Vertigo is a normal response to certain stimuli, such as looking down from heights and abnormal head movements. In addition, any dysfunction along the pathway that processes balance and gravity information (eg, the semicircular canals, acoustic nerve, and brainstem vestibular centers) can cause vertigo.

Migraine is significantly more common in patients with vertigo, and vertigo is significantly more common in migraineurs than in the general population. In addition, migraineurs are predisposed to motion sickness, which often includes vertigo. Migraineurs’ vestibular systems are more sensitive to stimuli than those of nonmigraine controls, and migraineurs experience vestibular stimulation as more unpleasant and more likely to cause emesis, compared with nonmigraine controls, Dr. Levin said.

The reasons for these correlations are unknown. It may be that heightened vestibular sensitivity in migraine is due to migraineurs perceiving all stimuli more intensely, or migraineurs may be more keenly aware of early signs of vestibulopathy. Vertigo may be a migraine trigger, or a subset of patients may have a type of migraine that includes vertigo as a key symptom, he said. This last possibility is the so-called vestibular migraine.

Recognizing Vestibular Migraine

Vestibular migraine, which also has been known as migraine-associated vertigo, migraine-associated dizziness, and migraine-associated vestibulopathy, has been difficult to define. The current generally accepted definition requires two basic diagnostic criteria: current or previous history of migraine and migraine features (eg, headache, photophobia, phonophobia, or visual aura) with at least half of the spells of vertigo.

Vestibular migraine is estimated to affect about 1% of the general population, 7% of patients at dizziness clinics, and 9% of patients at headache centers.

The duration of vertigo in vestibular migraine varies. About a third of the episodes last for minutes, a third for hours, and a third for days. Vertigo can occur between migraine attacks, prior to them, during, or after, and it tends to be spontaneous. Vestibular migraine is common in children and more common in women than in men. It generally arises years after migraines begin.

Unsteadiness and balance problems are common in vestibular migraine, and audiologic disturbances occur in a minority of patients. Migraine with brainstem aura (formerly called basilar migraine) can include vertigo, but the diagnosis also requires at least one other brainstem symptom (eg, tinnitus or dysarthria).

Evaluating Patients

When seeing patients, neurologists’ first step might be to try to distinguish between vertigo and other similar symptoms, such as presyncope, disorientation, or disequilibrium. “A sense of motion is the best indication of vertigo, though even that might be lacking,” Dr. Levin said.

Neurologists can determine whether position triggers vertigo and identify evidence of peripheral biologic problems (eg, tinnitus, changes in vision, or other focal neurologic signs and symptoms). Family history of migraine in people with episodic vertigo may be a clue that the patient has vestibular migraine versus other causes of vertigo, Dr. Levin said. A history of syncope or other signs may suggest that a patient’s symptoms are related to light-headedness instead of vertigo. Psychiatric illness, time course, drug exposure, and stroke or stroke risk factors also should be considered.

Diagnostic tests may help neurologists distinguish between vestibular migraine and other causes of vertigo. Audiograms can assess for hearing loss, and MRIs may rule out masses or other lesions. Brainstem auditory evoked responses, electronystagmography (ENG), and videonystagmography (VNG), which typically includes saccade, tracking, positional, and caloric testing, also can be useful.

Similar Conditions

One diagnostic entity that can be mistaken for vestibular migraine is mal de debarquement, which is marked by a persistent feeling of vertigo after a cruise or other motion experience. Patients with this condition also may experience symptoms such as blurred vision, inability to focus, cognitive changes, headaches, nausea, feelings of pressure, and trouble sleeping. “It can actually start sounding like migraine,” Dr. Levin said. “Strangely enough, patients may not mention their disembarkation from a trip. …You have to sometimes draw it out.”

Vestibular testing is normal in these patients, and oddly, they often feel better when they ride in a car or otherwise experience motion. Migraine treatment does not work for these patients. Benzodiazepines may help, but patients may become tolerant. Mal de debarquement tends to dampen and resolve in many patients.

Other causes of vertigo include Meniere’s disease, benign paroxysmal positional vertigo, meningeal infection or inflammation, labyrinthine or brainstem ischemia, perilymph fistula, and benign positional vertigo of childhood.

In the end, some diagnostic entities may be part of a spectrum, Dr. Levin said. Thirty-eight percent of vestibular migraines have auditory symptoms as in Meniere’s disease, and the prevalence of migraine in patients with Meniere’s disease is twice that of the general population. Many patients fit diagnostic criteria for vestibular migraine and Meniere’s disease.

The pathophysiology of vestibular migraine is unknown. Connections between vestibular nuclei in the brainstem and the trigeminal nuclei may underlie the condition. Vestibular and trigeminal nociceptive pathways may be activated in parallel. Alternatively, structural brain lesions in the temporal lobes or elsewhere may cause vestibular migraine.

Like other migraine auras, vestibular migraine may be a manifestation of focal or generalized cortical spreading depression. “There are cortical centers for vertigo,” Dr. Levin said. When these cortical centers are affected in patients with epilepsy, patients may experience “tornado seizures,” he said.

Treatment Approaches

Some studies suggest that migraine treatments might help patients with vestibular migraine. Zolmitriptan and rizatriptan at the time of vertigo have been tried, with some suggestion that they may provide benefit.

The best evidence for pharmacologic prevention exists for flunarizine, propranolol, and lamotrigine. Other trials suggest that vestibular rehabilitation and combined caffeine cessation, nortriptyline, and topiramate may be effective.

Limitations of trials in vestibular migraine have included small numbers of patients, noncontrolled designs, and inconsistent definitions of vestibular migraine. In addition, case reports have suggested that benzodiazepines, cinnarizine, selective serotonin reuptake inhibitors, pizotifen, dothiepin, acetazolamide, and behavioral modification may benefit patients. Investigators are enrolling patients in a double-blind, placebo-controlled trial that will evaluate the use of metoprolol for the preventive treatment of vestibular migraine.

If occurrences of vertigo are infrequent, symptomatic vertigo treatments are Dr. Levin’s first choice. “I have had good luck with scopolamine, for example,” he said. Dopamine antagonists, neuroleptics, sedatives, and benzodiazepines are also useful symptomatic treatments for vertigo. The Epley maneuver and other canalith repositioning maneuvers may benefit some patients. For acute treatment, it makes sense to try a triptan, Dr. Levin said. “Sometimes it does work. Other times it does not, and you have to resort to symptomatic medication,” he said.

—Jake Remaly

Suggested Reading

Akdal G, Ozge A, Ergör G. The prevalence of vestibular symptoms in migraine or tension-type headache. J Vestib Res. 2013;23(2):101-106.

Dieterich M, Brandt T. Episodic vertigo related to migraine (90 cases): vestibular migraine? J Neurol. 1999;246(10):883-892.

Dieterich M, Obermann M, Celebisoy N. Vestibular migraine: the most frequent entity of episodic vertigo. J Neurol. 2016;263 Suppl 1:S82-89.

Furman JM, Marcus DA, Balaban CD. Vestibular migraine: clinical aspects and pathophysiology. Lancet Neurol. 2013;12(7):706-715.

Lepcha A, Amalanathan S, Augustine AM, et al. Flunarizine in the prophylaxis of migrainous vertigo: a randomized controlled trial. Eur Arch Otorhinolaryngol. 2014;271(11):2931-2936.

Mikulec AA, Faraji F, Kinsella LJ. Evaluation of the efficacy of caffeine cessation, nortriptyline, and topiramate therapy in vestibular migraine and complex dizziness of unknown etiology. Am J Otolaryngol. 2012;33(1):121-127.

Murdin L, Davies RA, Bronstein AM. Vertigo as a migraine trigger. Neurology. 2009;73(8):638-642.

Neuhauser HK, Radtke A, von Brevern M, et al. Migrainous vertigo: prevalence and impact on quality of life. Neurology. 2006;67(6):1028-1033.

Salviz M, Yuce T, Acar H, et al. Propranolol and venlafaxine for vestibular migraine prophylaxis: A randomized controlled trial. Laryngoscope. 2016;126(1):169-174.

Van Ombergen A, Van Rompaey V, Van de Heyning P, Wuyts F. Vestibular migraine in an otolaryngology clinic: prevalence, associated symptoms, and prophylactic medication effectiveness. Otol Neurotol. 2015;36(1):133-138.

Vitkovic J, Winoto A, Rance G, et al. Vestibular rehabilitation outcomes in patients with and without vestibular migraine. J Neurol. 2013;260(12):3039-3048.

Vertigo is a normal response to certain stimuli, such as looking down from heights and abnormal head movements. In addition, any dysfunction along the pathway that processes balance and gravity information (eg, the semicircular canals, acoustic nerve, and brainstem vestibular centers) can cause vertigo.

Migraine is significantly more common in patients with vertigo, and vertigo is significantly more common in migraineurs than in the general population. In addition, migraineurs are predisposed to motion sickness, which often includes vertigo. Migraineurs’ vestibular systems are more sensitive to stimuli than those of nonmigraine controls, and migraineurs experience vestibular stimulation as more unpleasant and more likely to cause emesis, compared with nonmigraine controls, Dr. Levin said.

The reasons for these correlations are unknown. It may be that heightened vestibular sensitivity in migraine is due to migraineurs perceiving all stimuli more intensely, or migraineurs may be more keenly aware of early signs of vestibulopathy. Vertigo may be a migraine trigger, or a subset of patients may have a type of migraine that includes vertigo as a key symptom, he said. This last possibility is the so-called vestibular migraine.

Recognizing Vestibular Migraine

Vestibular migraine, which also has been known as migraine-associated vertigo, migraine-associated dizziness, and migraine-associated vestibulopathy, has been difficult to define. The current generally accepted definition requires two basic diagnostic criteria: current or previous history of migraine and migraine features (eg, headache, photophobia, phonophobia, or visual aura) with at least half of the spells of vertigo.

Vestibular migraine is estimated to affect about 1% of the general population, 7% of patients at dizziness clinics, and 9% of patients at headache centers.

The duration of vertigo in vestibular migraine varies. About a third of the episodes last for minutes, a third for hours, and a third for days. Vertigo can occur between migraine attacks, prior to them, during, or after, and it tends to be spontaneous. Vestibular migraine is common in children and more common in women than in men. It generally arises years after migraines begin.

Unsteadiness and balance problems are common in vestibular migraine, and audiologic disturbances occur in a minority of patients. Migraine with brainstem aura (formerly called basilar migraine) can include vertigo, but the diagnosis also requires at least one other brainstem symptom (eg, tinnitus or dysarthria).

Evaluating Patients

When seeing patients, neurologists’ first step might be to try to distinguish between vertigo and other similar symptoms, such as presyncope, disorientation, or disequilibrium. “A sense of motion is the best indication of vertigo, though even that might be lacking,” Dr. Levin said.

Neurologists can determine whether position triggers vertigo and identify evidence of peripheral biologic problems (eg, tinnitus, changes in vision, or other focal neurologic signs and symptoms). Family history of migraine in people with episodic vertigo may be a clue that the patient has vestibular migraine versus other causes of vertigo, Dr. Levin said. A history of syncope or other signs may suggest that a patient’s symptoms are related to light-headedness instead of vertigo. Psychiatric illness, time course, drug exposure, and stroke or stroke risk factors also should be considered.

Diagnostic tests may help neurologists distinguish between vestibular migraine and other causes of vertigo. Audiograms can assess for hearing loss, and MRIs may rule out masses or other lesions. Brainstem auditory evoked responses, electronystagmography (ENG), and videonystagmography (VNG), which typically includes saccade, tracking, positional, and caloric testing, also can be useful.

Similar Conditions

One diagnostic entity that can be mistaken for vestibular migraine is mal de debarquement, which is marked by a persistent feeling of vertigo after a cruise or other motion experience. Patients with this condition also may experience symptoms such as blurred vision, inability to focus, cognitive changes, headaches, nausea, feelings of pressure, and trouble sleeping. “It can actually start sounding like migraine,” Dr. Levin said. “Strangely enough, patients may not mention their disembarkation from a trip. …You have to sometimes draw it out.”

Vestibular testing is normal in these patients, and oddly, they often feel better when they ride in a car or otherwise experience motion. Migraine treatment does not work for these patients. Benzodiazepines may help, but patients may become tolerant. Mal de debarquement tends to dampen and resolve in many patients.

Other causes of vertigo include Meniere’s disease, benign paroxysmal positional vertigo, meningeal infection or inflammation, labyrinthine or brainstem ischemia, perilymph fistula, and benign positional vertigo of childhood.

In the end, some diagnostic entities may be part of a spectrum, Dr. Levin said. Thirty-eight percent of vestibular migraines have auditory symptoms as in Meniere’s disease, and the prevalence of migraine in patients with Meniere’s disease is twice that of the general population. Many patients fit diagnostic criteria for vestibular migraine and Meniere’s disease.

The pathophysiology of vestibular migraine is unknown. Connections between vestibular nuclei in the brainstem and the trigeminal nuclei may underlie the condition. Vestibular and trigeminal nociceptive pathways may be activated in parallel. Alternatively, structural brain lesions in the temporal lobes or elsewhere may cause vestibular migraine.

Like other migraine auras, vestibular migraine may be a manifestation of focal or generalized cortical spreading depression. “There are cortical centers for vertigo,” Dr. Levin said. When these cortical centers are affected in patients with epilepsy, patients may experience “tornado seizures,” he said.

Treatment Approaches

Some studies suggest that migraine treatments might help patients with vestibular migraine. Zolmitriptan and rizatriptan at the time of vertigo have been tried, with some suggestion that they may provide benefit.

The best evidence for pharmacologic prevention exists for flunarizine, propranolol, and lamotrigine. Other trials suggest that vestibular rehabilitation and combined caffeine cessation, nortriptyline, and topiramate may be effective.

Limitations of trials in vestibular migraine have included small numbers of patients, noncontrolled designs, and inconsistent definitions of vestibular migraine. In addition, case reports have suggested that benzodiazepines, cinnarizine, selective serotonin reuptake inhibitors, pizotifen, dothiepin, acetazolamide, and behavioral modification may benefit patients. Investigators are enrolling patients in a double-blind, placebo-controlled trial that will evaluate the use of metoprolol for the preventive treatment of vestibular migraine.

If occurrences of vertigo are infrequent, symptomatic vertigo treatments are Dr. Levin’s first choice. “I have had good luck with scopolamine, for example,” he said. Dopamine antagonists, neuroleptics, sedatives, and benzodiazepines are also useful symptomatic treatments for vertigo. The Epley maneuver and other canalith repositioning maneuvers may benefit some patients. For acute treatment, it makes sense to try a triptan, Dr. Levin said. “Sometimes it does work. Other times it does not, and you have to resort to symptomatic medication,” he said.

—Jake Remaly

Suggested Reading

Akdal G, Ozge A, Ergör G. The prevalence of vestibular symptoms in migraine or tension-type headache. J Vestib Res. 2013;23(2):101-106.

Dieterich M, Brandt T. Episodic vertigo related to migraine (90 cases): vestibular migraine? J Neurol. 1999;246(10):883-892.

Dieterich M, Obermann M, Celebisoy N. Vestibular migraine: the most frequent entity of episodic vertigo. J Neurol. 2016;263 Suppl 1:S82-89.

Furman JM, Marcus DA, Balaban CD. Vestibular migraine: clinical aspects and pathophysiology. Lancet Neurol. 2013;12(7):706-715.

Lepcha A, Amalanathan S, Augustine AM, et al. Flunarizine in the prophylaxis of migrainous vertigo: a randomized controlled trial. Eur Arch Otorhinolaryngol. 2014;271(11):2931-2936.

Mikulec AA, Faraji F, Kinsella LJ. Evaluation of the efficacy of caffeine cessation, nortriptyline, and topiramate therapy in vestibular migraine and complex dizziness of unknown etiology. Am J Otolaryngol. 2012;33(1):121-127.

Murdin L, Davies RA, Bronstein AM. Vertigo as a migraine trigger. Neurology. 2009;73(8):638-642.

Neuhauser HK, Radtke A, von Brevern M, et al. Migrainous vertigo: prevalence and impact on quality of life. Neurology. 2006;67(6):1028-1033.

Salviz M, Yuce T, Acar H, et al. Propranolol and venlafaxine for vestibular migraine prophylaxis: A randomized controlled trial. Laryngoscope. 2016;126(1):169-174.

Van Ombergen A, Van Rompaey V, Van de Heyning P, Wuyts F. Vestibular migraine in an otolaryngology clinic: prevalence, associated symptoms, and prophylactic medication effectiveness. Otol Neurotol. 2015;36(1):133-138.

Vitkovic J, Winoto A, Rance G, et al. Vestibular rehabilitation outcomes in patients with and without vestibular migraine. J Neurol. 2013;260(12):3039-3048.

Vertigo is a normal response to certain stimuli, such as looking down from heights and abnormal head movements. In addition, any dysfunction along the pathway that processes balance and gravity information (eg, the semicircular canals, acoustic nerve, and brainstem vestibular centers) can cause vertigo.

Migraine is significantly more common in patients with vertigo, and vertigo is significantly more common in migraineurs than in the general population. In addition, migraineurs are predisposed to motion sickness, which often includes vertigo. Migraineurs’ vestibular systems are more sensitive to stimuli than those of nonmigraine controls, and migraineurs experience vestibular stimulation as more unpleasant and more likely to cause emesis, compared with nonmigraine controls, Dr. Levin said.

The reasons for these correlations are unknown. It may be that heightened vestibular sensitivity in migraine is due to migraineurs perceiving all stimuli more intensely, or migraineurs may be more keenly aware of early signs of vestibulopathy. Vertigo may be a migraine trigger, or a subset of patients may have a type of migraine that includes vertigo as a key symptom, he said. This last possibility is the so-called vestibular migraine.

Recognizing Vestibular Migraine

Vestibular migraine, which also has been known as migraine-associated vertigo, migraine-associated dizziness, and migraine-associated vestibulopathy, has been difficult to define. The current generally accepted definition requires two basic diagnostic criteria: current or previous history of migraine and migraine features (eg, headache, photophobia, phonophobia, or visual aura) with at least half of the spells of vertigo.

Vestibular migraine is estimated to affect about 1% of the general population, 7% of patients at dizziness clinics, and 9% of patients at headache centers.

The duration of vertigo in vestibular migraine varies. About a third of the episodes last for minutes, a third for hours, and a third for days. Vertigo can occur between migraine attacks, prior to them, during, or after, and it tends to be spontaneous. Vestibular migraine is common in children and more common in women than in men. It generally arises years after migraines begin.

Unsteadiness and balance problems are common in vestibular migraine, and audiologic disturbances occur in a minority of patients. Migraine with brainstem aura (formerly called basilar migraine) can include vertigo, but the diagnosis also requires at least one other brainstem symptom (eg, tinnitus or dysarthria).

Evaluating Patients

When seeing patients, neurologists’ first step might be to try to distinguish between vertigo and other similar symptoms, such as presyncope, disorientation, or disequilibrium. “A sense of motion is the best indication of vertigo, though even that might be lacking,” Dr. Levin said.

Neurologists can determine whether position triggers vertigo and identify evidence of peripheral biologic problems (eg, tinnitus, changes in vision, or other focal neurologic signs and symptoms). Family history of migraine in people with episodic vertigo may be a clue that the patient has vestibular migraine versus other causes of vertigo, Dr. Levin said. A history of syncope or other signs may suggest that a patient’s symptoms are related to light-headedness instead of vertigo. Psychiatric illness, time course, drug exposure, and stroke or stroke risk factors also should be considered.

Diagnostic tests may help neurologists distinguish between vestibular migraine and other causes of vertigo. Audiograms can assess for hearing loss, and MRIs may rule out masses or other lesions. Brainstem auditory evoked responses, electronystagmography (ENG), and videonystagmography (VNG), which typically includes saccade, tracking, positional, and caloric testing, also can be useful.

Similar Conditions

One diagnostic entity that can be mistaken for vestibular migraine is mal de debarquement, which is marked by a persistent feeling of vertigo after a cruise or other motion experience. Patients with this condition also may experience symptoms such as blurred vision, inability to focus, cognitive changes, headaches, nausea, feelings of pressure, and trouble sleeping. “It can actually start sounding like migraine,” Dr. Levin said. “Strangely enough, patients may not mention their disembarkation from a trip. …You have to sometimes draw it out.”

Vestibular testing is normal in these patients, and oddly, they often feel better when they ride in a car or otherwise experience motion. Migraine treatment does not work for these patients. Benzodiazepines may help, but patients may become tolerant. Mal de debarquement tends to dampen and resolve in many patients.

Other causes of vertigo include Meniere’s disease, benign paroxysmal positional vertigo, meningeal infection or inflammation, labyrinthine or brainstem ischemia, perilymph fistula, and benign positional vertigo of childhood.

In the end, some diagnostic entities may be part of a spectrum, Dr. Levin said. Thirty-eight percent of vestibular migraines have auditory symptoms as in Meniere’s disease, and the prevalence of migraine in patients with Meniere’s disease is twice that of the general population. Many patients fit diagnostic criteria for vestibular migraine and Meniere’s disease.

The pathophysiology of vestibular migraine is unknown. Connections between vestibular nuclei in the brainstem and the trigeminal nuclei may underlie the condition. Vestibular and trigeminal nociceptive pathways may be activated in parallel. Alternatively, structural brain lesions in the temporal lobes or elsewhere may cause vestibular migraine.

Like other migraine auras, vestibular migraine may be a manifestation of focal or generalized cortical spreading depression. “There are cortical centers for vertigo,” Dr. Levin said. When these cortical centers are affected in patients with epilepsy, patients may experience “tornado seizures,” he said.

Treatment Approaches

Some studies suggest that migraine treatments might help patients with vestibular migraine. Zolmitriptan and rizatriptan at the time of vertigo have been tried, with some suggestion that they may provide benefit.

The best evidence for pharmacologic prevention exists for flunarizine, propranolol, and lamotrigine. Other trials suggest that vestibular rehabilitation and combined caffeine cessation, nortriptyline, and topiramate may be effective.

Limitations of trials in vestibular migraine have included small numbers of patients, noncontrolled designs, and inconsistent definitions of vestibular migraine. In addition, case reports have suggested that benzodiazepines, cinnarizine, selective serotonin reuptake inhibitors, pizotifen, dothiepin, acetazolamide, and behavioral modification may benefit patients. Investigators are enrolling patients in a double-blind, placebo-controlled trial that will evaluate the use of metoprolol for the preventive treatment of vestibular migraine.

If occurrences of vertigo are infrequent, symptomatic vertigo treatments are Dr. Levin’s first choice. “I have had good luck with scopolamine, for example,” he said. Dopamine antagonists, neuroleptics, sedatives, and benzodiazepines are also useful symptomatic treatments for vertigo. The Epley maneuver and other canalith repositioning maneuvers may benefit some patients. For acute treatment, it makes sense to try a triptan, Dr. Levin said. “Sometimes it does work. Other times it does not, and you have to resort to symptomatic medication,” he said.

—Jake Remaly

Suggested Reading

Akdal G, Ozge A, Ergör G. The prevalence of vestibular symptoms in migraine or tension-type headache. J Vestib Res. 2013;23(2):101-106.

Dieterich M, Brandt T. Episodic vertigo related to migraine (90 cases): vestibular migraine? J Neurol. 1999;246(10):883-892.

Dieterich M, Obermann M, Celebisoy N. Vestibular migraine: the most frequent entity of episodic vertigo. J Neurol. 2016;263 Suppl 1:S82-89.

Furman JM, Marcus DA, Balaban CD. Vestibular migraine: clinical aspects and pathophysiology. Lancet Neurol. 2013;12(7):706-715.

Lepcha A, Amalanathan S, Augustine AM, et al. Flunarizine in the prophylaxis of migrainous vertigo: a randomized controlled trial. Eur Arch Otorhinolaryngol. 2014;271(11):2931-2936.

Mikulec AA, Faraji F, Kinsella LJ. Evaluation of the efficacy of caffeine cessation, nortriptyline, and topiramate therapy in vestibular migraine and complex dizziness of unknown etiology. Am J Otolaryngol. 2012;33(1):121-127.

Murdin L, Davies RA, Bronstein AM. Vertigo as a migraine trigger. Neurology. 2009;73(8):638-642.

Neuhauser HK, Radtke A, von Brevern M, et al. Migrainous vertigo: prevalence and impact on quality of life. Neurology. 2006;67(6):1028-1033.

Salviz M, Yuce T, Acar H, et al. Propranolol and venlafaxine for vestibular migraine prophylaxis: A randomized controlled trial. Laryngoscope. 2016;126(1):169-174.

Van Ombergen A, Van Rompaey V, Van de Heyning P, Wuyts F. Vestibular migraine in an otolaryngology clinic: prevalence, associated symptoms, and prophylactic medication effectiveness. Otol Neurotol. 2015;36(1):133-138.

Vitkovic J, Winoto A, Rance G, et al. Vestibular rehabilitation outcomes in patients with and without vestibular migraine. J Neurol. 2013;260(12):3039-3048.

Indoor tanning among adolescents in the United States has dropped significantly, but fewer than half of schools in the United States reported sun safety practices to help minimize students’ UV exposure in the school setting, based on data from two studies presented at the annual meeting of the American Academy of Dermatology and published simultaneously in JAMA Dermatology.

“Data suggest that intermittent, recreational exposure (vs. chronic exposure, as with outdoor workers) more often leads to sunburn,” wrote Sherry Everett Jones, PhD, MPH, and Gery P. Guy Jr, PhD, MPH, of the Centers for Disease Control and Prevention. “Although a small proportion of school districts and schools have adopted policies to address sun safety, most have not, even though it is common for students to be outside during the midday hours or after school when the sun is still at peak intensity.”

To characterize sun safety practices at schools, the researchers reviewed data from the 2014 School Health Policies and Practices Study Healthy and Safe School Environment questionnaire including 577 elementary, middle, and high schools (JAMA Dermatol. 2017. doi: 10.1001/jamadermatol.2016.6274).

Overall, 48% of schools reported that teachers allowed students time to apply sunscreen at school (the most frequent sun safety practice). However, only 13% made sunscreen available, 16% asked parents to ensure sunscreen application before school, and 15% made an effort to avoid scheduling outdoor activities during times of peak sun intensity. High schools were less likely than elementary or middle schools to follow sun safety practices.

“None of the sun safety policies or practices were statistically significantly associated with metropolitan status,” the researchers noted. However, the findings were limited by the cross-sectional nature of the study and lack of data about natural shade and man made shade structures in outdoor areas of the schools.

“Interventions driven by the public health and medical community educating school leadership and policy makers about the importance of sun safety are needed regardless of level, location, size, and poverty concentration of the school. These efforts could be instrumental in increasing the adoption of sun safety practices among schools,” Dr. Jones and Dr. Guy emphasized.

However, data from another study showed a significant reduction in the prevalence of indoor tanning among adolescents.

In particular, indoor tanning among non-Hispanic white females (the group at highest risk for skin cancer) dropped from 37% in 2009 to 15% in 2015. CDC researchers led by Dr. Guy pooled data from the 2009, 2011, 2013, and 2015 national Youth Risk Behavior Surveillance System Surveys (JAMA Dermatol. 2017. doi:10.1001/jamadermatol.2016.6273). Overall, the prevalence of indoor tanning among U.S. high school students decreased from 16% in 2009 to 7% in 2015.

“Despite declines in indoor tanning, continued efforts are needed,” the researchers wrote. “Public health efforts could help address the misconception that indoor tanning protects against sunburn. The medical community also can play a key role in counseling adolescents and young adults in accordance with the U.S. Preventive Services Task Force guidelines.”

The findings were limited by several factors including the use of self-reports and the inability to control for skin type, the researchers wrote. However, “Reducing the proportion of youth who engage in indoor tanning and experience sunburns presents an important cancer prevention opportunity.”

None of the researchers on either study had relevant financial conflicts to disclose.

Indoor tanning among adolescents in the United States has dropped significantly, but fewer than half of schools in the United States reported sun safety practices to help minimize students’ UV exposure in the school setting, based on data from two studies presented at the annual meeting of the American Academy of Dermatology and published simultaneously in JAMA Dermatology.

“Data suggest that intermittent, recreational exposure (vs. chronic exposure, as with outdoor workers) more often leads to sunburn,” wrote Sherry Everett Jones, PhD, MPH, and Gery P. Guy Jr, PhD, MPH, of the Centers for Disease Control and Prevention. “Although a small proportion of school districts and schools have adopted policies to address sun safety, most have not, even though it is common for students to be outside during the midday hours or after school when the sun is still at peak intensity.”

To characterize sun safety practices at schools, the researchers reviewed data from the 2014 School Health Policies and Practices Study Healthy and Safe School Environment questionnaire including 577 elementary, middle, and high schools (JAMA Dermatol. 2017. doi: 10.1001/jamadermatol.2016.6274).

Overall, 48% of schools reported that teachers allowed students time to apply sunscreen at school (the most frequent sun safety practice). However, only 13% made sunscreen available, 16% asked parents to ensure sunscreen application before school, and 15% made an effort to avoid scheduling outdoor activities during times of peak sun intensity. High schools were less likely than elementary or middle schools to follow sun safety practices.

“None of the sun safety policies or practices were statistically significantly associated with metropolitan status,” the researchers noted. However, the findings were limited by the cross-sectional nature of the study and lack of data about natural shade and man made shade structures in outdoor areas of the schools.

“Interventions driven by the public health and medical community educating school leadership and policy makers about the importance of sun safety are needed regardless of level, location, size, and poverty concentration of the school. These efforts could be instrumental in increasing the adoption of sun safety practices among schools,” Dr. Jones and Dr. Guy emphasized.

However, data from another study showed a significant reduction in the prevalence of indoor tanning among adolescents.

In particular, indoor tanning among non-Hispanic white females (the group at highest risk for skin cancer) dropped from 37% in 2009 to 15% in 2015. CDC researchers led by Dr. Guy pooled data from the 2009, 2011, 2013, and 2015 national Youth Risk Behavior Surveillance System Surveys (JAMA Dermatol. 2017. doi:10.1001/jamadermatol.2016.6273). Overall, the prevalence of indoor tanning among U.S. high school students decreased from 16% in 2009 to 7% in 2015.

“Despite declines in indoor tanning, continued efforts are needed,” the researchers wrote. “Public health efforts could help address the misconception that indoor tanning protects against sunburn. The medical community also can play a key role in counseling adolescents and young adults in accordance with the U.S. Preventive Services Task Force guidelines.”

The findings were limited by several factors including the use of self-reports and the inability to control for skin type, the researchers wrote. However, “Reducing the proportion of youth who engage in indoor tanning and experience sunburns presents an important cancer prevention opportunity.”

None of the researchers on either study had relevant financial conflicts to disclose.

Indoor tanning among adolescents in the United States has dropped significantly, but fewer than half of schools in the United States reported sun safety practices to help minimize students’ UV exposure in the school setting, based on data from two studies presented at the annual meeting of the American Academy of Dermatology and published simultaneously in JAMA Dermatology.

“Data suggest that intermittent, recreational exposure (vs. chronic exposure, as with outdoor workers) more often leads to sunburn,” wrote Sherry Everett Jones, PhD, MPH, and Gery P. Guy Jr, PhD, MPH, of the Centers for Disease Control and Prevention. “Although a small proportion of school districts and schools have adopted policies to address sun safety, most have not, even though it is common for students to be outside during the midday hours or after school when the sun is still at peak intensity.”

To characterize sun safety practices at schools, the researchers reviewed data from the 2014 School Health Policies and Practices Study Healthy and Safe School Environment questionnaire including 577 elementary, middle, and high schools (JAMA Dermatol. 2017. doi: 10.1001/jamadermatol.2016.6274).

Overall, 48% of schools reported that teachers allowed students time to apply sunscreen at school (the most frequent sun safety practice). However, only 13% made sunscreen available, 16% asked parents to ensure sunscreen application before school, and 15% made an effort to avoid scheduling outdoor activities during times of peak sun intensity. High schools were less likely than elementary or middle schools to follow sun safety practices.

“None of the sun safety policies or practices were statistically significantly associated with metropolitan status,” the researchers noted. However, the findings were limited by the cross-sectional nature of the study and lack of data about natural shade and man made shade structures in outdoor areas of the schools.

“Interventions driven by the public health and medical community educating school leadership and policy makers about the importance of sun safety are needed regardless of level, location, size, and poverty concentration of the school. These efforts could be instrumental in increasing the adoption of sun safety practices among schools,” Dr. Jones and Dr. Guy emphasized.

However, data from another study showed a significant reduction in the prevalence of indoor tanning among adolescents.

In particular, indoor tanning among non-Hispanic white females (the group at highest risk for skin cancer) dropped from 37% in 2009 to 15% in 2015. CDC researchers led by Dr. Guy pooled data from the 2009, 2011, 2013, and 2015 national Youth Risk Behavior Surveillance System Surveys (JAMA Dermatol. 2017. doi:10.1001/jamadermatol.2016.6273). Overall, the prevalence of indoor tanning among U.S. high school students decreased from 16% in 2009 to 7% in 2015.

“Despite declines in indoor tanning, continued efforts are needed,” the researchers wrote. “Public health efforts could help address the misconception that indoor tanning protects against sunburn. The medical community also can play a key role in counseling adolescents and young adults in accordance with the U.S. Preventive Services Task Force guidelines.”

The findings were limited by several factors including the use of self-reports and the inability to control for skin type, the researchers wrote. However, “Reducing the proportion of youth who engage in indoor tanning and experience sunburns presents an important cancer prevention opportunity.”

None of the researchers on either study had relevant financial conflicts to disclose.

Reports of new cases of Zika infection in pregnant women held steady during the 2 weeks ending Feb. 21 as the number of new cases dropped in the territories and rose in the 50 states and D.C., according to the Centers for Disease Control and Prevention.

Compared with the previous 2-week period (Jan. 25-Feb.7), reports of new cases of pregnant women with laboratory evidence of Zika virus infection were up from 146 to 148, an increase from 61 to 79 in the states/D.C. and a decrease from 85 to 69 in the territories. The total number of Zika cases among pregnant women in the United States for 2016-2017 is 4,759, with 1,534 occurring in the states/D.C. and 3,225 in the territories, the CDC reported March 2.

[email protected]

Reports of new cases of Zika infection in pregnant women held steady during the 2 weeks ending Feb. 21 as the number of new cases dropped in the territories and rose in the 50 states and D.C., according to the Centers for Disease Control and Prevention.

Compared with the previous 2-week period (Jan. 25-Feb.7), reports of new cases of pregnant women with laboratory evidence of Zika virus infection were up from 146 to 148, an increase from 61 to 79 in the states/D.C. and a decrease from 85 to 69 in the territories. The total number of Zika cases among pregnant women in the United States for 2016-2017 is 4,759, with 1,534 occurring in the states/D.C. and 3,225 in the territories, the CDC reported March 2.

[email protected]

Reports of new cases of Zika infection in pregnant women held steady during the 2 weeks ending Feb. 21 as the number of new cases dropped in the territories and rose in the 50 states and D.C., according to the Centers for Disease Control and Prevention.

Compared with the previous 2-week period (Jan. 25-Feb.7), reports of new cases of pregnant women with laboratory evidence of Zika virus infection were up from 146 to 148, an increase from 61 to 79 in the states/D.C. and a decrease from 85 to 69 in the territories. The total number of Zika cases among pregnant women in the United States for 2016-2017 is 4,759, with 1,534 occurring in the states/D.C. and 3,225 in the territories, the CDC reported March 2.

[email protected]

Birth defects potentially linked to cases of Zika virus in the United States have increased by a factor of nearly 20 since the virus first made its way into the country, according to new findings by the Centers for Disease Control and Prevention.

“The higher proportion of these defects among pregnancies with laboratory evidence of Zika infection in USZPR [U.S. Zika Pregnancy Registry] supports the relationship between congenital Zika virus infection and these birth defects,” wrote the authors of a new report led by Janet D. Cragan, MD, of the National Center on Birth Defects and Developmental Disabilities at the CDC (MMWR Morb Mortal Wkly Rep. 2017;66:219-22).

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Dr. Cragan and her coauthors retrospectively examined data on birth defects in three regions of the country: Massachusetts during 2013, North Carolina during 2013, and Atlanta during 2013-2014. The investigators focused on birth defects associated with prenatal Zika virus infections, mainly brain abnormalities and microcephaly.

The rate of total birth defects across the three regions was 2.86 per 1,000 live births, with 747 infants and fetuses identified as having one or more defects. Microcephaly and brain abnormalities alone occurred at a rate of 1.50 per 1,000 live births, with eye abnormalities and central nervous system dysfunction also occurring.

These numbers are relatively low when compared with data from Jan. 15 through Sept. 22, 2016. The birth defect rate jumped up to 58.8 per 1,000 live births, according to data from the USZPR, which found evidence of 26 infants and fetuses with brain or cranial defects in 442 completed pregnancies. These infants were all born to mothers with laboratory-confirmed Zika virus infections.

“Among 410 (55%) infants or fetuses with information on the earliest age a birth defect was recorded, 371 (90%) had evidence of a birth defect meeting the Zika definition before age 3 months,” the authors explained. “More than half of those with brain abnormalities or microcephaly or with neural tube defects and other early brain malformations had evidence of these defects noted prenatally (55% and 89%, respectively).”

Dr. Cragan and her colleagues hope that this evidence will further solidify the link between Zika virus and birth defects and pave the way for more population-based studies.

“These data demonstrate the critical contribution of population-based birth defects surveillance to understanding the impact of Zika virus infection during pregnancy,” the authors concluded. “In 2016, CDC provided funding for 45 local, state, and territorial health departments to conduct rapid population-based surveillance for defects potentially related to Zika virus infection, which will provide essential data to monitor the impact of Zika virus infection in the United States.”

[email protected]

Birth defects potentially linked to cases of Zika virus in the United States have increased by a factor of nearly 20 since the virus first made its way into the country, according to new findings by the Centers for Disease Control and Prevention.

“The higher proportion of these defects among pregnancies with laboratory evidence of Zika infection in USZPR [U.S. Zika Pregnancy Registry] supports the relationship between congenital Zika virus infection and these birth defects,” wrote the authors of a new report led by Janet D. Cragan, MD, of the National Center on Birth Defects and Developmental Disabilities at the CDC (MMWR Morb Mortal Wkly Rep. 2017;66:219-22).

[[{"attributes":{},"fields":{}}]]

Dr. Cragan and her coauthors retrospectively examined data on birth defects in three regions of the country: Massachusetts during 2013, North Carolina during 2013, and Atlanta during 2013-2014. The investigators focused on birth defects associated with prenatal Zika virus infections, mainly brain abnormalities and microcephaly.

The rate of total birth defects across the three regions was 2.86 per 1,000 live births, with 747 infants and fetuses identified as having one or more defects. Microcephaly and brain abnormalities alone occurred at a rate of 1.50 per 1,000 live births, with eye abnormalities and central nervous system dysfunction also occurring.

These numbers are relatively low when compared with data from Jan. 15 through Sept. 22, 2016. The birth defect rate jumped up to 58.8 per 1,000 live births, according to data from the USZPR, which found evidence of 26 infants and fetuses with brain or cranial defects in 442 completed pregnancies. These infants were all born to mothers with laboratory-confirmed Zika virus infections.

“Among 410 (55%) infants or fetuses with information on the earliest age a birth defect was recorded, 371 (90%) had evidence of a birth defect meeting the Zika definition before age 3 months,” the authors explained. “More than half of those with brain abnormalities or microcephaly or with neural tube defects and other early brain malformations had evidence of these defects noted prenatally (55% and 89%, respectively).”

Dr. Cragan and her colleagues hope that this evidence will further solidify the link between Zika virus and birth defects and pave the way for more population-based studies.

“These data demonstrate the critical contribution of population-based birth defects surveillance to understanding the impact of Zika virus infection during pregnancy,” the authors concluded. “In 2016, CDC provided funding for 45 local, state, and territorial health departments to conduct rapid population-based surveillance for defects potentially related to Zika virus infection, which will provide essential data to monitor the impact of Zika virus infection in the United States.”

[email protected]

Birth defects potentially linked to cases of Zika virus in the United States have increased by a factor of nearly 20 since the virus first made its way into the country, according to new findings by the Centers for Disease Control and Prevention.

“The higher proportion of these defects among pregnancies with laboratory evidence of Zika infection in USZPR [U.S. Zika Pregnancy Registry] supports the relationship between congenital Zika virus infection and these birth defects,” wrote the authors of a new report led by Janet D. Cragan, MD, of the National Center on Birth Defects and Developmental Disabilities at the CDC (MMWR Morb Mortal Wkly Rep. 2017;66:219-22).

[[{"attributes":{},"fields":{}}]]

Dr. Cragan and her coauthors retrospectively examined data on birth defects in three regions of the country: Massachusetts during 2013, North Carolina during 2013, and Atlanta during 2013-2014. The investigators focused on birth defects associated with prenatal Zika virus infections, mainly brain abnormalities and microcephaly.

The rate of total birth defects across the three regions was 2.86 per 1,000 live births, with 747 infants and fetuses identified as having one or more defects. Microcephaly and brain abnormalities alone occurred at a rate of 1.50 per 1,000 live births, with eye abnormalities and central nervous system dysfunction also occurring.

These numbers are relatively low when compared with data from Jan. 15 through Sept. 22, 2016. The birth defect rate jumped up to 58.8 per 1,000 live births, according to data from the USZPR, which found evidence of 26 infants and fetuses with brain or cranial defects in 442 completed pregnancies. These infants were all born to mothers with laboratory-confirmed Zika virus infections.

“Among 410 (55%) infants or fetuses with information on the earliest age a birth defect was recorded, 371 (90%) had evidence of a birth defect meeting the Zika definition before age 3 months,” the authors explained. “More than half of those with brain abnormalities or microcephaly or with neural tube defects and other early brain malformations had evidence of these defects noted prenatally (55% and 89%, respectively).”

Dr. Cragan and her colleagues hope that this evidence will further solidify the link between Zika virus and birth defects and pave the way for more population-based studies.

“These data demonstrate the critical contribution of population-based birth defects surveillance to understanding the impact of Zika virus infection during pregnancy,” the authors concluded. “In 2016, CDC provided funding for 45 local, state, and territorial health departments to conduct rapid population-based surveillance for defects potentially related to Zika virus infection, which will provide essential data to monitor the impact of Zika virus infection in the United States.”

[email protected]

A majority of Chikungunya infections can cause arthritis and arthralgia months or years after the initial infection, based on data from a prospective study of 307 patients.

“The most common symptoms of Chikungunya virus infection are fever associated with rheumatic manifestations,” wrote rheumatologist Eric Bouquillard, MD, of Saint-Pierre, Reunion, France, and his colleagues.

CDC/Cynthia Goldsmith

A majority of Chikungunya infections can cause arthritis and arthralgia months or years after the initial infection, based on data from a prospective study of 307 patients.

“The most common symptoms of Chikungunya virus infection are fever associated with rheumatic manifestations,” wrote rheumatologist Eric Bouquillard, MD, of Saint-Pierre, Reunion, France, and his colleagues.

CDC/Cynthia Goldsmith

A majority of Chikungunya infections can cause arthritis and arthralgia months or years after the initial infection, based on data from a prospective study of 307 patients.

“The most common symptoms of Chikungunya virus infection are fever associated with rheumatic manifestations,” wrote rheumatologist Eric Bouquillard, MD, of Saint-Pierre, Reunion, France, and his colleagues.

CDC/Cynthia Goldsmith

The need for hospitalists continues to increase in Japan. There are approximately 9,000 hospitals in Japan, and approximately 80% of these hospitals are small- to medium-sized hospitals (<300 beds) where the need for hospital medicine is greatest. Historically, internal medicine subspecialists from nearly all subspecialties served as the primary attending physicians of hospitalized patients because inpatient internal medicine physicians, or hospitalists, did not exist.

Most subspecialists caring for hospitalized patients learned to practice internal medicine “on the fly” because they were not required to complete training in internal medicine before pursuing a subspecialty. After medical school, all graduates are required to complete a 2-year internship known as the National Obligatory Initial Postgraduate Clinical Training Program (NOIPCTP). The level of training during the NOIPCTP is similar to the third and fourth years of medical school in the United States. 

The aging population and increasing complexity of hospitalized patients are the two main drivers of hospital medicine in Japan. Recently, the number of patients who have had adverse events because of inpatient medical errors has risen, and the transparency of these adverse events is making the need for hospitalists more apparent. In addition to improving the day-to-day medical management of hospitalized patients, hospitalists are needed to serve as champions of quality improvement, patient safety, and hospital throughput.

Leaders of the Japanese health care system recognize the need to improve the quality of inpatient care. The first step is to establish internal medicine as a specialty with dedicated internal medicine residency training programs. The Japanese Board of Medical Specialties approved establishing standardized, 3-year internal medicine residency training programs starting this spring, but that decision has been met with resistance for various reasons, namely concern for creating a disparity due to the shortage of internists in rural areas. Therefore, launch of this initiative has been postponed until April 2018.

In the meantime, the concept of hospital-based internists has been gradually gaining the support of subspecialists in Japan. Hospitalists are anticipated to work as the primary medical team leaders, directing and coordinating care among subspecialists in the future. 
Despite its gradual spread, there are several challenges to growth. First, there are many terms for hospitalists, such as “hospital general practitioners” and “general internal medicine physicians.” A unified term for hospitalists would foster acceptance among Japanese physicians. 
Additionally, some physicians, namely subspecialists, still question whether hospitalists are needed in Japan (even though potential loss of clinical revenue is not a significant concern among subspecialists). 

Another challenge is lack of standardized training programs that define the skillset of hospitalists. Standardization of internal medicine training will also improve efficiency of communication between hospitalists and subspecialists.
An important milestone in the Japanese hospital medicine movement was the establishment of a society of hospitalists, known as the Japanese Hospitalist Network (JHN). The JHN has a quarterly publication (Hospitalist) targeted at junior faculty and residents that reviews topics in hospital medicine. 

The JHN is affiliated with a larger society, the Japanese Society of Hospital General Medicine (JSHGM), which holds meetings twice a year. A unique offering at the next JSHGM meeting in March is a point-of-care ultrasound training workshop. Although this is the first such workshop for hospitalists in Japan, there are many training courses designed for the country’s hospitalists. 

The emergence of such courses in Japan has paralleled the increasing need for hospitalists in Japan. We hope these courses for hospitalists will pave the road for the continued growth of hospital medicine in Japan.

Toru Yamada, MD
Dr. Yamada is an internist in the department of general medicine/family and community medicine at Nagoya (Japan) University and practices at Tokyo Bay Urayasu Ichikawa Medical Center in Chiba.
 

Taro Minami, MD
Dr. Minami is assistant professor of medicine in the division of pulmonary, critical care, and sleep medicine at Brown University in Providence, R.I., and director of ultrasound and simulation training at Memorial Hospital of Rhode Island.
 

Nilam J. Soni, MD, MS, FHM
Dr. Soni is associate professor of medicine in the division of hospital medicine at the University of Texas, San Antonio, and a hospitalist with the South Texas Veterans Health Care System in San Antonio.
 

The need for hospitalists continues to increase in Japan. There are approximately 9,000 hospitals in Japan, and approximately 80% of these hospitals are small- to medium-sized hospitals (<300 beds) where the need for hospital medicine is greatest. Historically, internal medicine subspecialists from nearly all subspecialties served as the primary attending physicians of hospitalized patients because inpatient internal medicine physicians, or hospitalists, did not exist.

Most subspecialists caring for hospitalized patients learned to practice internal medicine “on the fly” because they were not required to complete training in internal medicine before pursuing a subspecialty. After medical school, all graduates are required to complete a 2-year internship known as the National Obligatory Initial Postgraduate Clinical Training Program (NOIPCTP). The level of training during the NOIPCTP is similar to the third and fourth years of medical school in the United States. 

The aging population and increasing complexity of hospitalized patients are the two main drivers of hospital medicine in Japan. Recently, the number of patients who have had adverse events because of inpatient medical errors has risen, and the transparency of these adverse events is making the need for hospitalists more apparent. In addition to improving the day-to-day medical management of hospitalized patients, hospitalists are needed to serve as champions of quality improvement, patient safety, and hospital throughput.

Leaders of the Japanese health care system recognize the need to improve the quality of inpatient care. The first step is to establish internal medicine as a specialty with dedicated internal medicine residency training programs. The Japanese Board of Medical Specialties approved establishing standardized, 3-year internal medicine residency training programs starting this spring, but that decision has been met with resistance for various reasons, namely concern for creating a disparity due to the shortage of internists in rural areas. Therefore, launch of this initiative has been postponed until April 2018.

In the meantime, the concept of hospital-based internists has been gradually gaining the support of subspecialists in Japan. Hospitalists are anticipated to work as the primary medical team leaders, directing and coordinating care among subspecialists in the future. 
Despite its gradual spread, there are several challenges to growth. First, there are many terms for hospitalists, such as “hospital general practitioners” and “general internal medicine physicians.” A unified term for hospitalists would foster acceptance among Japanese physicians. 
Additionally, some physicians, namely subspecialists, still question whether hospitalists are needed in Japan (even though potential loss of clinical revenue is not a significant concern among subspecialists). 

Another challenge is lack of standardized training programs that define the skillset of hospitalists. Standardization of internal medicine training will also improve efficiency of communication between hospitalists and subspecialists.
An important milestone in the Japanese hospital medicine movement was the establishment of a society of hospitalists, known as the Japanese Hospitalist Network (JHN). The JHN has a quarterly publication (Hospitalist) targeted at junior faculty and residents that reviews topics in hospital medicine. 

The JHN is affiliated with a larger society, the Japanese Society of Hospital General Medicine (JSHGM), which holds meetings twice a year. A unique offering at the next JSHGM meeting in March is a point-of-care ultrasound training workshop. Although this is the first such workshop for hospitalists in Japan, there are many training courses designed for the country’s hospitalists. 

The emergence of such courses in Japan has paralleled the increasing need for hospitalists in Japan. We hope these courses for hospitalists will pave the road for the continued growth of hospital medicine in Japan.

Toru Yamada, MD
Dr. Yamada is an internist in the department of general medicine/family and community medicine at Nagoya (Japan) University and practices at Tokyo Bay Urayasu Ichikawa Medical Center in Chiba.
 

Taro Minami, MD
Dr. Minami is assistant professor of medicine in the division of pulmonary, critical care, and sleep medicine at Brown University in Providence, R.I., and director of ultrasound and simulation training at Memorial Hospital of Rhode Island.
 

Nilam J. Soni, MD, MS, FHM
Dr. Soni is associate professor of medicine in the division of hospital medicine at the University of Texas, San Antonio, and a hospitalist with the South Texas Veterans Health Care System in San Antonio.
 

The need for hospitalists continues to increase in Japan. There are approximately 9,000 hospitals in Japan, and approximately 80% of these hospitals are small- to medium-sized hospitals (<300 beds) where the need for hospital medicine is greatest. Historically, internal medicine subspecialists from nearly all subspecialties served as the primary attending physicians of hospitalized patients because inpatient internal medicine physicians, or hospitalists, did not exist.

Most subspecialists caring for hospitalized patients learned to practice internal medicine “on the fly” because they were not required to complete training in internal medicine before pursuing a subspecialty. After medical school, all graduates are required to complete a 2-year internship known as the National Obligatory Initial Postgraduate Clinical Training Program (NOIPCTP). The level of training during the NOIPCTP is similar to the third and fourth years of medical school in the United States. 

The aging population and increasing complexity of hospitalized patients are the two main drivers of hospital medicine in Japan. Recently, the number of patients who have had adverse events because of inpatient medical errors has risen, and the transparency of these adverse events is making the need for hospitalists more apparent. In addition to improving the day-to-day medical management of hospitalized patients, hospitalists are needed to serve as champions of quality improvement, patient safety, and hospital throughput.

Leaders of the Japanese health care system recognize the need to improve the quality of inpatient care. The first step is to establish internal medicine as a specialty with dedicated internal medicine residency training programs. The Japanese Board of Medical Specialties approved establishing standardized, 3-year internal medicine residency training programs starting this spring, but that decision has been met with resistance for various reasons, namely concern for creating a disparity due to the shortage of internists in rural areas. Therefore, launch of this initiative has been postponed until April 2018.

In the meantime, the concept of hospital-based internists has been gradually gaining the support of subspecialists in Japan. Hospitalists are anticipated to work as the primary medical team leaders, directing and coordinating care among subspecialists in the future. 
Despite its gradual spread, there are several challenges to growth. First, there are many terms for hospitalists, such as “hospital general practitioners” and “general internal medicine physicians.” A unified term for hospitalists would foster acceptance among Japanese physicians. 
Additionally, some physicians, namely subspecialists, still question whether hospitalists are needed in Japan (even though potential loss of clinical revenue is not a significant concern among subspecialists). 

Another challenge is lack of standardized training programs that define the skillset of hospitalists. Standardization of internal medicine training will also improve efficiency of communication between hospitalists and subspecialists.
An important milestone in the Japanese hospital medicine movement was the establishment of a society of hospitalists, known as the Japanese Hospitalist Network (JHN). The JHN has a quarterly publication (Hospitalist) targeted at junior faculty and residents that reviews topics in hospital medicine. 

The JHN is affiliated with a larger society, the Japanese Society of Hospital General Medicine (JSHGM), which holds meetings twice a year. A unique offering at the next JSHGM meeting in March is a point-of-care ultrasound training workshop. Although this is the first such workshop for hospitalists in Japan, there are many training courses designed for the country’s hospitalists. 

The emergence of such courses in Japan has paralleled the increasing need for hospitalists in Japan. We hope these courses for hospitalists will pave the road for the continued growth of hospital medicine in Japan.

Toru Yamada, MD
Dr. Yamada is an internist in the department of general medicine/family and community medicine at Nagoya (Japan) University and practices at Tokyo Bay Urayasu Ichikawa Medical Center in Chiba.
 

Taro Minami, MD
Dr. Minami is assistant professor of medicine in the division of pulmonary, critical care, and sleep medicine at Brown University in Providence, R.I., and director of ultrasound and simulation training at Memorial Hospital of Rhode Island.
 

Nilam J. Soni, MD, MS, FHM
Dr. Soni is associate professor of medicine in the division of hospital medicine at the University of Texas, San Antonio, and a hospitalist with the South Texas Veterans Health Care System in San Antonio.
 

Posttraumatic stress disorder (PTSD) is a mental health condition that may develop in response to a traumatic event, such as that experienced by a soldier during active combat duty. In 2009, more than 495,000 veterans within the VA health care system were treated for PTSD—nearly triple the number a decade earlier.¹ Core symptoms of PTSD include alterations in arousal and reactivity, avoidant behaviors, negative alterations in mood and cognition, and intrusive thoughts and nightmares. All of the symptoms can be debilitating. First-line pharmacotherapy options that target these core symptoms include selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs).²

The anxiolytic and sedative effects of benzodiazepines may provide quick relief from many of the secondary symptoms of PTSD, including sleep disturbances, irritability, and panic attacks. However, benzodiazepines potentially interfere with the extinction of conditioned fear—a goal integral to certain types of psychotherapy, such as exposure therapy.^3,4 In addition, the systematic review and meta-analysis by Guina and colleagues revealed that benzodiazepines are ineffective in the treatment of PTSD.⁵ The majority of the evaluated studies that used PTSD-specific measures (eg, Clinician-Administered PTSD Scale [CAPS]) found increased PTSD severity and worse prognosis with use of these medications.⁵ In 2010, the VA and the DoD released a joint guideline for PTSD management.² According to the guideline, benzodiazepines cause harm when used in PTSD and are relatively contraindicated in combat veterans because of the higher incidence of comorbid substance use disorders (SUDs) in these veterans relative to the general population.^2,6

Opioid use also has been linked to poor functional and clinical outcomes in veterans with PTSD. Among patients being treated for opioid use disorder, those with PTSD were less likely to endorse employment as a main source of income and had a higher incidence of recent attempted suicide.⁷ In a large retrospective cohort study, Operation Iraqi Freedom and Operation Enduring Freedom veterans with PTSD who were prescribed opioids were more likely to present to the emergency department (ED) and to be hospitalized for overdoses and injuries.⁸

Despite the risks of benzodiazepine and opioid use in this patient population, these medications are still often prescribed to veterans with PTSD for symptomatic relief. In fiscal year 2009, across the VHA system 37% of veterans diagnosed with PTSD were prescribed a benzodiazepine, 69% of the time by a mental health provider.⁹ Among Iraq and Afghanistan veterans, those with PTSD were significantly more likely to be prescribed an opioid for diagnosed pain—relative to those with a mental health disorder other than PTSD and those without a mental health disorder.⁸ Thus, there seems to be a disconnect between guideline recommendations and current practice.

The authors conducted a study to assess the potential risk of hospitalization for veterans with PTSD prescribed first-line pharmacotherapy and those also prescribed concurrent benzodiazepine and/or opioid therapy since the release of the PTSD guideline in 2010.²

Methods

In this retrospective cohort study, conducted at the Southern Arizona VA Health Care System (SAVAHCS), the authors analyzed electronic medical record data from November 1, 2009 to August 1, 2015. Study inclusion criteria were veteran, aged 18 to 89 years, diagnosis of PTSD (International Classification of Diseases, Ninth Revision, Clinical Modification code 309.81), and SSRI or SNRI newly prescribed between November 1, 2010 and August 1, 2013.

Any veteran prescribed at least one 30-day or longer supply of any benzodiazepine or opioid within 1 year before the SSRI/SNRI initial prescription date was excluded from the study. Also excluded was any patient treated for PTSD at a facility outside SAVAHCS or whose 2-year evaluation period extended past August 1, 2015.

Study Groups

An outpatient prescription was determined to be the initial SSRI/SNRI prescription for a patient who received less than a 30-day cumulative supply of any SSRI or SNRI within 1 year before that prescription date. Citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, paroxetine, sertraline, venlafaxine, vilazodone, and vortioxetine were the prespecified SSRI/SNRIs included in the study.

Patients who received at least 1 outpatient prescription for any benzodiazepine (minimum 30-day supply) within 1 year after the initial SSRI/SNRI prescription date were determined to be on concurrent SSRI/SNRI and benzodiazepine therapy. Alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, estazolam, flurazepam, lorazepam, oxazepam, temazepam, and triazolam were the prespecified benzodiazepines included in the study.

Patients who received at least 1 outpatient prescription for any opioid (minimum 30-day supply) within 1 year after the initial SSRI/SNRI prescription date were determined to be on concurrent SSRI/SNRI and opioid therapy. Codeine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, oxymorphone, pentazocine, propoxyphene, and tramadol were the prespecified opioids included in this study.

Patients who received at least 1 outpatient prescription for any benzodiazepine and any opioid (minimum 30-day supply) within 1 year after the initial SSRI/SNRI prescription date were determined to be on concurrent SSRI/SNRI, benzodiazepine, and opioid therapy.

The index date was defined as the first date of prescription overlap. If there was no benzodiazepine or opioid prescription within 1 year after the initial SSRI/SNRI prescription date, the patient was categorized as being on SSRI/SNRI monotherapy, and the index date was the date of the initial SSRI/SNRI prescription. For each patient, hospitalization data from the 2-year period after the index date were evaluated.

Outcomes and Data Collection

For evaluation of the primary outcome (2-year overall hospitalization risk), the number of unique mental health and medical/surgical hospitalizations was identified by the number of discharge summaries documented in the patient chart during the evaluation period. Time to first hospitalization was recorded for the survival data analysis. Secondary outcomes were mental health hospitalization risk, medical/surgical hospitalization risk, and all-cause mortality within 2 years.

Demographic data that were collected included age, sex, comorbid mental health disorders, comorbid SUDs, and concomitant use of psychotropic medications at index date (baseline). Select comorbid mental health disorders (anxiety, schizophrenia, depression, bipolar disorder) and substance use disorders (alcohol, opioid, illicit drug) also were identified. Data on insomnia and pain comorbidities (headaches or migraines; neuropathy; head, neck, back, arthritis, or joint pain) were collected, as these comorbidities could be indications for prescribing benzodiazepines and opioids. Concomitant baseline use of classes of psychotropic medications (antipsychotics, non-SSRI/SNRI antidepressants, mood stabilizers, anxiolytics, nonbenzodiazepine sedatives/hypnotics) also were documented. Last, hospitalizations within 6 months before the initial SSRI/SNRI prescription date were noted.

Statistical Analysis

Descriptive statistics were used to analyze all baseline demographic data. Continuous measures were evaluated with 1-way analyses of variance and post hoc Bonferroni-corrected pairwise comparisons, and categorical measures with contingency tables and χ² tests or Fisher exact tests. When the overall χ² test was significant across all 4 study groups, post hoc comparisons were performed between the SSRI/SNRI monotherapy group and each other group with Bonferroni adjusted for 3 comparisons.

Unadjusted and adjusted Weibull proportional hazard regression models were used to estimate hospitalization risk within 2 years after the index date for the different study groups with the SSRI/SNRI monotherapy group as the referent. Robust standard errors were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The Weibull model (and not the Cox model) was used because it does not assume hazard remains constant over time, which is appropriate in this instance, as the risk of an adverse event (AE) may be higher when first starting a medication or combination of medications relative to when doses are stabilized. Models were adjusted for age, sex, baseline mental health disorders, and baseline psychotropic medications. As earlier hospitalizations showed evidence of effect modification when this covariate was tested, hazard analyses were limited to patients not previously hospitalized.

The effect size of differences in hospitalization risk meeting statistical significance was assessed by estimating the number needed to harm (NNH) and 95% CIs (not shown) to observe 1 additional hospitalization in each medication group relative to the SSRI/SNRI monotherapy group over a 90-day period. A 95% CI for NNH that did not include 0 indicated the NNH was significant at the .05 level.¹⁰ All-cause mortality was evaluated with the Fisher exact test with post hoc Bonferroni-corrected comparisons as appropriate.

Results

Of 1,703 patients screened, 613 met all study inclusion criteria (Figure 1). 

Baseline characteristics revealed no significant differences between groups in age or comorbid depression, schizophrenia, or SUDs (Table 1). 

With the SSRI/SNRI monotherapy group as the referent, all concurrent therapy groups were at significantly increased risk for overall hospitalization within 2 years after the index date (Tables 2 & 3, Figure 2). 

Risk for mental health hospitalization was significantly increased in all concurrent therapy groups relative to the referent group.

Discussion

In 2013, Hawkins and colleagues evaluated hospitalization risk in veterans treated for PTSD within the Northwest VISN 20 between 2004 and 2010.¹¹ Compared with patients treated with only an SSRI or SNRI, those treated with 1 of those medications and a benzodiazepine were at significantly higher risk for overall hospitalization (AHR, 1.79; 95% CI, 1.38-2.32; P < .001) and mental health hospitalization (AHR, 1.87; 95% CI, 1.37-2.53; P < .001). Furthermore, those prescribed a benzodiazepine and an opioid along with an SSRI or SNRI were at higher risk for overall hospitalization (AHR, 2.98; 95% CI, 2.22-4.00; P < .001), mental health hospitalization (AHR, 2.00; 95% CI, 1.35-2.98; P < .01), medical/surgical hospitalization (AHR, 4.86; 95% CI, 3.30-7.14; P < .001), and ED visits (AHR, 2.01; 95% CI, 1.53-2.65; P < .001).

Findings from the present study, which covered a period after the newest PTSD guideline was released,support findings reported by Hawkins and colleagues in their retrospective cohort study covering an earlier period.^2,11 In the present study, compared with the monotherapy group, the SSRI/SNRI and benzodiazepine therapy group and the SSRI/SNRI, benzodiazepine, and opioid therapy group were at higher risk for both overall hospitalization and mental health hospitalization within 2 years. However, in a subset of PTSD patients prescribed opioids along with first-line pharmacotherapy, this study found that overall, mental health, and medical/surgical hospitalizations were significantly increased as well. Furthermore, this study found 2-year mortality was significantly higher for the SSRI/SNRI, benzodiazepine, and opioid therapy group than for the SSRI/SNRI monotherapy group.

Adjusted hazard ratios were higher in the present study than those in the study by Hawkins and colleagues,but CIs were wider as well.¹¹ These differences may be attributable to the relatively smaller sample size of the present study and may explain why the HR was higher for the SSRI/SNRI and opioid therapy group than for the SSRI/SNRI, benzodiazepine, and opioid therapy group.

Nevertheless, these results support the growing body of evidence establishing the many risks for AEs when benzodiazepines and opioids are prescribed in the setting of PTSD. Unfortunately, it seems that, against clear guideline recommendations and literature findings, these medications still are being prescribed to this vulnerable, high-risk population.

In the last few months of 2013, the VA health care system launched 2 important medication safety initiatives. The Psychotropic Drug Safety Initiative (PDSI) was established as a quality improvement initiative for evidence-based provision of psychotropic medications. One PDSI metric in particular focused on reducing the proportion of veterans with PTSD being treated with benzodiazepines. The Opioid Safety Initiative (OSI) came as a response to a dramatic increase in the number of fatal overdoses related to prescription opioids—an increase linked to an unprecedented jump in opioid use for nonmalignant pain. As the present study’s inclusion cutoff date of August 1, 2013, preceded the debut of both PDSI and OSI, the benzodiazepine and opioid prescription rates reported here might be higher than those currently being found under the 2 initiatives.

Limitations

This study had several limitations that might affect the interpretation or generalizability of findings. Requiring at least a 30-day supply for prescription eligibility was an attempt to focus on chronic use of medications rather than on, for example, onetime supplies of opioids for dental procedures. However, prescription fill history was not assessed. Therefore, patients could have been included in certain study groups even if their SSRI, SNRI, benzodiazepine, or opioid prescription was not refilled. Furthermore, only VA medical records were used; non-VA prescriptions were not captured.

In addition, this study was limited to patients who at bare minimum were prescribed an SSRI or an SNRI. Some patients may have been prescribed a benzodiazepine and/or an opioid but were not on appropriate first-line pharmacotherapy for PTSD. These patients were excluded from the study, and their relative hospitalization risk went unexplored. Therefore, the magnitude of the issue at hand might have been underestimated.

Although psychotherapy is a first-line treatment option for PTSD, the study did not assess the potential impact of psychotherapy on outcomes or the groups’ relative proportions of patients undergoing psychotherapy. It is unknown whether the groups were equivalent at baseline in regards to psychotherapy participation rates.

This study did not characterize the specific reasons for hospitalization beyond whether it was for a mental health or a medical/surgical issue; thus, no distinction was made between hospitalizations for an elective procedure and hospitalizations for a drug overdose or an injury. Investigators could characterize admission diagnoses to better assess whether hospitalizations are truly associated with study medications or whether patients are being hospitalized for unrelated reasons. In addition, they could elucidate the true nature of hospitalization risk associated with SSRI/SNRI, benzodiazepine, and opioid use by comparing admission diagnoses made before and after initiation of these pharmacologic therapies.

This study also could not assess outcomes for patients who presented to the ED but were not admitted. If the hospital’s floor and ED beds were at full capacity, some patients might have been transferred to an outside facility. However, this scenario is not common at SAVAHCS, where the study was conducted.

Although some comorbid conditions were noted, the study did not evaluate whether its patients had a compelling indication for benzodiazepines in particular. Opioid use is very limited to the treatment of pain, and the majority of the patients on opioid therapy in this study had a diagnosed pain syndrome.

Because of the study’s sample size and power limitations, patients were eligible to be included in a concurrent therapy group if a benzodiazepine, an opioid, or both were added no later than 1 year after SSRI/SNRI initiation. This gap of up to 1 year might have introduced some variability in exposure to risk from earlier prescribed medications. However, sensitivity analyses were performed with multiple constructed Weibull models of time to hospitalization based on subsets with varying overlapping medication gaps. Analyses revealed relatively stable HRs, suggesting that potential bias did not occur.

Future Directions

Investigators could explore the higher all-cause mortality rates in the SSRI/SNRI, benzodiazepine, and opioid therapy group, as this study did not assess cause of death in these patients. Whether any patients died of reasons directly attributable to benzodiazepines or opioids is unknown.

That SSRIs and SNRIs are the only established first-line pharmacologic treatment options for PTSD symptoms partly accounts for the widespread use of benzodiazepines in this population. For that reason, beyond characterizing the many risks associated with using benzodiazepines to manage these symptoms, there is a huge need to research the viability of other pharmacologic agents in treating PTSD. This is especially important given the slower onset to efficacy of the SSRIs and SNRIs; per estimates, only up to 60% of patients respond to SSRIs, and 20% to 30% achieve full remission of PTSD.¹² Furthermore, these rates likely are even lower for combat veterans than those for the general population. Several trials discussed in a 2009 guideline review of the treatment of patients with acute stress disorder and PTSD have called into question the efficacy of SSRIs for combat-related PTSD.¹³ In these randomized, controlled trials, change in PTSD symptom severity as measured with CAPS was not significantly reduced with SSRIs compared with placebo.

A systematic review revealed that, of the nonantidepressants used as adjuncts in treating patients who do not achieve remission with SSRIs, the atypical antipsychotic risperidone may have the strongest supporting evidence.¹² However, the present study found high rates of antipsychotic use in the SSRI/SNRI, benzodiazepine, and opioid therapy group, which also had the highest all-cause mortality rate. The safety of risperidone as an alternative treatment needs further evaluation.

Some prospective studies have suggested that the α₁ blockers doxazosin and prazosin, the latter of which is commonly used for PTSD nightmares, also may improve PTSD symptoms as assessed by CAPS.^14,15 Although these results are promising, the trials to date have been conducted with relatively small sample sizes.

With more veterans being treated for PTSD within the VA health care system, the central treatment goal remains: Adequately address the symptoms of PTSD while minimizing the harm caused by medications. Prescribers should limit benzodiazepine and opioid use in this population and consider safer nonpharmacologic and pharmacologic treatment options when possible.

Conclusion

Combat veterans with PTSD who are prescribed benzodiazepines and/or opioids in addition to first-line pharmacotherapy are at significantly increased risk for overall and mental health hospitalization.

Click here to read the digital edition.

Posttraumatic stress disorder (PTSD) is a mental health condition that may develop in response to a traumatic event, such as that experienced by a soldier during active combat duty. In 2009, more than 495,000 veterans within the VA health care system were treated for PTSD—nearly triple the number a decade earlier.¹ Core symptoms of PTSD include alterations in arousal and reactivity, avoidant behaviors, negative alterations in mood and cognition, and intrusive thoughts and nightmares. All of the symptoms can be debilitating. First-line pharmacotherapy options that target these core symptoms include selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs).²

The anxiolytic and sedative effects of benzodiazepines may provide quick relief from many of the secondary symptoms of PTSD, including sleep disturbances, irritability, and panic attacks. However, benzodiazepines potentially interfere with the extinction of conditioned fear—a goal integral to certain types of psychotherapy, such as exposure therapy.^3,4 In addition, the systematic review and meta-analysis by Guina and colleagues revealed that benzodiazepines are ineffective in the treatment of PTSD.⁵ The majority of the evaluated studies that used PTSD-specific measures (eg, Clinician-Administered PTSD Scale [CAPS]) found increased PTSD severity and worse prognosis with use of these medications.⁵ In 2010, the VA and the DoD released a joint guideline for PTSD management.² According to the guideline, benzodiazepines cause harm when used in PTSD and are relatively contraindicated in combat veterans because of the higher incidence of comorbid substance use disorders (SUDs) in these veterans relative to the general population.^2,6

Opioid use also has been linked to poor functional and clinical outcomes in veterans with PTSD. Among patients being treated for opioid use disorder, those with PTSD were less likely to endorse employment as a main source of income and had a higher incidence of recent attempted suicide.⁷ In a large retrospective cohort study, Operation Iraqi Freedom and Operation Enduring Freedom veterans with PTSD who were prescribed opioids were more likely to present to the emergency department (ED) and to be hospitalized for overdoses and injuries.⁸

Despite the risks of benzodiazepine and opioid use in this patient population, these medications are still often prescribed to veterans with PTSD for symptomatic relief. In fiscal year 2009, across the VHA system 37% of veterans diagnosed with PTSD were prescribed a benzodiazepine, 69% of the time by a mental health provider.⁹ Among Iraq and Afghanistan veterans, those with PTSD were significantly more likely to be prescribed an opioid for diagnosed pain—relative to those with a mental health disorder other than PTSD and those without a mental health disorder.⁸ Thus, there seems to be a disconnect between guideline recommendations and current practice.

The authors conducted a study to assess the potential risk of hospitalization for veterans with PTSD prescribed first-line pharmacotherapy and those also prescribed concurrent benzodiazepine and/or opioid therapy since the release of the PTSD guideline in 2010.²

Methods

In this retrospective cohort study, conducted at the Southern Arizona VA Health Care System (SAVAHCS), the authors analyzed electronic medical record data from November 1, 2009 to August 1, 2015. Study inclusion criteria were veteran, aged 18 to 89 years, diagnosis of PTSD (International Classification of Diseases, Ninth Revision, Clinical Modification code 309.81), and SSRI or SNRI newly prescribed between November 1, 2010 and August 1, 2013.

Any veteran prescribed at least one 30-day or longer supply of any benzodiazepine or opioid within 1 year before the SSRI/SNRI initial prescription date was excluded from the study. Also excluded was any patient treated for PTSD at a facility outside SAVAHCS or whose 2-year evaluation period extended past August 1, 2015.

Study Groups

An outpatient prescription was determined to be the initial SSRI/SNRI prescription for a patient who received less than a 30-day cumulative supply of any SSRI or SNRI within 1 year before that prescription date. Citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, paroxetine, sertraline, venlafaxine, vilazodone, and vortioxetine were the prespecified SSRI/SNRIs included in the study.

Patients who received at least 1 outpatient prescription for any benzodiazepine (minimum 30-day supply) within 1 year after the initial SSRI/SNRI prescription date were determined to be on concurrent SSRI/SNRI and benzodiazepine therapy. Alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, estazolam, flurazepam, lorazepam, oxazepam, temazepam, and triazolam were the prespecified benzodiazepines included in the study.

Patients who received at least 1 outpatient prescription for any opioid (minimum 30-day supply) within 1 year after the initial SSRI/SNRI prescription date were determined to be on concurrent SSRI/SNRI and opioid therapy. Codeine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, oxymorphone, pentazocine, propoxyphene, and tramadol were the prespecified opioids included in this study.

Patients who received at least 1 outpatient prescription for any benzodiazepine and any opioid (minimum 30-day supply) within 1 year after the initial SSRI/SNRI prescription date were determined to be on concurrent SSRI/SNRI, benzodiazepine, and opioid therapy.

The index date was defined as the first date of prescription overlap. If there was no benzodiazepine or opioid prescription within 1 year after the initial SSRI/SNRI prescription date, the patient was categorized as being on SSRI/SNRI monotherapy, and the index date was the date of the initial SSRI/SNRI prescription. For each patient, hospitalization data from the 2-year period after the index date were evaluated.

Outcomes and Data Collection

For evaluation of the primary outcome (2-year overall hospitalization risk), the number of unique mental health and medical/surgical hospitalizations was identified by the number of discharge summaries documented in the patient chart during the evaluation period. Time to first hospitalization was recorded for the survival data analysis. Secondary outcomes were mental health hospitalization risk, medical/surgical hospitalization risk, and all-cause mortality within 2 years.

Demographic data that were collected included age, sex, comorbid mental health disorders, comorbid SUDs, and concomitant use of psychotropic medications at index date (baseline). Select comorbid mental health disorders (anxiety, schizophrenia, depression, bipolar disorder) and substance use disorders (alcohol, opioid, illicit drug) also were identified. Data on insomnia and pain comorbidities (headaches or migraines; neuropathy; head, neck, back, arthritis, or joint pain) were collected, as these comorbidities could be indications for prescribing benzodiazepines and opioids. Concomitant baseline use of classes of psychotropic medications (antipsychotics, non-SSRI/SNRI antidepressants, mood stabilizers, anxiolytics, nonbenzodiazepine sedatives/hypnotics) also were documented. Last, hospitalizations within 6 months before the initial SSRI/SNRI prescription date were noted.

Statistical Analysis

Descriptive statistics were used to analyze all baseline demographic data. Continuous measures were evaluated with 1-way analyses of variance and post hoc Bonferroni-corrected pairwise comparisons, and categorical measures with contingency tables and χ² tests or Fisher exact tests. When the overall χ² test was significant across all 4 study groups, post hoc comparisons were performed between the SSRI/SNRI monotherapy group and each other group with Bonferroni adjusted for 3 comparisons.

Unadjusted and adjusted Weibull proportional hazard regression models were used to estimate hospitalization risk within 2 years after the index date for the different study groups with the SSRI/SNRI monotherapy group as the referent. Robust standard errors were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The Weibull model (and not the Cox model) was used because it does not assume hazard remains constant over time, which is appropriate in this instance, as the risk of an adverse event (AE) may be higher when first starting a medication or combination of medications relative to when doses are stabilized. Models were adjusted for age, sex, baseline mental health disorders, and baseline psychotropic medications. As earlier hospitalizations showed evidence of effect modification when this covariate was tested, hazard analyses were limited to patients not previously hospitalized.

The effect size of differences in hospitalization risk meeting statistical significance was assessed by estimating the number needed to harm (NNH) and 95% CIs (not shown) to observe 1 additional hospitalization in each medication group relative to the SSRI/SNRI monotherapy group over a 90-day period. A 95% CI for NNH that did not include 0 indicated the NNH was significant at the .05 level.¹⁰ All-cause mortality was evaluated with the Fisher exact test with post hoc Bonferroni-corrected comparisons as appropriate.

Results

Of 1,703 patients screened, 613 met all study inclusion criteria (Figure 1). 

Baseline characteristics revealed no significant differences between groups in age or comorbid depression, schizophrenia, or SUDs (Table 1). 

With the SSRI/SNRI monotherapy group as the referent, all concurrent therapy groups were at significantly increased risk for overall hospitalization within 2 years after the index date (Tables 2 & 3, Figure 2). 

Risk for mental health hospitalization was significantly increased in all concurrent therapy groups relative to the referent group.

Discussion

In 2013, Hawkins and colleagues evaluated hospitalization risk in veterans treated for PTSD within the Northwest VISN 20 between 2004 and 2010.¹¹ Compared with patients treated with only an SSRI or SNRI, those treated with 1 of those medications and a benzodiazepine were at significantly higher risk for overall hospitalization (AHR, 1.79; 95% CI, 1.38-2.32; P < .001) and mental health hospitalization (AHR, 1.87; 95% CI, 1.37-2.53; P < .001). Furthermore, those prescribed a benzodiazepine and an opioid along with an SSRI or SNRI were at higher risk for overall hospitalization (AHR, 2.98; 95% CI, 2.22-4.00; P < .001), mental health hospitalization (AHR, 2.00; 95% CI, 1.35-2.98; P < .01), medical/surgical hospitalization (AHR, 4.86; 95% CI, 3.30-7.14; P < .001), and ED visits (AHR, 2.01; 95% CI, 1.53-2.65; P < .001).

Findings from the present study, which covered a period after the newest PTSD guideline was released,support findings reported by Hawkins and colleagues in their retrospective cohort study covering an earlier period.^2,11 In the present study, compared with the monotherapy group, the SSRI/SNRI and benzodiazepine therapy group and the SSRI/SNRI, benzodiazepine, and opioid therapy group were at higher risk for both overall hospitalization and mental health hospitalization within 2 years. However, in a subset of PTSD patients prescribed opioids along with first-line pharmacotherapy, this study found that overall, mental health, and medical/surgical hospitalizations were significantly increased as well. Furthermore, this study found 2-year mortality was significantly higher for the SSRI/SNRI, benzodiazepine, and opioid therapy group than for the SSRI/SNRI monotherapy group.

Adjusted hazard ratios were higher in the present study than those in the study by Hawkins and colleagues,but CIs were wider as well.¹¹ These differences may be attributable to the relatively smaller sample size of the present study and may explain why the HR was higher for the SSRI/SNRI and opioid therapy group than for the SSRI/SNRI, benzodiazepine, and opioid therapy group.

Nevertheless, these results support the growing body of evidence establishing the many risks for AEs when benzodiazepines and opioids are prescribed in the setting of PTSD. Unfortunately, it seems that, against clear guideline recommendations and literature findings, these medications still are being prescribed to this vulnerable, high-risk population.

In the last few months of 2013, the VA health care system launched 2 important medication safety initiatives. The Psychotropic Drug Safety Initiative (PDSI) was established as a quality improvement initiative for evidence-based provision of psychotropic medications. One PDSI metric in particular focused on reducing the proportion of veterans with PTSD being treated with benzodiazepines. The Opioid Safety Initiative (OSI) came as a response to a dramatic increase in the number of fatal overdoses related to prescription opioids—an increase linked to an unprecedented jump in opioid use for nonmalignant pain. As the present study’s inclusion cutoff date of August 1, 2013, preceded the debut of both PDSI and OSI, the benzodiazepine and opioid prescription rates reported here might be higher than those currently being found under the 2 initiatives.

Limitations

This study had several limitations that might affect the interpretation or generalizability of findings. Requiring at least a 30-day supply for prescription eligibility was an attempt to focus on chronic use of medications rather than on, for example, onetime supplies of opioids for dental procedures. However, prescription fill history was not assessed. Therefore, patients could have been included in certain study groups even if their SSRI, SNRI, benzodiazepine, or opioid prescription was not refilled. Furthermore, only VA medical records were used; non-VA prescriptions were not captured.

In addition, this study was limited to patients who at bare minimum were prescribed an SSRI or an SNRI. Some patients may have been prescribed a benzodiazepine and/or an opioid but were not on appropriate first-line pharmacotherapy for PTSD. These patients were excluded from the study, and their relative hospitalization risk went unexplored. Therefore, the magnitude of the issue at hand might have been underestimated.

Although psychotherapy is a first-line treatment option for PTSD, the study did not assess the potential impact of psychotherapy on outcomes or the groups’ relative proportions of patients undergoing psychotherapy. It is unknown whether the groups were equivalent at baseline in regards to psychotherapy participation rates.

This study did not characterize the specific reasons for hospitalization beyond whether it was for a mental health or a medical/surgical issue; thus, no distinction was made between hospitalizations for an elective procedure and hospitalizations for a drug overdose or an injury. Investigators could characterize admission diagnoses to better assess whether hospitalizations are truly associated with study medications or whether patients are being hospitalized for unrelated reasons. In addition, they could elucidate the true nature of hospitalization risk associated with SSRI/SNRI, benzodiazepine, and opioid use by comparing admission diagnoses made before and after initiation of these pharmacologic therapies.

This study also could not assess outcomes for patients who presented to the ED but were not admitted. If the hospital’s floor and ED beds were at full capacity, some patients might have been transferred to an outside facility. However, this scenario is not common at SAVAHCS, where the study was conducted.

Although some comorbid conditions were noted, the study did not evaluate whether its patients had a compelling indication for benzodiazepines in particular. Opioid use is very limited to the treatment of pain, and the majority of the patients on opioid therapy in this study had a diagnosed pain syndrome.

Because of the study’s sample size and power limitations, patients were eligible to be included in a concurrent therapy group if a benzodiazepine, an opioid, or both were added no later than 1 year after SSRI/SNRI initiation. This gap of up to 1 year might have introduced some variability in exposure to risk from earlier prescribed medications. However, sensitivity analyses were performed with multiple constructed Weibull models of time to hospitalization based on subsets with varying overlapping medication gaps. Analyses revealed relatively stable HRs, suggesting that potential bias did not occur.

Future Directions

Investigators could explore the higher all-cause mortality rates in the SSRI/SNRI, benzodiazepine, and opioid therapy group, as this study did not assess cause of death in these patients. Whether any patients died of reasons directly attributable to benzodiazepines or opioids is unknown.

That SSRIs and SNRIs are the only established first-line pharmacologic treatment options for PTSD symptoms partly accounts for the widespread use of benzodiazepines in this population. For that reason, beyond characterizing the many risks associated with using benzodiazepines to manage these symptoms, there is a huge need to research the viability of other pharmacologic agents in treating PTSD. This is especially important given the slower onset to efficacy of the SSRIs and SNRIs; per estimates, only up to 60% of patients respond to SSRIs, and 20% to 30% achieve full remission of PTSD.¹² Furthermore, these rates likely are even lower for combat veterans than those for the general population. Several trials discussed in a 2009 guideline review of the treatment of patients with acute stress disorder and PTSD have called into question the efficacy of SSRIs for combat-related PTSD.¹³ In these randomized, controlled trials, change in PTSD symptom severity as measured with CAPS was not significantly reduced with SSRIs compared with placebo.

A systematic review revealed that, of the nonantidepressants used as adjuncts in treating patients who do not achieve remission with SSRIs, the atypical antipsychotic risperidone may have the strongest supporting evidence.¹² However, the present study found high rates of antipsychotic use in the SSRI/SNRI, benzodiazepine, and opioid therapy group, which also had the highest all-cause mortality rate. The safety of risperidone as an alternative treatment needs further evaluation.

Some prospective studies have suggested that the α₁ blockers doxazosin and prazosin, the latter of which is commonly used for PTSD nightmares, also may improve PTSD symptoms as assessed by CAPS.^14,15 Although these results are promising, the trials to date have been conducted with relatively small sample sizes.

With more veterans being treated for PTSD within the VA health care system, the central treatment goal remains: Adequately address the symptoms of PTSD while minimizing the harm caused by medications. Prescribers should limit benzodiazepine and opioid use in this population and consider safer nonpharmacologic and pharmacologic treatment options when possible.

Conclusion

Combat veterans with PTSD who are prescribed benzodiazepines and/or opioids in addition to first-line pharmacotherapy are at significantly increased risk for overall and mental health hospitalization.

Click here to read the digital edition.

Posttraumatic stress disorder (PTSD) is a mental health condition that may develop in response to a traumatic event, such as that experienced by a soldier during active combat duty. In 2009, more than 495,000 veterans within the VA health care system were treated for PTSD—nearly triple the number a decade earlier.¹ Core symptoms of PTSD include alterations in arousal and reactivity, avoidant behaviors, negative alterations in mood and cognition, and intrusive thoughts and nightmares. All of the symptoms can be debilitating. First-line pharmacotherapy options that target these core symptoms include selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs).²

The anxiolytic and sedative effects of benzodiazepines may provide quick relief from many of the secondary symptoms of PTSD, including sleep disturbances, irritability, and panic attacks. However, benzodiazepines potentially interfere with the extinction of conditioned fear—a goal integral to certain types of psychotherapy, such as exposure therapy.^3,4 In addition, the systematic review and meta-analysis by Guina and colleagues revealed that benzodiazepines are ineffective in the treatment of PTSD.⁵ The majority of the evaluated studies that used PTSD-specific measures (eg, Clinician-Administered PTSD Scale [CAPS]) found increased PTSD severity and worse prognosis with use of these medications.⁵ In 2010, the VA and the DoD released a joint guideline for PTSD management.² According to the guideline, benzodiazepines cause harm when used in PTSD and are relatively contraindicated in combat veterans because of the higher incidence of comorbid substance use disorders (SUDs) in these veterans relative to the general population.^2,6

Opioid use also has been linked to poor functional and clinical outcomes in veterans with PTSD. Among patients being treated for opioid use disorder, those with PTSD were less likely to endorse employment as a main source of income and had a higher incidence of recent attempted suicide.⁷ In a large retrospective cohort study, Operation Iraqi Freedom and Operation Enduring Freedom veterans with PTSD who were prescribed opioids were more likely to present to the emergency department (ED) and to be hospitalized for overdoses and injuries.⁸

Despite the risks of benzodiazepine and opioid use in this patient population, these medications are still often prescribed to veterans with PTSD for symptomatic relief. In fiscal year 2009, across the VHA system 37% of veterans diagnosed with PTSD were prescribed a benzodiazepine, 69% of the time by a mental health provider.⁹ Among Iraq and Afghanistan veterans, those with PTSD were significantly more likely to be prescribed an opioid for diagnosed pain—relative to those with a mental health disorder other than PTSD and those without a mental health disorder.⁸ Thus, there seems to be a disconnect between guideline recommendations and current practice.

The authors conducted a study to assess the potential risk of hospitalization for veterans with PTSD prescribed first-line pharmacotherapy and those also prescribed concurrent benzodiazepine and/or opioid therapy since the release of the PTSD guideline in 2010.²

Methods

In this retrospective cohort study, conducted at the Southern Arizona VA Health Care System (SAVAHCS), the authors analyzed electronic medical record data from November 1, 2009 to August 1, 2015. Study inclusion criteria were veteran, aged 18 to 89 years, diagnosis of PTSD (International Classification of Diseases, Ninth Revision, Clinical Modification code 309.81), and SSRI or SNRI newly prescribed between November 1, 2010 and August 1, 2013.

Any veteran prescribed at least one 30-day or longer supply of any benzodiazepine or opioid within 1 year before the SSRI/SNRI initial prescription date was excluded from the study. Also excluded was any patient treated for PTSD at a facility outside SAVAHCS or whose 2-year evaluation period extended past August 1, 2015.

Study Groups

An outpatient prescription was determined to be the initial SSRI/SNRI prescription for a patient who received less than a 30-day cumulative supply of any SSRI or SNRI within 1 year before that prescription date. Citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, paroxetine, sertraline, venlafaxine, vilazodone, and vortioxetine were the prespecified SSRI/SNRIs included in the study.

Patients who received at least 1 outpatient prescription for any benzodiazepine (minimum 30-day supply) within 1 year after the initial SSRI/SNRI prescription date were determined to be on concurrent SSRI/SNRI and benzodiazepine therapy. Alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, estazolam, flurazepam, lorazepam, oxazepam, temazepam, and triazolam were the prespecified benzodiazepines included in the study.

Patients who received at least 1 outpatient prescription for any opioid (minimum 30-day supply) within 1 year after the initial SSRI/SNRI prescription date were determined to be on concurrent SSRI/SNRI and opioid therapy. Codeine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, oxymorphone, pentazocine, propoxyphene, and tramadol were the prespecified opioids included in this study.

Patients who received at least 1 outpatient prescription for any benzodiazepine and any opioid (minimum 30-day supply) within 1 year after the initial SSRI/SNRI prescription date were determined to be on concurrent SSRI/SNRI, benzodiazepine, and opioid therapy.

The index date was defined as the first date of prescription overlap. If there was no benzodiazepine or opioid prescription within 1 year after the initial SSRI/SNRI prescription date, the patient was categorized as being on SSRI/SNRI monotherapy, and the index date was the date of the initial SSRI/SNRI prescription. For each patient, hospitalization data from the 2-year period after the index date were evaluated.

Outcomes and Data Collection

For evaluation of the primary outcome (2-year overall hospitalization risk), the number of unique mental health and medical/surgical hospitalizations was identified by the number of discharge summaries documented in the patient chart during the evaluation period. Time to first hospitalization was recorded for the survival data analysis. Secondary outcomes were mental health hospitalization risk, medical/surgical hospitalization risk, and all-cause mortality within 2 years.

Demographic data that were collected included age, sex, comorbid mental health disorders, comorbid SUDs, and concomitant use of psychotropic medications at index date (baseline). Select comorbid mental health disorders (anxiety, schizophrenia, depression, bipolar disorder) and substance use disorders (alcohol, opioid, illicit drug) also were identified. Data on insomnia and pain comorbidities (headaches or migraines; neuropathy; head, neck, back, arthritis, or joint pain) were collected, as these comorbidities could be indications for prescribing benzodiazepines and opioids. Concomitant baseline use of classes of psychotropic medications (antipsychotics, non-SSRI/SNRI antidepressants, mood stabilizers, anxiolytics, nonbenzodiazepine sedatives/hypnotics) also were documented. Last, hospitalizations within 6 months before the initial SSRI/SNRI prescription date were noted.

Statistical Analysis

Descriptive statistics were used to analyze all baseline demographic data. Continuous measures were evaluated with 1-way analyses of variance and post hoc Bonferroni-corrected pairwise comparisons, and categorical measures with contingency tables and χ² tests or Fisher exact tests. When the overall χ² test was significant across all 4 study groups, post hoc comparisons were performed between the SSRI/SNRI monotherapy group and each other group with Bonferroni adjusted for 3 comparisons.

Unadjusted and adjusted Weibull proportional hazard regression models were used to estimate hospitalization risk within 2 years after the index date for the different study groups with the SSRI/SNRI monotherapy group as the referent. Robust standard errors were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The Weibull model (and not the Cox model) was used because it does not assume hazard remains constant over time, which is appropriate in this instance, as the risk of an adverse event (AE) may be higher when first starting a medication or combination of medications relative to when doses are stabilized. Models were adjusted for age, sex, baseline mental health disorders, and baseline psychotropic medications. As earlier hospitalizations showed evidence of effect modification when this covariate was tested, hazard analyses were limited to patients not previously hospitalized.

The effect size of differences in hospitalization risk meeting statistical significance was assessed by estimating the number needed to harm (NNH) and 95% CIs (not shown) to observe 1 additional hospitalization in each medication group relative to the SSRI/SNRI monotherapy group over a 90-day period. A 95% CI for NNH that did not include 0 indicated the NNH was significant at the .05 level.¹⁰ All-cause mortality was evaluated with the Fisher exact test with post hoc Bonferroni-corrected comparisons as appropriate.

Results

Of 1,703 patients screened, 613 met all study inclusion criteria (Figure 1). 

Baseline characteristics revealed no significant differences between groups in age or comorbid depression, schizophrenia, or SUDs (Table 1). 

With the SSRI/SNRI monotherapy group as the referent, all concurrent therapy groups were at significantly increased risk for overall hospitalization within 2 years after the index date (Tables 2 & 3, Figure 2). 

Risk for mental health hospitalization was significantly increased in all concurrent therapy groups relative to the referent group.

Discussion

In 2013, Hawkins and colleagues evaluated hospitalization risk in veterans treated for PTSD within the Northwest VISN 20 between 2004 and 2010.¹¹ Compared with patients treated with only an SSRI or SNRI, those treated with 1 of those medications and a benzodiazepine were at significantly higher risk for overall hospitalization (AHR, 1.79; 95% CI, 1.38-2.32; P < .001) and mental health hospitalization (AHR, 1.87; 95% CI, 1.37-2.53; P < .001). Furthermore, those prescribed a benzodiazepine and an opioid along with an SSRI or SNRI were at higher risk for overall hospitalization (AHR, 2.98; 95% CI, 2.22-4.00; P < .001), mental health hospitalization (AHR, 2.00; 95% CI, 1.35-2.98; P < .01), medical/surgical hospitalization (AHR, 4.86; 95% CI, 3.30-7.14; P < .001), and ED visits (AHR, 2.01; 95% CI, 1.53-2.65; P < .001).

Findings from the present study, which covered a period after the newest PTSD guideline was released,support findings reported by Hawkins and colleagues in their retrospective cohort study covering an earlier period.^2,11 In the present study, compared with the monotherapy group, the SSRI/SNRI and benzodiazepine therapy group and the SSRI/SNRI, benzodiazepine, and opioid therapy group were at higher risk for both overall hospitalization and mental health hospitalization within 2 years. However, in a subset of PTSD patients prescribed opioids along with first-line pharmacotherapy, this study found that overall, mental health, and medical/surgical hospitalizations were significantly increased as well. Furthermore, this study found 2-year mortality was significantly higher for the SSRI/SNRI, benzodiazepine, and opioid therapy group than for the SSRI/SNRI monotherapy group.

Adjusted hazard ratios were higher in the present study than those in the study by Hawkins and colleagues,but CIs were wider as well.¹¹ These differences may be attributable to the relatively smaller sample size of the present study and may explain why the HR was higher for the SSRI/SNRI and opioid therapy group than for the SSRI/SNRI, benzodiazepine, and opioid therapy group.

Nevertheless, these results support the growing body of evidence establishing the many risks for AEs when benzodiazepines and opioids are prescribed in the setting of PTSD. Unfortunately, it seems that, against clear guideline recommendations and literature findings, these medications still are being prescribed to this vulnerable, high-risk population.

In the last few months of 2013, the VA health care system launched 2 important medication safety initiatives. The Psychotropic Drug Safety Initiative (PDSI) was established as a quality improvement initiative for evidence-based provision of psychotropic medications. One PDSI metric in particular focused on reducing the proportion of veterans with PTSD being treated with benzodiazepines. The Opioid Safety Initiative (OSI) came as a response to a dramatic increase in the number of fatal overdoses related to prescription opioids—an increase linked to an unprecedented jump in opioid use for nonmalignant pain. As the present study’s inclusion cutoff date of August 1, 2013, preceded the debut of both PDSI and OSI, the benzodiazepine and opioid prescription rates reported here might be higher than those currently being found under the 2 initiatives.

Limitations

This study had several limitations that might affect the interpretation or generalizability of findings. Requiring at least a 30-day supply for prescription eligibility was an attempt to focus on chronic use of medications rather than on, for example, onetime supplies of opioids for dental procedures. However, prescription fill history was not assessed. Therefore, patients could have been included in certain study groups even if their SSRI, SNRI, benzodiazepine, or opioid prescription was not refilled. Furthermore, only VA medical records were used; non-VA prescriptions were not captured.

In addition, this study was limited to patients who at bare minimum were prescribed an SSRI or an SNRI. Some patients may have been prescribed a benzodiazepine and/or an opioid but were not on appropriate first-line pharmacotherapy for PTSD. These patients were excluded from the study, and their relative hospitalization risk went unexplored. Therefore, the magnitude of the issue at hand might have been underestimated.

Although psychotherapy is a first-line treatment option for PTSD, the study did not assess the potential impact of psychotherapy on outcomes or the groups’ relative proportions of patients undergoing psychotherapy. It is unknown whether the groups were equivalent at baseline in regards to psychotherapy participation rates.

This study did not characterize the specific reasons for hospitalization beyond whether it was for a mental health or a medical/surgical issue; thus, no distinction was made between hospitalizations for an elective procedure and hospitalizations for a drug overdose or an injury. Investigators could characterize admission diagnoses to better assess whether hospitalizations are truly associated with study medications or whether patients are being hospitalized for unrelated reasons. In addition, they could elucidate the true nature of hospitalization risk associated with SSRI/SNRI, benzodiazepine, and opioid use by comparing admission diagnoses made before and after initiation of these pharmacologic therapies.

This study also could not assess outcomes for patients who presented to the ED but were not admitted. If the hospital’s floor and ED beds were at full capacity, some patients might have been transferred to an outside facility. However, this scenario is not common at SAVAHCS, where the study was conducted.

Although some comorbid conditions were noted, the study did not evaluate whether its patients had a compelling indication for benzodiazepines in particular. Opioid use is very limited to the treatment of pain, and the majority of the patients on opioid therapy in this study had a diagnosed pain syndrome.

Because of the study’s sample size and power limitations, patients were eligible to be included in a concurrent therapy group if a benzodiazepine, an opioid, or both were added no later than 1 year after SSRI/SNRI initiation. This gap of up to 1 year might have introduced some variability in exposure to risk from earlier prescribed medications. However, sensitivity analyses were performed with multiple constructed Weibull models of time to hospitalization based on subsets with varying overlapping medication gaps. Analyses revealed relatively stable HRs, suggesting that potential bias did not occur.

Future Directions

Investigators could explore the higher all-cause mortality rates in the SSRI/SNRI, benzodiazepine, and opioid therapy group, as this study did not assess cause of death in these patients. Whether any patients died of reasons directly attributable to benzodiazepines or opioids is unknown.

That SSRIs and SNRIs are the only established first-line pharmacologic treatment options for PTSD symptoms partly accounts for the widespread use of benzodiazepines in this population. For that reason, beyond characterizing the many risks associated with using benzodiazepines to manage these symptoms, there is a huge need to research the viability of other pharmacologic agents in treating PTSD. This is especially important given the slower onset to efficacy of the SSRIs and SNRIs; per estimates, only up to 60% of patients respond to SSRIs, and 20% to 30% achieve full remission of PTSD.¹² Furthermore, these rates likely are even lower for combat veterans than those for the general population. Several trials discussed in a 2009 guideline review of the treatment of patients with acute stress disorder and PTSD have called into question the efficacy of SSRIs for combat-related PTSD.¹³ In these randomized, controlled trials, change in PTSD symptom severity as measured with CAPS was not significantly reduced with SSRIs compared with placebo.

A systematic review revealed that, of the nonantidepressants used as adjuncts in treating patients who do not achieve remission with SSRIs, the atypical antipsychotic risperidone may have the strongest supporting evidence.¹² However, the present study found high rates of antipsychotic use in the SSRI/SNRI, benzodiazepine, and opioid therapy group, which also had the highest all-cause mortality rate. The safety of risperidone as an alternative treatment needs further evaluation.

Some prospective studies have suggested that the α₁ blockers doxazosin and prazosin, the latter of which is commonly used for PTSD nightmares, also may improve PTSD symptoms as assessed by CAPS.^14,15 Although these results are promising, the trials to date have been conducted with relatively small sample sizes.

With more veterans being treated for PTSD within the VA health care system, the central treatment goal remains: Adequately address the symptoms of PTSD while minimizing the harm caused by medications. Prescribers should limit benzodiazepine and opioid use in this population and consider safer nonpharmacologic and pharmacologic treatment options when possible.

Conclusion

Combat veterans with PTSD who are prescribed benzodiazepines and/or opioids in addition to first-line pharmacotherapy are at significantly increased risk for overall and mental health hospitalization.

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RIVIERA BEACH, FL—Neurologists sometimes encounter patients with headaches that have not responded to prior treatment. These patients may be demoralized, and neurologists may be at a loss for a way to relieve their pain. Effective treatment is possible for many of these patients, according to Thomas N. Ward, MD, Emeritus Professor of Neurology at Dartmouth College in Hanover, New Hampshire. He described the process of differential diagnosis, as well as outpatient and inpatient therapeutic options for refractory headache, at the 44th Annual Meeting of the Southern Clinical Neurological Society.

Confirm the Diagnosis

When faced with a patient with refractory headache, a neurologist should first verify the diagnosis and rule out the possibility of secondary headache. These steps will improve the likelihood of a positive outcome. “If you follow the fundamentals and treat the type of headache it is, you usually get a pretty good result,” said Dr. Ward.

A patient with headache on 15 days per month or more has chronic daily headache. The duration of the headaches can provide the basis for a more specific diagnosis. Headaches of short duration (ie, less than four hours) may be symptoms of cluster headache, chronic paroxysmal hemicrania, hypnic headache, or trigeminal neuralgia. Headaches of long duration (ie, more than four hours) may indicate chronic migraine, chronic tension-type headache, hemicrania continua, or new daily persistent headache.

A patient with headache on 15 or more days per month, and for whom headaches on at least eight days per month meet the criteria of migraine, has chronic migraine. The two best-supported treatments for chronic migraine are topiramate and onabotulinumtoxinA. In patients with chronic migraine, what appears to be a tension-type headache may eventually declare its true nature and become a migraine headache with accompanying pounding and photophobia. What looks like a tension-type headache in a migraineur may respond to a triptan, said Dr. Ward.

Stop Medication Overuse

Medication overuse can confound the diagnosis and alter the headache itself. Many patients with refractory headache overuse medication but may fail to mention this to a neurologist. The overused medication may be a prescription or an over-the-counter drug such as ibuprofen, acetaminophen, or a combination that includes caffeine. Drugs with short half-lives appear to be particularly likely to cause medication overuse headache.

Some patients may be overusing opioids for their headache. “Opioids for headache are not a good idea,” said Dr. Ward. “Nothing good will come of it.” These drugs may cause central sensitization and reduce the efficacy of other headache remedies.

The risk of medication overuse headache increases if the patient uses combination analgesics, ergotamine, or triptans on 10 or more days per month, or simple analgesics on more than 15 days per month. “The clinical question I always ask patients is, ‘Are you taking more pills and having more headaches?’ If the answer is ‘yes,’ then they have medication overuse headache,” said Dr. Ward.

If patients stop taking the overused medication, they may have a withdrawal headache that is worse than their normal headache. Medication overuse headache usually resolves itself after the overuse is stopped, and bridge therapies such as steroids, nonsteroidal anti-inflammatory drugs, or dihydroergotamine may alleviate pain during withdrawal. “If you can get the patient over that hump, which can be several days of bad headache, they often do remarkably better,” said Dr. Ward.

Get Back to Basics

Taking a careful history is essential to successful treatment. “If you do not get the original history, you could miss the diagnosis,” said Dr. Ward. The neurologist must know about the mode of onset of the patient’s headache, and also know all about his or her prior headaches.

A patient with refractory headache should undergo a thorough head and neck examination, but physicians sometimes neglect to perform it. An MRI of the brain with gadolinium generally is warranted. About 90% of patients with low CSF pressure have pachymeningeal enhancement, which is visible on MRI performed with gadolinium, said Dr. Ward. Blood work, however, usually reveals little and appears normal. Sometimes thyroid tests, a Lyme test, a blood count, and a serum creatinine test are helpful, and a serum erythrocyte sedimentation rate test in those over age 50 is important to obtain.

Lumbar punctures may be underused, said Dr. Ward. Although it is uncommon, some patients present with high intracranial pressure, but without papilledema. The correct diagnosis can lead to effective treatment for these patients.

Effective treatment also is more likely when the neurologist gets to know the patient. He or she can use preventive medications to reduce the number of headache days. The literature suggests that successful preventive therapy should achieve a target of four headache days or fewer per month.

Neurologists also should treat the patient’s comorbid conditions, which often are psychiatric in people with refractory headache. It is unusual to see a patient with chronic migraine who does not have anxiety and depression, said Dr. Ward. Patients with refractory headache also may have phobias, bipolar disorder, or posttraumatic stress disorder, which is a significant confounder.

To Admit or Not to Admit?

A neurologist may have to decide whether to admit to the hospital a patient with chronic headache who is not doing well. First, the neurologist and patient should agree on a therapeutic target. Outpatient treatment works well if the patient is motivated and compliant and does not have confounding conditions. If the therapeutic target cannot be met through outpatient treatment, the neurologist should consider hospital admission. Insurance companies generally will cover three days of inpatient treatment, said Dr. Ward.

Neurologists have many options for inpatient treatment of refractory headache. Repetitive dihydroergotamine, known as the Raskin protocol, is highly effective if administered correctly. Dihydroergotamine should be given three times per day. “If you order it q. 8 h., the nurse will wake your patient up in the middle of the night, and waking up a patient with benign headaches is not a good idea,” said Dr. Ward. The dose must not be sufficient to cause nausea, because nauseating the patient can exacerbate headaches. “We usually premedicate with metoclopramide or prochlorperazine for nausea, but both of those drugs … also are good headache remedies.”

The Raskin protocol requires the withdrawal of other analgesics. The protocol typically lasts for three days, and most patients have good outcomes at this point. Extending the protocol to six or seven days may increase the number of patients with good outcomes. The success rate for the Raskin protocol is between 60% and 70%, said Dr. Ward. Patients who are pregnant or who have coronary artery disease should not receive dihydroergotamine, however.

Another option for inpatient treatment is IV chlorpromazine. The goal of this treatment is to induce a light sleep and maintain it for two or three days. The neurologist may start with a dose of 10 mg t.i.d. and monitor the patient’s response. The drug effectively suppresses narcotic withdrawal symptoms, so the neurologist may withdraw overused medications while the patient is asleep. Chlorpromazine may cause QT prolongation, so the patient should undergo cardiac monitoring. The drug also causes orthostatic hypotension, so patients should remain on bed rest and receive prophylaxis for deep venous thrombosis, said Dr. Ward.

IV valproate is an excellent choice if the patient has cardiac problems or bipolar disease, he added. The drug can be administered in a single dose of between 300 mg and 500 mg run in rapidly. “You can run in a whole loading dose in five or 10 minutes with virtually no side effects,” said Dr. Ward. Treatment can be administered b.i.d. or t.i.d. for two or three days. Pregnant patients should not receive valproate, however. Yet another option is IV magnesium, although the evidence for its efficacy is mostly anecdotal. A protocol of 1 to 2 g administered over 10 to 20 minutes, repeated several times per day, may be effective. It is advisable to monitor the patient’s serum magnesium levels to ensure that they do not become excessive. Magnesium may adversely affect fetal bone development, so neurologists should exercise caution when considering the drug for a pregnant patient. IV magnesium is “an excellent choice for hemiplegic migraine,” said Dr. Ward.

If the patient’s occipital nerves are tender, occipital nerve blockade may relieve pain. IV ketorolac, in 30-mg doses t.i.d. or q.i.d., may alleviate breakthrough headaches. Lidocaine patches can reduce back or neck pain for as long as 12 hours daily.

Abruptly withdrawing butalbital entails a risk of seizures and delirium. Neurologists may wish to administer phenobarbital in its place, as a single bedtime dose, while they are tapering or stopping butalbital. A 30-mg dose of phenobarbital may be substituted for every 100 mg of butalbital, said Dr. Ward.

Suggested Reading

Ford RG, Ford KT. Continuous intravenous dihydroergotamine in the treatment of intractable headache. Headache. 1997;37(3):129-136.

Lai TH, Wang SJ. Update of inpatient treatment for refractory chronic daily headache. Curr Pain Headache Rep. 2016;20(1):5.

Levin M. Opioids in headache. Headache. 2014;54(1):12-21.

Lipton RB, Silberstein SD, Saper JR, et al. Why headache treatment fails. Neurology. 2003;60(7):1064-1070.

RIVIERA BEACH, FL—Neurologists sometimes encounter patients with headaches that have not responded to prior treatment. These patients may be demoralized, and neurologists may be at a loss for a way to relieve their pain. Effective treatment is possible for many of these patients, according to Thomas N. Ward, MD, Emeritus Professor of Neurology at Dartmouth College in Hanover, New Hampshire. He described the process of differential diagnosis, as well as outpatient and inpatient therapeutic options for refractory headache, at the 44th Annual Meeting of the Southern Clinical Neurological Society.

Confirm the Diagnosis

When faced with a patient with refractory headache, a neurologist should first verify the diagnosis and rule out the possibility of secondary headache. These steps will improve the likelihood of a positive outcome. “If you follow the fundamentals and treat the type of headache it is, you usually get a pretty good result,” said Dr. Ward.

A patient with headache on 15 days per month or more has chronic daily headache. The duration of the headaches can provide the basis for a more specific diagnosis. Headaches of short duration (ie, less than four hours) may be symptoms of cluster headache, chronic paroxysmal hemicrania, hypnic headache, or trigeminal neuralgia. Headaches of long duration (ie, more than four hours) may indicate chronic migraine, chronic tension-type headache, hemicrania continua, or new daily persistent headache.

A patient with headache on 15 or more days per month, and for whom headaches on at least eight days per month meet the criteria of migraine, has chronic migraine. The two best-supported treatments for chronic migraine are topiramate and onabotulinumtoxinA. In patients with chronic migraine, what appears to be a tension-type headache may eventually declare its true nature and become a migraine headache with accompanying pounding and photophobia. What looks like a tension-type headache in a migraineur may respond to a triptan, said Dr. Ward.

Stop Medication Overuse

Medication overuse can confound the diagnosis and alter the headache itself. Many patients with refractory headache overuse medication but may fail to mention this to a neurologist. The overused medication may be a prescription or an over-the-counter drug such as ibuprofen, acetaminophen, or a combination that includes caffeine. Drugs with short half-lives appear to be particularly likely to cause medication overuse headache.

Some patients may be overusing opioids for their headache. “Opioids for headache are not a good idea,” said Dr. Ward. “Nothing good will come of it.” These drugs may cause central sensitization and reduce the efficacy of other headache remedies.

The risk of medication overuse headache increases if the patient uses combination analgesics, ergotamine, or triptans on 10 or more days per month, or simple analgesics on more than 15 days per month. “The clinical question I always ask patients is, ‘Are you taking more pills and having more headaches?’ If the answer is ‘yes,’ then they have medication overuse headache,” said Dr. Ward.

If patients stop taking the overused medication, they may have a withdrawal headache that is worse than their normal headache. Medication overuse headache usually resolves itself after the overuse is stopped, and bridge therapies such as steroids, nonsteroidal anti-inflammatory drugs, or dihydroergotamine may alleviate pain during withdrawal. “If you can get the patient over that hump, which can be several days of bad headache, they often do remarkably better,” said Dr. Ward.

Get Back to Basics

Taking a careful history is essential to successful treatment. “If you do not get the original history, you could miss the diagnosis,” said Dr. Ward. The neurologist must know about the mode of onset of the patient’s headache, and also know all about his or her prior headaches.

A patient with refractory headache should undergo a thorough head and neck examination, but physicians sometimes neglect to perform it. An MRI of the brain with gadolinium generally is warranted. About 90% of patients with low CSF pressure have pachymeningeal enhancement, which is visible on MRI performed with gadolinium, said Dr. Ward. Blood work, however, usually reveals little and appears normal. Sometimes thyroid tests, a Lyme test, a blood count, and a serum creatinine test are helpful, and a serum erythrocyte sedimentation rate test in those over age 50 is important to obtain.

Lumbar punctures may be underused, said Dr. Ward. Although it is uncommon, some patients present with high intracranial pressure, but without papilledema. The correct diagnosis can lead to effective treatment for these patients.

Effective treatment also is more likely when the neurologist gets to know the patient. He or she can use preventive medications to reduce the number of headache days. The literature suggests that successful preventive therapy should achieve a target of four headache days or fewer per month.

Neurologists also should treat the patient’s comorbid conditions, which often are psychiatric in people with refractory headache. It is unusual to see a patient with chronic migraine who does not have anxiety and depression, said Dr. Ward. Patients with refractory headache also may have phobias, bipolar disorder, or posttraumatic stress disorder, which is a significant confounder.

To Admit or Not to Admit?

A neurologist may have to decide whether to admit to the hospital a patient with chronic headache who is not doing well. First, the neurologist and patient should agree on a therapeutic target. Outpatient treatment works well if the patient is motivated and compliant and does not have confounding conditions. If the therapeutic target cannot be met through outpatient treatment, the neurologist should consider hospital admission. Insurance companies generally will cover three days of inpatient treatment, said Dr. Ward.

Neurologists have many options for inpatient treatment of refractory headache. Repetitive dihydroergotamine, known as the Raskin protocol, is highly effective if administered correctly. Dihydroergotamine should be given three times per day. “If you order it q. 8 h., the nurse will wake your patient up in the middle of the night, and waking up a patient with benign headaches is not a good idea,” said Dr. Ward. The dose must not be sufficient to cause nausea, because nauseating the patient can exacerbate headaches. “We usually premedicate with metoclopramide or prochlorperazine for nausea, but both of those drugs … also are good headache remedies.”

The Raskin protocol requires the withdrawal of other analgesics. The protocol typically lasts for three days, and most patients have good outcomes at this point. Extending the protocol to six or seven days may increase the number of patients with good outcomes. The success rate for the Raskin protocol is between 60% and 70%, said Dr. Ward. Patients who are pregnant or who have coronary artery disease should not receive dihydroergotamine, however.

Another option for inpatient treatment is IV chlorpromazine. The goal of this treatment is to induce a light sleep and maintain it for two or three days. The neurologist may start with a dose of 10 mg t.i.d. and monitor the patient’s response. The drug effectively suppresses narcotic withdrawal symptoms, so the neurologist may withdraw overused medications while the patient is asleep. Chlorpromazine may cause QT prolongation, so the patient should undergo cardiac monitoring. The drug also causes orthostatic hypotension, so patients should remain on bed rest and receive prophylaxis for deep venous thrombosis, said Dr. Ward.

IV valproate is an excellent choice if the patient has cardiac problems or bipolar disease, he added. The drug can be administered in a single dose of between 300 mg and 500 mg run in rapidly. “You can run in a whole loading dose in five or 10 minutes with virtually no side effects,” said Dr. Ward. Treatment can be administered b.i.d. or t.i.d. for two or three days. Pregnant patients should not receive valproate, however. Yet another option is IV magnesium, although the evidence for its efficacy is mostly anecdotal. A protocol of 1 to 2 g administered over 10 to 20 minutes, repeated several times per day, may be effective. It is advisable to monitor the patient’s serum magnesium levels to ensure that they do not become excessive. Magnesium may adversely affect fetal bone development, so neurologists should exercise caution when considering the drug for a pregnant patient. IV magnesium is “an excellent choice for hemiplegic migraine,” said Dr. Ward.

If the patient’s occipital nerves are tender, occipital nerve blockade may relieve pain. IV ketorolac, in 30-mg doses t.i.d. or q.i.d., may alleviate breakthrough headaches. Lidocaine patches can reduce back or neck pain for as long as 12 hours daily.

Abruptly withdrawing butalbital entails a risk of seizures and delirium. Neurologists may wish to administer phenobarbital in its place, as a single bedtime dose, while they are tapering or stopping butalbital. A 30-mg dose of phenobarbital may be substituted for every 100 mg of butalbital, said Dr. Ward.

Suggested Reading

Ford RG, Ford KT. Continuous intravenous dihydroergotamine in the treatment of intractable headache. Headache. 1997;37(3):129-136.

Lai TH, Wang SJ. Update of inpatient treatment for refractory chronic daily headache. Curr Pain Headache Rep. 2016;20(1):5.

Levin M. Opioids in headache. Headache. 2014;54(1):12-21.

Lipton RB, Silberstein SD, Saper JR, et al. Why headache treatment fails. Neurology. 2003;60(7):1064-1070.

RIVIERA BEACH, FL—Neurologists sometimes encounter patients with headaches that have not responded to prior treatment. These patients may be demoralized, and neurologists may be at a loss for a way to relieve their pain. Effective treatment is possible for many of these patients, according to Thomas N. Ward, MD, Emeritus Professor of Neurology at Dartmouth College in Hanover, New Hampshire. He described the process of differential diagnosis, as well as outpatient and inpatient therapeutic options for refractory headache, at the 44th Annual Meeting of the Southern Clinical Neurological Society.

Confirm the Diagnosis

When faced with a patient with refractory headache, a neurologist should first verify the diagnosis and rule out the possibility of secondary headache. These steps will improve the likelihood of a positive outcome. “If you follow the fundamentals and treat the type of headache it is, you usually get a pretty good result,” said Dr. Ward.

A patient with headache on 15 days per month or more has chronic daily headache. The duration of the headaches can provide the basis for a more specific diagnosis. Headaches of short duration (ie, less than four hours) may be symptoms of cluster headache, chronic paroxysmal hemicrania, hypnic headache, or trigeminal neuralgia. Headaches of long duration (ie, more than four hours) may indicate chronic migraine, chronic tension-type headache, hemicrania continua, or new daily persistent headache.

A patient with headache on 15 or more days per month, and for whom headaches on at least eight days per month meet the criteria of migraine, has chronic migraine. The two best-supported treatments for chronic migraine are topiramate and onabotulinumtoxinA. In patients with chronic migraine, what appears to be a tension-type headache may eventually declare its true nature and become a migraine headache with accompanying pounding and photophobia. What looks like a tension-type headache in a migraineur may respond to a triptan, said Dr. Ward.

Stop Medication Overuse

Medication overuse can confound the diagnosis and alter the headache itself. Many patients with refractory headache overuse medication but may fail to mention this to a neurologist. The overused medication may be a prescription or an over-the-counter drug such as ibuprofen, acetaminophen, or a combination that includes caffeine. Drugs with short half-lives appear to be particularly likely to cause medication overuse headache.

Some patients may be overusing opioids for their headache. “Opioids for headache are not a good idea,” said Dr. Ward. “Nothing good will come of it.” These drugs may cause central sensitization and reduce the efficacy of other headache remedies.

The risk of medication overuse headache increases if the patient uses combination analgesics, ergotamine, or triptans on 10 or more days per month, or simple analgesics on more than 15 days per month. “The clinical question I always ask patients is, ‘Are you taking more pills and having more headaches?’ If the answer is ‘yes,’ then they have medication overuse headache,” said Dr. Ward.

If patients stop taking the overused medication, they may have a withdrawal headache that is worse than their normal headache. Medication overuse headache usually resolves itself after the overuse is stopped, and bridge therapies such as steroids, nonsteroidal anti-inflammatory drugs, or dihydroergotamine may alleviate pain during withdrawal. “If you can get the patient over that hump, which can be several days of bad headache, they often do remarkably better,” said Dr. Ward.

Get Back to Basics

Taking a careful history is essential to successful treatment. “If you do not get the original history, you could miss the diagnosis,” said Dr. Ward. The neurologist must know about the mode of onset of the patient’s headache, and also know all about his or her prior headaches.

A patient with refractory headache should undergo a thorough head and neck examination, but physicians sometimes neglect to perform it. An MRI of the brain with gadolinium generally is warranted. About 90% of patients with low CSF pressure have pachymeningeal enhancement, which is visible on MRI performed with gadolinium, said Dr. Ward. Blood work, however, usually reveals little and appears normal. Sometimes thyroid tests, a Lyme test, a blood count, and a serum creatinine test are helpful, and a serum erythrocyte sedimentation rate test in those over age 50 is important to obtain.

Lumbar punctures may be underused, said Dr. Ward. Although it is uncommon, some patients present with high intracranial pressure, but without papilledema. The correct diagnosis can lead to effective treatment for these patients.

Effective treatment also is more likely when the neurologist gets to know the patient. He or she can use preventive medications to reduce the number of headache days. The literature suggests that successful preventive therapy should achieve a target of four headache days or fewer per month.

Neurologists also should treat the patient’s comorbid conditions, which often are psychiatric in people with refractory headache. It is unusual to see a patient with chronic migraine who does not have anxiety and depression, said Dr. Ward. Patients with refractory headache also may have phobias, bipolar disorder, or posttraumatic stress disorder, which is a significant confounder.

To Admit or Not to Admit?

A neurologist may have to decide whether to admit to the hospital a patient with chronic headache who is not doing well. First, the neurologist and patient should agree on a therapeutic target. Outpatient treatment works well if the patient is motivated and compliant and does not have confounding conditions. If the therapeutic target cannot be met through outpatient treatment, the neurologist should consider hospital admission. Insurance companies generally will cover three days of inpatient treatment, said Dr. Ward.

Neurologists have many options for inpatient treatment of refractory headache. Repetitive dihydroergotamine, known as the Raskin protocol, is highly effective if administered correctly. Dihydroergotamine should be given three times per day. “If you order it q. 8 h., the nurse will wake your patient up in the middle of the night, and waking up a patient with benign headaches is not a good idea,” said Dr. Ward. The dose must not be sufficient to cause nausea, because nauseating the patient can exacerbate headaches. “We usually premedicate with metoclopramide or prochlorperazine for nausea, but both of those drugs … also are good headache remedies.”

The Raskin protocol requires the withdrawal of other analgesics. The protocol typically lasts for three days, and most patients have good outcomes at this point. Extending the protocol to six or seven days may increase the number of patients with good outcomes. The success rate for the Raskin protocol is between 60% and 70%, said Dr. Ward. Patients who are pregnant or who have coronary artery disease should not receive dihydroergotamine, however.

Another option for inpatient treatment is IV chlorpromazine. The goal of this treatment is to induce a light sleep and maintain it for two or three days. The neurologist may start with a dose of 10 mg t.i.d. and monitor the patient’s response. The drug effectively suppresses narcotic withdrawal symptoms, so the neurologist may withdraw overused medications while the patient is asleep. Chlorpromazine may cause QT prolongation, so the patient should undergo cardiac monitoring. The drug also causes orthostatic hypotension, so patients should remain on bed rest and receive prophylaxis for deep venous thrombosis, said Dr. Ward.

IV valproate is an excellent choice if the patient has cardiac problems or bipolar disease, he added. The drug can be administered in a single dose of between 300 mg and 500 mg run in rapidly. “You can run in a whole loading dose in five or 10 minutes with virtually no side effects,” said Dr. Ward. Treatment can be administered b.i.d. or t.i.d. for two or three days. Pregnant patients should not receive valproate, however. Yet another option is IV magnesium, although the evidence for its efficacy is mostly anecdotal. A protocol of 1 to 2 g administered over 10 to 20 minutes, repeated several times per day, may be effective. It is advisable to monitor the patient’s serum magnesium levels to ensure that they do not become excessive. Magnesium may adversely affect fetal bone development, so neurologists should exercise caution when considering the drug for a pregnant patient. IV magnesium is “an excellent choice for hemiplegic migraine,” said Dr. Ward.

If the patient’s occipital nerves are tender, occipital nerve blockade may relieve pain. IV ketorolac, in 30-mg doses t.i.d. or q.i.d., may alleviate breakthrough headaches. Lidocaine patches can reduce back or neck pain for as long as 12 hours daily.

Abruptly withdrawing butalbital entails a risk of seizures and delirium. Neurologists may wish to administer phenobarbital in its place, as a single bedtime dose, while they are tapering or stopping butalbital. A 30-mg dose of phenobarbital may be substituted for every 100 mg of butalbital, said Dr. Ward.

Suggested Reading

Ford RG, Ford KT. Continuous intravenous dihydroergotamine in the treatment of intractable headache. Headache. 1997;37(3):129-136.

Lai TH, Wang SJ. Update of inpatient treatment for refractory chronic daily headache. Curr Pain Headache Rep. 2016;20(1):5.

Levin M. Opioids in headache. Headache. 2014;54(1):12-21.

Lipton RB, Silberstein SD, Saper JR, et al. Why headache treatment fails. Neurology. 2003;60(7):1064-1070.

For minimally invasive surgeons throughout the world, particularly in the United States, as well as the patients we treat, April 17, 2014, is our day of infamy. It was on this day that the Food and Drug Administration recommended against the use of the electronic power morcellator. The basis of the agency’s decision was the concern about inadvertent spread of sarcomatous tissue. Many hospitals, medical centers, and hospital systems subsequently banned the use of power morcellation. With such bans, a subsequent study by Wright et al. noted a decrease in the percentage of both laparoscopic and vaginal hysterectomy (JAMA. 2016 Aug 23-30;316[8]:877-8). This is concerning when you consider that the complication rate for abdominal hysterectomy is around 17%, compared with about 4% for the minimally invasive procedure.

Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL and the International Society for Gynecologic Endoscopy. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/SRS fellowship in minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. He reported receiving research funds from Espiner Medical Inc., and being a consultant to Olympus, which manufacturers the PneumoLiner.

For minimally invasive surgeons throughout the world, particularly in the United States, as well as the patients we treat, April 17, 2014, is our day of infamy. It was on this day that the Food and Drug Administration recommended against the use of the electronic power morcellator. The basis of the agency’s decision was the concern about inadvertent spread of sarcomatous tissue. Many hospitals, medical centers, and hospital systems subsequently banned the use of power morcellation. With such bans, a subsequent study by Wright et al. noted a decrease in the percentage of both laparoscopic and vaginal hysterectomy (JAMA. 2016 Aug 23-30;316[8]:877-8). This is concerning when you consider that the complication rate for abdominal hysterectomy is around 17%, compared with about 4% for the minimally invasive procedure.

Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL and the International Society for Gynecologic Endoscopy. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/SRS fellowship in minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. He reported receiving research funds from Espiner Medical Inc., and being a consultant to Olympus, which manufacturers the PneumoLiner.

For minimally invasive surgeons throughout the world, particularly in the United States, as well as the patients we treat, April 17, 2014, is our day of infamy. It was on this day that the Food and Drug Administration recommended against the use of the electronic power morcellator. The basis of the agency’s decision was the concern about inadvertent spread of sarcomatous tissue. Many hospitals, medical centers, and hospital systems subsequently banned the use of power morcellation. With such bans, a subsequent study by Wright et al. noted a decrease in the percentage of both laparoscopic and vaginal hysterectomy (JAMA. 2016 Aug 23-30;316[8]:877-8). This is concerning when you consider that the complication rate for abdominal hysterectomy is around 17%, compared with about 4% for the minimally invasive procedure.

Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL and the International Society for Gynecologic Endoscopy. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/SRS fellowship in minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. He reported receiving research funds from Espiner Medical Inc., and being a consultant to Olympus, which manufacturers the PneumoLiner.

Experience with electromechanical power morcellation in a bag has advanced in the last several years in an effort to achieve safe tissue removal for minimally invasive procedures such as myomectomy, laparoscopic supracervical hysterectomy, or total hysterectomy of a large uterus.

Tissue extraction using contained power morcellation has become favored over contained morcellation using a scalpel – not only because the latter approach is cumbersome but because of the risk of bag puncture and subsequent organ injury. Surgeons have experimented with various sizes and types of retrieval bags and with various techniques for contained power morcellation.

Courtesy Dr. Tony Shibley

Courtesy Olympus

Courtesy Dr. Tony Shibley

The technique

The PneumoLiner comes loaded in an insertion tube for placement. It has a plunger to deploy the device and a retrieval lanyard that closes the bag around the specimen, enabling retrieval of the neck of the bag outside the abdomen.

Courtesy Olympus

Included with the PneumoLiner is a multi-instrument port that can be used during the laparoscopic procedure and then converted to the active port for morcellation. The port has an opening for the laparoscope (either a 5-mm 30-degree straight or a 5-mm articulating laparoscope) and an opening for the morcellator, as well as two small openings for insufflation and for smoke exhaustion.

Surgery may be performed using this single-port or a multiport laparoscopic or robotic approach. For morcellation, the approach converts to a single-site technique that involves only one entry point for all instruments and no perforation of the bag.

At the beginning of the procedure (or at the end of the case if preferred), a 25-mm incision is made in the umbilicus and the system’s port is inserted and trimmed. The port cap is placed, the abdomen is insufflated, and the laparoscope is inserted. If placed at the beginning of the case, this port can be used as a camera or accessory port.

Before deployment of the PneumoLiner, the uterus or target tissue is placed out of the way; I recommend the upper right quadrant. The PneumoLiner is then inserted with its directional tab pointing upward, and the system’s plunger is depressed while the sleeve is pulled back. In essence, the PneumoLiner is advanced while the sleeve is simultaneously withdrawn, laying it flat in the pelvis.
 

With an atraumatic grasper, the uterus is placed within the opening of the bag, and the bag is grasped at the collar and elevated up and around the specimen. When full containment of the specimen is visualized, the retrieval lanyard is withdrawn until an opening ring partially protrudes outside the port. All lateral trocars must have been withdrawn prior to inflation of the bag to prevent it from being damaged.

At this point, the port cap is removed and the PneumoLiner neck is withdrawn until a black grid pattern on the bag is visible. The surgeon should then ensure there are no twists in the bag before replacing the port cap and insufflating the bag to a pressure of 15 mm Hg.*

The bag must be correctly in place and fully insufflated before the laparoscope is inserted. The laparoscope must be inserted prior to the morcellator. When the morcellator is inserted, care must be taken to ensure that the morcellator probe is in place.

Once the morcellator is placed, the probe is withdrawn and a closed tenaculum is placed. With the closed tenaculum, the surgeon can manipulate tissue and gauge depth and bearings without inadvertently grabbing the bag. The black grid pattern on the bag assists with estimation of tissue fragment size; morcellation proceeds under direct vision until the tissue fragments are smaller than four printed grids.

Instrumentation is removed in a set order, with the morcellator first and the laparoscope last. The port cap is detached and the PneumoLiner is removed while allowing fumes to escape. The morcellator, camera, tenaculum, and port cap are considered contaminated at this point and should not re-enter the field.

Pearls for morcellation

• The single-site nature of the procedure can sometimes be challenging. If you’ve placed your laparoscope and are having difficulty locating the morcellator, bring your laparoscope and morcellator shaft in parallel to each other, and you’ll be able to better orient yourself.
• To enlarge your field of view after you’ve inflated the PneumoLiner and captured the tissue within the bag, level the patient a bit and move the tissue further away from the laparoscope.
• If the morcellator tube is limiting visualization of the tenaculum tip, slide the morcellator back while leaving the tenaculum in a fixed position.

  The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel

Courtesy Dr. Tony Shibley and Olympus

Dr. Shibley is an ob.gyn. in private practice in the Minneapolis area. He receives royalties from Advanced Surgical Concepts and serves as a consultant for Olympus.

*Correction 3/8/17: An earlier version of this article misstated the name of the Pneumoliner device in a photo caption. The pressure of the morcellation bag also was misstated.

Experience with electromechanical power morcellation in a bag has advanced in the last several years in an effort to achieve safe tissue removal for minimally invasive procedures such as myomectomy, laparoscopic supracervical hysterectomy, or total hysterectomy of a large uterus.

Tissue extraction using contained power morcellation has become favored over contained morcellation using a scalpel – not only because the latter approach is cumbersome but because of the risk of bag puncture and subsequent organ injury. Surgeons have experimented with various sizes and types of retrieval bags and with various techniques for contained power morcellation.

Courtesy Dr. Tony Shibley

Courtesy Olympus

Courtesy Dr. Tony Shibley

The technique

The PneumoLiner comes loaded in an insertion tube for placement. It has a plunger to deploy the device and a retrieval lanyard that closes the bag around the specimen, enabling retrieval of the neck of the bag outside the abdomen.

Courtesy Olympus

Included with the PneumoLiner is a multi-instrument port that can be used during the laparoscopic procedure and then converted to the active port for morcellation. The port has an opening for the laparoscope (either a 5-mm 30-degree straight or a 5-mm articulating laparoscope) and an opening for the morcellator, as well as two small openings for insufflation and for smoke exhaustion.

Surgery may be performed using this single-port or a multiport laparoscopic or robotic approach. For morcellation, the approach converts to a single-site technique that involves only one entry point for all instruments and no perforation of the bag.

At the beginning of the procedure (or at the end of the case if preferred), a 25-mm incision is made in the umbilicus and the system’s port is inserted and trimmed. The port cap is placed, the abdomen is insufflated, and the laparoscope is inserted. If placed at the beginning of the case, this port can be used as a camera or accessory port.

Before deployment of the PneumoLiner, the uterus or target tissue is placed out of the way; I recommend the upper right quadrant. The PneumoLiner is then inserted with its directional tab pointing upward, and the system’s plunger is depressed while the sleeve is pulled back. In essence, the PneumoLiner is advanced while the sleeve is simultaneously withdrawn, laying it flat in the pelvis.
 

With an atraumatic grasper, the uterus is placed within the opening of the bag, and the bag is grasped at the collar and elevated up and around the specimen. When full containment of the specimen is visualized, the retrieval lanyard is withdrawn until an opening ring partially protrudes outside the port. All lateral trocars must have been withdrawn prior to inflation of the bag to prevent it from being damaged.

At this point, the port cap is removed and the PneumoLiner neck is withdrawn until a black grid pattern on the bag is visible. The surgeon should then ensure there are no twists in the bag before replacing the port cap and insufflating the bag to a pressure of 15 mm Hg.*

The bag must be correctly in place and fully insufflated before the laparoscope is inserted. The laparoscope must be inserted prior to the morcellator. When the morcellator is inserted, care must be taken to ensure that the morcellator probe is in place.

Once the morcellator is placed, the probe is withdrawn and a closed tenaculum is placed. With the closed tenaculum, the surgeon can manipulate tissue and gauge depth and bearings without inadvertently grabbing the bag. The black grid pattern on the bag assists with estimation of tissue fragment size; morcellation proceeds under direct vision until the tissue fragments are smaller than four printed grids.

Instrumentation is removed in a set order, with the morcellator first and the laparoscope last. The port cap is detached and the PneumoLiner is removed while allowing fumes to escape. The morcellator, camera, tenaculum, and port cap are considered contaminated at this point and should not re-enter the field.

Pearls for morcellation

• The single-site nature of the procedure can sometimes be challenging. If you’ve placed your laparoscope and are having difficulty locating the morcellator, bring your laparoscope and morcellator shaft in parallel to each other, and you’ll be able to better orient yourself.
• To enlarge your field of view after you’ve inflated the PneumoLiner and captured the tissue within the bag, level the patient a bit and move the tissue further away from the laparoscope.
• If the morcellator tube is limiting visualization of the tenaculum tip, slide the morcellator back while leaving the tenaculum in a fixed position.

  The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel

Courtesy Dr. Tony Shibley and Olympus

Dr. Shibley is an ob.gyn. in private practice in the Minneapolis area. He receives royalties from Advanced Surgical Concepts and serves as a consultant for Olympus.

*Correction 3/8/17: An earlier version of this article misstated the name of the Pneumoliner device in a photo caption. The pressure of the morcellation bag also was misstated.

Experience with electromechanical power morcellation in a bag has advanced in the last several years in an effort to achieve safe tissue removal for minimally invasive procedures such as myomectomy, laparoscopic supracervical hysterectomy, or total hysterectomy of a large uterus.

Tissue extraction using contained power morcellation has become favored over contained morcellation using a scalpel – not only because the latter approach is cumbersome but because of the risk of bag puncture and subsequent organ injury. Surgeons have experimented with various sizes and types of retrieval bags and with various techniques for contained power morcellation.

Courtesy Dr. Tony Shibley

Courtesy Olympus

Courtesy Dr. Tony Shibley

The technique

The PneumoLiner comes loaded in an insertion tube for placement. It has a plunger to deploy the device and a retrieval lanyard that closes the bag around the specimen, enabling retrieval of the neck of the bag outside the abdomen.

Courtesy Olympus

Included with the PneumoLiner is a multi-instrument port that can be used during the laparoscopic procedure and then converted to the active port for morcellation. The port has an opening for the laparoscope (either a 5-mm 30-degree straight or a 5-mm articulating laparoscope) and an opening for the morcellator, as well as two small openings for insufflation and for smoke exhaustion.

Surgery may be performed using this single-port or a multiport laparoscopic or robotic approach. For morcellation, the approach converts to a single-site technique that involves only one entry point for all instruments and no perforation of the bag.

At the beginning of the procedure (or at the end of the case if preferred), a 25-mm incision is made in the umbilicus and the system’s port is inserted and trimmed. The port cap is placed, the abdomen is insufflated, and the laparoscope is inserted. If placed at the beginning of the case, this port can be used as a camera or accessory port.

Before deployment of the PneumoLiner, the uterus or target tissue is placed out of the way; I recommend the upper right quadrant. The PneumoLiner is then inserted with its directional tab pointing upward, and the system’s plunger is depressed while the sleeve is pulled back. In essence, the PneumoLiner is advanced while the sleeve is simultaneously withdrawn, laying it flat in the pelvis.
 

With an atraumatic grasper, the uterus is placed within the opening of the bag, and the bag is grasped at the collar and elevated up and around the specimen. When full containment of the specimen is visualized, the retrieval lanyard is withdrawn until an opening ring partially protrudes outside the port. All lateral trocars must have been withdrawn prior to inflation of the bag to prevent it from being damaged.

At this point, the port cap is removed and the PneumoLiner neck is withdrawn until a black grid pattern on the bag is visible. The surgeon should then ensure there are no twists in the bag before replacing the port cap and insufflating the bag to a pressure of 15 mm Hg.*

The bag must be correctly in place and fully insufflated before the laparoscope is inserted. The laparoscope must be inserted prior to the morcellator. When the morcellator is inserted, care must be taken to ensure that the morcellator probe is in place.

Once the morcellator is placed, the probe is withdrawn and a closed tenaculum is placed. With the closed tenaculum, the surgeon can manipulate tissue and gauge depth and bearings without inadvertently grabbing the bag. The black grid pattern on the bag assists with estimation of tissue fragment size; morcellation proceeds under direct vision until the tissue fragments are smaller than four printed grids.

Instrumentation is removed in a set order, with the morcellator first and the laparoscope last. The port cap is detached and the PneumoLiner is removed while allowing fumes to escape. The morcellator, camera, tenaculum, and port cap are considered contaminated at this point and should not re-enter the field.

Pearls for morcellation

• The single-site nature of the procedure can sometimes be challenging. If you’ve placed your laparoscope and are having difficulty locating the morcellator, bring your laparoscope and morcellator shaft in parallel to each other, and you’ll be able to better orient yourself.
• To enlarge your field of view after you’ve inflated the PneumoLiner and captured the tissue within the bag, level the patient a bit and move the tissue further away from the laparoscope.
• If the morcellator tube is limiting visualization of the tenaculum tip, slide the morcellator back while leaving the tenaculum in a fixed position.

  The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel

Courtesy Dr. Tony Shibley and Olympus

Dr. Shibley is an ob.gyn. in private practice in the Minneapolis area. He receives royalties from Advanced Surgical Concepts and serves as a consultant for Olympus.

*Correction 3/8/17: An earlier version of this article misstated the name of the Pneumoliner device in a photo caption. The pressure of the morcellation bag also was misstated.