Migraine ICYMI

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Youth with continuous headache from migraine, persistent post-traumatic headache (PPTH), and new daily persistent headache (NDPH) presented remarkably similar headache features, with most PPTH and NDPH cases resembling abrupt onset of migraine.

Major finding: Youths with migraine, PPTH, and NDPH had similar median usual headache severity score (P  =  .55), similar frequency of bad headaches (P  =  .63), and similar raw Pediatric Migraine Disability Assessment score (P  =  .28). Overall, 72% youths with PPTH and 64% of youths with NDPH met all four diagnostic criteria for migraine.

Study details: This cross-sectional study included 150 age- and sex-matched youths with continuous headache from migraine, PPTH, or NDPH who had prior exposure to ≤2 preventive medications.

Disclosures: This study was supported by the National Institute of Neurological Disorders and Stroke of the US National Institutes of Health and other sources. All authors declared receiving research grants, salary support, or compensation for serving as consultants for or owning stock options in various sources.

Source: Gentile CP et al. Comparison of continuous headache features in youth with migraine, new daily persistent headache, and persistent post-traumatic headache. Cephalalgia. 2023 (Jan 1). Doi: 10.1177/03331024221131331

Key clinical point: Youth with continuous headache from migraine, persistent post-traumatic headache (PPTH), and new daily persistent headache (NDPH) presented remarkably similar headache features, with most PPTH and NDPH cases resembling abrupt onset of migraine.

Major finding: Youths with migraine, PPTH, and NDPH had similar median usual headache severity score (P  =  .55), similar frequency of bad headaches (P  =  .63), and similar raw Pediatric Migraine Disability Assessment score (P  =  .28). Overall, 72% youths with PPTH and 64% of youths with NDPH met all four diagnostic criteria for migraine.

Study details: This cross-sectional study included 150 age- and sex-matched youths with continuous headache from migraine, PPTH, or NDPH who had prior exposure to ≤2 preventive medications.

Disclosures: This study was supported by the National Institute of Neurological Disorders and Stroke of the US National Institutes of Health and other sources. All authors declared receiving research grants, salary support, or compensation for serving as consultants for or owning stock options in various sources.

Source: Gentile CP et al. Comparison of continuous headache features in youth with migraine, new daily persistent headache, and persistent post-traumatic headache. Cephalalgia. 2023 (Jan 1). Doi: 10.1177/03331024221131331

Key clinical point: Youth with continuous headache from migraine, persistent post-traumatic headache (PPTH), and new daily persistent headache (NDPH) presented remarkably similar headache features, with most PPTH and NDPH cases resembling abrupt onset of migraine.

Major finding: Youths with migraine, PPTH, and NDPH had similar median usual headache severity score (P  =  .55), similar frequency of bad headaches (P  =  .63), and similar raw Pediatric Migraine Disability Assessment score (P  =  .28). Overall, 72% youths with PPTH and 64% of youths with NDPH met all four diagnostic criteria for migraine.

Study details: This cross-sectional study included 150 age- and sex-matched youths with continuous headache from migraine, PPTH, or NDPH who had prior exposure to ≤2 preventive medications.

Disclosures: This study was supported by the National Institute of Neurological Disorders and Stroke of the US National Institutes of Health and other sources. All authors declared receiving research grants, salary support, or compensation for serving as consultants for or owning stock options in various sources.

Source: Gentile CP et al. Comparison of continuous headache features in youth with migraine, new daily persistent headache, and persistent post-traumatic headache. Cephalalgia. 2023 (Jan 1). Doi: 10.1177/03331024221131331

Use of a remote electrical neuromodulation device every other day helped patients significantly reduce the number of migraine days compared with a placebo device, according to recent research published in the journal Headache.

The prospective, randomized, double-blind, placebo-controlled, multicenter trial showed that remote electrical neuromodulation (REN) with Nerivio (Theranica Bio-Electronics Ltd.; Bridgewater, N.J.) found a mean reduction/decrease in the number of migraine days by an average of 4.0 days per month, according to Stewart J. Tepper MD, of the Geisel School of Medicine at Dartmouth in Hanover, N.H., and colleagues.*

“The statistically significant results were maintained in separate subanalyses of the chronic and episodic subsamples, as well as in the separate subanalyses of participants who used and did not use migraine prophylaxis,” Dr. Tepper and colleagues wrote.

A nonpharmacological alternative

Researchers randomized 248 participants into active and placebo groups, with 95 participants in the active group and 84 participants in the placebo group meeting the criteria for a modified intention-to-treat (mITT) analysis. Most of the participants in the ITT dataset were women (85.9%) with an average age of 41.7 years, and a baseline average of 12.2 migraine days and 15.6 headache days. Overall, 52.4% of participants in the ITT dataset had chronic migraine, 25.0% had migraine with aura, and 41.1% were taking preventative medication.

Dr. Tepper and colleagues followed participants for 4 weeks at baseline for observation followed by 8 weeks of participants using the REN device every other day for 45 minutes, or a placebo device that “produces electrical pulses of the same maximum intensity (34 mA) and overall energy, but with different pulse durations and much lower frequencies compared with the active device.” Participants completed a daily diary where they recorded their symptoms.

Researchers assessed the mean change in number of migraine days per month as a primary outcome, and evaluated participants who experienced episodic and chronic migraines separately in subgroup analyses. Secondary outcome measures included mean change in number of moderate or severe headache days, 50% reduction in mean number of headache days compared with baseline, Headache Impact Test short form (HIT-6) and Migraine Specific Quality of Life Questionnaire (MSQ) Role Function Domain total score mean change at 12 weeks compared with week 1, and reduction in mean number of days taking acute headache or migraine medication.

Participants receiving REN treatment had a significant reduction in mean migraine days per month compared with the placebo group (4.0 days vs. 1.3 days; 95% confidence interval, –3.9 days to –1.5 days; P < .001). In subgroup analyses, a significant reduction in migraine days was seen in participants receiving REN treatment with episodic migraine (3.2 days vs. 1.0 days; P = .003) and chronic migraine (4.7 days vs. 1.6 days; P = .001) compared with placebo.

Dr. Tepper and colleagues found a significant reduction in moderate and/or severe headache days among participants receiving REN treatment compared with placebo (3.8 days vs. 2.2 days; P = .005), a significant reduction in headache days overall compared with placebo (4.5 days vs. 1.8 days; P < .001), a significant percentage of patients who experienced 50% reduction in moderate and/or severe headache days compared with placebo (51.6% vs. 35.7%; P = .033), and a significant reduction in acute medication days compared with placebo (3.5 days vs. 1.4 days; P = .001). Dr. Tepper and colleagues found no serious device-related adverse events in either group.

The researchers noted that REN therapy is a “much-needed nonpharmacological alternative” to other preventive and acute treatments for migraine. “Given the previously well-established clinical efficacy and high safety profile in acute treatment of migraine, REN can cover the entire treatment spectrum of migraine, including both acute and preventive treatments,” they said.

‘A good place to start’

Commenting on the study, Alan M. Rapoport, MD, clinical professor of neurology at University of California, Los Angeles; past president of the International Headache Society; and editor-in-chief of Neurology Reviews, said the study was well designed, but acknowledged the 8-week follow-up time for participants as one potential area where he would have wanted to see more data.

As a medical device cleared for use by the Food and Drug Administration for acute treatment of migraine, the REM device also appears to be effective as a migraine preventative based on the results of the study with “virtually no adverse events,” he noted.

“I think this is a great treatment. I think it’s a good place to start,” Dr. Rapoport said. Given the low adverse event rate, he said he would be willing to offer the device to patients as a first option for preventing migraine and either switch to another preventative option or add an additional medication in combination based on how the patient responds. However, at the moment, he noted that this device is not covered by insurance.

Now that a REN device has been shown to work in the acute setting and as a preventative, Dr. Rapoport said he is interested in seeing other devices that have been cleared by the FDA as migraine treatments evaluated in migraine prevention. “I think we need more patients tried on the devices so we get an idea of which ones work acutely, which ones work preventively,” he said.

The authors reported personal and institutional relationships in the form of advisory board positions, consultancies, grants, research principal investigator roles, royalties, speakers bureau positions, and stockholders for a variety of pharmaceutical companies, agencies, and other organizations. Several authors disclosed ties with Theranica, the manufacturer of the REN device used in the study. Dr. Rapoport is editor-in-chief of Neurology Reviews and a consultant for Theranica, but was not involved in studies associated with the REN device.

Correction, 2/10/23: An earlier version of this article misstated the reduction in number of migraine days.

Use of a remote electrical neuromodulation device every other day helped patients significantly reduce the number of migraine days compared with a placebo device, according to recent research published in the journal Headache.

The prospective, randomized, double-blind, placebo-controlled, multicenter trial showed that remote electrical neuromodulation (REN) with Nerivio (Theranica Bio-Electronics Ltd.; Bridgewater, N.J.) found a mean reduction/decrease in the number of migraine days by an average of 4.0 days per month, according to Stewart J. Tepper MD, of the Geisel School of Medicine at Dartmouth in Hanover, N.H., and colleagues.*

“The statistically significant results were maintained in separate subanalyses of the chronic and episodic subsamples, as well as in the separate subanalyses of participants who used and did not use migraine prophylaxis,” Dr. Tepper and colleagues wrote.

A nonpharmacological alternative

Researchers randomized 248 participants into active and placebo groups, with 95 participants in the active group and 84 participants in the placebo group meeting the criteria for a modified intention-to-treat (mITT) analysis. Most of the participants in the ITT dataset were women (85.9%) with an average age of 41.7 years, and a baseline average of 12.2 migraine days and 15.6 headache days. Overall, 52.4% of participants in the ITT dataset had chronic migraine, 25.0% had migraine with aura, and 41.1% were taking preventative medication.

Dr. Tepper and colleagues followed participants for 4 weeks at baseline for observation followed by 8 weeks of participants using the REN device every other day for 45 minutes, or a placebo device that “produces electrical pulses of the same maximum intensity (34 mA) and overall energy, but with different pulse durations and much lower frequencies compared with the active device.” Participants completed a daily diary where they recorded their symptoms.

Researchers assessed the mean change in number of migraine days per month as a primary outcome, and evaluated participants who experienced episodic and chronic migraines separately in subgroup analyses. Secondary outcome measures included mean change in number of moderate or severe headache days, 50% reduction in mean number of headache days compared with baseline, Headache Impact Test short form (HIT-6) and Migraine Specific Quality of Life Questionnaire (MSQ) Role Function Domain total score mean change at 12 weeks compared with week 1, and reduction in mean number of days taking acute headache or migraine medication.

Participants receiving REN treatment had a significant reduction in mean migraine days per month compared with the placebo group (4.0 days vs. 1.3 days; 95% confidence interval, –3.9 days to –1.5 days; P < .001). In subgroup analyses, a significant reduction in migraine days was seen in participants receiving REN treatment with episodic migraine (3.2 days vs. 1.0 days; P = .003) and chronic migraine (4.7 days vs. 1.6 days; P = .001) compared with placebo.

Dr. Tepper and colleagues found a significant reduction in moderate and/or severe headache days among participants receiving REN treatment compared with placebo (3.8 days vs. 2.2 days; P = .005), a significant reduction in headache days overall compared with placebo (4.5 days vs. 1.8 days; P < .001), a significant percentage of patients who experienced 50% reduction in moderate and/or severe headache days compared with placebo (51.6% vs. 35.7%; P = .033), and a significant reduction in acute medication days compared with placebo (3.5 days vs. 1.4 days; P = .001). Dr. Tepper and colleagues found no serious device-related adverse events in either group.

The researchers noted that REN therapy is a “much-needed nonpharmacological alternative” to other preventive and acute treatments for migraine. “Given the previously well-established clinical efficacy and high safety profile in acute treatment of migraine, REN can cover the entire treatment spectrum of migraine, including both acute and preventive treatments,” they said.

‘A good place to start’

Commenting on the study, Alan M. Rapoport, MD, clinical professor of neurology at University of California, Los Angeles; past president of the International Headache Society; and editor-in-chief of Neurology Reviews, said the study was well designed, but acknowledged the 8-week follow-up time for participants as one potential area where he would have wanted to see more data.

As a medical device cleared for use by the Food and Drug Administration for acute treatment of migraine, the REM device also appears to be effective as a migraine preventative based on the results of the study with “virtually no adverse events,” he noted.

“I think this is a great treatment. I think it’s a good place to start,” Dr. Rapoport said. Given the low adverse event rate, he said he would be willing to offer the device to patients as a first option for preventing migraine and either switch to another preventative option or add an additional medication in combination based on how the patient responds. However, at the moment, he noted that this device is not covered by insurance.

Now that a REN device has been shown to work in the acute setting and as a preventative, Dr. Rapoport said he is interested in seeing other devices that have been cleared by the FDA as migraine treatments evaluated in migraine prevention. “I think we need more patients tried on the devices so we get an idea of which ones work acutely, which ones work preventively,” he said.

The authors reported personal and institutional relationships in the form of advisory board positions, consultancies, grants, research principal investigator roles, royalties, speakers bureau positions, and stockholders for a variety of pharmaceutical companies, agencies, and other organizations. Several authors disclosed ties with Theranica, the manufacturer of the REN device used in the study. Dr. Rapoport is editor-in-chief of Neurology Reviews and a consultant for Theranica, but was not involved in studies associated with the REN device.

Correction, 2/10/23: An earlier version of this article misstated the reduction in number of migraine days.

Use of a remote electrical neuromodulation device every other day helped patients significantly reduce the number of migraine days compared with a placebo device, according to recent research published in the journal Headache.

The prospective, randomized, double-blind, placebo-controlled, multicenter trial showed that remote electrical neuromodulation (REN) with Nerivio (Theranica Bio-Electronics Ltd.; Bridgewater, N.J.) found a mean reduction/decrease in the number of migraine days by an average of 4.0 days per month, according to Stewart J. Tepper MD, of the Geisel School of Medicine at Dartmouth in Hanover, N.H., and colleagues.*

“The statistically significant results were maintained in separate subanalyses of the chronic and episodic subsamples, as well as in the separate subanalyses of participants who used and did not use migraine prophylaxis,” Dr. Tepper and colleagues wrote.

A nonpharmacological alternative

Researchers randomized 248 participants into active and placebo groups, with 95 participants in the active group and 84 participants in the placebo group meeting the criteria for a modified intention-to-treat (mITT) analysis. Most of the participants in the ITT dataset were women (85.9%) with an average age of 41.7 years, and a baseline average of 12.2 migraine days and 15.6 headache days. Overall, 52.4% of participants in the ITT dataset had chronic migraine, 25.0% had migraine with aura, and 41.1% were taking preventative medication.

Dr. Tepper and colleagues followed participants for 4 weeks at baseline for observation followed by 8 weeks of participants using the REN device every other day for 45 minutes, or a placebo device that “produces electrical pulses of the same maximum intensity (34 mA) and overall energy, but with different pulse durations and much lower frequencies compared with the active device.” Participants completed a daily diary where they recorded their symptoms.

Researchers assessed the mean change in number of migraine days per month as a primary outcome, and evaluated participants who experienced episodic and chronic migraines separately in subgroup analyses. Secondary outcome measures included mean change in number of moderate or severe headache days, 50% reduction in mean number of headache days compared with baseline, Headache Impact Test short form (HIT-6) and Migraine Specific Quality of Life Questionnaire (MSQ) Role Function Domain total score mean change at 12 weeks compared with week 1, and reduction in mean number of days taking acute headache or migraine medication.

Participants receiving REN treatment had a significant reduction in mean migraine days per month compared with the placebo group (4.0 days vs. 1.3 days; 95% confidence interval, –3.9 days to –1.5 days; P < .001). In subgroup analyses, a significant reduction in migraine days was seen in participants receiving REN treatment with episodic migraine (3.2 days vs. 1.0 days; P = .003) and chronic migraine (4.7 days vs. 1.6 days; P = .001) compared with placebo.

Dr. Tepper and colleagues found a significant reduction in moderate and/or severe headache days among participants receiving REN treatment compared with placebo (3.8 days vs. 2.2 days; P = .005), a significant reduction in headache days overall compared with placebo (4.5 days vs. 1.8 days; P < .001), a significant percentage of patients who experienced 50% reduction in moderate and/or severe headache days compared with placebo (51.6% vs. 35.7%; P = .033), and a significant reduction in acute medication days compared with placebo (3.5 days vs. 1.4 days; P = .001). Dr. Tepper and colleagues found no serious device-related adverse events in either group.

The researchers noted that REN therapy is a “much-needed nonpharmacological alternative” to other preventive and acute treatments for migraine. “Given the previously well-established clinical efficacy and high safety profile in acute treatment of migraine, REN can cover the entire treatment spectrum of migraine, including both acute and preventive treatments,” they said.

‘A good place to start’

Commenting on the study, Alan M. Rapoport, MD, clinical professor of neurology at University of California, Los Angeles; past president of the International Headache Society; and editor-in-chief of Neurology Reviews, said the study was well designed, but acknowledged the 8-week follow-up time for participants as one potential area where he would have wanted to see more data.

As a medical device cleared for use by the Food and Drug Administration for acute treatment of migraine, the REM device also appears to be effective as a migraine preventative based on the results of the study with “virtually no adverse events,” he noted.

“I think this is a great treatment. I think it’s a good place to start,” Dr. Rapoport said. Given the low adverse event rate, he said he would be willing to offer the device to patients as a first option for preventing migraine and either switch to another preventative option or add an additional medication in combination based on how the patient responds. However, at the moment, he noted that this device is not covered by insurance.

Now that a REN device has been shown to work in the acute setting and as a preventative, Dr. Rapoport said he is interested in seeing other devices that have been cleared by the FDA as migraine treatments evaluated in migraine prevention. “I think we need more patients tried on the devices so we get an idea of which ones work acutely, which ones work preventively,” he said.

The authors reported personal and institutional relationships in the form of advisory board positions, consultancies, grants, research principal investigator roles, royalties, speakers bureau positions, and stockholders for a variety of pharmaceutical companies, agencies, and other organizations. Several authors disclosed ties with Theranica, the manufacturer of the REN device used in the study. Dr. Rapoport is editor-in-chief of Neurology Reviews and a consultant for Theranica, but was not involved in studies associated with the REN device.

Correction, 2/10/23: An earlier version of this article misstated the reduction in number of migraine days.

Medication overuse headache, previously known as rebound headache or medication-induced headache, may be caused by the frequent or excessive use of various acute care medications. When these medications are used too frequently, they can cause headaches rather than relieving them. (Some headache specialists feel that MOH is the result of recurring severe headaches, and the patients’ overuse of medications to relieve them.) These medications, some of which are painkillers or analgesics, include over-the-counter products such as acetaminophen, aspirin, and anti-inflammatories, as well as prescription medications such as triptans, ergots opioids, opioids, and barbiturates. The one category of acute care medication that does not seem to cause MOH is the gepants, such as rimegepant and ubrogepant.

MOH is the fourth most common headache disorder. It is defined by the International Classification of Headache Disorders (ICHD-3) as a headache present 15 days per month, evolving from regular use of strong acute medication (10 or more days of triptans, ergotamines, butalbital medications, opioids, or combination medications or 15 or more days per month of simple analgesics such as aspirin, acetaminophen, or nonsteroidal anti-inflammatories) for 3 months. 

Patients are usually not aware they have MOH, and this is the most problematic aspect of the condition. Patients do not realize that the medicine they are taking is making their headaches worse. It can be difficult to explain to the patient exactly what is going on with MOH, and why they are doing the wrong thing by taking the very medication that was prescribed by their doctor to stop a migraine attack. Many doctors do not fully understand MOH either, which can make it difficult to treat patients with this type of headache; therefore, it is imperative to educate both doctors and patients on the causes and treatments of MOH.

One of the most important facets of treating MOH traditionally has been the process of detoxifying patients from their overused medication by gradually or precipitously withdrawing the offending medication. There is variability in how detoxification can be accomplished. Some of my patients stopped medications abruptly and experienced very bad headaches. Others tried reducing dosages on their own and reported experiencing the worst headaches of their lives—some of which lasted for a few weeks. I have found that if patients can endure 2 to 3 weeks of detox, they start to feel better. But because the headaches can worsen before they get better, patients understandably try to avoid the detoxification process. 

I start patients on preventive medicine, then slowly increase it to an effective dose, and have them come back in a month for an evaluation. I then have them gradually reduce, but not completely stop, the pain medication before they return. Once I feel their preventive medication is at a therapeutic level, I have them begin a slow detox. After a month of preventive medication, there is a reasonable chance that headaches will start to decrease and be less severe. I tell them that if their headache is less severe try to avoid taking the medicine that they were overusing to prevent perpetuating the MOH.

One plausible physiologic mechanism behind MOH is that chronic exposure to acute care migraine treatment leads to suppression of the serotonergic/norepinephrinergic  endogenous antinociceptive system in the upper brain stem, with facilitation of the trigeminal nociceptive process via up-regulation of calcitonin gene-related peptide (CGRP).This increase in CGRP at the end of peripheral nerve terminals in the trigeminovascular system may facilitate pain transmission. An increase in cortical CGRP may cause cortical spreading depression: a wave of excitement traveling through the cortex, followed by a wave of electrical depression seems to cause headache.  

Good, effective prevention often helps avoid MOH; medications such as topiramate, nortriptyline, gabapentin, onabotulinumtoxinA, and CGRP monoclonal antibodies or some type of local nerve block have improved MOH in patients, but detoxification is usually necessary is some patients. 

Monoclonal antibodies targeting CGRP or its receptor (CGRP-R), given by subcutaneous or intravenous injection or small molecule CGRP receptor antagonists given orally (gepants), seem to be able to treat MOH in some patients without a detoxification. This has been best demonstrated in the monoclonal antibody group, but there is some evidence showing that it may also occur with gepants. These treatments seem to work even when patients are overusing acute care medications; this helps some patients to self-detoxify at their own pace, which is easier for both the patient and the doctor.

Currently, there are 4 monoclonal antibodies against CGRP or the CGRP-R. Erenumab is the only completely human one and the only antibody that blocks the CGRP receptor to prevent the CGRP ligand from docking and exerting its effect. The other 3 (fremanezumab, galcanezumab, and eptinezumab) are humanized monoclonal antibodies that selectively bind to the CGRP ligand, preventing it from docking on its receptor.  Patients started on the monoclonal antibodies against CGRP or its receptor usually have fewer headaches in the first week or two of therapy, and this helps make the self-detox easier for the patient. 

Further, substantial data have shown that onabotulinumtoxinA reduces the number/frequency of headaches and reduces the need for patients to take acute medication. OnabotulinumtoxinA is currently the only medication approved for preventive treatment of chronic migraine; it has long-term safety data available and has reported efficacy lasting for up to 3 years when given in multiple injection sites every 3 months. Interestingly, although topiramate is used as a preventive medication, a recent study comparing erenumab vs topiramate for reducing monthly migraine days (MMD) showed that erenumab outperformed topiramate with a 50% reduction in MMD, and with fewer reported adverse events.

We are just starting to learn about some other potential cellular mechanisms that could be causing MOH in patients; these data could help create new and improved therapies for treating and possibly preventing MOH in the future. Patient outcomes could also be improved by encouraging the inclusion of MOH as part of a continuing education program for physicians who could potentially be treating new patients presenting with MOH. 

Medication overuse headache, previously known as rebound headache or medication-induced headache, may be caused by the frequent or excessive use of various acute care medications. When these medications are used too frequently, they can cause headaches rather than relieving them. (Some headache specialists feel that MOH is the result of recurring severe headaches, and the patients’ overuse of medications to relieve them.) These medications, some of which are painkillers or analgesics, include over-the-counter products such as acetaminophen, aspirin, and anti-inflammatories, as well as prescription medications such as triptans, ergots opioids, opioids, and barbiturates. The one category of acute care medication that does not seem to cause MOH is the gepants, such as rimegepant and ubrogepant.

MOH is the fourth most common headache disorder. It is defined by the International Classification of Headache Disorders (ICHD-3) as a headache present 15 days per month, evolving from regular use of strong acute medication (10 or more days of triptans, ergotamines, butalbital medications, opioids, or combination medications or 15 or more days per month of simple analgesics such as aspirin, acetaminophen, or nonsteroidal anti-inflammatories) for 3 months. 

Patients are usually not aware they have MOH, and this is the most problematic aspect of the condition. Patients do not realize that the medicine they are taking is making their headaches worse. It can be difficult to explain to the patient exactly what is going on with MOH, and why they are doing the wrong thing by taking the very medication that was prescribed by their doctor to stop a migraine attack. Many doctors do not fully understand MOH either, which can make it difficult to treat patients with this type of headache; therefore, it is imperative to educate both doctors and patients on the causes and treatments of MOH.

One of the most important facets of treating MOH traditionally has been the process of detoxifying patients from their overused medication by gradually or precipitously withdrawing the offending medication. There is variability in how detoxification can be accomplished. Some of my patients stopped medications abruptly and experienced very bad headaches. Others tried reducing dosages on their own and reported experiencing the worst headaches of their lives—some of which lasted for a few weeks. I have found that if patients can endure 2 to 3 weeks of detox, they start to feel better. But because the headaches can worsen before they get better, patients understandably try to avoid the detoxification process. 

I start patients on preventive medicine, then slowly increase it to an effective dose, and have them come back in a month for an evaluation. I then have them gradually reduce, but not completely stop, the pain medication before they return. Once I feel their preventive medication is at a therapeutic level, I have them begin a slow detox. After a month of preventive medication, there is a reasonable chance that headaches will start to decrease and be less severe. I tell them that if their headache is less severe try to avoid taking the medicine that they were overusing to prevent perpetuating the MOH.

One plausible physiologic mechanism behind MOH is that chronic exposure to acute care migraine treatment leads to suppression of the serotonergic/norepinephrinergic  endogenous antinociceptive system in the upper brain stem, with facilitation of the trigeminal nociceptive process via up-regulation of calcitonin gene-related peptide (CGRP).This increase in CGRP at the end of peripheral nerve terminals in the trigeminovascular system may facilitate pain transmission. An increase in cortical CGRP may cause cortical spreading depression: a wave of excitement traveling through the cortex, followed by a wave of electrical depression seems to cause headache.  

Good, effective prevention often helps avoid MOH; medications such as topiramate, nortriptyline, gabapentin, onabotulinumtoxinA, and CGRP monoclonal antibodies or some type of local nerve block have improved MOH in patients, but detoxification is usually necessary is some patients. 

Monoclonal antibodies targeting CGRP or its receptor (CGRP-R), given by subcutaneous or intravenous injection or small molecule CGRP receptor antagonists given orally (gepants), seem to be able to treat MOH in some patients without a detoxification. This has been best demonstrated in the monoclonal antibody group, but there is some evidence showing that it may also occur with gepants. These treatments seem to work even when patients are overusing acute care medications; this helps some patients to self-detoxify at their own pace, which is easier for both the patient and the doctor.

Currently, there are 4 monoclonal antibodies against CGRP or the CGRP-R. Erenumab is the only completely human one and the only antibody that blocks the CGRP receptor to prevent the CGRP ligand from docking and exerting its effect. The other 3 (fremanezumab, galcanezumab, and eptinezumab) are humanized monoclonal antibodies that selectively bind to the CGRP ligand, preventing it from docking on its receptor.  Patients started on the monoclonal antibodies against CGRP or its receptor usually have fewer headaches in the first week or two of therapy, and this helps make the self-detox easier for the patient. 

Further, substantial data have shown that onabotulinumtoxinA reduces the number/frequency of headaches and reduces the need for patients to take acute medication. OnabotulinumtoxinA is currently the only medication approved for preventive treatment of chronic migraine; it has long-term safety data available and has reported efficacy lasting for up to 3 years when given in multiple injection sites every 3 months. Interestingly, although topiramate is used as a preventive medication, a recent study comparing erenumab vs topiramate for reducing monthly migraine days (MMD) showed that erenumab outperformed topiramate with a 50% reduction in MMD, and with fewer reported adverse events.

We are just starting to learn about some other potential cellular mechanisms that could be causing MOH in patients; these data could help create new and improved therapies for treating and possibly preventing MOH in the future. Patient outcomes could also be improved by encouraging the inclusion of MOH as part of a continuing education program for physicians who could potentially be treating new patients presenting with MOH. 

Medication overuse headache, previously known as rebound headache or medication-induced headache, may be caused by the frequent or excessive use of various acute care medications. When these medications are used too frequently, they can cause headaches rather than relieving them. (Some headache specialists feel that MOH is the result of recurring severe headaches, and the patients’ overuse of medications to relieve them.) These medications, some of which are painkillers or analgesics, include over-the-counter products such as acetaminophen, aspirin, and anti-inflammatories, as well as prescription medications such as triptans, ergots opioids, opioids, and barbiturates. The one category of acute care medication that does not seem to cause MOH is the gepants, such as rimegepant and ubrogepant.

MOH is the fourth most common headache disorder. It is defined by the International Classification of Headache Disorders (ICHD-3) as a headache present 15 days per month, evolving from regular use of strong acute medication (10 or more days of triptans, ergotamines, butalbital medications, opioids, or combination medications or 15 or more days per month of simple analgesics such as aspirin, acetaminophen, or nonsteroidal anti-inflammatories) for 3 months. 

Patients are usually not aware they have MOH, and this is the most problematic aspect of the condition. Patients do not realize that the medicine they are taking is making their headaches worse. It can be difficult to explain to the patient exactly what is going on with MOH, and why they are doing the wrong thing by taking the very medication that was prescribed by their doctor to stop a migraine attack. Many doctors do not fully understand MOH either, which can make it difficult to treat patients with this type of headache; therefore, it is imperative to educate both doctors and patients on the causes and treatments of MOH.

One of the most important facets of treating MOH traditionally has been the process of detoxifying patients from their overused medication by gradually or precipitously withdrawing the offending medication. There is variability in how detoxification can be accomplished. Some of my patients stopped medications abruptly and experienced very bad headaches. Others tried reducing dosages on their own and reported experiencing the worst headaches of their lives—some of which lasted for a few weeks. I have found that if patients can endure 2 to 3 weeks of detox, they start to feel better. But because the headaches can worsen before they get better, patients understandably try to avoid the detoxification process. 

I start patients on preventive medicine, then slowly increase it to an effective dose, and have them come back in a month for an evaluation. I then have them gradually reduce, but not completely stop, the pain medication before they return. Once I feel their preventive medication is at a therapeutic level, I have them begin a slow detox. After a month of preventive medication, there is a reasonable chance that headaches will start to decrease and be less severe. I tell them that if their headache is less severe try to avoid taking the medicine that they were overusing to prevent perpetuating the MOH.

One plausible physiologic mechanism behind MOH is that chronic exposure to acute care migraine treatment leads to suppression of the serotonergic/norepinephrinergic  endogenous antinociceptive system in the upper brain stem, with facilitation of the trigeminal nociceptive process via up-regulation of calcitonin gene-related peptide (CGRP).This increase in CGRP at the end of peripheral nerve terminals in the trigeminovascular system may facilitate pain transmission. An increase in cortical CGRP may cause cortical spreading depression: a wave of excitement traveling through the cortex, followed by a wave of electrical depression seems to cause headache.  

Good, effective prevention often helps avoid MOH; medications such as topiramate, nortriptyline, gabapentin, onabotulinumtoxinA, and CGRP monoclonal antibodies or some type of local nerve block have improved MOH in patients, but detoxification is usually necessary is some patients. 

Monoclonal antibodies targeting CGRP or its receptor (CGRP-R), given by subcutaneous or intravenous injection or small molecule CGRP receptor antagonists given orally (gepants), seem to be able to treat MOH in some patients without a detoxification. This has been best demonstrated in the monoclonal antibody group, but there is some evidence showing that it may also occur with gepants. These treatments seem to work even when patients are overusing acute care medications; this helps some patients to self-detoxify at their own pace, which is easier for both the patient and the doctor.

Currently, there are 4 monoclonal antibodies against CGRP or the CGRP-R. Erenumab is the only completely human one and the only antibody that blocks the CGRP receptor to prevent the CGRP ligand from docking and exerting its effect. The other 3 (fremanezumab, galcanezumab, and eptinezumab) are humanized monoclonal antibodies that selectively bind to the CGRP ligand, preventing it from docking on its receptor.  Patients started on the monoclonal antibodies against CGRP or its receptor usually have fewer headaches in the first week or two of therapy, and this helps make the self-detox easier for the patient. 

Further, substantial data have shown that onabotulinumtoxinA reduces the number/frequency of headaches and reduces the need for patients to take acute medication. OnabotulinumtoxinA is currently the only medication approved for preventive treatment of chronic migraine; it has long-term safety data available and has reported efficacy lasting for up to 3 years when given in multiple injection sites every 3 months. Interestingly, although topiramate is used as a preventive medication, a recent study comparing erenumab vs topiramate for reducing monthly migraine days (MMD) showed that erenumab outperformed topiramate with a 50% reduction in MMD, and with fewer reported adverse events.

We are just starting to learn about some other potential cellular mechanisms that could be causing MOH in patients; these data could help create new and improved therapies for treating and possibly preventing MOH in the future. Patient outcomes could also be improved by encouraging the inclusion of MOH as part of a continuing education program for physicians who could potentially be treating new patients presenting with MOH. 

People with higher dietary zinc intake have a nearly one-third lower risk of migraine than those who get little zinc in their diets, according to results from a cross-sectional study of more than 11,000 American adults.

For their research, published online in Headache, Huanxian Liu, MD, and colleagues at Chinese PLA General Hospital in Beijing, analyzed publicly available data from the U.S. National Health and Nutrition Examination Survey to determine whether people self-reporting migraine or severe headache saw lower zinc intake, compared with people without migraine. The data used in the analysis was collected between 1999 and 2004, and contained information on foods and drinks consumed by participants in a 24-hour period, along with additional health information.
 

An inverse relationship

The investigators divided their study’s 11,088 participants (mean age, 46.5 years; 50% female) into quintiles based on dietary zinc consumption as inferred from foods eaten. They also considered zinc supplementation, for which data was available for 4,324 participants, of whom 2,607 reported use of supplements containing zinc.

Some 20% of the cohort (n = 2,236) reported migraine or severe headache within the previous 3 months. Pregnant women were excluded from analysis, and the investigators adjusted for a range of covariates, including age, sex, ethnicity, education level, body mass, smoking, diabetes, cardiovascular disease, and nutritional factors.

Dr. Liu and colleagues reported an inverse association between dietary zinc consumption and migraine, with the highest-consuming quintile of the cohort (15.8 mg or more zinc per day) seeing lowest risk of migraine (odds ratio, 0.70; 95% confidence interval, 0.52-0.94; P = .029), compared with the low-consuming quintile (5.9 mg or less daily). Among people getting high levels of zinc (19.3-32.5 mg daily) through supplements, risk of migraine was lower still, to between an OR of 0.62 (95% CI: 0.46–0.83, P = 0.019) and an OR of 0.67 (95% CI, 0.49–0.91; P = .045).

While the investigators acknowledged limitations of the study, including its cross-sectional design and use of a broad question to discern prevalence of migraine, the findings suggest that “zinc is an important nutrient that influences migraine,” they wrote, citing evidence for its antioxidant and anti-inflammatory properties.
 

The importance of nutritional factors

Commenting on the research findings, Deborah I. Friedman, MD, MPH, a headache specialist in Dallas, said that Dr. Liu and colleagues’ findings added to a growing information base about nutritional factors and migraine. For example, “low magnesium levels are common in people with migraine, and magnesium supplementation is a recommended preventive treatment for migraine.”

Dr. Friedman cited a recent study showing that vitamin B₁₂ and magnesium supplementation in women (, combined with high-intensity interval training, “silenced” the inflammation signaling pathway, helped migraine pain and decreased levels of calcitonin gene-related peptide. A 2022 randomized trial found that alpha lipoic acid supplementation reduced migraine severity, frequency and disability in women with episodic migraine.

Vitamin D levels are also lower in people with migraine, compared with controls, Dr. Friedman noted, and a randomized trial of 2,000 IU of vitamin D₃ daily saw reduced monthly headache days, attack duration, severe headaches, and analgesic use, compared with placebo. Other nutrients implicated in migraine include coenzyme Q10, calcium, folic acid, vitamin B₆, and vitamin B₁.

“What should a patient with migraine do with all of this information? First, eat a healthy and balanced diet,” Dr. Friedman said. “Sources of dietary zinc include red meat, nuts, legumes, poultry, shellfish (especially oysters), whole grains, some cereals, and even dark chocolate. The recommended daily dosage of zinc is 9.5 mg in men and 7 mg in women. Most people get enough zinc in their diet; vegetarians, vegans, pregnant or breastfeeding women, and adults over age 65 may need to take supplemental zinc.”

Dr. Liu and colleagues’ work was supported by China’s National Natural Science Foundation. The investigators reported no financial conflicts of interest. Dr. Friedman has received financial support from Alder, Allergan, Amgen, Biohaven, Eli Lilly, Merck, Teva, and other pharmaceutical manufacturers.

People with higher dietary zinc intake have a nearly one-third lower risk of migraine than those who get little zinc in their diets, according to results from a cross-sectional study of more than 11,000 American adults.

For their research, published online in Headache, Huanxian Liu, MD, and colleagues at Chinese PLA General Hospital in Beijing, analyzed publicly available data from the U.S. National Health and Nutrition Examination Survey to determine whether people self-reporting migraine or severe headache saw lower zinc intake, compared with people without migraine. The data used in the analysis was collected between 1999 and 2004, and contained information on foods and drinks consumed by participants in a 24-hour period, along with additional health information.
 

An inverse relationship

The investigators divided their study’s 11,088 participants (mean age, 46.5 years; 50% female) into quintiles based on dietary zinc consumption as inferred from foods eaten. They also considered zinc supplementation, for which data was available for 4,324 participants, of whom 2,607 reported use of supplements containing zinc.

Some 20% of the cohort (n = 2,236) reported migraine or severe headache within the previous 3 months. Pregnant women were excluded from analysis, and the investigators adjusted for a range of covariates, including age, sex, ethnicity, education level, body mass, smoking, diabetes, cardiovascular disease, and nutritional factors.

Dr. Liu and colleagues reported an inverse association between dietary zinc consumption and migraine, with the highest-consuming quintile of the cohort (15.8 mg or more zinc per day) seeing lowest risk of migraine (odds ratio, 0.70; 95% confidence interval, 0.52-0.94; P = .029), compared with the low-consuming quintile (5.9 mg or less daily). Among people getting high levels of zinc (19.3-32.5 mg daily) through supplements, risk of migraine was lower still, to between an OR of 0.62 (95% CI: 0.46–0.83, P = 0.019) and an OR of 0.67 (95% CI, 0.49–0.91; P = .045).

While the investigators acknowledged limitations of the study, including its cross-sectional design and use of a broad question to discern prevalence of migraine, the findings suggest that “zinc is an important nutrient that influences migraine,” they wrote, citing evidence for its antioxidant and anti-inflammatory properties.
 

The importance of nutritional factors

Commenting on the research findings, Deborah I. Friedman, MD, MPH, a headache specialist in Dallas, said that Dr. Liu and colleagues’ findings added to a growing information base about nutritional factors and migraine. For example, “low magnesium levels are common in people with migraine, and magnesium supplementation is a recommended preventive treatment for migraine.”

Dr. Friedman cited a recent study showing that vitamin B₁₂ and magnesium supplementation in women (, combined with high-intensity interval training, “silenced” the inflammation signaling pathway, helped migraine pain and decreased levels of calcitonin gene-related peptide. A 2022 randomized trial found that alpha lipoic acid supplementation reduced migraine severity, frequency and disability in women with episodic migraine.

Vitamin D levels are also lower in people with migraine, compared with controls, Dr. Friedman noted, and a randomized trial of 2,000 IU of vitamin D₃ daily saw reduced monthly headache days, attack duration, severe headaches, and analgesic use, compared with placebo. Other nutrients implicated in migraine include coenzyme Q10, calcium, folic acid, vitamin B₆, and vitamin B₁.

“What should a patient with migraine do with all of this information? First, eat a healthy and balanced diet,” Dr. Friedman said. “Sources of dietary zinc include red meat, nuts, legumes, poultry, shellfish (especially oysters), whole grains, some cereals, and even dark chocolate. The recommended daily dosage of zinc is 9.5 mg in men and 7 mg in women. Most people get enough zinc in their diet; vegetarians, vegans, pregnant or breastfeeding women, and adults over age 65 may need to take supplemental zinc.”

Dr. Liu and colleagues’ work was supported by China’s National Natural Science Foundation. The investigators reported no financial conflicts of interest. Dr. Friedman has received financial support from Alder, Allergan, Amgen, Biohaven, Eli Lilly, Merck, Teva, and other pharmaceutical manufacturers.

People with higher dietary zinc intake have a nearly one-third lower risk of migraine than those who get little zinc in their diets, according to results from a cross-sectional study of more than 11,000 American adults.

For their research, published online in Headache, Huanxian Liu, MD, and colleagues at Chinese PLA General Hospital in Beijing, analyzed publicly available data from the U.S. National Health and Nutrition Examination Survey to determine whether people self-reporting migraine or severe headache saw lower zinc intake, compared with people without migraine. The data used in the analysis was collected between 1999 and 2004, and contained information on foods and drinks consumed by participants in a 24-hour period, along with additional health information.
 

An inverse relationship

The investigators divided their study’s 11,088 participants (mean age, 46.5 years; 50% female) into quintiles based on dietary zinc consumption as inferred from foods eaten. They also considered zinc supplementation, for which data was available for 4,324 participants, of whom 2,607 reported use of supplements containing zinc.

Some 20% of the cohort (n = 2,236) reported migraine or severe headache within the previous 3 months. Pregnant women were excluded from analysis, and the investigators adjusted for a range of covariates, including age, sex, ethnicity, education level, body mass, smoking, diabetes, cardiovascular disease, and nutritional factors.

Dr. Liu and colleagues reported an inverse association between dietary zinc consumption and migraine, with the highest-consuming quintile of the cohort (15.8 mg or more zinc per day) seeing lowest risk of migraine (odds ratio, 0.70; 95% confidence interval, 0.52-0.94; P = .029), compared with the low-consuming quintile (5.9 mg or less daily). Among people getting high levels of zinc (19.3-32.5 mg daily) through supplements, risk of migraine was lower still, to between an OR of 0.62 (95% CI: 0.46–0.83, P = 0.019) and an OR of 0.67 (95% CI, 0.49–0.91; P = .045).

While the investigators acknowledged limitations of the study, including its cross-sectional design and use of a broad question to discern prevalence of migraine, the findings suggest that “zinc is an important nutrient that influences migraine,” they wrote, citing evidence for its antioxidant and anti-inflammatory properties.
 

The importance of nutritional factors

Commenting on the research findings, Deborah I. Friedman, MD, MPH, a headache specialist in Dallas, said that Dr. Liu and colleagues’ findings added to a growing information base about nutritional factors and migraine. For example, “low magnesium levels are common in people with migraine, and magnesium supplementation is a recommended preventive treatment for migraine.”

Dr. Friedman cited a recent study showing that vitamin B₁₂ and magnesium supplementation in women (, combined with high-intensity interval training, “silenced” the inflammation signaling pathway, helped migraine pain and decreased levels of calcitonin gene-related peptide. A 2022 randomized trial found that alpha lipoic acid supplementation reduced migraine severity, frequency and disability in women with episodic migraine.

Vitamin D levels are also lower in people with migraine, compared with controls, Dr. Friedman noted, and a randomized trial of 2,000 IU of vitamin D₃ daily saw reduced monthly headache days, attack duration, severe headaches, and analgesic use, compared with placebo. Other nutrients implicated in migraine include coenzyme Q10, calcium, folic acid, vitamin B₆, and vitamin B₁.

“What should a patient with migraine do with all of this information? First, eat a healthy and balanced diet,” Dr. Friedman said. “Sources of dietary zinc include red meat, nuts, legumes, poultry, shellfish (especially oysters), whole grains, some cereals, and even dark chocolate. The recommended daily dosage of zinc is 9.5 mg in men and 7 mg in women. Most people get enough zinc in their diet; vegetarians, vegans, pregnant or breastfeeding women, and adults over age 65 may need to take supplemental zinc.”

Dr. Liu and colleagues’ work was supported by China’s National Natural Science Foundation. The investigators reported no financial conflicts of interest. Dr. Friedman has received financial support from Alder, Allergan, Amgen, Biohaven, Eli Lilly, Merck, Teva, and other pharmaceutical manufacturers.

January's theme is migraine triggers. We'll take a look at three recent studies that have tried to better determine the nature of specific triggers for headache.

One of the most common and reportedly consistent migraine triggers is exposure to alcohol, and the International Classification of Headache Disorders (ICHD-3) includes alcohol-induced headache as a secondary headache. Little is known regarding the association between migraine and alcohol. Vives-Mestres and colleagues investigated the alcohol intake of people using a digital health diary for headache. They specifically looked at the 48 hours preceding a migraine attack and whether alcohol was consumed, and also the number of beverages consumed. This was further adjusted for sex, age, and average weekly alcohol intake.

The N1-Headache Tracker is a digital headache diary that patients use to track their daily headache symptoms and inform them of potential migraine risk factors. Over a 90-day period, this study followed patients that did not meet the criteria for a diagnosis of chronic migraine. They also reported on their intake to the platform that they regularly consume alcohol. Of note, persons who never tracked alcohol consumption were excluded from this study. On intake to the platform, alcohol exposure was characterized both as whether daily consumption of alcohol was occurring and as the total daily number of alcoholic beverages.

The primary outcome of this study was migraine attack 1 day after alcohol consumption. Participants were specifically asked if their headaches were diagnosed as migraine by a physician. Migraine attack onset was considered binary, and a logistic model was used to estimate the probability of having a migraine attack on any given day with the association of alcohol intake for up to 48 hours prior to that day.

A total of 487 people with migraine were included in this trial and they collectively contributed over 43,000 diary days; almost 6000 were first days of a migraine attack. Overall alcohol consumption was not considered high and was noted to vary between groups; people with lower frequency migraine tended to have higher rates of alcohol intake. No significant correlation was observed between the presence of migraine attacks within 48 hours after alcohol consumption. This did not vary among different probability models; a population-level model showed that the probability of a migraine attack 2 days after alcohol intake was 25% lower than the probability of an attack with no alcohol consumption. This was also true after adjustment for age, sex, and average number of alcoholic beverages per week.

The association between migraine and alcohol is complicated, and the concept of migraine triggers in general is very complex. Although over 70% of people with migraine say that they have a consistent trigger, and alcohol is consistently at the top of the list of those reported triggers, there does not appear to be a direct correlation between migraine and alcohol exposure. The greatest caveat of this study is the fact that people with chronic migraine were excluded. Further research should specifically investigate triggers such as alcohol in this population.

The use of proton pump inhibitors (PPI) has been shown in previous studies over the past few years to be associated with a number of neurologic events and risks, including impaired hearing, vision, and memory, as well as migraine occurrence. The specifics of this association are not well known — specifically, whether the duration of use is the main factor, or whether it is acute exposure to a PPI medication that is a trigger. Kang and colleagues reviewed data in the Korean national database and developed a case-control model to study this association specifically.

The migraine and control groups were equally matched: They had the same demographics, smoking status, alcohol consumption, blood pressure range, fasting glucose, and total cholesterol. Past and current PPI use and comparisons of migraine occurrence were further differentiated among patients who were exposed to PPI medications for < 30 days, 30-365 days, and > 365 days.

The use of PPI treatments was noted to be linked to increased migraine regardless of duration, and regardless of the acute presence of the PPI. Even a history of prior PPI use was noted to increase the odds ratio of migraine development. This was significant among all subgroups, independent of age, sex, and other comorbidities. There was no difference in the presence of aura associated with migraine.

As we noted above, the concept of migraine triggers is overall poorly understood. This is even more the case when it comes to historical exposures. Although the use of PPI medications appears to be associated with the occurrence of migraine in this population, these medications are necessary in many instances, including in patients with severe gastritis and gastroesophageal reflux refractory to diet changes. It remains to be seen precisely how PPI medications would potentially lead to a higher incidence of migraine.

Among many of the triggers discussed, specific foods are commonly thought to be associated with migraine. Although there is scant evidence for a specific diet to improve migraine frequency, many patients are very interested in potential dietary changes that may help them. Prior studies and reviews have looked at gluten-free, dairy-free, low-carbohydrate, low-tyramine, and elimination diets — all of which were not associated with a significant improvement in migraine frequency or severity. Bakıran and colleagues sought to investigate an antioxidant-rich diet that included polyphenols and carotenoids — substances that may improve systemic inflammation, glucose metabolism, and oxidative stress.

Phytochemical-rich foods include fruits and vegetables (excluding potatoes) as well as nuts, whole grains, pulses, and olive oil. The phytochemical index is a tool used by dietitians and nutritionists to assess the phytochemical content in a diet.

A total of 90 patients who had a diagnosis of episodic migraine by a neurologist were enrolled. Individuals were excluded if they had a body mass index > 40 or < 18 or had other significant chronic comorbidities, such as hypertension, diabetes, hepatic or renal disease, or other neurologic conditions. Participants filled out a headache diary over 3 months; the Migraine Disability Assessment (MIDAS) questionnaire was also followed in order to assess migraine-related disability. Diet quality was cataloged as per patient records; patients also filled out a 3-day nonconsecutive food diary. This information was added to a food software program that calculated specific nutrients, including the phytochemical index.

Participants were divided into groups with good diet quality and poor diet quality based on their phytochemical index. No differences were seen in migraine frequency or disability between these groups, although mean attack duration was lower in those with poor diet quality. Severity was noted to be higher in those with poor diet quality; 75% of participants with poor diet quality experienced severe attacks.

Overall, the results of this study are very mixed. Participants on the recommended high phytochemical diet were seen to have lower severity of migraine but a prolonged duration of attack. There also was no correlation between this diet and either frequency or disability. This was a small study, and further research should focus on this among other diet changes that have the possibility to improve the quality of life of people with migraine.

January's theme is migraine triggers. We'll take a look at three recent studies that have tried to better determine the nature of specific triggers for headache.

One of the most common and reportedly consistent migraine triggers is exposure to alcohol, and the International Classification of Headache Disorders (ICHD-3) includes alcohol-induced headache as a secondary headache. Little is known regarding the association between migraine and alcohol. Vives-Mestres and colleagues investigated the alcohol intake of people using a digital health diary for headache. They specifically looked at the 48 hours preceding a migraine attack and whether alcohol was consumed, and also the number of beverages consumed. This was further adjusted for sex, age, and average weekly alcohol intake.

The N1-Headache Tracker is a digital headache diary that patients use to track their daily headache symptoms and inform them of potential migraine risk factors. Over a 90-day period, this study followed patients that did not meet the criteria for a diagnosis of chronic migraine. They also reported on their intake to the platform that they regularly consume alcohol. Of note, persons who never tracked alcohol consumption were excluded from this study. On intake to the platform, alcohol exposure was characterized both as whether daily consumption of alcohol was occurring and as the total daily number of alcoholic beverages.

The primary outcome of this study was migraine attack 1 day after alcohol consumption. Participants were specifically asked if their headaches were diagnosed as migraine by a physician. Migraine attack onset was considered binary, and a logistic model was used to estimate the probability of having a migraine attack on any given day with the association of alcohol intake for up to 48 hours prior to that day.

A total of 487 people with migraine were included in this trial and they collectively contributed over 43,000 diary days; almost 6000 were first days of a migraine attack. Overall alcohol consumption was not considered high and was noted to vary between groups; people with lower frequency migraine tended to have higher rates of alcohol intake. No significant correlation was observed between the presence of migraine attacks within 48 hours after alcohol consumption. This did not vary among different probability models; a population-level model showed that the probability of a migraine attack 2 days after alcohol intake was 25% lower than the probability of an attack with no alcohol consumption. This was also true after adjustment for age, sex, and average number of alcoholic beverages per week.

The association between migraine and alcohol is complicated, and the concept of migraine triggers in general is very complex. Although over 70% of people with migraine say that they have a consistent trigger, and alcohol is consistently at the top of the list of those reported triggers, there does not appear to be a direct correlation between migraine and alcohol exposure. The greatest caveat of this study is the fact that people with chronic migraine were excluded. Further research should specifically investigate triggers such as alcohol in this population.

The use of proton pump inhibitors (PPI) has been shown in previous studies over the past few years to be associated with a number of neurologic events and risks, including impaired hearing, vision, and memory, as well as migraine occurrence. The specifics of this association are not well known — specifically, whether the duration of use is the main factor, or whether it is acute exposure to a PPI medication that is a trigger. Kang and colleagues reviewed data in the Korean national database and developed a case-control model to study this association specifically.

The migraine and control groups were equally matched: They had the same demographics, smoking status, alcohol consumption, blood pressure range, fasting glucose, and total cholesterol. Past and current PPI use and comparisons of migraine occurrence were further differentiated among patients who were exposed to PPI medications for < 30 days, 30-365 days, and > 365 days.

The use of PPI treatments was noted to be linked to increased migraine regardless of duration, and regardless of the acute presence of the PPI. Even a history of prior PPI use was noted to increase the odds ratio of migraine development. This was significant among all subgroups, independent of age, sex, and other comorbidities. There was no difference in the presence of aura associated with migraine.

As we noted above, the concept of migraine triggers is overall poorly understood. This is even more the case when it comes to historical exposures. Although the use of PPI medications appears to be associated with the occurrence of migraine in this population, these medications are necessary in many instances, including in patients with severe gastritis and gastroesophageal reflux refractory to diet changes. It remains to be seen precisely how PPI medications would potentially lead to a higher incidence of migraine.

Among many of the triggers discussed, specific foods are commonly thought to be associated with migraine. Although there is scant evidence for a specific diet to improve migraine frequency, many patients are very interested in potential dietary changes that may help them. Prior studies and reviews have looked at gluten-free, dairy-free, low-carbohydrate, low-tyramine, and elimination diets — all of which were not associated with a significant improvement in migraine frequency or severity. Bakıran and colleagues sought to investigate an antioxidant-rich diet that included polyphenols and carotenoids — substances that may improve systemic inflammation, glucose metabolism, and oxidative stress.

Phytochemical-rich foods include fruits and vegetables (excluding potatoes) as well as nuts, whole grains, pulses, and olive oil. The phytochemical index is a tool used by dietitians and nutritionists to assess the phytochemical content in a diet.

A total of 90 patients who had a diagnosis of episodic migraine by a neurologist were enrolled. Individuals were excluded if they had a body mass index > 40 or < 18 or had other significant chronic comorbidities, such as hypertension, diabetes, hepatic or renal disease, or other neurologic conditions. Participants filled out a headache diary over 3 months; the Migraine Disability Assessment (MIDAS) questionnaire was also followed in order to assess migraine-related disability. Diet quality was cataloged as per patient records; patients also filled out a 3-day nonconsecutive food diary. This information was added to a food software program that calculated specific nutrients, including the phytochemical index.

Participants were divided into groups with good diet quality and poor diet quality based on their phytochemical index. No differences were seen in migraine frequency or disability between these groups, although mean attack duration was lower in those with poor diet quality. Severity was noted to be higher in those with poor diet quality; 75% of participants with poor diet quality experienced severe attacks.

Overall, the results of this study are very mixed. Participants on the recommended high phytochemical diet were seen to have lower severity of migraine but a prolonged duration of attack. There also was no correlation between this diet and either frequency or disability. This was a small study, and further research should focus on this among other diet changes that have the possibility to improve the quality of life of people with migraine.

January's theme is migraine triggers. We'll take a look at three recent studies that have tried to better determine the nature of specific triggers for headache.

One of the most common and reportedly consistent migraine triggers is exposure to alcohol, and the International Classification of Headache Disorders (ICHD-3) includes alcohol-induced headache as a secondary headache. Little is known regarding the association between migraine and alcohol. Vives-Mestres and colleagues investigated the alcohol intake of people using a digital health diary for headache. They specifically looked at the 48 hours preceding a migraine attack and whether alcohol was consumed, and also the number of beverages consumed. This was further adjusted for sex, age, and average weekly alcohol intake.

The N1-Headache Tracker is a digital headache diary that patients use to track their daily headache symptoms and inform them of potential migraine risk factors. Over a 90-day period, this study followed patients that did not meet the criteria for a diagnosis of chronic migraine. They also reported on their intake to the platform that they regularly consume alcohol. Of note, persons who never tracked alcohol consumption were excluded from this study. On intake to the platform, alcohol exposure was characterized both as whether daily consumption of alcohol was occurring and as the total daily number of alcoholic beverages.

The primary outcome of this study was migraine attack 1 day after alcohol consumption. Participants were specifically asked if their headaches were diagnosed as migraine by a physician. Migraine attack onset was considered binary, and a logistic model was used to estimate the probability of having a migraine attack on any given day with the association of alcohol intake for up to 48 hours prior to that day.

A total of 487 people with migraine were included in this trial and they collectively contributed over 43,000 diary days; almost 6000 were first days of a migraine attack. Overall alcohol consumption was not considered high and was noted to vary between groups; people with lower frequency migraine tended to have higher rates of alcohol intake. No significant correlation was observed between the presence of migraine attacks within 48 hours after alcohol consumption. This did not vary among different probability models; a population-level model showed that the probability of a migraine attack 2 days after alcohol intake was 25% lower than the probability of an attack with no alcohol consumption. This was also true after adjustment for age, sex, and average number of alcoholic beverages per week.

The association between migraine and alcohol is complicated, and the concept of migraine triggers in general is very complex. Although over 70% of people with migraine say that they have a consistent trigger, and alcohol is consistently at the top of the list of those reported triggers, there does not appear to be a direct correlation between migraine and alcohol exposure. The greatest caveat of this study is the fact that people with chronic migraine were excluded. Further research should specifically investigate triggers such as alcohol in this population.

The use of proton pump inhibitors (PPI) has been shown in previous studies over the past few years to be associated with a number of neurologic events and risks, including impaired hearing, vision, and memory, as well as migraine occurrence. The specifics of this association are not well known — specifically, whether the duration of use is the main factor, or whether it is acute exposure to a PPI medication that is a trigger. Kang and colleagues reviewed data in the Korean national database and developed a case-control model to study this association specifically.

The migraine and control groups were equally matched: They had the same demographics, smoking status, alcohol consumption, blood pressure range, fasting glucose, and total cholesterol. Past and current PPI use and comparisons of migraine occurrence were further differentiated among patients who were exposed to PPI medications for < 30 days, 30-365 days, and > 365 days.

The use of PPI treatments was noted to be linked to increased migraine regardless of duration, and regardless of the acute presence of the PPI. Even a history of prior PPI use was noted to increase the odds ratio of migraine development. This was significant among all subgroups, independent of age, sex, and other comorbidities. There was no difference in the presence of aura associated with migraine.

As we noted above, the concept of migraine triggers is overall poorly understood. This is even more the case when it comes to historical exposures. Although the use of PPI medications appears to be associated with the occurrence of migraine in this population, these medications are necessary in many instances, including in patients with severe gastritis and gastroesophageal reflux refractory to diet changes. It remains to be seen precisely how PPI medications would potentially lead to a higher incidence of migraine.

Among many of the triggers discussed, specific foods are commonly thought to be associated with migraine. Although there is scant evidence for a specific diet to improve migraine frequency, many patients are very interested in potential dietary changes that may help them. Prior studies and reviews have looked at gluten-free, dairy-free, low-carbohydrate, low-tyramine, and elimination diets — all of which were not associated with a significant improvement in migraine frequency or severity. Bakıran and colleagues sought to investigate an antioxidant-rich diet that included polyphenols and carotenoids — substances that may improve systemic inflammation, glucose metabolism, and oxidative stress.

Phytochemical-rich foods include fruits and vegetables (excluding potatoes) as well as nuts, whole grains, pulses, and olive oil. The phytochemical index is a tool used by dietitians and nutritionists to assess the phytochemical content in a diet.

A total of 90 patients who had a diagnosis of episodic migraine by a neurologist were enrolled. Individuals were excluded if they had a body mass index > 40 or < 18 or had other significant chronic comorbidities, such as hypertension, diabetes, hepatic or renal disease, or other neurologic conditions. Participants filled out a headache diary over 3 months; the Migraine Disability Assessment (MIDAS) questionnaire was also followed in order to assess migraine-related disability. Diet quality was cataloged as per patient records; patients also filled out a 3-day nonconsecutive food diary. This information was added to a food software program that calculated specific nutrients, including the phytochemical index.

Participants were divided into groups with good diet quality and poor diet quality based on their phytochemical index. No differences were seen in migraine frequency or disability between these groups, although mean attack duration was lower in those with poor diet quality. Severity was noted to be higher in those with poor diet quality; 75% of participants with poor diet quality experienced severe attacks.

Overall, the results of this study are very mixed. Participants on the recommended high phytochemical diet were seen to have lower severity of migraine but a prolonged duration of attack. There also was no correlation between this diet and either frequency or disability. This was a small study, and further research should focus on this among other diet changes that have the possibility to improve the quality of life of people with migraine.

Cluster headache is associated with a significantly increased risk for comorbid conditions, including mental disorders and other neurologic disease, leading to significant disability and absenteeism, new research shows.

Results from a Swedish register-based study also showed that patients with cluster headache had a sixfold increased risk for central nervous system disorders and a twofold increased risk for musculoskeletal disorders.

Although cluster headaches are often more prevalent in men, researchers found that multimorbidity rates were significantly higher in women. In addition, rates of external injuries were significantly higher among individuals with cluster headache than among persons without cluster headache.

“The findings very clearly indicate that cluster headache patients suffer from other health issues as well and that they are at risk of having longer periods of times when they cannot work,” said lead investigator Caroline Ran, PhD, a research specialist in the department of neuroscience at the Karolinska Institutet, Stockholm.

“It’s really important for clinicians to look at cluster headache from a broader perspective and make sure that patients are followed up so that they don’t risk ending up in a situation where they have several comorbidities,” Dr. Ran added.

The findings were published online in Neurology.
 

‘Striking’ finding

Cluster headache is one of the most severe and debilitating types of headache. It causes intense pain behind the eyes, which has been described as being worse than pain associated with childbirth or kidney stones.

Attacks can occur multiple times in a single day and can last up to 3 hours. Cluster headache is rare, occurring in about 1 in 1,000 individuals, and is more common in men. Underdiagnosis is common – especially in women.

The study drew on two Swedish population-based registries and included 3,240 patients with cluster headache aged 16-64 years and 16,200 matched control persons. The analysis covered medical visits from 2001 to 2010.

Results showed that 91.9% of participants with cluster headache had some type of multimorbidity. By comparison, 77.6% of the control group had some type of multimorbidity (odds ratio, 3.26; P < .0001).

Prior studies have shown a higher incidence of mental health and behavioral disorders among patients with cluster headache. However, when the researchers removed those conditions along with external injuries from the dataset, patients with headache were still significantly more likely to have multiple co-occurring illnesses (86.7% vs. 68.8%; OR, 2.95; P < .0001).

The most common comorbid conditions in the overall cluster headache group were diseases of the nervous system (OR, 5.9; 95% CI, 5.46 -6.42); 51.8% of the cluster headache group reported these disorders, compared with just 15.4% of the control group.

Diseases of the eye, the respiratory, gastrointestinal, and musculoskeletal systems, and connective tissue were also significantly more common among patients with cluster headache.

“For each diagnosis that we investigated, we found a higher incidence in the cluster headache group, and we thought this was a very striking finding and worth discussing in the clinical setting that these patients are at risk of general ill health,” Dr. Ran said.
 

Risky behavior?

Another novel finding was the higher rate of external injuries among the cluster headache group, compared with the control group. The finding seems to back up the theory that patients with cluster headache are more likely to engage in risky behaviors, the researchers noted.

In the cluster headache group, external injuries were reported by 47.1% of men and 41% of women, versus 34.9% and 26.0%, respectively, in the control group.

“Now we can also show that cluster headache patients have more injuries and that is totally unrelated to the biological health of the individuals, so that could also indicate higher risk taking,” Dr. Ran said.

Overall multimorbidity rates and diagnoses in each medical category except external injury were higher among women with cluster headache than men with headaches. In addition, the mean number of days on sick leave and disability pension was higher among women with cluster headache than among men with cluster headache (83.71 days vs. 52.56 days).

Overall, the mean number of sickness absence and disability pension net days in 2010 was nearly twice as high in the cluster headache group as in the control group (63.15 days vs. 34.08 days).

Removing mental and behavioral health disorders from the mix did not lower those numbers.

“Our numbers indicate that the mental health issues that are related to cluster headache might not impact their work situation as much as the other comorbidities,” Dr. Ran said.
 

Struggle is real

Commenting on the findings, Heidi Schwarz, MD, professor of clinical neurology at the University of Rochester (N.Y.) Medical Center, called the study a “valuable contribution” to the field and to the treatment of cluster headache.

“It’s a good study that addresses factors that really need to be considered as you take care of these patients,” said Dr. Schwarz, who was not involved with the research.

“The most salient features of this is that cluster headache is quite disabling, and if you add a comorbidity to it, it’s even more disabling,” she said.

Dr. Schwarz noted that cluster headache is often misdiagnosed as migraine or is overlooked altogether, especially in women. These data underscore that, although cluster headache is more common in men, it affects women too and could lead to even greater disability.

“This has a direct impact on patient quality of life, and in the end, that really should be what we’re looking to enhance,” Dr. Schwarz said. “When a patient with cluster comes in and they tell you they’re really struggling, believe them because it’s quite real.”

The findings also fill a gap in the literature and offer the kind of data that could not be collected in the United States, she noted. Sweden provides paid sick time for all workers aged 16 and older and offers a disability pension to all workers whose ability to work is temporarily or permanently inhibited because of illness or injury.

“You will never get this kind of data in the United States because this kind of data comes from two datasets that are extremely inclusive and detailed in a society, Sweden, where they have a social support system,” Dr. Schwarz said.

The study was funded by the Swedish Research Council, the Swedish Brain Foundation, and Mellby Gård, Region Stockholm, Märta Lundkvist stiftelse and Karolinska Institutet research funds. Dr. Ran and Dr. Schwarz report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Cluster headache is associated with a significantly increased risk for comorbid conditions, including mental disorders and other neurologic disease, leading to significant disability and absenteeism, new research shows.

Results from a Swedish register-based study also showed that patients with cluster headache had a sixfold increased risk for central nervous system disorders and a twofold increased risk for musculoskeletal disorders.

Although cluster headaches are often more prevalent in men, researchers found that multimorbidity rates were significantly higher in women. In addition, rates of external injuries were significantly higher among individuals with cluster headache than among persons without cluster headache.

“The findings very clearly indicate that cluster headache patients suffer from other health issues as well and that they are at risk of having longer periods of times when they cannot work,” said lead investigator Caroline Ran, PhD, a research specialist in the department of neuroscience at the Karolinska Institutet, Stockholm.

“It’s really important for clinicians to look at cluster headache from a broader perspective and make sure that patients are followed up so that they don’t risk ending up in a situation where they have several comorbidities,” Dr. Ran added.

The findings were published online in Neurology.
 

‘Striking’ finding

Cluster headache is one of the most severe and debilitating types of headache. It causes intense pain behind the eyes, which has been described as being worse than pain associated with childbirth or kidney stones.

Attacks can occur multiple times in a single day and can last up to 3 hours. Cluster headache is rare, occurring in about 1 in 1,000 individuals, and is more common in men. Underdiagnosis is common – especially in women.

The study drew on two Swedish population-based registries and included 3,240 patients with cluster headache aged 16-64 years and 16,200 matched control persons. The analysis covered medical visits from 2001 to 2010.

Results showed that 91.9% of participants with cluster headache had some type of multimorbidity. By comparison, 77.6% of the control group had some type of multimorbidity (odds ratio, 3.26; P < .0001).

Prior studies have shown a higher incidence of mental health and behavioral disorders among patients with cluster headache. However, when the researchers removed those conditions along with external injuries from the dataset, patients with headache were still significantly more likely to have multiple co-occurring illnesses (86.7% vs. 68.8%; OR, 2.95; P < .0001).

The most common comorbid conditions in the overall cluster headache group were diseases of the nervous system (OR, 5.9; 95% CI, 5.46 -6.42); 51.8% of the cluster headache group reported these disorders, compared with just 15.4% of the control group.

Diseases of the eye, the respiratory, gastrointestinal, and musculoskeletal systems, and connective tissue were also significantly more common among patients with cluster headache.

“For each diagnosis that we investigated, we found a higher incidence in the cluster headache group, and we thought this was a very striking finding and worth discussing in the clinical setting that these patients are at risk of general ill health,” Dr. Ran said.
 

Risky behavior?

Another novel finding was the higher rate of external injuries among the cluster headache group, compared with the control group. The finding seems to back up the theory that patients with cluster headache are more likely to engage in risky behaviors, the researchers noted.

In the cluster headache group, external injuries were reported by 47.1% of men and 41% of women, versus 34.9% and 26.0%, respectively, in the control group.

“Now we can also show that cluster headache patients have more injuries and that is totally unrelated to the biological health of the individuals, so that could also indicate higher risk taking,” Dr. Ran said.

Overall multimorbidity rates and diagnoses in each medical category except external injury were higher among women with cluster headache than men with headaches. In addition, the mean number of days on sick leave and disability pension was higher among women with cluster headache than among men with cluster headache (83.71 days vs. 52.56 days).

Overall, the mean number of sickness absence and disability pension net days in 2010 was nearly twice as high in the cluster headache group as in the control group (63.15 days vs. 34.08 days).

Removing mental and behavioral health disorders from the mix did not lower those numbers.

“Our numbers indicate that the mental health issues that are related to cluster headache might not impact their work situation as much as the other comorbidities,” Dr. Ran said.
 

Struggle is real

Commenting on the findings, Heidi Schwarz, MD, professor of clinical neurology at the University of Rochester (N.Y.) Medical Center, called the study a “valuable contribution” to the field and to the treatment of cluster headache.

“It’s a good study that addresses factors that really need to be considered as you take care of these patients,” said Dr. Schwarz, who was not involved with the research.

“The most salient features of this is that cluster headache is quite disabling, and if you add a comorbidity to it, it’s even more disabling,” she said.

Dr. Schwarz noted that cluster headache is often misdiagnosed as migraine or is overlooked altogether, especially in women. These data underscore that, although cluster headache is more common in men, it affects women too and could lead to even greater disability.

“This has a direct impact on patient quality of life, and in the end, that really should be what we’re looking to enhance,” Dr. Schwarz said. “When a patient with cluster comes in and they tell you they’re really struggling, believe them because it’s quite real.”

The findings also fill a gap in the literature and offer the kind of data that could not be collected in the United States, she noted. Sweden provides paid sick time for all workers aged 16 and older and offers a disability pension to all workers whose ability to work is temporarily or permanently inhibited because of illness or injury.

“You will never get this kind of data in the United States because this kind of data comes from two datasets that are extremely inclusive and detailed in a society, Sweden, where they have a social support system,” Dr. Schwarz said.

The study was funded by the Swedish Research Council, the Swedish Brain Foundation, and Mellby Gård, Region Stockholm, Märta Lundkvist stiftelse and Karolinska Institutet research funds. Dr. Ran and Dr. Schwarz report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Cluster headache is associated with a significantly increased risk for comorbid conditions, including mental disorders and other neurologic disease, leading to significant disability and absenteeism, new research shows.

Results from a Swedish register-based study also showed that patients with cluster headache had a sixfold increased risk for central nervous system disorders and a twofold increased risk for musculoskeletal disorders.

Although cluster headaches are often more prevalent in men, researchers found that multimorbidity rates were significantly higher in women. In addition, rates of external injuries were significantly higher among individuals with cluster headache than among persons without cluster headache.

“The findings very clearly indicate that cluster headache patients suffer from other health issues as well and that they are at risk of having longer periods of times when they cannot work,” said lead investigator Caroline Ran, PhD, a research specialist in the department of neuroscience at the Karolinska Institutet, Stockholm.

“It’s really important for clinicians to look at cluster headache from a broader perspective and make sure that patients are followed up so that they don’t risk ending up in a situation where they have several comorbidities,” Dr. Ran added.

The findings were published online in Neurology.
 

‘Striking’ finding

Cluster headache is one of the most severe and debilitating types of headache. It causes intense pain behind the eyes, which has been described as being worse than pain associated with childbirth or kidney stones.

Attacks can occur multiple times in a single day and can last up to 3 hours. Cluster headache is rare, occurring in about 1 in 1,000 individuals, and is more common in men. Underdiagnosis is common – especially in women.

The study drew on two Swedish population-based registries and included 3,240 patients with cluster headache aged 16-64 years and 16,200 matched control persons. The analysis covered medical visits from 2001 to 2010.

Results showed that 91.9% of participants with cluster headache had some type of multimorbidity. By comparison, 77.6% of the control group had some type of multimorbidity (odds ratio, 3.26; P < .0001).

Prior studies have shown a higher incidence of mental health and behavioral disorders among patients with cluster headache. However, when the researchers removed those conditions along with external injuries from the dataset, patients with headache were still significantly more likely to have multiple co-occurring illnesses (86.7% vs. 68.8%; OR, 2.95; P < .0001).

The most common comorbid conditions in the overall cluster headache group were diseases of the nervous system (OR, 5.9; 95% CI, 5.46 -6.42); 51.8% of the cluster headache group reported these disorders, compared with just 15.4% of the control group.

Diseases of the eye, the respiratory, gastrointestinal, and musculoskeletal systems, and connective tissue were also significantly more common among patients with cluster headache.

“For each diagnosis that we investigated, we found a higher incidence in the cluster headache group, and we thought this was a very striking finding and worth discussing in the clinical setting that these patients are at risk of general ill health,” Dr. Ran said.
 

Risky behavior?

Another novel finding was the higher rate of external injuries among the cluster headache group, compared with the control group. The finding seems to back up the theory that patients with cluster headache are more likely to engage in risky behaviors, the researchers noted.

In the cluster headache group, external injuries were reported by 47.1% of men and 41% of women, versus 34.9% and 26.0%, respectively, in the control group.

“Now we can also show that cluster headache patients have more injuries and that is totally unrelated to the biological health of the individuals, so that could also indicate higher risk taking,” Dr. Ran said.

Overall multimorbidity rates and diagnoses in each medical category except external injury were higher among women with cluster headache than men with headaches. In addition, the mean number of days on sick leave and disability pension was higher among women with cluster headache than among men with cluster headache (83.71 days vs. 52.56 days).

Overall, the mean number of sickness absence and disability pension net days in 2010 was nearly twice as high in the cluster headache group as in the control group (63.15 days vs. 34.08 days).

Removing mental and behavioral health disorders from the mix did not lower those numbers.

“Our numbers indicate that the mental health issues that are related to cluster headache might not impact their work situation as much as the other comorbidities,” Dr. Ran said.
 

Struggle is real

Commenting on the findings, Heidi Schwarz, MD, professor of clinical neurology at the University of Rochester (N.Y.) Medical Center, called the study a “valuable contribution” to the field and to the treatment of cluster headache.

“It’s a good study that addresses factors that really need to be considered as you take care of these patients,” said Dr. Schwarz, who was not involved with the research.

“The most salient features of this is that cluster headache is quite disabling, and if you add a comorbidity to it, it’s even more disabling,” she said.

Dr. Schwarz noted that cluster headache is often misdiagnosed as migraine or is overlooked altogether, especially in women. These data underscore that, although cluster headache is more common in men, it affects women too and could lead to even greater disability.

“This has a direct impact on patient quality of life, and in the end, that really should be what we’re looking to enhance,” Dr. Schwarz said. “When a patient with cluster comes in and they tell you they’re really struggling, believe them because it’s quite real.”

The findings also fill a gap in the literature and offer the kind of data that could not be collected in the United States, she noted. Sweden provides paid sick time for all workers aged 16 and older and offers a disability pension to all workers whose ability to work is temporarily or permanently inhibited because of illness or injury.

“You will never get this kind of data in the United States because this kind of data comes from two datasets that are extremely inclusive and detailed in a society, Sweden, where they have a social support system,” Dr. Schwarz said.

The study was funded by the Swedish Research Council, the Swedish Brain Foundation, and Mellby Gård, Region Stockholm, Märta Lundkvist stiftelse and Karolinska Institutet research funds. Dr. Ran and Dr. Schwarz report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Key clinical point: Migraine or severe headache is a significant risk factor for cardiovascular diseases and significantly increases the risk for angina and stroke.

Major finding: Migraine or severe headache increased the overall risk for cardiovascular diseases (adjusted odds ratio [aOR] 2.77; P = .001), angina (aOR 2.27; P = .046), and stroke (aOR 3.80; P = .006), with the increased risk for cardiovascular diseases being the most prominent among participants with migraine who were women (aOR 6.02; P < .001), aged >60 years (aOR 2.69; P = .049), or had hypertension (aOR 3.57; P < .001) or hyperlipidemia (aOR 2.74; P = .003).

Study details: This cross-sectional study evaluated 5692 participants from the US National Health and Nutrition Examination Survey (NHANES), of which 1090 had migraine or severe headache.

Disclosures: This study was supported by grants from the National Natural Science Foundation of China and the Natural Science Foundation of Jiangsu Province. The authors declared no conflicts of interest.

Source: Wang K et al. Association between migraine and cardiovascular disease: A cross-sectional study. Front Cardiovasc Med. 2022;9:1044465 (Nov 24). Doi: 10.3389/fcvm.2022.1044465

Key clinical point: Migraine or severe headache is a significant risk factor for cardiovascular diseases and significantly increases the risk for angina and stroke.

Major finding: Migraine or severe headache increased the overall risk for cardiovascular diseases (adjusted odds ratio [aOR] 2.77; P = .001), angina (aOR 2.27; P = .046), and stroke (aOR 3.80; P = .006), with the increased risk for cardiovascular diseases being the most prominent among participants with migraine who were women (aOR 6.02; P < .001), aged >60 years (aOR 2.69; P = .049), or had hypertension (aOR 3.57; P < .001) or hyperlipidemia (aOR 2.74; P = .003).

Study details: This cross-sectional study evaluated 5692 participants from the US National Health and Nutrition Examination Survey (NHANES), of which 1090 had migraine or severe headache.

Disclosures: This study was supported by grants from the National Natural Science Foundation of China and the Natural Science Foundation of Jiangsu Province. The authors declared no conflicts of interest.

Source: Wang K et al. Association between migraine and cardiovascular disease: A cross-sectional study. Front Cardiovasc Med. 2022;9:1044465 (Nov 24). Doi: 10.3389/fcvm.2022.1044465

Key clinical point: Migraine or severe headache is a significant risk factor for cardiovascular diseases and significantly increases the risk for angina and stroke.

Major finding: Migraine or severe headache increased the overall risk for cardiovascular diseases (adjusted odds ratio [aOR] 2.77; P = .001), angina (aOR 2.27; P = .046), and stroke (aOR 3.80; P = .006), with the increased risk for cardiovascular diseases being the most prominent among participants with migraine who were women (aOR 6.02; P < .001), aged >60 years (aOR 2.69; P = .049), or had hypertension (aOR 3.57; P < .001) or hyperlipidemia (aOR 2.74; P = .003).

Study details: This cross-sectional study evaluated 5692 participants from the US National Health and Nutrition Examination Survey (NHANES), of which 1090 had migraine or severe headache.

Disclosures: This study was supported by grants from the National Natural Science Foundation of China and the Natural Science Foundation of Jiangsu Province. The authors declared no conflicts of interest.

Source: Wang K et al. Association between migraine and cardiovascular disease: A cross-sectional study. Front Cardiovasc Med. 2022;9:1044465 (Nov 24). Doi: 10.3389/fcvm.2022.1044465

Key clinical point: The COVID-19 pandemic adversely affected psychological functioning in young US college students with migraine and increased depression and anxiety, attenuating potential improvements achieved in headache-related disability during the pandemic.

Major finding: Levels of depression, anxiety, and stress were significantly higher during vs before the COVID-19 pandemic (all P ≤ .01), whereas headache-related disability was lower (direct effect [c′] −1.6; 95% CI −3.1 to −0.1). However, anxiety (indirect effect [b] 0.3; 95% CI 0.01-0.9) and depression (b 0.7; 95% CI 0.07-1.4) mediated an increase in headache-related disability during vs before the pandemic, thereby canceling improvements achieved during the pandemic.

Study details: This cross-sectional study included 365 undergraduate students aged ≥18 years with episodic migraine with or without aura or chronic migraine who were surveyed before (n = 223) or during (n = 142) the COVID-19 pandemic.

Disclosures: This study did not receive any specific funding. TA Smitherman reported previously serving on the advisory board for Teva Pharmaceuticals (unrelated to this study).

Source: Thaxter LY and Smitherman TA. The effect of the COVID-19 pandemic on headache-related disability among young adults with migraine. Headache. 2022;62(10):1293-1301 (Nov 23). Doi: 10.1111/head.14411

Key clinical point: The COVID-19 pandemic adversely affected psychological functioning in young US college students with migraine and increased depression and anxiety, attenuating potential improvements achieved in headache-related disability during the pandemic.

Major finding: Levels of depression, anxiety, and stress were significantly higher during vs before the COVID-19 pandemic (all P ≤ .01), whereas headache-related disability was lower (direct effect [c′] −1.6; 95% CI −3.1 to −0.1). However, anxiety (indirect effect [b] 0.3; 95% CI 0.01-0.9) and depression (b 0.7; 95% CI 0.07-1.4) mediated an increase in headache-related disability during vs before the pandemic, thereby canceling improvements achieved during the pandemic.

Study details: This cross-sectional study included 365 undergraduate students aged ≥18 years with episodic migraine with or without aura or chronic migraine who were surveyed before (n = 223) or during (n = 142) the COVID-19 pandemic.

Disclosures: This study did not receive any specific funding. TA Smitherman reported previously serving on the advisory board for Teva Pharmaceuticals (unrelated to this study).

Source: Thaxter LY and Smitherman TA. The effect of the COVID-19 pandemic on headache-related disability among young adults with migraine. Headache. 2022;62(10):1293-1301 (Nov 23). Doi: 10.1111/head.14411

Key clinical point: The COVID-19 pandemic adversely affected psychological functioning in young US college students with migraine and increased depression and anxiety, attenuating potential improvements achieved in headache-related disability during the pandemic.

Major finding: Levels of depression, anxiety, and stress were significantly higher during vs before the COVID-19 pandemic (all P ≤ .01), whereas headache-related disability was lower (direct effect [c′] −1.6; 95% CI −3.1 to −0.1). However, anxiety (indirect effect [b] 0.3; 95% CI 0.01-0.9) and depression (b 0.7; 95% CI 0.07-1.4) mediated an increase in headache-related disability during vs before the pandemic, thereby canceling improvements achieved during the pandemic.

Study details: This cross-sectional study included 365 undergraduate students aged ≥18 years with episodic migraine with or without aura or chronic migraine who were surveyed before (n = 223) or during (n = 142) the COVID-19 pandemic.

Disclosures: This study did not receive any specific funding. TA Smitherman reported previously serving on the advisory board for Teva Pharmaceuticals (unrelated to this study).

Source: Thaxter LY and Smitherman TA. The effect of the COVID-19 pandemic on headache-related disability among young adults with migraine. Headache. 2022;62(10):1293-1301 (Nov 23). Doi: 10.1111/head.14411