphobia as a feature of high-frequency migraine: a pilot study. J Headache Pain 2013; 14:49. doi:10.1186/1129-2377-14-49
  73. Westergaard ML, Glumer C, Hansen EH, Jensen RH. Medication overuse, healthy lifestyle behaviour and stress in chronic headache: results from a population-based representative survey. Cephalalgia 2016; 36(1):15–28. doi:10.1177/0333102415578430
  74. Christiansen S, Jurgens TP, Klinger R. Outpatient combined group and individual cognitive-behavioral treatment for patients with migraine and tension-type headache in a routine clinical setting. Headache 2015; 55(8):1072–1091. doi:10.1111/head.12626
  75. Martin PR, Aiello R, Gilson K, Meadows G, Milgrom J, Reece J. Cognitive behavior therapy for comorbid migraine and/or tension-type headache and major depressive disorder: an exploratory randomized controlled trial. Behav Res Ther 2015; 73:8–18. doi:10.1016/j.brat.2015.07.005
  76. Nash JM, Park ER, Walker BB, Gordon N, Nicholson RA. Cognitive-behavioral group treatment for disabling headache. Pain Med 2004; 5(2):178–186. doi:10.1111/j.1526-4637.2004.04031.x
  77. Sorbi MJ, Balk Y, Kleiboer AM, Couturier EG. Follow-up over 20 months confirms gains of online behavioural training in frequent episodic migraine. Cephalalgia 2017; 37(3):236–250. doi:10.1177/0333102416657145
  78. Thorn BE, Pence LB, Ward LC, et al. A randomized clinical trial of targeted cognitive behavioral treatment to reduce catastrophizing in chronic headache sufferers. J Pain 2007; 8(12):938–949. doi:10.1016/j.jpain.2007.06.010
  79. Nestoriuc Y, Martin A. Efficacy of biofeedback for migraine: a meta-analysis. Pain 2007; 128(1–2):111–127. doi:10.1016/j.pain.2006.09.007
  80. Blanchard EB, Appelbaum KA, Nicholson NL, et al. A controlled evaluation of the addition of cognitive therapy to a home-based biofeedback and relaxation treatment of vascular headache. Headache 1990; 30(6):371–376. pmid:2196240
  81. Gu Q, Hou JC, Fang XM. Mindfulness meditation for primary headache pain: a meta-analysis. Chin Med J (Engl) 2018; 131(7):829–838. doi:10.4103/0366-6999.228242
  82. Day MA, Thorn BE. The mediating role of pain acceptance during mindfulness-based cognitive therapy for headache. Complement Ther Med 2016; 25:51–54. doi:10.1016/j.ctim.2016.01.002
  83. Williamson DA, Monguillot JE, Jarrell MP, Cohen RA, Pratt JM, Blouin DC. Relaxation for the treatment of headache. Controlled evaluation of two group programs. Behav Modif 1984; 8(3):407–424. doi:10.1177/01454455840083007
  84. Merelle SY, Sorbi MJ, Duivenvoorden HJ, Passchier J. Qualities and health of lay trainers with migraine for behavioral attack prevention. Headache 2010; 50(4):613–625. doi:10.1111/j.1526-4610.2008.01241.x
  85. Gaul C, van Doorn C, Webering N, et al. Clinical outcome of a headache-specific multidisciplinary treatment program and adherence to treatment recommendations in a tertiary headache center: an observational study. J Headache Pain 2011; 12(4):475–483. doi:10.1007/s10194-011-0348-y
  86. Wallasch TM, Kropp P. Multidisciplinary integrated headache care: a prospective 12-month follow-up observational study. J Headache Pain 2012; 13(7):521–529. doi:10.1007/s10194-012-0469-y
  87. Lemstra M, Stewart B, Olszynski WP. Effectiveness of multidisciplinary intervention in the treatment of migraine: a randomized clinical trial. Headache 2002; 42(9):845–854. pmid:12390609
  88. Krause SJ, Stillman MJ, Tepper DE, Zajac D. A prospective cohort study of outpatient interdisciplinary rehabilitation of chronic headache patients. Headache 2017; 57(3):428–440. doi:10.1111/head.13020
Issue
Cleveland Clinic Journal of Medicine - 86(11)
Issue
Cleveland Clinic Journal of Medicine - 86(11)
Page Number
741-749
Page Number
741-749
Publications
Publications
Topics
Article Type
Display Headline
SEEDS for success: Lifestyle management in migraine
Display Headline
SEEDS for success: Lifestyle management in migraine
Legacy Keywords
migraine, headache, lifestyle, SEEDS, sleep, exercise, eat, diary, stress, sleep hygiene, STOP-Bang, behavioral modification, elimination diet, gluten-free diet, immunoglobulin G-elimination diet, antihistamine diet, tyramine-free diet, low-fat diet, low-glycemic index diet, ketogenic diet, hydration, caffeine, headache diary, biofeedback, mindfulness, relaxation, Jennifer Robblee, Amaal Starling
Legacy Keywords
migraine, headache, lifestyle, SEEDS, sleep, exercise, eat, diary, stress, sleep hygiene, STOP-Bang, behavioral modification, elimination diet, gluten-free diet, immunoglobulin G-elimination diet, antihistamine diet, tyramine-free diet, low-fat diet, low-glycemic index diet, ketogenic diet, hydration, caffeine, headache diary, biofeedback, mindfulness, relaxation, Jennifer Robblee, Amaal Starling
Sections
Inside the Article

KEY POINTS

  • Sleep: Standard sleep hygiene recommendations to maximize sleep quantity and quality.
  • Exercise: 30 to 60 minutes 3 to 5 times a week.
  • Eat: Regular healthy meals, adequate hydration, and low or stable caffeine intake.
  • Diary: Establish a baseline pattern, assess response to treatment, and monitor analgesia to improve accuracy of migraine diagnosis.
  • Stress: Cognitive behavioral therapy, mindfulness, relaxation, biofeedback, and provider-patient trust to minimize anxiety.
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Gate On Date
Wed, 10/30/2019 - 07:45
Un-Gate On Date
Wed, 10/30/2019 - 07:45
Use ProPublica
CFC Schedule Remove Status
Wed, 10/30/2019 - 07:45
Hide sidebar & use full width
render the right sidebar.
Article PDF Media

Stay Informed About Informed Consent

Article Type
Changed
Tue, 10/29/2019 - 14:29
Display Headline
Stay Informed About Informed Consent

On May 24, 2011, a 53-year-old woman presented to a Wisconsin hospital emergency ­department (ED) with complaints of severe abdominal pain, a rapid heartbeat, and a fever of 101.3°F. During her 9-hour visit, she was treated by a PA and his supervising physician. She was seen by the physician for a total of 6 minutes; the rest of her care was provided by the PA. The patient was discharged around midnight with instructions to contact her gynecologist in the morning for management of uterine fibroids. At the time of discharge, her temperature was 102.9°F.

The following day, May 25, the patient collapsed in her home and was transported to another hospital. She was treated for septic shock from a group A streptococcus infection. Although the infection was halted, the patient sustained ischemic damage to her extremities and a month later required amputation of her 4 limbs.The plaintiff claimed that the supervising physician was negligent in failing to diagnose the strep A infection, which, left undetected, led to septic shock. She also alleged that the PA should have recognized the potential for her condition’s severity to quickly escalate. She maintained that the supervising physician should have been more involved in her case because of its complexity.

Plaintiff’s counsel also argued that the PA should have provided “alternative medical diagnoses,” which would have prompted consideration of other treatment options. The plaintiff contended that under Wisconsin’s informed consent law, both the PA and the physician failed to disclose enough information about her condition and failed to inform her of any choices for treatment.

The defense argued that the plaintiff received proper treatment based on the information available to the providers at the time.

VERDICT

The jury found for the plaintiff and apportioned 65% liability to the physician and 35% liability to the PA. A total of $25,342,096 was awarded to the plaintiff.

COMMENTARY

This is a huge verdict. Cases involving group A strep or necrotizing fasciitis frequently give rise to large medical malpractice verdicts, because everything about them is difficult to defend: Although there is typically trivial to no trauma involved, the wounds from these infections provide explicit images of damage, intra­operatively and postoperatively. Vasopressors required for hemodynamic support or sepsis itself frequently result in limb ischemia, gangrene, and amputation. In this case, the plaintiff, as a quadruple amputee, was a sympathetic and impressive courtroom presence—the personal toll was evident to anyone in the room.

Two providers—a PA and a physician—saw the patient. We are told only that she complained of severe abdominal pain, rapid heartbeat, and fever, which increased at some point during her ED stay. We aren’t given specifics on the rest of the patient’s vital signs or examination details. However, we can infer that the exam and lab findings were not impressive, because they weren’t mentioned in the case report. But as a result of the failure to catch the group A strep infection, the plaintiff suffered what one judge hearing the case described as a harrowing and unimaginable ordeal: the life-changing amputation of 4 limbs.1 While the jury did not find the PA or physician negligent, they still found the clinicians liable and awarded a staggering verdict.

Continue to: How could this happen?

 

 

How could this happen? The answer is the theory of recovery: The jury found that the physician and the PA failed to provide the patient with informed consent in the form of “alternative medical diagnoses.”2 The plaintiff’s attorney argued that the patient was never told a life-threatening bacterial infection was one possible diagnosis and claimed that if she had known, the patient would have pursued other treatment.

As in many malpractice cases, the plaintiff alleged failure to diagnose and failure to provide informed consent. Depending on state law, there are 3 standards for informed consent: subjective patient, reasonable patient, and reasonable physician.3 About half of the states have a physician-focused standard, while the other half have a patient-focused standard.3

Under the subjective patient standard, we would ask, “What would this patient need to know and understand to make an informed decision?”4 The subjective standard requires the clinician to essentially “get in the head” of a specific patient to determine what he or she would want to know when making a medical decision. This standard is problematic because it requires the clinician to have an intimate familiarity with the patient’s belief system and medical decision-making process—a daunting requirement for many clinicians, particularly in the absence of a longstanding clinician-patient relationship, as is the case in most emergency settings. Thankfully, the subjective patient standard is not followed by most states that have a patient-focused standard.

Under the objective reasonable patient standard, we would ask “What would the average patient need to know to be an informed participant in the decision?”4 One could argue that this standard more adequately allows the patient to be an active participant in shared decision-making. However, the drawback is that what is “reasonable” often falls on a spectrum, which would require the clinician to gauge the volume and type of information a patient cohort would want to have when making a medical decision. Under this standard, the plaintiff must prove that the clinician omitted information that a reasonable patient would want to know. Therefore, these standards are more friendly to the plaintiff, whereas the reasonable physician standard is more defendant friendly.

To meet the standard of care under a reasonable physician standard, information must be provided to the patient that a “reasonably prudent practitioner in the same field of practice or specialty” would provide to a patient.5 For a plaintiff to successfully sue under this standard, the plaintiff’s expert must testify that a reasonably prudent physician would have disclosed the omitted information.6 The reasonable physician standard is obviously better for malpractice defendants.

Continue to: While reasonable clinicians...

 

 

While reasonable clinicians can disagree (as can reasonable patients), clinicians are more likely to be closer in opinion. Clinicians are a smaller group whose opinions are underpinned by similar education, training, and experience. By contrast, among the general population, beliefs held by one hypothetical “reasonable person” are much less settled, and in some cases, wildly divergent from another’s. For example, vaccine skepticism would probably be considered unreasonable in the majority of jury pools but absolutely reasonable in some. The large size of the general population, coupled with opinions untethered to any definable discipline, make the reasonable patient standard hard to predict.

Additionally, the reasonable physician standard forces the plaintiff to prove his or her case by producing an expert witness (clinician) to specifically testify that the standard of care required the defendant clinician to disclose certain specific information, and that disclosure was lacking. That is an important requirement. Under patient-focused standards, the plaintiff doesn’t need a medical expert on this point and can simply argue to the jury that a reasonable patient would require an exhaustive discussion of each possibility in the differential diagnosis. Therefore, I would argue that the reasonable physician standard is more predictable and workable and should be followed.

At the time of this case, Wisconsin’s informed consent law was based on the reasonable patient standard. As a result of this case, Wisconsin lawmakers changed the law to a “reasonable physician standard,” which states “any physician who treats a patient shall inform the patient about the availability of reasonable alternate medical modes of treatment and about the benefits and risks of these treatments.”7 However, the law stipulates that this duty to inform does not require disclosure of (among others):

  • Detailed technical information that in all probability a patient would not understand
  • Risks apparent or known to the patient
  • Extremely remote possibilities that might falsely or detrimentally alarm the patient
  • Information about alternate medical modes of treatment for any condition the physician has not included in his or her diagnosis at the time the physician informs the patient.7

Finally, this case involved an extremely high verdict of more than $25 million. It may surprise you to learn that many states have caps for medical malpractice awards for noneconomic damages, such as pain and suffering. If you’re having a holiday dinner with friends or family members who are plaintiff’s attorneys and you’re itching for a good argument, skip current politics and go all-in: How about liability caps, Uncle Jim? Get ready for a lively debate.

Of the $25 million verdict, $16.5 million was awarded for pain and suffering—the jury was obviously shocked by the extent of the life-changing nature of the plaintiff’s injuries. At the time of this case, Wisconsin had a cap of $750,000 for noneconomic damages.8 However, plaintiffs may challenge state constitutionality of these caps when they feel they have the right case, which the plaintiff and her attorney felt they did. Two lower courts found the state cap unconstitutional and gave the plaintiff the full award. But the state Supreme Court later reversed that decision, upholding the cap.1 The court decided that the legislature had a rational basis for making the law and changes to it should occur through the legislature, not the courts. The dissenting justices argued that there was no rational basis for the $750,000 cap, because there was no evidence that clinicians would flee the state fearing malpractice liability, or practice more defensive medicine, or suffer runaway malpractice insurance premiums without the cap. As a result of this case, the cap was upheld, and there was a “lively debate” on this issue at the highest levels of government.

Continue to: IN SUM

 

 

IN SUM

Become familiar with your state’s informed consent laws. Involve patients in decision-making, and convey information related to reasonable treatment options and risks. Document all of these discussions. Lastly, state-level political discussions on issues of tort reform, caps, and malpractice matters are ongoing—so take notice.

References

1. Mayo v Wisconsin Injured Patients & Families Compensation Fund. WI 78 (2018).
2. Spivak C. Jury awards Milwaukee woman $25.3 million in medical malpractice case. Milwaukee Journal Sentinel. July 7, 2014.
3. Moore GP, Matlock AG, Kiley JL, et al. Emergency physicians: beware of the consent standard of care. Clin Pract Cases Emerg Med. 2018; 2(2):109-111.
4. Gossman W, Thornton I, Hipskind JE. Informed Consent. StatPearls. www.ncbi.nlm.nih.gov/books/NBK430827/. Updated July 10, 2019. Accessed October 25, 2019.
5. King JS, Moulton BW. Rethinking informed consent: the case for shared medical decision-making. Am J Law Med. 2006;32:429-501.
6. Tashman v Gibbs, 556 SE 2d 772 (263 Va 2002).
7. Wis Stat subchapter 2, §448.30.
8. Wis Stat §893.55.

Article PDF
Author and Disclosure Information

David M. Lang is a malpractice defense attorney practicing in Granite Bay, California.

Issue
Clinician Reviews - 29(10)
Publications
Topics
Page Number
17e-19e
Sections
Author and Disclosure Information

David M. Lang is a malpractice defense attorney practicing in Granite Bay, California.

Author and Disclosure Information

David M. Lang is a malpractice defense attorney practicing in Granite Bay, California.

Article PDF
Article PDF

On May 24, 2011, a 53-year-old woman presented to a Wisconsin hospital emergency ­department (ED) with complaints of severe abdominal pain, a rapid heartbeat, and a fever of 101.3°F. During her 9-hour visit, she was treated by a PA and his supervising physician. She was seen by the physician for a total of 6 minutes; the rest of her care was provided by the PA. The patient was discharged around midnight with instructions to contact her gynecologist in the morning for management of uterine fibroids. At the time of discharge, her temperature was 102.9°F.

The following day, May 25, the patient collapsed in her home and was transported to another hospital. She was treated for septic shock from a group A streptococcus infection. Although the infection was halted, the patient sustained ischemic damage to her extremities and a month later required amputation of her 4 limbs.The plaintiff claimed that the supervising physician was negligent in failing to diagnose the strep A infection, which, left undetected, led to septic shock. She also alleged that the PA should have recognized the potential for her condition’s severity to quickly escalate. She maintained that the supervising physician should have been more involved in her case because of its complexity.

Plaintiff’s counsel also argued that the PA should have provided “alternative medical diagnoses,” which would have prompted consideration of other treatment options. The plaintiff contended that under Wisconsin’s informed consent law, both the PA and the physician failed to disclose enough information about her condition and failed to inform her of any choices for treatment.

The defense argued that the plaintiff received proper treatment based on the information available to the providers at the time.

VERDICT

The jury found for the plaintiff and apportioned 65% liability to the physician and 35% liability to the PA. A total of $25,342,096 was awarded to the plaintiff.

COMMENTARY

This is a huge verdict. Cases involving group A strep or necrotizing fasciitis frequently give rise to large medical malpractice verdicts, because everything about them is difficult to defend: Although there is typically trivial to no trauma involved, the wounds from these infections provide explicit images of damage, intra­operatively and postoperatively. Vasopressors required for hemodynamic support or sepsis itself frequently result in limb ischemia, gangrene, and amputation. In this case, the plaintiff, as a quadruple amputee, was a sympathetic and impressive courtroom presence—the personal toll was evident to anyone in the room.

Two providers—a PA and a physician—saw the patient. We are told only that she complained of severe abdominal pain, rapid heartbeat, and fever, which increased at some point during her ED stay. We aren’t given specifics on the rest of the patient’s vital signs or examination details. However, we can infer that the exam and lab findings were not impressive, because they weren’t mentioned in the case report. But as a result of the failure to catch the group A strep infection, the plaintiff suffered what one judge hearing the case described as a harrowing and unimaginable ordeal: the life-changing amputation of 4 limbs.1 While the jury did not find the PA or physician negligent, they still found the clinicians liable and awarded a staggering verdict.

Continue to: How could this happen?

 

 

How could this happen? The answer is the theory of recovery: The jury found that the physician and the PA failed to provide the patient with informed consent in the form of “alternative medical diagnoses.”2 The plaintiff’s attorney argued that the patient was never told a life-threatening bacterial infection was one possible diagnosis and claimed that if she had known, the patient would have pursued other treatment.

As in many malpractice cases, the plaintiff alleged failure to diagnose and failure to provide informed consent. Depending on state law, there are 3 standards for informed consent: subjective patient, reasonable patient, and reasonable physician.3 About half of the states have a physician-focused standard, while the other half have a patient-focused standard.3

Under the subjective patient standard, we would ask, “What would this patient need to know and understand to make an informed decision?”4 The subjective standard requires the clinician to essentially “get in the head” of a specific patient to determine what he or she would want to know when making a medical decision. This standard is problematic because it requires the clinician to have an intimate familiarity with the patient’s belief system and medical decision-making process—a daunting requirement for many clinicians, particularly in the absence of a longstanding clinician-patient relationship, as is the case in most emergency settings. Thankfully, the subjective patient standard is not followed by most states that have a patient-focused standard.

Under the objective reasonable patient standard, we would ask “What would the average patient need to know to be an informed participant in the decision?”4 One could argue that this standard more adequately allows the patient to be an active participant in shared decision-making. However, the drawback is that what is “reasonable” often falls on a spectrum, which would require the clinician to gauge the volume and type of information a patient cohort would want to have when making a medical decision. Under this standard, the plaintiff must prove that the clinician omitted information that a reasonable patient would want to know. Therefore, these standards are more friendly to the plaintiff, whereas the reasonable physician standard is more defendant friendly.

To meet the standard of care under a reasonable physician standard, information must be provided to the patient that a “reasonably prudent practitioner in the same field of practice or specialty” would provide to a patient.5 For a plaintiff to successfully sue under this standard, the plaintiff’s expert must testify that a reasonably prudent physician would have disclosed the omitted information.6 The reasonable physician standard is obviously better for malpractice defendants.

Continue to: While reasonable clinicians...

 

 

While reasonable clinicians can disagree (as can reasonable patients), clinicians are more likely to be closer in opinion. Clinicians are a smaller group whose opinions are underpinned by similar education, training, and experience. By contrast, among the general population, beliefs held by one hypothetical “reasonable person” are much less settled, and in some cases, wildly divergent from another’s. For example, vaccine skepticism would probably be considered unreasonable in the majority of jury pools but absolutely reasonable in some. The large size of the general population, coupled with opinions untethered to any definable discipline, make the reasonable patient standard hard to predict.

Additionally, the reasonable physician standard forces the plaintiff to prove his or her case by producing an expert witness (clinician) to specifically testify that the standard of care required the defendant clinician to disclose certain specific information, and that disclosure was lacking. That is an important requirement. Under patient-focused standards, the plaintiff doesn’t need a medical expert on this point and can simply argue to the jury that a reasonable patient would require an exhaustive discussion of each possibility in the differential diagnosis. Therefore, I would argue that the reasonable physician standard is more predictable and workable and should be followed.

At the time of this case, Wisconsin’s informed consent law was based on the reasonable patient standard. As a result of this case, Wisconsin lawmakers changed the law to a “reasonable physician standard,” which states “any physician who treats a patient shall inform the patient about the availability of reasonable alternate medical modes of treatment and about the benefits and risks of these treatments.”7 However, the law stipulates that this duty to inform does not require disclosure of (among others):

  • Detailed technical information that in all probability a patient would not understand
  • Risks apparent or known to the patient
  • Extremely remote possibilities that might falsely or detrimentally alarm the patient
  • Information about alternate medical modes of treatment for any condition the physician has not included in his or her diagnosis at the time the physician informs the patient.7

Finally, this case involved an extremely high verdict of more than $25 million. It may surprise you to learn that many states have caps for medical malpractice awards for noneconomic damages, such as pain and suffering. If you’re having a holiday dinner with friends or family members who are plaintiff’s attorneys and you’re itching for a good argument, skip current politics and go all-in: How about liability caps, Uncle Jim? Get ready for a lively debate.

Of the $25 million verdict, $16.5 million was awarded for pain and suffering—the jury was obviously shocked by the extent of the life-changing nature of the plaintiff’s injuries. At the time of this case, Wisconsin had a cap of $750,000 for noneconomic damages.8 However, plaintiffs may challenge state constitutionality of these caps when they feel they have the right case, which the plaintiff and her attorney felt they did. Two lower courts found the state cap unconstitutional and gave the plaintiff the full award. But the state Supreme Court later reversed that decision, upholding the cap.1 The court decided that the legislature had a rational basis for making the law and changes to it should occur through the legislature, not the courts. The dissenting justices argued that there was no rational basis for the $750,000 cap, because there was no evidence that clinicians would flee the state fearing malpractice liability, or practice more defensive medicine, or suffer runaway malpractice insurance premiums without the cap. As a result of this case, the cap was upheld, and there was a “lively debate” on this issue at the highest levels of government.

Continue to: IN SUM

 

 

IN SUM

Become familiar with your state’s informed consent laws. Involve patients in decision-making, and convey information related to reasonable treatment options and risks. Document all of these discussions. Lastly, state-level political discussions on issues of tort reform, caps, and malpractice matters are ongoing—so take notice.

On May 24, 2011, a 53-year-old woman presented to a Wisconsin hospital emergency ­department (ED) with complaints of severe abdominal pain, a rapid heartbeat, and a fever of 101.3°F. During her 9-hour visit, she was treated by a PA and his supervising physician. She was seen by the physician for a total of 6 minutes; the rest of her care was provided by the PA. The patient was discharged around midnight with instructions to contact her gynecologist in the morning for management of uterine fibroids. At the time of discharge, her temperature was 102.9°F.

The following day, May 25, the patient collapsed in her home and was transported to another hospital. She was treated for septic shock from a group A streptococcus infection. Although the infection was halted, the patient sustained ischemic damage to her extremities and a month later required amputation of her 4 limbs.The plaintiff claimed that the supervising physician was negligent in failing to diagnose the strep A infection, which, left undetected, led to septic shock. She also alleged that the PA should have recognized the potential for her condition’s severity to quickly escalate. She maintained that the supervising physician should have been more involved in her case because of its complexity.

Plaintiff’s counsel also argued that the PA should have provided “alternative medical diagnoses,” which would have prompted consideration of other treatment options. The plaintiff contended that under Wisconsin’s informed consent law, both the PA and the physician failed to disclose enough information about her condition and failed to inform her of any choices for treatment.

The defense argued that the plaintiff received proper treatment based on the information available to the providers at the time.

VERDICT

The jury found for the plaintiff and apportioned 65% liability to the physician and 35% liability to the PA. A total of $25,342,096 was awarded to the plaintiff.

COMMENTARY

This is a huge verdict. Cases involving group A strep or necrotizing fasciitis frequently give rise to large medical malpractice verdicts, because everything about them is difficult to defend: Although there is typically trivial to no trauma involved, the wounds from these infections provide explicit images of damage, intra­operatively and postoperatively. Vasopressors required for hemodynamic support or sepsis itself frequently result in limb ischemia, gangrene, and amputation. In this case, the plaintiff, as a quadruple amputee, was a sympathetic and impressive courtroom presence—the personal toll was evident to anyone in the room.

Two providers—a PA and a physician—saw the patient. We are told only that she complained of severe abdominal pain, rapid heartbeat, and fever, which increased at some point during her ED stay. We aren’t given specifics on the rest of the patient’s vital signs or examination details. However, we can infer that the exam and lab findings were not impressive, because they weren’t mentioned in the case report. But as a result of the failure to catch the group A strep infection, the plaintiff suffered what one judge hearing the case described as a harrowing and unimaginable ordeal: the life-changing amputation of 4 limbs.1 While the jury did not find the PA or physician negligent, they still found the clinicians liable and awarded a staggering verdict.

Continue to: How could this happen?

 

 

How could this happen? The answer is the theory of recovery: The jury found that the physician and the PA failed to provide the patient with informed consent in the form of “alternative medical diagnoses.”2 The plaintiff’s attorney argued that the patient was never told a life-threatening bacterial infection was one possible diagnosis and claimed that if she had known, the patient would have pursued other treatment.

As in many malpractice cases, the plaintiff alleged failure to diagnose and failure to provide informed consent. Depending on state law, there are 3 standards for informed consent: subjective patient, reasonable patient, and reasonable physician.3 About half of the states have a physician-focused standard, while the other half have a patient-focused standard.3

Under the subjective patient standard, we would ask, “What would this patient need to know and understand to make an informed decision?”4 The subjective standard requires the clinician to essentially “get in the head” of a specific patient to determine what he or she would want to know when making a medical decision. This standard is problematic because it requires the clinician to have an intimate familiarity with the patient’s belief system and medical decision-making process—a daunting requirement for many clinicians, particularly in the absence of a longstanding clinician-patient relationship, as is the case in most emergency settings. Thankfully, the subjective patient standard is not followed by most states that have a patient-focused standard.

Under the objective reasonable patient standard, we would ask “What would the average patient need to know to be an informed participant in the decision?”4 One could argue that this standard more adequately allows the patient to be an active participant in shared decision-making. However, the drawback is that what is “reasonable” often falls on a spectrum, which would require the clinician to gauge the volume and type of information a patient cohort would want to have when making a medical decision. Under this standard, the plaintiff must prove that the clinician omitted information that a reasonable patient would want to know. Therefore, these standards are more friendly to the plaintiff, whereas the reasonable physician standard is more defendant friendly.

To meet the standard of care under a reasonable physician standard, information must be provided to the patient that a “reasonably prudent practitioner in the same field of practice or specialty” would provide to a patient.5 For a plaintiff to successfully sue under this standard, the plaintiff’s expert must testify that a reasonably prudent physician would have disclosed the omitted information.6 The reasonable physician standard is obviously better for malpractice defendants.

Continue to: While reasonable clinicians...

 

 

While reasonable clinicians can disagree (as can reasonable patients), clinicians are more likely to be closer in opinion. Clinicians are a smaller group whose opinions are underpinned by similar education, training, and experience. By contrast, among the general population, beliefs held by one hypothetical “reasonable person” are much less settled, and in some cases, wildly divergent from another’s. For example, vaccine skepticism would probably be considered unreasonable in the majority of jury pools but absolutely reasonable in some. The large size of the general population, coupled with opinions untethered to any definable discipline, make the reasonable patient standard hard to predict.

Additionally, the reasonable physician standard forces the plaintiff to prove his or her case by producing an expert witness (clinician) to specifically testify that the standard of care required the defendant clinician to disclose certain specific information, and that disclosure was lacking. That is an important requirement. Under patient-focused standards, the plaintiff doesn’t need a medical expert on this point and can simply argue to the jury that a reasonable patient would require an exhaustive discussion of each possibility in the differential diagnosis. Therefore, I would argue that the reasonable physician standard is more predictable and workable and should be followed.

At the time of this case, Wisconsin’s informed consent law was based on the reasonable patient standard. As a result of this case, Wisconsin lawmakers changed the law to a “reasonable physician standard,” which states “any physician who treats a patient shall inform the patient about the availability of reasonable alternate medical modes of treatment and about the benefits and risks of these treatments.”7 However, the law stipulates that this duty to inform does not require disclosure of (among others):

  • Detailed technical information that in all probability a patient would not understand
  • Risks apparent or known to the patient
  • Extremely remote possibilities that might falsely or detrimentally alarm the patient
  • Information about alternate medical modes of treatment for any condition the physician has not included in his or her diagnosis at the time the physician informs the patient.7

Finally, this case involved an extremely high verdict of more than $25 million. It may surprise you to learn that many states have caps for medical malpractice awards for noneconomic damages, such as pain and suffering. If you’re having a holiday dinner with friends or family members who are plaintiff’s attorneys and you’re itching for a good argument, skip current politics and go all-in: How about liability caps, Uncle Jim? Get ready for a lively debate.

Of the $25 million verdict, $16.5 million was awarded for pain and suffering—the jury was obviously shocked by the extent of the life-changing nature of the plaintiff’s injuries. At the time of this case, Wisconsin had a cap of $750,000 for noneconomic damages.8 However, plaintiffs may challenge state constitutionality of these caps when they feel they have the right case, which the plaintiff and her attorney felt they did. Two lower courts found the state cap unconstitutional and gave the plaintiff the full award. But the state Supreme Court later reversed that decision, upholding the cap.1 The court decided that the legislature had a rational basis for making the law and changes to it should occur through the legislature, not the courts. The dissenting justices argued that there was no rational basis for the $750,000 cap, because there was no evidence that clinicians would flee the state fearing malpractice liability, or practice more defensive medicine, or suffer runaway malpractice insurance premiums without the cap. As a result of this case, the cap was upheld, and there was a “lively debate” on this issue at the highest levels of government.

Continue to: IN SUM

 

 

IN SUM

Become familiar with your state’s informed consent laws. Involve patients in decision-making, and convey information related to reasonable treatment options and risks. Document all of these discussions. Lastly, state-level political discussions on issues of tort reform, caps, and malpractice matters are ongoing—so take notice.

References

1. Mayo v Wisconsin Injured Patients & Families Compensation Fund. WI 78 (2018).
2. Spivak C. Jury awards Milwaukee woman $25.3 million in medical malpractice case. Milwaukee Journal Sentinel. July 7, 2014.
3. Moore GP, Matlock AG, Kiley JL, et al. Emergency physicians: beware of the consent standard of care. Clin Pract Cases Emerg Med. 2018; 2(2):109-111.
4. Gossman W, Thornton I, Hipskind JE. Informed Consent. StatPearls. www.ncbi.nlm.nih.gov/books/NBK430827/. Updated July 10, 2019. Accessed October 25, 2019.
5. King JS, Moulton BW. Rethinking informed consent: the case for shared medical decision-making. Am J Law Med. 2006;32:429-501.
6. Tashman v Gibbs, 556 SE 2d 772 (263 Va 2002).
7. Wis Stat subchapter 2, §448.30.
8. Wis Stat §893.55.

References

1. Mayo v Wisconsin Injured Patients & Families Compensation Fund. WI 78 (2018).
2. Spivak C. Jury awards Milwaukee woman $25.3 million in medical malpractice case. Milwaukee Journal Sentinel. July 7, 2014.
3. Moore GP, Matlock AG, Kiley JL, et al. Emergency physicians: beware of the consent standard of care. Clin Pract Cases Emerg Med. 2018; 2(2):109-111.
4. Gossman W, Thornton I, Hipskind JE. Informed Consent. StatPearls. www.ncbi.nlm.nih.gov/books/NBK430827/. Updated July 10, 2019. Accessed October 25, 2019.
5. King JS, Moulton BW. Rethinking informed consent: the case for shared medical decision-making. Am J Law Med. 2006;32:429-501.
6. Tashman v Gibbs, 556 SE 2d 772 (263 Va 2002).
7. Wis Stat subchapter 2, §448.30.
8. Wis Stat §893.55.

Issue
Clinician Reviews - 29(10)
Issue
Clinician Reviews - 29(10)
Page Number
17e-19e
Page Number
17e-19e
Publications
Publications
Topics
Article Type
Display Headline
Stay Informed About Informed Consent
Display Headline
Stay Informed About Informed Consent
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.
Article PDF Media

CBD: What physicians need to know about it

Article Type
Changed
Wed, 05/06/2020 - 12:37

 

Cannabidiol is a derivative of marijuana that is sold everywhere from medical marijuana stores to health food markets to gas stations. While this chemical is derived from marijuana plants, it can be sold in many states as a supplement and is largely unregulated. The ubiquity of cannabidiol (CBD) and its potential benefits means that doctors need to be able to counsel patients about what we know, what we don’t, and how to use it safely. For conditions such as chronic pain and addiction, where we have few safe and effective alternatives, CBD may be reasonable to recommend.

Dr. Elisabeth Poorman

To find out what physicians need to know about CBD, Elisabeth Poorman, MD, a general internist at a University of Washington neighborhood clinic in Kent and member of the editorial advisory board of Internal Medicine News, interviewed Peter Grinspoon, MD, who provides free consultation to primary care patients on the benefits and risks of using various forms of cannabis, including CBD. Dr. Grinspoon is an internist at Massachusetts General Hospital Chelsea Healthcare Center and is an instructor at Harvard Medical School, Boston. He has contributed to the Harvard Health Blog on the topic of medical marijuana, delivered grand rounds on cannabis at Massachusetts General Hospital, and lectured at the American College of Physicians. Dr. Grinspoon is also medical director for Galenas, a medical marijuana company.

Dr. Grinspoon is the son of Lester Grinspoon, MD, associate professor emeritus of psychiatry at Harvard Medical School, who researched the medicinal legitimacy of marijuana prohibition and has authored books on the medical benefits of marijuana.

Dr. Poorman queried Dr. Peter Grinspoon about his experiences treating patients with CBD and his knowledge of CBD’s efficacy for various medical conditions. Below are excerpts from that conversation.


Dr. Poorman: How do you explain the difference between THC and CBD to patients?

Dr. Grinspoon: Cannabis contains at least a hundred different chemicals called cannabinoids, of which tetrahydrocannabinol (THC) and CBD are the most prevalent. THC is the one that gets you high and can be used recreationally and medically. The CBD molecule is not intoxicating, and people use it for a variety of medical purposes, most commonly to treat anxiety, insomnia, and pain.

Dr. Poorman: There are a lot of gaps in what we now about CBD’s potential benefits. Why don’t we know more?

Dr. Grinspoon: CBD has no abuse liability according to the World Health Organization, but because it is a cannabinoid, it is still technically a schedule I substance under the Controlled Substances Act, and that makes it difficult to study.


Dr. Poorman: What kinds of conditions can CBD treat?

Dr. Grinspoon: In anxiety, the enthusiasm has outpaced the science; there’s no question about that. And most of the studies have done in animals. That said, some studies have shown that CBD helps treat components of anxiety, like public speaking. Unlike THC, it is nonintoxicating and non–habit forming. But we don’t have the wealth of randomized controlled trials that we have for official psychiatric medications.

CBD’s benefits have been most extensively studied in pediatric epilepsy. The one Food and Drug Administration–approved drug derived from cannabis is Epidiolex, used to treat rare forms of childhood epilepsy. There is some evidence that as an adjunct, it can be used for glioblastoma multiforme in patients receiving other appropriate therapy. There is also some preliminary evidence that it can be used for addiction, including to opioids, cannabis, tobacco, and stimulants.

Most of the evidence for using CBD in chronic pain comes from animal studies, including a study published in the European Journal of Pain in 2016. Among my patients to whom I have suggested CBD for chronic pain, a few have noticed great benefit, a few have noticed some benefit, and a lot have noticed no benefit. For those who have said they noticed benefit it is unclear whether that benefit was just the placebo effect.

In insomnia, I usually have them take CBD under the tongue half an hour time before bedtime, or if it’s an edible, an hour before bedtime. I start with a lower dose and slowly try higher doses. I also encourage them to do the other sleep hygiene things, like no screens, increasing exercise, and decreasing caffeine. It seems that CBD helps them fall asleep, though it’s hard to know if it’s the CBD or the fact that they have started taking something, and have simultaneously made various lifestyle changes.


Dr. Poorman: Can CBD interfere with your normal sleep architecture, the way benzodiazepines and Benadryl can?

Dr. Grinspoon: We know that THC affects your sleep architecture and affects what percentage of REM sleep you have. But I don’t know if the effects of CBD on sleep architecture have been studied.


Dr. Poorman: What harms do you counsel patients about when discussing CBD?

Dr. Grinspoon: There are four main harms. The first is the price. It’s overpriced, and the doses are very low. In most animal studies, the doses are about 20 milligrams per kilogram of weight. And you go to the market, and it’s like a dollar for a hundredth of that.

Number two is that it’s not regulated; it’s a supplement. A few years ago, the government tested a bunch of samples of CBD, and some didn’t actually contain CBD, some didn’t have the right amount; and worse, some contained THC that had not been disclosed in the packaging. So you can’t just go to a roadside gas station and assume that if you buy CBD, it’s actually that. You want a place that has a certificate of assurance. Make sure third-party testing was done, including testing for pesticides and other heavy metals.

The third thing is drug interactions. It affects the body like grapefruit and inhibits the cytochrome P450 system. The medications doctors should be most concerned about are blood thinners like Coumadin. And if you’re on blood thinners, you definitely want to tell your doctor that you are on CBD and he or she might want to check your blood levels more frequently than they usually do.

The fourth concern is liver inflammation. In the childhood epilepsy studies, a bump in some liver enzymes was seen, although I haven’t heard of any clinically significant cases of chemical hepatitis related to CBD. But if someone has liver disease you want to keep an eye on their liver enzymes.

Dr. Poorman: What methods of ingestion do you recommend or not recommend?

Dr. Grinspoon: It’s basically trial and error, but I usually recommend oral form. If people feel comfortable taking a gummy bear, or a pill, I’m not particular about that. If the product being taken contains less than 0.3% THC, it won’t get you high.

The topical form probably works better for treating chronic pain if it contains some THC, suggests a review article published in the Cleveland Clinic Journal of Medicine. Topical THC is nonintoxicating, unless you managed to sit in a bathtub for 8 hours after applying it.

I don’t recommend smoking CBD, and right now, I don’t recommend vaping anything.

If people have severe pain, like moderately severe arthritis, CBD may not be enough, whereas medical cannabis with THC could help, a report suggests.


Dr. Poorman: Do you ever encourage patients to stop using CBD products?

Dr. Grinspoon: I work in a low-income area, and my patients don’t have a ton of disposable income. If it’s not working, I worry about the expense.


Dr. Poorman: The CBD industry is growing quickly. What changes are you seeing in what products are out there, and what changes would you like to see?

Dr. Grinspoon: CBD is being put in everything, and it’s comical. On the one hand, you can say if people want to waste their money on a CBD emitting pillowcase, that’s fine. On the other hand, you can say that certainly seems like misleading advertising, because a CBD emitting pillowcase isn’t going to help you sleep any better.

I think the purported benefits are far beyond what we can say scientifically. We do know that CBD has anti-inflammatory characteristics. But that doesn’t mean that putting CBD in all skin products is good for your skin. It’s bad for your pocketbook, though. I would like there to be less of a gap between the claims and the science.
 

Dr. Elisabeth Poorman has no conflicts to disclose.

Publications
Topics
Sections

 

Cannabidiol is a derivative of marijuana that is sold everywhere from medical marijuana stores to health food markets to gas stations. While this chemical is derived from marijuana plants, it can be sold in many states as a supplement and is largely unregulated. The ubiquity of cannabidiol (CBD) and its potential benefits means that doctors need to be able to counsel patients about what we know, what we don’t, and how to use it safely. For conditions such as chronic pain and addiction, where we have few safe and effective alternatives, CBD may be reasonable to recommend.

Dr. Elisabeth Poorman

To find out what physicians need to know about CBD, Elisabeth Poorman, MD, a general internist at a University of Washington neighborhood clinic in Kent and member of the editorial advisory board of Internal Medicine News, interviewed Peter Grinspoon, MD, who provides free consultation to primary care patients on the benefits and risks of using various forms of cannabis, including CBD. Dr. Grinspoon is an internist at Massachusetts General Hospital Chelsea Healthcare Center and is an instructor at Harvard Medical School, Boston. He has contributed to the Harvard Health Blog on the topic of medical marijuana, delivered grand rounds on cannabis at Massachusetts General Hospital, and lectured at the American College of Physicians. Dr. Grinspoon is also medical director for Galenas, a medical marijuana company.

Dr. Grinspoon is the son of Lester Grinspoon, MD, associate professor emeritus of psychiatry at Harvard Medical School, who researched the medicinal legitimacy of marijuana prohibition and has authored books on the medical benefits of marijuana.

Dr. Poorman queried Dr. Peter Grinspoon about his experiences treating patients with CBD and his knowledge of CBD’s efficacy for various medical conditions. Below are excerpts from that conversation.


Dr. Poorman: How do you explain the difference between THC and CBD to patients?

Dr. Grinspoon: Cannabis contains at least a hundred different chemicals called cannabinoids, of which tetrahydrocannabinol (THC) and CBD are the most prevalent. THC is the one that gets you high and can be used recreationally and medically. The CBD molecule is not intoxicating, and people use it for a variety of medical purposes, most commonly to treat anxiety, insomnia, and pain.

Dr. Poorman: There are a lot of gaps in what we now about CBD’s potential benefits. Why don’t we know more?

Dr. Grinspoon: CBD has no abuse liability according to the World Health Organization, but because it is a cannabinoid, it is still technically a schedule I substance under the Controlled Substances Act, and that makes it difficult to study.


Dr. Poorman: What kinds of conditions can CBD treat?

Dr. Grinspoon: In anxiety, the enthusiasm has outpaced the science; there’s no question about that. And most of the studies have done in animals. That said, some studies have shown that CBD helps treat components of anxiety, like public speaking. Unlike THC, it is nonintoxicating and non–habit forming. But we don’t have the wealth of randomized controlled trials that we have for official psychiatric medications.

CBD’s benefits have been most extensively studied in pediatric epilepsy. The one Food and Drug Administration–approved drug derived from cannabis is Epidiolex, used to treat rare forms of childhood epilepsy. There is some evidence that as an adjunct, it can be used for glioblastoma multiforme in patients receiving other appropriate therapy. There is also some preliminary evidence that it can be used for addiction, including to opioids, cannabis, tobacco, and stimulants.

Most of the evidence for using CBD in chronic pain comes from animal studies, including a study published in the European Journal of Pain in 2016. Among my patients to whom I have suggested CBD for chronic pain, a few have noticed great benefit, a few have noticed some benefit, and a lot have noticed no benefit. For those who have said they noticed benefit it is unclear whether that benefit was just the placebo effect.

In insomnia, I usually have them take CBD under the tongue half an hour time before bedtime, or if it’s an edible, an hour before bedtime. I start with a lower dose and slowly try higher doses. I also encourage them to do the other sleep hygiene things, like no screens, increasing exercise, and decreasing caffeine. It seems that CBD helps them fall asleep, though it’s hard to know if it’s the CBD or the fact that they have started taking something, and have simultaneously made various lifestyle changes.


Dr. Poorman: Can CBD interfere with your normal sleep architecture, the way benzodiazepines and Benadryl can?

Dr. Grinspoon: We know that THC affects your sleep architecture and affects what percentage of REM sleep you have. But I don’t know if the effects of CBD on sleep architecture have been studied.


Dr. Poorman: What harms do you counsel patients about when discussing CBD?

Dr. Grinspoon: There are four main harms. The first is the price. It’s overpriced, and the doses are very low. In most animal studies, the doses are about 20 milligrams per kilogram of weight. And you go to the market, and it’s like a dollar for a hundredth of that.

Number two is that it’s not regulated; it’s a supplement. A few years ago, the government tested a bunch of samples of CBD, and some didn’t actually contain CBD, some didn’t have the right amount; and worse, some contained THC that had not been disclosed in the packaging. So you can’t just go to a roadside gas station and assume that if you buy CBD, it’s actually that. You want a place that has a certificate of assurance. Make sure third-party testing was done, including testing for pesticides and other heavy metals.

The third thing is drug interactions. It affects the body like grapefruit and inhibits the cytochrome P450 system. The medications doctors should be most concerned about are blood thinners like Coumadin. And if you’re on blood thinners, you definitely want to tell your doctor that you are on CBD and he or she might want to check your blood levels more frequently than they usually do.

The fourth concern is liver inflammation. In the childhood epilepsy studies, a bump in some liver enzymes was seen, although I haven’t heard of any clinically significant cases of chemical hepatitis related to CBD. But if someone has liver disease you want to keep an eye on their liver enzymes.

Dr. Poorman: What methods of ingestion do you recommend or not recommend?

Dr. Grinspoon: It’s basically trial and error, but I usually recommend oral form. If people feel comfortable taking a gummy bear, or a pill, I’m not particular about that. If the product being taken contains less than 0.3% THC, it won’t get you high.

The topical form probably works better for treating chronic pain if it contains some THC, suggests a review article published in the Cleveland Clinic Journal of Medicine. Topical THC is nonintoxicating, unless you managed to sit in a bathtub for 8 hours after applying it.

I don’t recommend smoking CBD, and right now, I don’t recommend vaping anything.

If people have severe pain, like moderately severe arthritis, CBD may not be enough, whereas medical cannabis with THC could help, a report suggests.


Dr. Poorman: Do you ever encourage patients to stop using CBD products?

Dr. Grinspoon: I work in a low-income area, and my patients don’t have a ton of disposable income. If it’s not working, I worry about the expense.


Dr. Poorman: The CBD industry is growing quickly. What changes are you seeing in what products are out there, and what changes would you like to see?

Dr. Grinspoon: CBD is being put in everything, and it’s comical. On the one hand, you can say if people want to waste their money on a CBD emitting pillowcase, that’s fine. On the other hand, you can say that certainly seems like misleading advertising, because a CBD emitting pillowcase isn’t going to help you sleep any better.

I think the purported benefits are far beyond what we can say scientifically. We do know that CBD has anti-inflammatory characteristics. But that doesn’t mean that putting CBD in all skin products is good for your skin. It’s bad for your pocketbook, though. I would like there to be less of a gap between the claims and the science.
 

Dr. Elisabeth Poorman has no conflicts to disclose.

 

Cannabidiol is a derivative of marijuana that is sold everywhere from medical marijuana stores to health food markets to gas stations. While this chemical is derived from marijuana plants, it can be sold in many states as a supplement and is largely unregulated. The ubiquity of cannabidiol (CBD) and its potential benefits means that doctors need to be able to counsel patients about what we know, what we don’t, and how to use it safely. For conditions such as chronic pain and addiction, where we have few safe and effective alternatives, CBD may be reasonable to recommend.

Dr. Elisabeth Poorman

To find out what physicians need to know about CBD, Elisabeth Poorman, MD, a general internist at a University of Washington neighborhood clinic in Kent and member of the editorial advisory board of Internal Medicine News, interviewed Peter Grinspoon, MD, who provides free consultation to primary care patients on the benefits and risks of using various forms of cannabis, including CBD. Dr. Grinspoon is an internist at Massachusetts General Hospital Chelsea Healthcare Center and is an instructor at Harvard Medical School, Boston. He has contributed to the Harvard Health Blog on the topic of medical marijuana, delivered grand rounds on cannabis at Massachusetts General Hospital, and lectured at the American College of Physicians. Dr. Grinspoon is also medical director for Galenas, a medical marijuana company.

Dr. Grinspoon is the son of Lester Grinspoon, MD, associate professor emeritus of psychiatry at Harvard Medical School, who researched the medicinal legitimacy of marijuana prohibition and has authored books on the medical benefits of marijuana.

Dr. Poorman queried Dr. Peter Grinspoon about his experiences treating patients with CBD and his knowledge of CBD’s efficacy for various medical conditions. Below are excerpts from that conversation.


Dr. Poorman: How do you explain the difference between THC and CBD to patients?

Dr. Grinspoon: Cannabis contains at least a hundred different chemicals called cannabinoids, of which tetrahydrocannabinol (THC) and CBD are the most prevalent. THC is the one that gets you high and can be used recreationally and medically. The CBD molecule is not intoxicating, and people use it for a variety of medical purposes, most commonly to treat anxiety, insomnia, and pain.

Dr. Poorman: There are a lot of gaps in what we now about CBD’s potential benefits. Why don’t we know more?

Dr. Grinspoon: CBD has no abuse liability according to the World Health Organization, but because it is a cannabinoid, it is still technically a schedule I substance under the Controlled Substances Act, and that makes it difficult to study.


Dr. Poorman: What kinds of conditions can CBD treat?

Dr. Grinspoon: In anxiety, the enthusiasm has outpaced the science; there’s no question about that. And most of the studies have done in animals. That said, some studies have shown that CBD helps treat components of anxiety, like public speaking. Unlike THC, it is nonintoxicating and non–habit forming. But we don’t have the wealth of randomized controlled trials that we have for official psychiatric medications.

CBD’s benefits have been most extensively studied in pediatric epilepsy. The one Food and Drug Administration–approved drug derived from cannabis is Epidiolex, used to treat rare forms of childhood epilepsy. There is some evidence that as an adjunct, it can be used for glioblastoma multiforme in patients receiving other appropriate therapy. There is also some preliminary evidence that it can be used for addiction, including to opioids, cannabis, tobacco, and stimulants.

Most of the evidence for using CBD in chronic pain comes from animal studies, including a study published in the European Journal of Pain in 2016. Among my patients to whom I have suggested CBD for chronic pain, a few have noticed great benefit, a few have noticed some benefit, and a lot have noticed no benefit. For those who have said they noticed benefit it is unclear whether that benefit was just the placebo effect.

In insomnia, I usually have them take CBD under the tongue half an hour time before bedtime, or if it’s an edible, an hour before bedtime. I start with a lower dose and slowly try higher doses. I also encourage them to do the other sleep hygiene things, like no screens, increasing exercise, and decreasing caffeine. It seems that CBD helps them fall asleep, though it’s hard to know if it’s the CBD or the fact that they have started taking something, and have simultaneously made various lifestyle changes.


Dr. Poorman: Can CBD interfere with your normal sleep architecture, the way benzodiazepines and Benadryl can?

Dr. Grinspoon: We know that THC affects your sleep architecture and affects what percentage of REM sleep you have. But I don’t know if the effects of CBD on sleep architecture have been studied.


Dr. Poorman: What harms do you counsel patients about when discussing CBD?

Dr. Grinspoon: There are four main harms. The first is the price. It’s overpriced, and the doses are very low. In most animal studies, the doses are about 20 milligrams per kilogram of weight. And you go to the market, and it’s like a dollar for a hundredth of that.

Number two is that it’s not regulated; it’s a supplement. A few years ago, the government tested a bunch of samples of CBD, and some didn’t actually contain CBD, some didn’t have the right amount; and worse, some contained THC that had not been disclosed in the packaging. So you can’t just go to a roadside gas station and assume that if you buy CBD, it’s actually that. You want a place that has a certificate of assurance. Make sure third-party testing was done, including testing for pesticides and other heavy metals.

The third thing is drug interactions. It affects the body like grapefruit and inhibits the cytochrome P450 system. The medications doctors should be most concerned about are blood thinners like Coumadin. And if you’re on blood thinners, you definitely want to tell your doctor that you are on CBD and he or she might want to check your blood levels more frequently than they usually do.

The fourth concern is liver inflammation. In the childhood epilepsy studies, a bump in some liver enzymes was seen, although I haven’t heard of any clinically significant cases of chemical hepatitis related to CBD. But if someone has liver disease you want to keep an eye on their liver enzymes.

Dr. Poorman: What methods of ingestion do you recommend or not recommend?

Dr. Grinspoon: It’s basically trial and error, but I usually recommend oral form. If people feel comfortable taking a gummy bear, or a pill, I’m not particular about that. If the product being taken contains less than 0.3% THC, it won’t get you high.

The topical form probably works better for treating chronic pain if it contains some THC, suggests a review article published in the Cleveland Clinic Journal of Medicine. Topical THC is nonintoxicating, unless you managed to sit in a bathtub for 8 hours after applying it.

I don’t recommend smoking CBD, and right now, I don’t recommend vaping anything.

If people have severe pain, like moderately severe arthritis, CBD may not be enough, whereas medical cannabis with THC could help, a report suggests.


Dr. Poorman: Do you ever encourage patients to stop using CBD products?

Dr. Grinspoon: I work in a low-income area, and my patients don’t have a ton of disposable income. If it’s not working, I worry about the expense.


Dr. Poorman: The CBD industry is growing quickly. What changes are you seeing in what products are out there, and what changes would you like to see?

Dr. Grinspoon: CBD is being put in everything, and it’s comical. On the one hand, you can say if people want to waste their money on a CBD emitting pillowcase, that’s fine. On the other hand, you can say that certainly seems like misleading advertising, because a CBD emitting pillowcase isn’t going to help you sleep any better.

I think the purported benefits are far beyond what we can say scientifically. We do know that CBD has anti-inflammatory characteristics. But that doesn’t mean that putting CBD in all skin products is good for your skin. It’s bad for your pocketbook, though. I would like there to be less of a gap between the claims and the science.
 

Dr. Elisabeth Poorman has no conflicts to disclose.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.

Opioids, benzodiazepines carry greater risk of COPD-related hospitalization

Article Type
Changed
Wed, 12/04/2019 - 14:47

 

Patients with chronic obstructive pulmonary disease who received opioids or benzodiazepines had a greater risk of hospitalization for respiratory-related adverse events, according to recent research from Annals of the American Thoracic Society.

opioid pills in pill bottles
sdominick/Getty Images

In addition, the risk of hospitalization because of respiratory events for patients with chronic obstructive pulmonary disease (COPD) was greater when opioid and benzodiazepine medications were combined, compared with patients who did not take either medication, Jacques G. Baillargeon, PhD, of the department of preventive medicine and community health at the University of Texas, Galveston, and colleagues wrote.

“Patients with COPD and their physicians should judiciously assess the risks and benefits of opioids and benzodiazepines, alone and in combination, and preferentially recommend nonopioid and nonbenzodiazepine approaches for pain, sleep, and anxiety management in patients with COPD,” the investigators wrote.

The researchers performed a case-control study of 3,232 Medicare beneficiary cases of COPD patients who were aged at least 66 years. Patients were included if they experienced a hospitalization related to a COPD-related adverse event with a respiratory diagnosis in 2014 and then matched to one or two control patients (total, 6,247 patients) based on age at hospitalization, gender, COPD medication, COPD complexity, obstructive sleep apnea, and socioeconomic status. COPD complexity was assigned to three levels (low, moderate, high) and calculated using the patient’s comorbid respiratory conditions and associated medical procedures in the 12 months prior to their hospitalization.

They found that, in the 30 days before COPD-related hospitalization, use of opioids was associated with greater likelihood of hospitalization (adjusted odds ratio, 1.73; 95% confidence interval, 1.52-1.97), as was use of benzodiazepines (aOR, 1.42; 95% CI, 1.21-1.66). When patients used both opioids and benzodiazepines, they had a significantly higher risk of hospitalization, compared with patients who did not use opioids or benzodiazepines (aOR, 2.32; 95% CI, 1.94-2.77).

In the 60 days prior to hospitalization, there was also a greater likelihood of hospitalization among COPD patients who used opioids (aOR, 1.66; 95% CI, 1.47-1.88), benzodiazepines (aOR, 1.44; 95% CI, 1.24-1.67), and both opioids and benzodiazepines (aOR, 2.27; 95% CI, 1.93-2.67); at 90 days, this higher risk of hospitalization persisted among COPD patients taking opioids (aOR, 1.58; 95% CI, 1.40-1.78), benzodiazepines (aOR, 1.40; 95% CI, 1.20-1.63), and both opioids and benzodiazepines (aOR, 2.21; 95% CI, 1.88-2.59).

The researchers acknowledged that one potential limitation in the study was how COPD diagnoses were obtained through coding performed by clinicians instead of from laboratory testing. Confounding by COPD indication and severity; use of over-the-counter medication or opioids and benzodiazepines received illegally; and lack of analyses of potential confounders such as diet, alcohol use, smoking status and herbal supplement use were other limitations.

This study was supported by an award from the National Center for Advancing Translational Sciences and National Institutes of Health. Dr. Baillargeon had no disclosures.

SOURCE: Baillargeon JG et al. Ann Am Thorac Soc. 2019 Oct 1. doi: 10.1513/AnnalsATS.201901-024OC.

Publications
Topics
Sections

 

Patients with chronic obstructive pulmonary disease who received opioids or benzodiazepines had a greater risk of hospitalization for respiratory-related adverse events, according to recent research from Annals of the American Thoracic Society.

opioid pills in pill bottles
sdominick/Getty Images

In addition, the risk of hospitalization because of respiratory events for patients with chronic obstructive pulmonary disease (COPD) was greater when opioid and benzodiazepine medications were combined, compared with patients who did not take either medication, Jacques G. Baillargeon, PhD, of the department of preventive medicine and community health at the University of Texas, Galveston, and colleagues wrote.

“Patients with COPD and their physicians should judiciously assess the risks and benefits of opioids and benzodiazepines, alone and in combination, and preferentially recommend nonopioid and nonbenzodiazepine approaches for pain, sleep, and anxiety management in patients with COPD,” the investigators wrote.

The researchers performed a case-control study of 3,232 Medicare beneficiary cases of COPD patients who were aged at least 66 years. Patients were included if they experienced a hospitalization related to a COPD-related adverse event with a respiratory diagnosis in 2014 and then matched to one or two control patients (total, 6,247 patients) based on age at hospitalization, gender, COPD medication, COPD complexity, obstructive sleep apnea, and socioeconomic status. COPD complexity was assigned to three levels (low, moderate, high) and calculated using the patient’s comorbid respiratory conditions and associated medical procedures in the 12 months prior to their hospitalization.

They found that, in the 30 days before COPD-related hospitalization, use of opioids was associated with greater likelihood of hospitalization (adjusted odds ratio, 1.73; 95% confidence interval, 1.52-1.97), as was use of benzodiazepines (aOR, 1.42; 95% CI, 1.21-1.66). When patients used both opioids and benzodiazepines, they had a significantly higher risk of hospitalization, compared with patients who did not use opioids or benzodiazepines (aOR, 2.32; 95% CI, 1.94-2.77).

In the 60 days prior to hospitalization, there was also a greater likelihood of hospitalization among COPD patients who used opioids (aOR, 1.66; 95% CI, 1.47-1.88), benzodiazepines (aOR, 1.44; 95% CI, 1.24-1.67), and both opioids and benzodiazepines (aOR, 2.27; 95% CI, 1.93-2.67); at 90 days, this higher risk of hospitalization persisted among COPD patients taking opioids (aOR, 1.58; 95% CI, 1.40-1.78), benzodiazepines (aOR, 1.40; 95% CI, 1.20-1.63), and both opioids and benzodiazepines (aOR, 2.21; 95% CI, 1.88-2.59).

The researchers acknowledged that one potential limitation in the study was how COPD diagnoses were obtained through coding performed by clinicians instead of from laboratory testing. Confounding by COPD indication and severity; use of over-the-counter medication or opioids and benzodiazepines received illegally; and lack of analyses of potential confounders such as diet, alcohol use, smoking status and herbal supplement use were other limitations.

This study was supported by an award from the National Center for Advancing Translational Sciences and National Institutes of Health. Dr. Baillargeon had no disclosures.

SOURCE: Baillargeon JG et al. Ann Am Thorac Soc. 2019 Oct 1. doi: 10.1513/AnnalsATS.201901-024OC.

 

Patients with chronic obstructive pulmonary disease who received opioids or benzodiazepines had a greater risk of hospitalization for respiratory-related adverse events, according to recent research from Annals of the American Thoracic Society.

opioid pills in pill bottles
sdominick/Getty Images

In addition, the risk of hospitalization because of respiratory events for patients with chronic obstructive pulmonary disease (COPD) was greater when opioid and benzodiazepine medications were combined, compared with patients who did not take either medication, Jacques G. Baillargeon, PhD, of the department of preventive medicine and community health at the University of Texas, Galveston, and colleagues wrote.

“Patients with COPD and their physicians should judiciously assess the risks and benefits of opioids and benzodiazepines, alone and in combination, and preferentially recommend nonopioid and nonbenzodiazepine approaches for pain, sleep, and anxiety management in patients with COPD,” the investigators wrote.

The researchers performed a case-control study of 3,232 Medicare beneficiary cases of COPD patients who were aged at least 66 years. Patients were included if they experienced a hospitalization related to a COPD-related adverse event with a respiratory diagnosis in 2014 and then matched to one or two control patients (total, 6,247 patients) based on age at hospitalization, gender, COPD medication, COPD complexity, obstructive sleep apnea, and socioeconomic status. COPD complexity was assigned to three levels (low, moderate, high) and calculated using the patient’s comorbid respiratory conditions and associated medical procedures in the 12 months prior to their hospitalization.

They found that, in the 30 days before COPD-related hospitalization, use of opioids was associated with greater likelihood of hospitalization (adjusted odds ratio, 1.73; 95% confidence interval, 1.52-1.97), as was use of benzodiazepines (aOR, 1.42; 95% CI, 1.21-1.66). When patients used both opioids and benzodiazepines, they had a significantly higher risk of hospitalization, compared with patients who did not use opioids or benzodiazepines (aOR, 2.32; 95% CI, 1.94-2.77).

In the 60 days prior to hospitalization, there was also a greater likelihood of hospitalization among COPD patients who used opioids (aOR, 1.66; 95% CI, 1.47-1.88), benzodiazepines (aOR, 1.44; 95% CI, 1.24-1.67), and both opioids and benzodiazepines (aOR, 2.27; 95% CI, 1.93-2.67); at 90 days, this higher risk of hospitalization persisted among COPD patients taking opioids (aOR, 1.58; 95% CI, 1.40-1.78), benzodiazepines (aOR, 1.40; 95% CI, 1.20-1.63), and both opioids and benzodiazepines (aOR, 2.21; 95% CI, 1.88-2.59).

The researchers acknowledged that one potential limitation in the study was how COPD diagnoses were obtained through coding performed by clinicians instead of from laboratory testing. Confounding by COPD indication and severity; use of over-the-counter medication or opioids and benzodiazepines received illegally; and lack of analyses of potential confounders such as diet, alcohol use, smoking status and herbal supplement use were other limitations.

This study was supported by an award from the National Center for Advancing Translational Sciences and National Institutes of Health. Dr. Baillargeon had no disclosures.

SOURCE: Baillargeon JG et al. Ann Am Thorac Soc. 2019 Oct 1. doi: 10.1513/AnnalsATS.201901-024OC.

Publications
Publications
Topics
Article Type
Sections
Article Source

FROM ANNALS OF THE AMERICAN THORACIC SOCIETY

Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.

Clinical interventions for global drug use need updating

Article Type
Changed
Thu, 10/24/2019 - 10:40

Public health approach requires greater emphasis on harms, benefits of substance use.

 

Strategies aimed at reducing drug-related harm should be informed by evidence, and recognize the contribution of social and economic factors to drug use, report the authors of a series of four papers published in The Lancet.

Louisa Degenhardt, PhD, and coauthors wrote in the first paper that, although the availability and use of drugs have been transformed over recent decades – including the emergence of hundreds of new psychoactive substances – professional and public policy has not yet adapted to those new realities (Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32229-9).

“In many instances we have, in many countries, and in many debates, the things that are implemented are not evidence-based, and the discussion around illicit drugs is often in an incredibly emotive and morally laden one, in a way that you don’t see in other areas of public health,” Dr. Degenhardt, of the National Drug and Alcohol Research Centre at the University of New South Wales in Sydney, said in an interview. “There has been an increasing level of awareness of issues but also level of recognition that we need to have hard evidence to work out the best ways to respond.”

The paper by Dr. Degenhardt and coauthors addressed the issue of opioid use and dependence around the world, citing evidence that in 2017, 40.5 million people were dependent on opioids and 109,500 deaths were attributable to opioid overdose. An effective treatment exists in the form of opioid agonists methadone and buprenorphine, both of which are recognized as World Health Organization essential medicines.

While the best evidence for positive outcomes from opioid agonist treatment is in people using illicit opioids such as heroin, there is also evidence for their effectiveness in people with pharmaceutical opioid dependence. A study in Kentucky suggested that scaling up the use and retention of opioid agonist treatment, including in prison, could prevent 57% of overdose deaths among injecting drug users.

“Despite strong evidence for the effectiveness of a range of interventions to improve the health and well-being of people who are dependent on opioids, coverage is low, even in high-income countries,” the authors wrote. They also called for international efforts to eliminate marketing strategies that have contributed to the increase in opioid prescription and harms in North America.

The second paper examined the public health implications of legalizing cannabis for medicinal and recreational use (Hall W et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)31789-1). Cannabis has been considered an illicit drug for more than 50 years but recently has been decriminalized or legalized in many parts of the world in recognition of the lower levels of harm, compared with other illicit substances.

Cannabis is used to treat a range of medical conditions, including muscle spasticity in multiple sclerosis. It also is used to treat pain, nausea, and vomiting in palliative care, and to reduce seizures in epilepsy. However, the authors noted that the evidence for many medical applications was absent, and that weakly regulated medical cannabis programs in some U.S. states were blurring the boundaries between medicinal and nonmedicinal use.

They also wrote that the public health effects of legalization could not be assessed, because legalization had happened only in the last 5 years.

“A major determinant of the public health effect of cannabis legalization will be the effect that it has on alcohol use,” they wrote. “The substitution of cannabis for alcohol would produce substantial public health gains, but any increase in the combined use of alcohol and cannabis could increase harm.”

The authors also looked at the effect of use of stimulants such as cocaine and amphetamines. While their use is associated with higher mortality, increased incidence of HIV and hepatitis C infection, poor mental health, and increased risk of cardiovascular events, no effective pharmacotherapies are available, and psychosocial interventions such as cognitive-behavioral therapy have only a weak effect.

“Many governments rely on punitive responses, such as involuntary detention in drug centers, despite the absence of evidence for their effectiveness and their potential to increase harm,” the authors wrote. “Substantial research investment is needed to develop more effective, innovative, and impactful prevention and treatment” (Farrell M et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32230-5).

They focused on interventions to prevent the transmission of blood-borne and sexually transmitted infections – such as the provision of safe injecting equipment, condoms or pre-exposure prophylaxis against HIV – and improve treatment of these, and interventions to prevent and treat overdose, injury, and other harms.

The final paper in the series explored new psychoactive substances, such as synthetic cannabinoids, stimulants, hallucinogens, and dissociative and depressant substances (Peacock A et al. Lancet 2019 Oct 23. doi: 10.1016/S0140-6736(19)32231-7).

There really needs to be massive change in systems in terms of the way monitoring occurs and the speed with which new drugs are identified, Dr. Degenhardt said in the interview. She also said the risks that are identified need to be communicated more effectively.

“At the moment, the way that drug surveillance works in most countries, things come and then particular drugs may spread in use, cause massive harm, and all of our systems of detecting and responding are not fit to detect those things in a timely way and disseminate information to reduce those risks.”

The papers were supported by European Monitoring Centre on Drugs and Drug Addiction, and the Australian National Drug and Alcohol Research Centre. The authors declared support from a range of institutions and funding bodies, and several also declared unrelated grants, funding, and other support from the pharmaceutical sector.

SOURCES: Degenhardt L et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32229-9; Hall W et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)31789-1; Farrell M et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32230-5; and Peacock A et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32231-7.

Publications
Topics
Sections

Public health approach requires greater emphasis on harms, benefits of substance use.

Public health approach requires greater emphasis on harms, benefits of substance use.

 

Strategies aimed at reducing drug-related harm should be informed by evidence, and recognize the contribution of social and economic factors to drug use, report the authors of a series of four papers published in The Lancet.

Louisa Degenhardt, PhD, and coauthors wrote in the first paper that, although the availability and use of drugs have been transformed over recent decades – including the emergence of hundreds of new psychoactive substances – professional and public policy has not yet adapted to those new realities (Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32229-9).

“In many instances we have, in many countries, and in many debates, the things that are implemented are not evidence-based, and the discussion around illicit drugs is often in an incredibly emotive and morally laden one, in a way that you don’t see in other areas of public health,” Dr. Degenhardt, of the National Drug and Alcohol Research Centre at the University of New South Wales in Sydney, said in an interview. “There has been an increasing level of awareness of issues but also level of recognition that we need to have hard evidence to work out the best ways to respond.”

The paper by Dr. Degenhardt and coauthors addressed the issue of opioid use and dependence around the world, citing evidence that in 2017, 40.5 million people were dependent on opioids and 109,500 deaths were attributable to opioid overdose. An effective treatment exists in the form of opioid agonists methadone and buprenorphine, both of which are recognized as World Health Organization essential medicines.

While the best evidence for positive outcomes from opioid agonist treatment is in people using illicit opioids such as heroin, there is also evidence for their effectiveness in people with pharmaceutical opioid dependence. A study in Kentucky suggested that scaling up the use and retention of opioid agonist treatment, including in prison, could prevent 57% of overdose deaths among injecting drug users.

“Despite strong evidence for the effectiveness of a range of interventions to improve the health and well-being of people who are dependent on opioids, coverage is low, even in high-income countries,” the authors wrote. They also called for international efforts to eliminate marketing strategies that have contributed to the increase in opioid prescription and harms in North America.

The second paper examined the public health implications of legalizing cannabis for medicinal and recreational use (Hall W et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)31789-1). Cannabis has been considered an illicit drug for more than 50 years but recently has been decriminalized or legalized in many parts of the world in recognition of the lower levels of harm, compared with other illicit substances.

Cannabis is used to treat a range of medical conditions, including muscle spasticity in multiple sclerosis. It also is used to treat pain, nausea, and vomiting in palliative care, and to reduce seizures in epilepsy. However, the authors noted that the evidence for many medical applications was absent, and that weakly regulated medical cannabis programs in some U.S. states were blurring the boundaries between medicinal and nonmedicinal use.

They also wrote that the public health effects of legalization could not be assessed, because legalization had happened only in the last 5 years.

“A major determinant of the public health effect of cannabis legalization will be the effect that it has on alcohol use,” they wrote. “The substitution of cannabis for alcohol would produce substantial public health gains, but any increase in the combined use of alcohol and cannabis could increase harm.”

The authors also looked at the effect of use of stimulants such as cocaine and amphetamines. While their use is associated with higher mortality, increased incidence of HIV and hepatitis C infection, poor mental health, and increased risk of cardiovascular events, no effective pharmacotherapies are available, and psychosocial interventions such as cognitive-behavioral therapy have only a weak effect.

“Many governments rely on punitive responses, such as involuntary detention in drug centers, despite the absence of evidence for their effectiveness and their potential to increase harm,” the authors wrote. “Substantial research investment is needed to develop more effective, innovative, and impactful prevention and treatment” (Farrell M et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32230-5).

They focused on interventions to prevent the transmission of blood-borne and sexually transmitted infections – such as the provision of safe injecting equipment, condoms or pre-exposure prophylaxis against HIV – and improve treatment of these, and interventions to prevent and treat overdose, injury, and other harms.

The final paper in the series explored new psychoactive substances, such as synthetic cannabinoids, stimulants, hallucinogens, and dissociative and depressant substances (Peacock A et al. Lancet 2019 Oct 23. doi: 10.1016/S0140-6736(19)32231-7).

There really needs to be massive change in systems in terms of the way monitoring occurs and the speed with which new drugs are identified, Dr. Degenhardt said in the interview. She also said the risks that are identified need to be communicated more effectively.

“At the moment, the way that drug surveillance works in most countries, things come and then particular drugs may spread in use, cause massive harm, and all of our systems of detecting and responding are not fit to detect those things in a timely way and disseminate information to reduce those risks.”

The papers were supported by European Monitoring Centre on Drugs and Drug Addiction, and the Australian National Drug and Alcohol Research Centre. The authors declared support from a range of institutions and funding bodies, and several also declared unrelated grants, funding, and other support from the pharmaceutical sector.

SOURCES: Degenhardt L et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32229-9; Hall W et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)31789-1; Farrell M et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32230-5; and Peacock A et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32231-7.

 

Strategies aimed at reducing drug-related harm should be informed by evidence, and recognize the contribution of social and economic factors to drug use, report the authors of a series of four papers published in The Lancet.

Louisa Degenhardt, PhD, and coauthors wrote in the first paper that, although the availability and use of drugs have been transformed over recent decades – including the emergence of hundreds of new psychoactive substances – professional and public policy has not yet adapted to those new realities (Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32229-9).

“In many instances we have, in many countries, and in many debates, the things that are implemented are not evidence-based, and the discussion around illicit drugs is often in an incredibly emotive and morally laden one, in a way that you don’t see in other areas of public health,” Dr. Degenhardt, of the National Drug and Alcohol Research Centre at the University of New South Wales in Sydney, said in an interview. “There has been an increasing level of awareness of issues but also level of recognition that we need to have hard evidence to work out the best ways to respond.”

The paper by Dr. Degenhardt and coauthors addressed the issue of opioid use and dependence around the world, citing evidence that in 2017, 40.5 million people were dependent on opioids and 109,500 deaths were attributable to opioid overdose. An effective treatment exists in the form of opioid agonists methadone and buprenorphine, both of which are recognized as World Health Organization essential medicines.

While the best evidence for positive outcomes from opioid agonist treatment is in people using illicit opioids such as heroin, there is also evidence for their effectiveness in people with pharmaceutical opioid dependence. A study in Kentucky suggested that scaling up the use and retention of opioid agonist treatment, including in prison, could prevent 57% of overdose deaths among injecting drug users.

“Despite strong evidence for the effectiveness of a range of interventions to improve the health and well-being of people who are dependent on opioids, coverage is low, even in high-income countries,” the authors wrote. They also called for international efforts to eliminate marketing strategies that have contributed to the increase in opioid prescription and harms in North America.

The second paper examined the public health implications of legalizing cannabis for medicinal and recreational use (Hall W et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)31789-1). Cannabis has been considered an illicit drug for more than 50 years but recently has been decriminalized or legalized in many parts of the world in recognition of the lower levels of harm, compared with other illicit substances.

Cannabis is used to treat a range of medical conditions, including muscle spasticity in multiple sclerosis. It also is used to treat pain, nausea, and vomiting in palliative care, and to reduce seizures in epilepsy. However, the authors noted that the evidence for many medical applications was absent, and that weakly regulated medical cannabis programs in some U.S. states were blurring the boundaries between medicinal and nonmedicinal use.

They also wrote that the public health effects of legalization could not be assessed, because legalization had happened only in the last 5 years.

“A major determinant of the public health effect of cannabis legalization will be the effect that it has on alcohol use,” they wrote. “The substitution of cannabis for alcohol would produce substantial public health gains, but any increase in the combined use of alcohol and cannabis could increase harm.”

The authors also looked at the effect of use of stimulants such as cocaine and amphetamines. While their use is associated with higher mortality, increased incidence of HIV and hepatitis C infection, poor mental health, and increased risk of cardiovascular events, no effective pharmacotherapies are available, and psychosocial interventions such as cognitive-behavioral therapy have only a weak effect.

“Many governments rely on punitive responses, such as involuntary detention in drug centers, despite the absence of evidence for their effectiveness and their potential to increase harm,” the authors wrote. “Substantial research investment is needed to develop more effective, innovative, and impactful prevention and treatment” (Farrell M et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32230-5).

They focused on interventions to prevent the transmission of blood-borne and sexually transmitted infections – such as the provision of safe injecting equipment, condoms or pre-exposure prophylaxis against HIV – and improve treatment of these, and interventions to prevent and treat overdose, injury, and other harms.

The final paper in the series explored new psychoactive substances, such as synthetic cannabinoids, stimulants, hallucinogens, and dissociative and depressant substances (Peacock A et al. Lancet 2019 Oct 23. doi: 10.1016/S0140-6736(19)32231-7).

There really needs to be massive change in systems in terms of the way monitoring occurs and the speed with which new drugs are identified, Dr. Degenhardt said in the interview. She also said the risks that are identified need to be communicated more effectively.

“At the moment, the way that drug surveillance works in most countries, things come and then particular drugs may spread in use, cause massive harm, and all of our systems of detecting and responding are not fit to detect those things in a timely way and disseminate information to reduce those risks.”

The papers were supported by European Monitoring Centre on Drugs and Drug Addiction, and the Australian National Drug and Alcohol Research Centre. The authors declared support from a range of institutions and funding bodies, and several also declared unrelated grants, funding, and other support from the pharmaceutical sector.

SOURCES: Degenhardt L et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32229-9; Hall W et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)31789-1; Farrell M et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32230-5; and Peacock A et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32231-7.

Publications
Publications
Topics
Article Type
Click for Credit Status
Ready
Sections
Article Source

FROM THE LANCET

Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Vitals

 

Key clinical point: People with drug use disorders around the world need evidence-based and nonjudgmental clinical care.

Major finding: Many interventions aimed at reducing the harm of illicit drug use are not informed by evidence.

Study details: Series of four papers reviewing the evidence on cannabinoids, opioids, new psychoactive substances, and stimulants.

Disclosures: The papers were supported by European Monitoring Centre on Drugs and Drug Addiction, and the Australian National Drug and Alcohol Research Centre. The authors declared support from a range of institutions and funding bodies, and several also declared unrelated grants, funding, and other support from the pharmaceutical sector.

Sources: Degenhardt L et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32229-9; Hall W et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)31789-1; Farrell M et al. Lancet. 2019 Oct 23. doi: 10.1016/S0140-6736(19)32230-5; and Peacock A et al. Lancet 2019 Oct 23. doi: 10.1016/S0140-6736(19)32231-7.

Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.

Is carpal tunnel syndrome the tip of the iceberg?

Article Type
Changed
Wed, 11/20/2019 - 08:54

 

A 69-year-old man presents with increasing dyspnea on exertion. He has had recent orthopnea and paroxysmal nocturnal dyspnoea. He has a history of well controlled hypertension and hyperlipidemia. He takes the following medications: felodipine and atorvastatin. On exam, his blood pressure is 110/60 mm Hg, and his pulse is 90 beats per minute.

Dr. Douglas S. Paauw

A cardiac examination found normal heart sounds with no murmurs.

A chest examination found dullness to percussion at both bases and rales.

A chest x-ray showed bilateral effusions and mild pulmonary edema.

The brain natriuretic peptide test found a level of 1,300 picograms/mL.

An ECG found increased ventricular wall thickness, an ejection fraction of 32%, and normal aortic and mitral valves.

What history would be the most helpful in making a diagnosis?
 

A. History of prostate cancer

B. History of carpal tunnel syndrome

C. History of playing professional football

D. History of hyperlipidemia

E. History of ulcerative colitis

The correct answer here would be B. history of carpal tunnel syndrome (CTS). This patient has clinical heart failure, without a history of clinical ischemic disease. The differential diagnosis for causes of heart failure is long, with the most common causes being chronic hypertension and ischemic heart disease. Other common causes include chronic untreated sleep apnea and valvular heart disease.

This patient really does not have clear reasons for having clinical heart failure. His cardiovascular risk factors have been well controlled, and no valvular disease was found on ECG.

Several recent reports have raised the importance of a history of CTS significantly increasing the likelihood of amyloidosis being the cause of underlying heart failure.

CTS is such a common clinical entity that it is easy to not appreciate its presence as a clue to possible amyloid cardiomyopathy. Fosbøl et al. reported that a diagnosis of CTS was associated with a higher incidence of heart failure (hazard ratio, 1.54; CI, 1.45-1.64).1 They found a highly increased risk of amyloid (HR, 12.2) in patients who had surgery for CTS.

Sperry et al. found that over 10% of patients who underwent carpal tunnel release stained for amyloid on biopsy specimens, and that concomitant cardiac evaluation identified patients with cardiac involvement.2

Pinney et al. found that 48% of patients with transthyretin amyloidosis had a history of CTS.3

In a retrospective study of patients with wild-type transthyretin amyloid (253), patients with hereditary transthyretin amyloid (136), and asymptomatic gene carriers (77), participants were screened for a history of spinal stenosis and CTS.4 Almost 60% of the patients with amyloid had a history of CTS, and 11% had a history of spinal stenosis. Patients with CTS and hereditary amyloid had thicker interventricular septums, higher left ventricular mass, and lower Karnovsky index than those without CTS.

The diagnosis of CTS, especially in those who need surgery for treatment or have bilateral disease, should make us consider the possibility of underlying amyloidosis.

Pearl: In patients who have heart failure and a history of CTS, amyloidosis should be considered as a cause.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at that university. Contact Dr. Paauw at [email protected].

References

1. Fosbøl EL et al. J Am Coll Cardiol. 2019;74:15-23.

2. Sperry BW et al. J Am Coll Cardiol. 2018 Oct 23;72(17):2040-50.

3. Pinney JH et al. J Am Heart Assoc. 2013 Apr 22;2(2):e000098.

4. Aus dem Siepen F et al. Clin Res Cardiol. 2019 Apr 5. doi: 10.1007/s00392-019-01467-1.
 

Publications
Topics
Sections

 

A 69-year-old man presents with increasing dyspnea on exertion. He has had recent orthopnea and paroxysmal nocturnal dyspnoea. He has a history of well controlled hypertension and hyperlipidemia. He takes the following medications: felodipine and atorvastatin. On exam, his blood pressure is 110/60 mm Hg, and his pulse is 90 beats per minute.

Dr. Douglas S. Paauw

A cardiac examination found normal heart sounds with no murmurs.

A chest examination found dullness to percussion at both bases and rales.

A chest x-ray showed bilateral effusions and mild pulmonary edema.

The brain natriuretic peptide test found a level of 1,300 picograms/mL.

An ECG found increased ventricular wall thickness, an ejection fraction of 32%, and normal aortic and mitral valves.

What history would be the most helpful in making a diagnosis?
 

A. History of prostate cancer

B. History of carpal tunnel syndrome

C. History of playing professional football

D. History of hyperlipidemia

E. History of ulcerative colitis

The correct answer here would be B. history of carpal tunnel syndrome (CTS). This patient has clinical heart failure, without a history of clinical ischemic disease. The differential diagnosis for causes of heart failure is long, with the most common causes being chronic hypertension and ischemic heart disease. Other common causes include chronic untreated sleep apnea and valvular heart disease.

This patient really does not have clear reasons for having clinical heart failure. His cardiovascular risk factors have been well controlled, and no valvular disease was found on ECG.

Several recent reports have raised the importance of a history of CTS significantly increasing the likelihood of amyloidosis being the cause of underlying heart failure.

CTS is such a common clinical entity that it is easy to not appreciate its presence as a clue to possible amyloid cardiomyopathy. Fosbøl et al. reported that a diagnosis of CTS was associated with a higher incidence of heart failure (hazard ratio, 1.54; CI, 1.45-1.64).1 They found a highly increased risk of amyloid (HR, 12.2) in patients who had surgery for CTS.

Sperry et al. found that over 10% of patients who underwent carpal tunnel release stained for amyloid on biopsy specimens, and that concomitant cardiac evaluation identified patients with cardiac involvement.2

Pinney et al. found that 48% of patients with transthyretin amyloidosis had a history of CTS.3

In a retrospective study of patients with wild-type transthyretin amyloid (253), patients with hereditary transthyretin amyloid (136), and asymptomatic gene carriers (77), participants were screened for a history of spinal stenosis and CTS.4 Almost 60% of the patients with amyloid had a history of CTS, and 11% had a history of spinal stenosis. Patients with CTS and hereditary amyloid had thicker interventricular septums, higher left ventricular mass, and lower Karnovsky index than those without CTS.

The diagnosis of CTS, especially in those who need surgery for treatment or have bilateral disease, should make us consider the possibility of underlying amyloidosis.

Pearl: In patients who have heart failure and a history of CTS, amyloidosis should be considered as a cause.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at that university. Contact Dr. Paauw at [email protected].

References

1. Fosbøl EL et al. J Am Coll Cardiol. 2019;74:15-23.

2. Sperry BW et al. J Am Coll Cardiol. 2018 Oct 23;72(17):2040-50.

3. Pinney JH et al. J Am Heart Assoc. 2013 Apr 22;2(2):e000098.

4. Aus dem Siepen F et al. Clin Res Cardiol. 2019 Apr 5. doi: 10.1007/s00392-019-01467-1.
 

 

A 69-year-old man presents with increasing dyspnea on exertion. He has had recent orthopnea and paroxysmal nocturnal dyspnoea. He has a history of well controlled hypertension and hyperlipidemia. He takes the following medications: felodipine and atorvastatin. On exam, his blood pressure is 110/60 mm Hg, and his pulse is 90 beats per minute.

Dr. Douglas S. Paauw

A cardiac examination found normal heart sounds with no murmurs.

A chest examination found dullness to percussion at both bases and rales.

A chest x-ray showed bilateral effusions and mild pulmonary edema.

The brain natriuretic peptide test found a level of 1,300 picograms/mL.

An ECG found increased ventricular wall thickness, an ejection fraction of 32%, and normal aortic and mitral valves.

What history would be the most helpful in making a diagnosis?
 

A. History of prostate cancer

B. History of carpal tunnel syndrome

C. History of playing professional football

D. History of hyperlipidemia

E. History of ulcerative colitis

The correct answer here would be B. history of carpal tunnel syndrome (CTS). This patient has clinical heart failure, without a history of clinical ischemic disease. The differential diagnosis for causes of heart failure is long, with the most common causes being chronic hypertension and ischemic heart disease. Other common causes include chronic untreated sleep apnea and valvular heart disease.

This patient really does not have clear reasons for having clinical heart failure. His cardiovascular risk factors have been well controlled, and no valvular disease was found on ECG.

Several recent reports have raised the importance of a history of CTS significantly increasing the likelihood of amyloidosis being the cause of underlying heart failure.

CTS is such a common clinical entity that it is easy to not appreciate its presence as a clue to possible amyloid cardiomyopathy. Fosbøl et al. reported that a diagnosis of CTS was associated with a higher incidence of heart failure (hazard ratio, 1.54; CI, 1.45-1.64).1 They found a highly increased risk of amyloid (HR, 12.2) in patients who had surgery for CTS.

Sperry et al. found that over 10% of patients who underwent carpal tunnel release stained for amyloid on biopsy specimens, and that concomitant cardiac evaluation identified patients with cardiac involvement.2

Pinney et al. found that 48% of patients with transthyretin amyloidosis had a history of CTS.3

In a retrospective study of patients with wild-type transthyretin amyloid (253), patients with hereditary transthyretin amyloid (136), and asymptomatic gene carriers (77), participants were screened for a history of spinal stenosis and CTS.4 Almost 60% of the patients with amyloid had a history of CTS, and 11% had a history of spinal stenosis. Patients with CTS and hereditary amyloid had thicker interventricular septums, higher left ventricular mass, and lower Karnovsky index than those without CTS.

The diagnosis of CTS, especially in those who need surgery for treatment or have bilateral disease, should make us consider the possibility of underlying amyloidosis.

Pearl: In patients who have heart failure and a history of CTS, amyloidosis should be considered as a cause.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at that university. Contact Dr. Paauw at [email protected].

References

1. Fosbøl EL et al. J Am Coll Cardiol. 2019;74:15-23.

2. Sperry BW et al. J Am Coll Cardiol. 2018 Oct 23;72(17):2040-50.

3. Pinney JH et al. J Am Heart Assoc. 2013 Apr 22;2(2):e000098.

4. Aus dem Siepen F et al. Clin Res Cardiol. 2019 Apr 5. doi: 10.1007/s00392-019-01467-1.
 

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.

Drug crisis continues to evolve beyond opioids

Article Type
Changed
Tue, 10/22/2019 - 11:34

 

Almost three-quarters of primary care physicians believe that their patients will take their controlled medications as prescribed, but more than half of drug-monitoring lab tests show signs of misuse, according to a new report from Quest Diagnostics.

Primary care physicians, who are on the front lines of the drug epidemic, are well intentioned but underprepared and may miss some of the drug misuse risks affecting their patients,” report coauthor Harvey W. Kaufman, MD, Quest’s senior medical director, said in a written statement.

Analysis of more than 4.4 million drug-monitoring tests showed that 51% involved an inconsistent result, such as detection of a nonprescribed drug or nondetection of a drug that was prescribed. The report also included a survey of 500 primary care physicians, of whom 72% said they trusted their patents to properly use opioids and other controlled substances.

“The intersection of these two data sets reveals, for the first time, the contrast between physician expectations about patient drug use and the evolution of the drug epidemic and actual patient behavior, as revealed by objective lab data, amid a national drug crisis that claimed an estimated 68,500 lives last year,” the report said.

A majority (62%) of the physicians surveyed also said that the opioid crisis will evolve into a new prescription drug crisis, and even more (72%) think that patients with chronic pain will use illicit drugs if they cannot get prescription opioids. Evidence from the drug test dataset suggests that “misuse of nonprescribed fentanyl and nonprescribed gabapentin warrant[s] a closer look,” the report said. In the survey, 78% of respondents reported prescribing gabapentin as an alternative to opioids for patients with chronic pain.



Those two drugs, along with alcohol, are the only three drug groups for which misuse increased from 2017 to 2018, and both are frequently involved in drug mixing, which is the most common form of misuse. Gabapentin went from 9.6% of all nonprescribed misuse in 2017 to 13.4% in 2018, an increase of 40%. Nonprescribed fentanyl was found in 64% of test results that were positive for heroin and 24% that were positive for cocaine, the Quest data showed.

The survey results, however, suggest that gabapentin is not on physicians’ radar, as only 34% said that they were concerned about its misuse, compared with 96% for opioids and 90% for benzodiazepines, according to the report.

“While gabapentin may not have opioids’ addictive potential, it can exaggerate euphoric effects when combined with opioids or anxiety medications. This drug mixing is dangerous,” said report coauthor Jeffrey Gudin, MD, senior medical advisor, prescription drug monitoring, for Quest Diagnostics.

The survey was conducted online among family physicians, general practitioners, and internists from July 31 to Aug. 16, 2019, by the Harris Poll on behalf of Quest and Center for Addiction. The test result data were collected in all 50 states and Washington, D.C., from 2011 to 2018, and results from drug rehabilitation clinics and addiction specialists were excluded from the analysis, so actual misuse rates are probably higher than reported.

Publications
Topics
Sections

 

Almost three-quarters of primary care physicians believe that their patients will take their controlled medications as prescribed, but more than half of drug-monitoring lab tests show signs of misuse, according to a new report from Quest Diagnostics.

Primary care physicians, who are on the front lines of the drug epidemic, are well intentioned but underprepared and may miss some of the drug misuse risks affecting their patients,” report coauthor Harvey W. Kaufman, MD, Quest’s senior medical director, said in a written statement.

Analysis of more than 4.4 million drug-monitoring tests showed that 51% involved an inconsistent result, such as detection of a nonprescribed drug or nondetection of a drug that was prescribed. The report also included a survey of 500 primary care physicians, of whom 72% said they trusted their patents to properly use opioids and other controlled substances.

“The intersection of these two data sets reveals, for the first time, the contrast between physician expectations about patient drug use and the evolution of the drug epidemic and actual patient behavior, as revealed by objective lab data, amid a national drug crisis that claimed an estimated 68,500 lives last year,” the report said.

A majority (62%) of the physicians surveyed also said that the opioid crisis will evolve into a new prescription drug crisis, and even more (72%) think that patients with chronic pain will use illicit drugs if they cannot get prescription opioids. Evidence from the drug test dataset suggests that “misuse of nonprescribed fentanyl and nonprescribed gabapentin warrant[s] a closer look,” the report said. In the survey, 78% of respondents reported prescribing gabapentin as an alternative to opioids for patients with chronic pain.



Those two drugs, along with alcohol, are the only three drug groups for which misuse increased from 2017 to 2018, and both are frequently involved in drug mixing, which is the most common form of misuse. Gabapentin went from 9.6% of all nonprescribed misuse in 2017 to 13.4% in 2018, an increase of 40%. Nonprescribed fentanyl was found in 64% of test results that were positive for heroin and 24% that were positive for cocaine, the Quest data showed.

The survey results, however, suggest that gabapentin is not on physicians’ radar, as only 34% said that they were concerned about its misuse, compared with 96% for opioids and 90% for benzodiazepines, according to the report.

“While gabapentin may not have opioids’ addictive potential, it can exaggerate euphoric effects when combined with opioids or anxiety medications. This drug mixing is dangerous,” said report coauthor Jeffrey Gudin, MD, senior medical advisor, prescription drug monitoring, for Quest Diagnostics.

The survey was conducted online among family physicians, general practitioners, and internists from July 31 to Aug. 16, 2019, by the Harris Poll on behalf of Quest and Center for Addiction. The test result data were collected in all 50 states and Washington, D.C., from 2011 to 2018, and results from drug rehabilitation clinics and addiction specialists were excluded from the analysis, so actual misuse rates are probably higher than reported.

 

Almost three-quarters of primary care physicians believe that their patients will take their controlled medications as prescribed, but more than half of drug-monitoring lab tests show signs of misuse, according to a new report from Quest Diagnostics.

Primary care physicians, who are on the front lines of the drug epidemic, are well intentioned but underprepared and may miss some of the drug misuse risks affecting their patients,” report coauthor Harvey W. Kaufman, MD, Quest’s senior medical director, said in a written statement.

Analysis of more than 4.4 million drug-monitoring tests showed that 51% involved an inconsistent result, such as detection of a nonprescribed drug or nondetection of a drug that was prescribed. The report also included a survey of 500 primary care physicians, of whom 72% said they trusted their patents to properly use opioids and other controlled substances.

“The intersection of these two data sets reveals, for the first time, the contrast between physician expectations about patient drug use and the evolution of the drug epidemic and actual patient behavior, as revealed by objective lab data, amid a national drug crisis that claimed an estimated 68,500 lives last year,” the report said.

A majority (62%) of the physicians surveyed also said that the opioid crisis will evolve into a new prescription drug crisis, and even more (72%) think that patients with chronic pain will use illicit drugs if they cannot get prescription opioids. Evidence from the drug test dataset suggests that “misuse of nonprescribed fentanyl and nonprescribed gabapentin warrant[s] a closer look,” the report said. In the survey, 78% of respondents reported prescribing gabapentin as an alternative to opioids for patients with chronic pain.



Those two drugs, along with alcohol, are the only three drug groups for which misuse increased from 2017 to 2018, and both are frequently involved in drug mixing, which is the most common form of misuse. Gabapentin went from 9.6% of all nonprescribed misuse in 2017 to 13.4% in 2018, an increase of 40%. Nonprescribed fentanyl was found in 64% of test results that were positive for heroin and 24% that were positive for cocaine, the Quest data showed.

The survey results, however, suggest that gabapentin is not on physicians’ radar, as only 34% said that they were concerned about its misuse, compared with 96% for opioids and 90% for benzodiazepines, according to the report.

“While gabapentin may not have opioids’ addictive potential, it can exaggerate euphoric effects when combined with opioids or anxiety medications. This drug mixing is dangerous,” said report coauthor Jeffrey Gudin, MD, senior medical advisor, prescription drug monitoring, for Quest Diagnostics.

The survey was conducted online among family physicians, general practitioners, and internists from July 31 to Aug. 16, 2019, by the Harris Poll on behalf of Quest and Center for Addiction. The test result data were collected in all 50 states and Washington, D.C., from 2011 to 2018, and results from drug rehabilitation clinics and addiction specialists were excluded from the analysis, so actual misuse rates are probably higher than reported.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.

FDA approves Reyvow for acute migraine treatment

Article Type
Changed
Wed, 10/30/2019 - 14:09

 

The Food and Drug Administration has approved lasmiditan (Reyvow) for acute treatment of migraines with and without auras in adults.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The agency’s Oct. 11 announcement said the approval is based on results from a pair of randomized, double-blind, placebo-controlled trials that included 3,177 adult patients with a history of migraine with and without aura. The percentage of patients whose pain and most bothersome migraine symptom (nausea, light sensitivity, or sound sensitivity) resolved after 2 hours was higher in patients receiving lasmiditan than in patients receiving placebo.

Lasmiditan is a serotonin 5-hydroxytryptamine1F–receptor agonist, giving it a unique mechanism of action as compared with other migraine treatments.



The most common adverse events associated with lasmiditan include dizziness, fatigue, paresthesia, and sedation. There is a risk of driving impairment while taking the medication, and patients are advised not to operate or drive machinery for 8 hours after taking lasmiditan.

“Reyvow is a new option for the acute treatment of migraine, a painful condition that affects one in seven Americans. We know that the migraine community is keenly interested in additional treatment options, and we remain committed to continuing to work with stakeholders to promote the development of new therapies for the acute and preventive treatment of migraine,” said Nick Kozauer, MD, acting deputy director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research.



Eli Lilly, the drug’s manufacturer, said in a news release that “the recommended controlled substance classification for Reyvow is currently under review by the Drug Enforcement Administration and is expected within 90 days of today’s FDA approval, after which Reyvow will be available to patients in retail pharmacies” in oral doses of 50 mg, 100 mg, and 200 mg.

Issue
Neurology Reviews- 27(11)
Publications
Topics
Sections

 

The Food and Drug Administration has approved lasmiditan (Reyvow) for acute treatment of migraines with and without auras in adults.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The agency’s Oct. 11 announcement said the approval is based on results from a pair of randomized, double-blind, placebo-controlled trials that included 3,177 adult patients with a history of migraine with and without aura. The percentage of patients whose pain and most bothersome migraine symptom (nausea, light sensitivity, or sound sensitivity) resolved after 2 hours was higher in patients receiving lasmiditan than in patients receiving placebo.

Lasmiditan is a serotonin 5-hydroxytryptamine1F–receptor agonist, giving it a unique mechanism of action as compared with other migraine treatments.



The most common adverse events associated with lasmiditan include dizziness, fatigue, paresthesia, and sedation. There is a risk of driving impairment while taking the medication, and patients are advised not to operate or drive machinery for 8 hours after taking lasmiditan.

“Reyvow is a new option for the acute treatment of migraine, a painful condition that affects one in seven Americans. We know that the migraine community is keenly interested in additional treatment options, and we remain committed to continuing to work with stakeholders to promote the development of new therapies for the acute and preventive treatment of migraine,” said Nick Kozauer, MD, acting deputy director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research.



Eli Lilly, the drug’s manufacturer, said in a news release that “the recommended controlled substance classification for Reyvow is currently under review by the Drug Enforcement Administration and is expected within 90 days of today’s FDA approval, after which Reyvow will be available to patients in retail pharmacies” in oral doses of 50 mg, 100 mg, and 200 mg.

 

The Food and Drug Administration has approved lasmiditan (Reyvow) for acute treatment of migraines with and without auras in adults.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The agency’s Oct. 11 announcement said the approval is based on results from a pair of randomized, double-blind, placebo-controlled trials that included 3,177 adult patients with a history of migraine with and without aura. The percentage of patients whose pain and most bothersome migraine symptom (nausea, light sensitivity, or sound sensitivity) resolved after 2 hours was higher in patients receiving lasmiditan than in patients receiving placebo.

Lasmiditan is a serotonin 5-hydroxytryptamine1F–receptor agonist, giving it a unique mechanism of action as compared with other migraine treatments.



The most common adverse events associated with lasmiditan include dizziness, fatigue, paresthesia, and sedation. There is a risk of driving impairment while taking the medication, and patients are advised not to operate or drive machinery for 8 hours after taking lasmiditan.

“Reyvow is a new option for the acute treatment of migraine, a painful condition that affects one in seven Americans. We know that the migraine community is keenly interested in additional treatment options, and we remain committed to continuing to work with stakeholders to promote the development of new therapies for the acute and preventive treatment of migraine,” said Nick Kozauer, MD, acting deputy director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research.



Eli Lilly, the drug’s manufacturer, said in a news release that “the recommended controlled substance classification for Reyvow is currently under review by the Drug Enforcement Administration and is expected within 90 days of today’s FDA approval, after which Reyvow will be available to patients in retail pharmacies” in oral doses of 50 mg, 100 mg, and 200 mg.

Issue
Neurology Reviews- 27(11)
Issue
Neurology Reviews- 27(11)
Publications
Publications
Topics
Article Type
Sections
Citation Override
Publish date: October 14, 2019
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.

Preop IV dexamethasone conveys relief after total knee surgery

Article Type
Changed
Sun, 10/13/2019 - 14:47

 

Patients given a single preoperative dose of intravenous dexamethasone had significantly less pain after total knee arthroplasty than did those given a placebo in a randomized controlled study of 100 adults.

“Corticosteroids were introduced several years ago for relieving postoperative pain in total joint replacement but, unfortunately, are not widely used due to surgeons’ concerns and the limited supporting evidence,” wrote Nattapol Tammachote, MD, of Thammasat University, Khlong Luang, Pathumthani, Thailand, and colleagues.

In a study published in the Journal of Arthroplasty, the researchers randomized 50 adults undergoing unilateral total knee surgery to a preoperative IV dexamethasone dose of 0.15 mg/kg diluted with normal saline or saline placebo. Patients, who were aged 50-85 years, were assessed every 3 hours after surgery, up to 48 hours; the primary outcomes were pain level, using the visual analog pain scale (VAS), and morphine use.

Overall, patients in the treatment group reported significant reductions on the VAS in mean pain scores of 11 points at rest and 15 points with knee movement. No significant differences in morphine use were noted between groups overall or at 12-hour intervals post-surgery.

In the first 24-48 hours after surgery dexamethasone was associated with a significantly lower rate of nausea and vomiting vs. placebo (58% vs. 84%), and a lower average C-reactive protein level (89 mg/L vs. 167 mg/L) at 48 hours after surgery. Hospital stays averaged 3 days for both groups, and no wound infections were reported.

Scores on tests of knee function using the modified Western Ontario and McMaster University Osteoarthritis Index scores and range of motion of the knee at three months were similar between the groups.

The study findings were limited by several factors, including the small sample size and use of multimodal pain control that may have impacted morphine use, a lack of data on hyperglycemia, and variation in doses of ketorolac given to patients in both groups, the researchers noted.

The results nevertheless support the potential of preoperative dexamethasone as “a promising approach in postoperative pain management and may be suitable for patients with contraindication to multimodal pain regimens,” they concluded.

The researchers reported no financial conflicts.

SOURCE: Tammachote N et al. J Arthroplasty. 2019. doi: https://doi.org/10.1016/ j.arth.2019.09.002.

Publications
Topics
Sections

 

Patients given a single preoperative dose of intravenous dexamethasone had significantly less pain after total knee arthroplasty than did those given a placebo in a randomized controlled study of 100 adults.

“Corticosteroids were introduced several years ago for relieving postoperative pain in total joint replacement but, unfortunately, are not widely used due to surgeons’ concerns and the limited supporting evidence,” wrote Nattapol Tammachote, MD, of Thammasat University, Khlong Luang, Pathumthani, Thailand, and colleagues.

In a study published in the Journal of Arthroplasty, the researchers randomized 50 adults undergoing unilateral total knee surgery to a preoperative IV dexamethasone dose of 0.15 mg/kg diluted with normal saline or saline placebo. Patients, who were aged 50-85 years, were assessed every 3 hours after surgery, up to 48 hours; the primary outcomes were pain level, using the visual analog pain scale (VAS), and morphine use.

Overall, patients in the treatment group reported significant reductions on the VAS in mean pain scores of 11 points at rest and 15 points with knee movement. No significant differences in morphine use were noted between groups overall or at 12-hour intervals post-surgery.

In the first 24-48 hours after surgery dexamethasone was associated with a significantly lower rate of nausea and vomiting vs. placebo (58% vs. 84%), and a lower average C-reactive protein level (89 mg/L vs. 167 mg/L) at 48 hours after surgery. Hospital stays averaged 3 days for both groups, and no wound infections were reported.

Scores on tests of knee function using the modified Western Ontario and McMaster University Osteoarthritis Index scores and range of motion of the knee at three months were similar between the groups.

The study findings were limited by several factors, including the small sample size and use of multimodal pain control that may have impacted morphine use, a lack of data on hyperglycemia, and variation in doses of ketorolac given to patients in both groups, the researchers noted.

The results nevertheless support the potential of preoperative dexamethasone as “a promising approach in postoperative pain management and may be suitable for patients with contraindication to multimodal pain regimens,” they concluded.

The researchers reported no financial conflicts.

SOURCE: Tammachote N et al. J Arthroplasty. 2019. doi: https://doi.org/10.1016/ j.arth.2019.09.002.

 

Patients given a single preoperative dose of intravenous dexamethasone had significantly less pain after total knee arthroplasty than did those given a placebo in a randomized controlled study of 100 adults.

“Corticosteroids were introduced several years ago for relieving postoperative pain in total joint replacement but, unfortunately, are not widely used due to surgeons’ concerns and the limited supporting evidence,” wrote Nattapol Tammachote, MD, of Thammasat University, Khlong Luang, Pathumthani, Thailand, and colleagues.

In a study published in the Journal of Arthroplasty, the researchers randomized 50 adults undergoing unilateral total knee surgery to a preoperative IV dexamethasone dose of 0.15 mg/kg diluted with normal saline or saline placebo. Patients, who were aged 50-85 years, were assessed every 3 hours after surgery, up to 48 hours; the primary outcomes were pain level, using the visual analog pain scale (VAS), and morphine use.

Overall, patients in the treatment group reported significant reductions on the VAS in mean pain scores of 11 points at rest and 15 points with knee movement. No significant differences in morphine use were noted between groups overall or at 12-hour intervals post-surgery.

In the first 24-48 hours after surgery dexamethasone was associated with a significantly lower rate of nausea and vomiting vs. placebo (58% vs. 84%), and a lower average C-reactive protein level (89 mg/L vs. 167 mg/L) at 48 hours after surgery. Hospital stays averaged 3 days for both groups, and no wound infections were reported.

Scores on tests of knee function using the modified Western Ontario and McMaster University Osteoarthritis Index scores and range of motion of the knee at three months were similar between the groups.

The study findings were limited by several factors, including the small sample size and use of multimodal pain control that may have impacted morphine use, a lack of data on hyperglycemia, and variation in doses of ketorolac given to patients in both groups, the researchers noted.

The results nevertheless support the potential of preoperative dexamethasone as “a promising approach in postoperative pain management and may be suitable for patients with contraindication to multimodal pain regimens,” they concluded.

The researchers reported no financial conflicts.

SOURCE: Tammachote N et al. J Arthroplasty. 2019. doi: https://doi.org/10.1016/ j.arth.2019.09.002.

Publications
Publications
Topics
Article Type
Click for Credit Status
Ready
Sections
Article Source

FROM THE JOURNAL OF ARTHROPLASTY

Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.