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Headache May Be Independent of Idiopathic Intracranial Hypertension
Headache in idiopathic intracranial hypertension (IIH) appears to be clinically independent of raised intracranial pressure and may require a different treatment approach than lowering intracranial pressure, according to a study published online ahead of print July 28 in Headache.
The researchers examined data from 165 patients with untreated IIH and mild vision loss. The participants had been randomized to weight loss plus acetazolamide or placebo as a part of the IIH Treatment Trial.
In the 139 patients with headaches at baseline, the researchers saw no significant correlation between lumbar puncture opening pressure, which was measured at baseline and six months, and Headache Impact Test-6 (HIT-6) scores, or with the presence or absence of headache.
The researchers found no significant difference in headache outcomes between the acetazolamide and placebo groups at six months. Headaches in both groups improved overall during the course of the study, however.
At baseline, participants with headache reported taking various symptomatic headache treatments, including acetaminophen, ibuprofen, naproxen, and combination medications. Some also reported taking hydrocodone, tramadol, or combination formulations containing codeine.
Approximately 37% of the participants overused symptomatic pain medication. Fifteen of these patients met the criteria for overuse of opioids or combination medications. The mean HIT-6 scores were significantly higher in those who were overusing medications, compared with those who were not.
The most common headache phenotype was migraine (52%), followed by tension-type headache (22%), probable migraine (16%), and probable tension-type headache (4%), with 7% unclassified. Patients with headache also experienced associated symptoms such as photophobia, phonophobia, nausea, vomiting, visual loss or obscurations, diplopia, and dizziness.
—Bianca Nogrady
Suggested Reading
Friedman DI, Quiros PA, Subramanian PS, et al. Headache in idiopathic intracranial hypertension: Findings from the Idiopathic Intracranial Hypertension Treatment Trial. Headache. 2017 July 28 [Epub ahead of print].
Yri HM, Rönnbäck C, Wegener M, et al. The course of headache in idiopathic intracranial hypertension: a 12-month prospective follow-up study. Eur J Neurol. 2014;21(12):1458-1464.
Headache in idiopathic intracranial hypertension (IIH) appears to be clinically independent of raised intracranial pressure and may require a different treatment approach than lowering intracranial pressure, according to a study published online ahead of print July 28 in Headache.
The researchers examined data from 165 patients with untreated IIH and mild vision loss. The participants had been randomized to weight loss plus acetazolamide or placebo as a part of the IIH Treatment Trial.
In the 139 patients with headaches at baseline, the researchers saw no significant correlation between lumbar puncture opening pressure, which was measured at baseline and six months, and Headache Impact Test-6 (HIT-6) scores, or with the presence or absence of headache.
The researchers found no significant difference in headache outcomes between the acetazolamide and placebo groups at six months. Headaches in both groups improved overall during the course of the study, however.
At baseline, participants with headache reported taking various symptomatic headache treatments, including acetaminophen, ibuprofen, naproxen, and combination medications. Some also reported taking hydrocodone, tramadol, or combination formulations containing codeine.
Approximately 37% of the participants overused symptomatic pain medication. Fifteen of these patients met the criteria for overuse of opioids or combination medications. The mean HIT-6 scores were significantly higher in those who were overusing medications, compared with those who were not.
The most common headache phenotype was migraine (52%), followed by tension-type headache (22%), probable migraine (16%), and probable tension-type headache (4%), with 7% unclassified. Patients with headache also experienced associated symptoms such as photophobia, phonophobia, nausea, vomiting, visual loss or obscurations, diplopia, and dizziness.
—Bianca Nogrady
Suggested Reading
Friedman DI, Quiros PA, Subramanian PS, et al. Headache in idiopathic intracranial hypertension: Findings from the Idiopathic Intracranial Hypertension Treatment Trial. Headache. 2017 July 28 [Epub ahead of print].
Yri HM, Rönnbäck C, Wegener M, et al. The course of headache in idiopathic intracranial hypertension: a 12-month prospective follow-up study. Eur J Neurol. 2014;21(12):1458-1464.
Headache in idiopathic intracranial hypertension (IIH) appears to be clinically independent of raised intracranial pressure and may require a different treatment approach than lowering intracranial pressure, according to a study published online ahead of print July 28 in Headache.
The researchers examined data from 165 patients with untreated IIH and mild vision loss. The participants had been randomized to weight loss plus acetazolamide or placebo as a part of the IIH Treatment Trial.
In the 139 patients with headaches at baseline, the researchers saw no significant correlation between lumbar puncture opening pressure, which was measured at baseline and six months, and Headache Impact Test-6 (HIT-6) scores, or with the presence or absence of headache.
The researchers found no significant difference in headache outcomes between the acetazolamide and placebo groups at six months. Headaches in both groups improved overall during the course of the study, however.
At baseline, participants with headache reported taking various symptomatic headache treatments, including acetaminophen, ibuprofen, naproxen, and combination medications. Some also reported taking hydrocodone, tramadol, or combination formulations containing codeine.
Approximately 37% of the participants overused symptomatic pain medication. Fifteen of these patients met the criteria for overuse of opioids or combination medications. The mean HIT-6 scores were significantly higher in those who were overusing medications, compared with those who were not.
The most common headache phenotype was migraine (52%), followed by tension-type headache (22%), probable migraine (16%), and probable tension-type headache (4%), with 7% unclassified. Patients with headache also experienced associated symptoms such as photophobia, phonophobia, nausea, vomiting, visual loss or obscurations, diplopia, and dizziness.
—Bianca Nogrady
Suggested Reading
Friedman DI, Quiros PA, Subramanian PS, et al. Headache in idiopathic intracranial hypertension: Findings from the Idiopathic Intracranial Hypertension Treatment Trial. Headache. 2017 July 28 [Epub ahead of print].
Yri HM, Rönnbäck C, Wegener M, et al. The course of headache in idiopathic intracranial hypertension: a 12-month prospective follow-up study. Eur J Neurol. 2014;21(12):1458-1464.
A Migraineur’s Headache Frequency Varies Over Time
BOSTON—Patients with migraine may have greater fluctuation in headache frequency than was previously understood. The rate of transition from episodic migraine to chronic migraine is higher than previously reported, and about three-quarters of people with chronic migraine have a period of episodic migraine during one year, according to a study described at the 59th Annual Scientific Meeting of the American Headache Society.
An Analysis of CaMEO Data
Epidemiologic research has provided information about the profiles of people with chronic migraine and people with episodic migraine. Investigators also have clarified the frequency with which people transition from episodic to chronic migraine. Comparatively little is known, however, about individual variation in headache frequency.
Dr. Lipton and colleagues conducted a study to assess the rates of transition between episodic and chronic migraine and to model the variation in headache days over the course of one year. The investigators examined data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, which includes a representative sample of Americans with episodic migraine or chronic migraine.
Dr. Lipton’s group screened participants with an electronic version of the American Migraine Study/the American Migraine Prevalence and Prevention diagnostic module. They used modified International Classification of Headache Disorders 3-beta criteria to classify people as having episodic migraine, and modified Silberstein–Lipton criteria to classify patients as having chronic migraine. Every three months, the researchers asked participants how many days they had had headache during the previous quarter. Participants completed as many as five surveys during 2012 and 2013. 
To examine within-person change in headache frequency over time, the investigators asked about chronic migraine onset in people with episodic migraine at baseline, and asked about transition to episodic migraine in people with chronic migraine at baseline. Finally, Dr. Lipton and colleagues plotted participants’ longitudinal data and modeled them using adjusted and unadjusted generalized linear mixed models.
High Variation in Headache Days
At baseline, 15,313 respondents had episodic migraine, and 32.4% of them had episodic migraine at baseline only. In addition, 1,476 had chronic migraine at baseline, and 62.3% of them had chronic migraine at baseline only. The investigators observed a “striking level of within-person variation in headache days,” said Dr. Lipton. The number of headache days per month ranged from none to 31.
In further analyses, the investigators examined subpopulations of participants who provided data most consistently throughout the study. Of the 5,464 patients with episodic migraine at baseline for whom at least four completed surveys were available, 92.4% had episodic migraine at every follow-up. In addition, 7.6% of these participants crossed the diagnostic threshold into chronic migraine during at least one quarter. “In the American Migraine Prevalence and Prevention study, the transition rate from episodic migraine to chronic migraine was about 2.5%,” said Dr. Lipton.
A total of 526 patients had chronic migraine at baseline and completed at least four surveys. Of this subpopulation, 26.6% had chronic migraine at every time point, and 73.4% had episodic migraine during at least one quarter. “My suspicion is that the patients that we see in our practices are the people with chronic migraine that remain chronic migraine,” said Dr. Liption, “or at least that our headache practices are enriched with these people whose chronic migraine persists until we make heroic efforts to cause their headache to abate.”
A model unadjusted for covariates, but adjusted for random effects, indicated that the rate of headache days increased by 19% per quarter for participants with chronic migraine, compared with those with episodic migraine. After the researchers adjusted the model for covariates and random effects, it indicated that headache days increased by 26% per quarter for participants with chronic migraine, compared with those with episodic migraine.
Results May Influence Future Investigations
An appropriate goal of future studies would be to clarify the concept of chronic migraine, said Dr. Lipton. Allodynia, comorbidity, and treatment refractoriness are essential components of this disease and may help clarify the border between episodic and chronic migraine. Research also could attempt to identify trait predictors of episodic migraine and chronic migraine.
Furthermore, the findings suggest that the methodology of future epidemiologic studies should be reconsidered. “More frequent sampling will likely identify higher rates of chronic migraine onset,” said Dr. Lipton. The results also suggest that enrolling people with 15 or more headache days per month into clinical trials may lead to reductions in headache frequency that are unrelated to treatment, which could contribute to a strong placebo response.
On July 13, the Italian Society for the Study of Headaches recognized Drs. Lipton, Serrano, and colleagues for their research with the 2017 Enrico Greppi Award. The manuscript will be published in the Journal of Headache and Pain.
—Erik Greb
Suggested Reading
Adams AM, Serrano D, Buse DC, et al. The impact of chronic migraine: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study methods and baseline results. Cephalalgia. 2015;35(7):563-578.
Lipton RB, Bigal ME, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343-349.
BOSTON—Patients with migraine may have greater fluctuation in headache frequency than was previously understood. The rate of transition from episodic migraine to chronic migraine is higher than previously reported, and about three-quarters of people with chronic migraine have a period of episodic migraine during one year, according to a study described at the 59th Annual Scientific Meeting of the American Headache Society.
An Analysis of CaMEO Data
Epidemiologic research has provided information about the profiles of people with chronic migraine and people with episodic migraine. Investigators also have clarified the frequency with which people transition from episodic to chronic migraine. Comparatively little is known, however, about individual variation in headache frequency.
Dr. Lipton and colleagues conducted a study to assess the rates of transition between episodic and chronic migraine and to model the variation in headache days over the course of one year. The investigators examined data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, which includes a representative sample of Americans with episodic migraine or chronic migraine.
Dr. Lipton’s group screened participants with an electronic version of the American Migraine Study/the American Migraine Prevalence and Prevention diagnostic module. They used modified International Classification of Headache Disorders 3-beta criteria to classify people as having episodic migraine, and modified Silberstein–Lipton criteria to classify patients as having chronic migraine. Every three months, the researchers asked participants how many days they had had headache during the previous quarter. Participants completed as many as five surveys during 2012 and 2013.
To examine within-person change in headache frequency over time, the investigators asked about chronic migraine onset in people with episodic migraine at baseline, and asked about transition to episodic migraine in people with chronic migraine at baseline. Finally, Dr. Lipton and colleagues plotted participants’ longitudinal data and modeled them using adjusted and unadjusted generalized linear mixed models.
High Variation in Headache Days
At baseline, 15,313 respondents had episodic migraine, and 32.4% of them had episodic migraine at baseline only. In addition, 1,476 had chronic migraine at baseline, and 62.3% of them had chronic migraine at baseline only. The investigators observed a “striking level of within-person variation in headache days,” said Dr. Lipton. The number of headache days per month ranged from none to 31.
In further analyses, the investigators examined subpopulations of participants who provided data most consistently throughout the study. Of the 5,464 patients with episodic migraine at baseline for whom at least four completed surveys were available, 92.4% had episodic migraine at every follow-up. In addition, 7.6% of these participants crossed the diagnostic threshold into chronic migraine during at least one quarter. “In the American Migraine Prevalence and Prevention study, the transition rate from episodic migraine to chronic migraine was about 2.5%,” said Dr. Lipton.
A total of 526 patients had chronic migraine at baseline and completed at least four surveys. Of this subpopulation, 26.6% had chronic migraine at every time point, and 73.4% had episodic migraine during at least one quarter. “My suspicion is that the patients that we see in our practices are the people with chronic migraine that remain chronic migraine,” said Dr. Liption, “or at least that our headache practices are enriched with these people whose chronic migraine persists until we make heroic efforts to cause their headache to abate.”
A model unadjusted for covariates, but adjusted for random effects, indicated that the rate of headache days increased by 19% per quarter for participants with chronic migraine, compared with those with episodic migraine. After the researchers adjusted the model for covariates and random effects, it indicated that headache days increased by 26% per quarter for participants with chronic migraine, compared with those with episodic migraine.
Results May Influence Future Investigations
An appropriate goal of future studies would be to clarify the concept of chronic migraine, said Dr. Lipton. Allodynia, comorbidity, and treatment refractoriness are essential components of this disease and may help clarify the border between episodic and chronic migraine. Research also could attempt to identify trait predictors of episodic migraine and chronic migraine.
Furthermore, the findings suggest that the methodology of future epidemiologic studies should be reconsidered. “More frequent sampling will likely identify higher rates of chronic migraine onset,” said Dr. Lipton. The results also suggest that enrolling people with 15 or more headache days per month into clinical trials may lead to reductions in headache frequency that are unrelated to treatment, which could contribute to a strong placebo response.
On July 13, the Italian Society for the Study of Headaches recognized Drs. Lipton, Serrano, and colleagues for their research with the 2017 Enrico Greppi Award. The manuscript will be published in the Journal of Headache and Pain.
—Erik Greb
Suggested Reading
Adams AM, Serrano D, Buse DC, et al. The impact of chronic migraine: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study methods and baseline results. Cephalalgia. 2015;35(7):563-578.
Lipton RB, Bigal ME, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343-349.
BOSTON—Patients with migraine may have greater fluctuation in headache frequency than was previously understood. The rate of transition from episodic migraine to chronic migraine is higher than previously reported, and about three-quarters of people with chronic migraine have a period of episodic migraine during one year, according to a study described at the 59th Annual Scientific Meeting of the American Headache Society.
An Analysis of CaMEO Data
Epidemiologic research has provided information about the profiles of people with chronic migraine and people with episodic migraine. Investigators also have clarified the frequency with which people transition from episodic to chronic migraine. Comparatively little is known, however, about individual variation in headache frequency.
Dr. Lipton and colleagues conducted a study to assess the rates of transition between episodic and chronic migraine and to model the variation in headache days over the course of one year. The investigators examined data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, which includes a representative sample of Americans with episodic migraine or chronic migraine.
Dr. Lipton’s group screened participants with an electronic version of the American Migraine Study/the American Migraine Prevalence and Prevention diagnostic module. They used modified International Classification of Headache Disorders 3-beta criteria to classify people as having episodic migraine, and modified Silberstein–Lipton criteria to classify patients as having chronic migraine. Every three months, the researchers asked participants how many days they had had headache during the previous quarter. Participants completed as many as five surveys during 2012 and 2013.
To examine within-person change in headache frequency over time, the investigators asked about chronic migraine onset in people with episodic migraine at baseline, and asked about transition to episodic migraine in people with chronic migraine at baseline. Finally, Dr. Lipton and colleagues plotted participants’ longitudinal data and modeled them using adjusted and unadjusted generalized linear mixed models.
High Variation in Headache Days
At baseline, 15,313 respondents had episodic migraine, and 32.4% of them had episodic migraine at baseline only. In addition, 1,476 had chronic migraine at baseline, and 62.3% of them had chronic migraine at baseline only. The investigators observed a “striking level of within-person variation in headache days,” said Dr. Lipton. The number of headache days per month ranged from none to 31.
In further analyses, the investigators examined subpopulations of participants who provided data most consistently throughout the study. Of the 5,464 patients with episodic migraine at baseline for whom at least four completed surveys were available, 92.4% had episodic migraine at every follow-up. In addition, 7.6% of these participants crossed the diagnostic threshold into chronic migraine during at least one quarter. “In the American Migraine Prevalence and Prevention study, the transition rate from episodic migraine to chronic migraine was about 2.5%,” said Dr. Lipton.
A total of 526 patients had chronic migraine at baseline and completed at least four surveys. Of this subpopulation, 26.6% had chronic migraine at every time point, and 73.4% had episodic migraine during at least one quarter. “My suspicion is that the patients that we see in our practices are the people with chronic migraine that remain chronic migraine,” said Dr. Liption, “or at least that our headache practices are enriched with these people whose chronic migraine persists until we make heroic efforts to cause their headache to abate.”
A model unadjusted for covariates, but adjusted for random effects, indicated that the rate of headache days increased by 19% per quarter for participants with chronic migraine, compared with those with episodic migraine. After the researchers adjusted the model for covariates and random effects, it indicated that headache days increased by 26% per quarter for participants with chronic migraine, compared with those with episodic migraine.
Results May Influence Future Investigations
An appropriate goal of future studies would be to clarify the concept of chronic migraine, said Dr. Lipton. Allodynia, comorbidity, and treatment refractoriness are essential components of this disease and may help clarify the border between episodic and chronic migraine. Research also could attempt to identify trait predictors of episodic migraine and chronic migraine.
Furthermore, the findings suggest that the methodology of future epidemiologic studies should be reconsidered. “More frequent sampling will likely identify higher rates of chronic migraine onset,” said Dr. Lipton. The results also suggest that enrolling people with 15 or more headache days per month into clinical trials may lead to reductions in headache frequency that are unrelated to treatment, which could contribute to a strong placebo response.
On July 13, the Italian Society for the Study of Headaches recognized Drs. Lipton, Serrano, and colleagues for their research with the 2017 Enrico Greppi Award. The manuscript will be published in the Journal of Headache and Pain.
—Erik Greb
Suggested Reading
Adams AM, Serrano D, Buse DC, et al. The impact of chronic migraine: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study methods and baseline results. Cephalalgia. 2015;35(7):563-578.
Lipton RB, Bigal ME, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343-349.
Pooled Analysis Clarifies VNS Efficacy in Cluster Headache
BOSTON—Noninvasive vagal nerve stimulation (VNS) is well tolerated and effectively aborts episodic cluster headache attacks, according to a pooled analysis described at the 59th Annual Scientific Meeting of the American Headache Society. The treatment does not effectively abort attacks in chronic cluster headache, however.
A Pooled Analysis of Two Trials
He and his colleagues studied ElectroCore's gammaCore noninvasive VNS device as an acute treatment of cluster headache in the double-blind, randomized, controlled ACT1 and ACT2 trials. Each trial included more than 100 patients with episodic or chronic cluster headache. The two studies took place at 20 centers in the United States and nine centers in the United Kingdom and Europe.
Treatment was delivered on the patient's right side in ACT1, and on the side ipsilateral to the attack in ACT2. In ACT1, patients were allowed three stimulations, or a total of six minutes of treatment per attack. In ACT2, patients were permitted as many as six stimulations, representing 12 minutes of treatment per attack. In ACT1, the primary end point was response rate (ie, the proportion of patients who achieved pain relief at 15 minutes). The primary end point in ACT2 was pain freedom at 15 minutes, and a secondary end point was the 50% responder rate (ie, mild or no pain) at 15 minutes.
Each study was underpowered for an analysis of results according to headache frequency, so the investigators performed a pooled analysis of the two studies. This examination included a fixed-effects meta-analysis and a first-order interaction test between the treatment group and the cluster headache subgroup to determine whether the magnitude of treatment effect varied significantly by cluster headache subtype.
In all, 253 patients were included in the pooled analysis, 131 of whom had episodic cluster headache, and 122 of whom had chronic cluster headache. Patients' mean age was 46.6. Approximately 21% of patients were female, 2.4% were Asian, and 4.7% were black.
Efficacy in Episodic, But Not Chronic Cluster Headache
Among patients with episodic cluster headache, the rate of pain freedom for all treated attacks at 15 minutes was significantly higher with VNS than with sham (15% vs 6% in ACT1, 35% vs 7% in ACT2, and 24% vs 7% in the pooled analysis). Among patients with chronic cluster headache, the researchers did not find significant differences in this end point between treatment groups (5% vs 14% in ACT1, 7% vs 9% in ACT2, and 7% vs 11% in the pooled analysis).
For patients with episodic cluster headache, the 50% responder rate was 34% in ACT1, 64% in ACT2, and 42% in the pooled analysis. For patients with chronic cluster headache, the responder rates were 13.6% in ACT1, 29.4% in ACT2, and 23.2% in the pooled analysis. For the proportion of attacks that became pain free, the interaction test was significant for ACT1 and the pooled analysis, but it was not significant for ACT2. For the 50% responder end point, the interaction test was significant for ACT1, ACT2, and the pooled analysis.
In April 2017, the FDA cleared the gammaCore device for the acute treatment of pain associated with episodic cluster headache in adults. The device is now available in the US, said Mr. Liebler.
“We are going to continue to examine the mechanism of action [of noninvasive VNS] and the reasons for possible [treatment] failure in chronic cluster headache,” said Mr. Liebler. These investigations could provide further clinical insight and clarify the pathogenesis of cluster headache, he added.
—Erik Greb
Suggested Reading
Silberstein SD, Mechtler LL, Kudrow DB, et al. Non-invasive vagus nerve stimulation for the acute treatment of cluster headache: findings from the randomized, double-blind, sham-controlled ACT1 study. Headache. 2016;56(8):1317-1332.
BOSTON—Noninvasive vagal nerve stimulation (VNS) is well tolerated and effectively aborts episodic cluster headache attacks, according to a pooled analysis described at the 59th Annual Scientific Meeting of the American Headache Society. The treatment does not effectively abort attacks in chronic cluster headache, however.
A Pooled Analysis of Two Trials
He and his colleagues studied ElectroCore's gammaCore noninvasive VNS device as an acute treatment of cluster headache in the double-blind, randomized, controlled ACT1 and ACT2 trials. Each trial included more than 100 patients with episodic or chronic cluster headache. The two studies took place at 20 centers in the United States and nine centers in the United Kingdom and Europe.
Treatment was delivered on the patient's right side in ACT1, and on the side ipsilateral to the attack in ACT2. In ACT1, patients were allowed three stimulations, or a total of six minutes of treatment per attack. In ACT2, patients were permitted as many as six stimulations, representing 12 minutes of treatment per attack. In ACT1, the primary end point was response rate (ie, the proportion of patients who achieved pain relief at 15 minutes). The primary end point in ACT2 was pain freedom at 15 minutes, and a secondary end point was the 50% responder rate (ie, mild or no pain) at 15 minutes.
Each study was underpowered for an analysis of results according to headache frequency, so the investigators performed a pooled analysis of the two studies. This examination included a fixed-effects meta-analysis and a first-order interaction test between the treatment group and the cluster headache subgroup to determine whether the magnitude of treatment effect varied significantly by cluster headache subtype.
In all, 253 patients were included in the pooled analysis, 131 of whom had episodic cluster headache, and 122 of whom had chronic cluster headache. Patients' mean age was 46.6. Approximately 21% of patients were female, 2.4% were Asian, and 4.7% were black.
Efficacy in Episodic, But Not Chronic Cluster Headache
Among patients with episodic cluster headache, the rate of pain freedom for all treated attacks at 15 minutes was significantly higher with VNS than with sham (15% vs 6% in ACT1, 35% vs 7% in ACT2, and 24% vs 7% in the pooled analysis). Among patients with chronic cluster headache, the researchers did not find significant differences in this end point between treatment groups (5% vs 14% in ACT1, 7% vs 9% in ACT2, and 7% vs 11% in the pooled analysis).
For patients with episodic cluster headache, the 50% responder rate was 34% in ACT1, 64% in ACT2, and 42% in the pooled analysis. For patients with chronic cluster headache, the responder rates were 13.6% in ACT1, 29.4% in ACT2, and 23.2% in the pooled analysis. For the proportion of attacks that became pain free, the interaction test was significant for ACT1 and the pooled analysis, but it was not significant for ACT2. For the 50% responder end point, the interaction test was significant for ACT1, ACT2, and the pooled analysis.
In April 2017, the FDA cleared the gammaCore device for the acute treatment of pain associated with episodic cluster headache in adults. The device is now available in the US, said Mr. Liebler.
“We are going to continue to examine the mechanism of action [of noninvasive VNS] and the reasons for possible [treatment] failure in chronic cluster headache,” said Mr. Liebler. These investigations could provide further clinical insight and clarify the pathogenesis of cluster headache, he added.
—Erik Greb
Suggested Reading
Silberstein SD, Mechtler LL, Kudrow DB, et al. Non-invasive vagus nerve stimulation for the acute treatment of cluster headache: findings from the randomized, double-blind, sham-controlled ACT1 study. Headache. 2016;56(8):1317-1332.
BOSTON—Noninvasive vagal nerve stimulation (VNS) is well tolerated and effectively aborts episodic cluster headache attacks, according to a pooled analysis described at the 59th Annual Scientific Meeting of the American Headache Society. The treatment does not effectively abort attacks in chronic cluster headache, however.
A Pooled Analysis of Two Trials
He and his colleagues studied ElectroCore's gammaCore noninvasive VNS device as an acute treatment of cluster headache in the double-blind, randomized, controlled ACT1 and ACT2 trials. Each trial included more than 100 patients with episodic or chronic cluster headache. The two studies took place at 20 centers in the United States and nine centers in the United Kingdom and Europe.
Treatment was delivered on the patient's right side in ACT1, and on the side ipsilateral to the attack in ACT2. In ACT1, patients were allowed three stimulations, or a total of six minutes of treatment per attack. In ACT2, patients were permitted as many as six stimulations, representing 12 minutes of treatment per attack. In ACT1, the primary end point was response rate (ie, the proportion of patients who achieved pain relief at 15 minutes). The primary end point in ACT2 was pain freedom at 15 minutes, and a secondary end point was the 50% responder rate (ie, mild or no pain) at 15 minutes.
Each study was underpowered for an analysis of results according to headache frequency, so the investigators performed a pooled analysis of the two studies. This examination included a fixed-effects meta-analysis and a first-order interaction test between the treatment group and the cluster headache subgroup to determine whether the magnitude of treatment effect varied significantly by cluster headache subtype.
In all, 253 patients were included in the pooled analysis, 131 of whom had episodic cluster headache, and 122 of whom had chronic cluster headache. Patients' mean age was 46.6. Approximately 21% of patients were female, 2.4% were Asian, and 4.7% were black.
Efficacy in Episodic, But Not Chronic Cluster Headache
Among patients with episodic cluster headache, the rate of pain freedom for all treated attacks at 15 minutes was significantly higher with VNS than with sham (15% vs 6% in ACT1, 35% vs 7% in ACT2, and 24% vs 7% in the pooled analysis). Among patients with chronic cluster headache, the researchers did not find significant differences in this end point between treatment groups (5% vs 14% in ACT1, 7% vs 9% in ACT2, and 7% vs 11% in the pooled analysis).
For patients with episodic cluster headache, the 50% responder rate was 34% in ACT1, 64% in ACT2, and 42% in the pooled analysis. For patients with chronic cluster headache, the responder rates were 13.6% in ACT1, 29.4% in ACT2, and 23.2% in the pooled analysis. For the proportion of attacks that became pain free, the interaction test was significant for ACT1 and the pooled analysis, but it was not significant for ACT2. For the 50% responder end point, the interaction test was significant for ACT1, ACT2, and the pooled analysis.
In April 2017, the FDA cleared the gammaCore device for the acute treatment of pain associated with episodic cluster headache in adults. The device is now available in the US, said Mr. Liebler.
“We are going to continue to examine the mechanism of action [of noninvasive VNS] and the reasons for possible [treatment] failure in chronic cluster headache,” said Mr. Liebler. These investigations could provide further clinical insight and clarify the pathogenesis of cluster headache, he added.
—Erik Greb
Suggested Reading
Silberstein SD, Mechtler LL, Kudrow DB, et al. Non-invasive vagus nerve stimulation for the acute treatment of cluster headache: findings from the randomized, double-blind, sham-controlled ACT1 study. Headache. 2016;56(8):1317-1332.
Headache Trajectories Differ Five Years After TBI
BOSTON—Over five years after traumatic brain injury (TBI), a relatively large (24% to 30%) group of individuals experience chronic headache pain and a significant functional impact of headache, according to a pattern analysis of headache pain and impact following moderate to severe TBI. These results were presented at the 59th Annual Scientific Meeting of the American Headache Society. “Identification of members within these groups may be important to assist with an appropriate intensity of treatment to improve satisfaction with life and employment opportunity after TBI,” said Sylvia Lucas, MD, PhD, Clinical Professor of Neurology and Neurological Surgery at the University of Washington in Seattle. “The identification of trajectory membership may also be useful in evaluation of appropriate subjects for inclusion in studies of headache treatment after TBI.” 
Headache is the most common symptom following TBI of any severity. Dr. Lucas and her research colleagues have previously reported high rates of headache in a prospective cohort of patients who experienced moderate to severe TBI. These patients have been followed for five years. New or worse headache occurred at a rate of 37% at three months, 33% at six months, 34% at 12 months, and 35% at 60 months post injury. The present study examined whether certain patterns or trajectories of headache occur over five years after TBI and whether demographic or injury characteristics are related to these trajectories. Trajectory type was also examined in relation to satisfaction with life and employment status five years after injury.
Data on 316 individuals were evaluated at five years. These patients were initially enrolled during inpatient rehabilitation after moderate to severe TBI. Enrollment was performed in person in the hospital. Structured telephone interviews were conducted at three, six, 12, and 60 months after TBI. At each time point, individuals who reported headache in the previous three months were asked to rate their headache pain on a 0 to 10 scale (0 = no pain, 10 = worst pain) and to complete the Headache Impact Test (HIT-6). Discrete mixture modeling was used to estimate trajectory groups based on pain rating and on headache impact scores.
Four trajectories were found for headache pain over five years: minimal pain over time (25% of individuals), worsening pain over time (37%), improving pain over time (7%), and chronic pain over time (30%). A chronic pain trajectory was more common in females, those incurring TBI by violence, those who were unemployed prior to injury, those with a headache history prior to injury, and those with mental health problems. Those with a chronic pain trajectory had significantly lower satisfaction with life five years after injury, compared with other trajectory groups.
A chronic impact trajectory was more common in females and in those who incurred TBI by violence, had a prior history of headache, or were unemployed prior to injury. At five years post TBI, the chronic impact group was significantly more likely to be unemployed and less satisfied with life, compared with individuals in the minimal or worsening impact trajectory groups. Those employed prior to injury were more frequently in the worsening group for pain and impact, compared with those not employed prior to injury. No relationship was found for other demographic and injury data, including age, posttraumatic amnesia, or substance abuse prior to injury.
BOSTON—Over five years after traumatic brain injury (TBI), a relatively large (24% to 30%) group of individuals experience chronic headache pain and a significant functional impact of headache, according to a pattern analysis of headache pain and impact following moderate to severe TBI. These results were presented at the 59th Annual Scientific Meeting of the American Headache Society. “Identification of members within these groups may be important to assist with an appropriate intensity of treatment to improve satisfaction with life and employment opportunity after TBI,” said Sylvia Lucas, MD, PhD, Clinical Professor of Neurology and Neurological Surgery at the University of Washington in Seattle. “The identification of trajectory membership may also be useful in evaluation of appropriate subjects for inclusion in studies of headache treatment after TBI.”
Headache is the most common symptom following TBI of any severity. Dr. Lucas and her research colleagues have previously reported high rates of headache in a prospective cohort of patients who experienced moderate to severe TBI. These patients have been followed for five years. New or worse headache occurred at a rate of 37% at three months, 33% at six months, 34% at 12 months, and 35% at 60 months post injury. The present study examined whether certain patterns or trajectories of headache occur over five years after TBI and whether demographic or injury characteristics are related to these trajectories. Trajectory type was also examined in relation to satisfaction with life and employment status five years after injury.
Data on 316 individuals were evaluated at five years. These patients were initially enrolled during inpatient rehabilitation after moderate to severe TBI. Enrollment was performed in person in the hospital. Structured telephone interviews were conducted at three, six, 12, and 60 months after TBI. At each time point, individuals who reported headache in the previous three months were asked to rate their headache pain on a 0 to 10 scale (0 = no pain, 10 = worst pain) and to complete the Headache Impact Test (HIT-6). Discrete mixture modeling was used to estimate trajectory groups based on pain rating and on headache impact scores.
Four trajectories were found for headache pain over five years: minimal pain over time (25% of individuals), worsening pain over time (37%), improving pain over time (7%), and chronic pain over time (30%). A chronic pain trajectory was more common in females, those incurring TBI by violence, those who were unemployed prior to injury, those with a headache history prior to injury, and those with mental health problems. Those with a chronic pain trajectory had significantly lower satisfaction with life five years after injury, compared with other trajectory groups.
A chronic impact trajectory was more common in females and in those who incurred TBI by violence, had a prior history of headache, or were unemployed prior to injury. At five years post TBI, the chronic impact group was significantly more likely to be unemployed and less satisfied with life, compared with individuals in the minimal or worsening impact trajectory groups. Those employed prior to injury were more frequently in the worsening group for pain and impact, compared with those not employed prior to injury. No relationship was found for other demographic and injury data, including age, posttraumatic amnesia, or substance abuse prior to injury.
BOSTON—Over five years after traumatic brain injury (TBI), a relatively large (24% to 30%) group of individuals experience chronic headache pain and a significant functional impact of headache, according to a pattern analysis of headache pain and impact following moderate to severe TBI. These results were presented at the 59th Annual Scientific Meeting of the American Headache Society. “Identification of members within these groups may be important to assist with an appropriate intensity of treatment to improve satisfaction with life and employment opportunity after TBI,” said Sylvia Lucas, MD, PhD, Clinical Professor of Neurology and Neurological Surgery at the University of Washington in Seattle. “The identification of trajectory membership may also be useful in evaluation of appropriate subjects for inclusion in studies of headache treatment after TBI.”
Headache is the most common symptom following TBI of any severity. Dr. Lucas and her research colleagues have previously reported high rates of headache in a prospective cohort of patients who experienced moderate to severe TBI. These patients have been followed for five years. New or worse headache occurred at a rate of 37% at three months, 33% at six months, 34% at 12 months, and 35% at 60 months post injury. The present study examined whether certain patterns or trajectories of headache occur over five years after TBI and whether demographic or injury characteristics are related to these trajectories. Trajectory type was also examined in relation to satisfaction with life and employment status five years after injury.
Data on 316 individuals were evaluated at five years. These patients were initially enrolled during inpatient rehabilitation after moderate to severe TBI. Enrollment was performed in person in the hospital. Structured telephone interviews were conducted at three, six, 12, and 60 months after TBI. At each time point, individuals who reported headache in the previous three months were asked to rate their headache pain on a 0 to 10 scale (0 = no pain, 10 = worst pain) and to complete the Headache Impact Test (HIT-6). Discrete mixture modeling was used to estimate trajectory groups based on pain rating and on headache impact scores.
Four trajectories were found for headache pain over five years: minimal pain over time (25% of individuals), worsening pain over time (37%), improving pain over time (7%), and chronic pain over time (30%). A chronic pain trajectory was more common in females, those incurring TBI by violence, those who were unemployed prior to injury, those with a headache history prior to injury, and those with mental health problems. Those with a chronic pain trajectory had significantly lower satisfaction with life five years after injury, compared with other trajectory groups.
A chronic impact trajectory was more common in females and in those who incurred TBI by violence, had a prior history of headache, or were unemployed prior to injury. At five years post TBI, the chronic impact group was significantly more likely to be unemployed and less satisfied with life, compared with individuals in the minimal or worsening impact trajectory groups. Those employed prior to injury were more frequently in the worsening group for pain and impact, compared with those not employed prior to injury. No relationship was found for other demographic and injury data, including age, posttraumatic amnesia, or substance abuse prior to injury.
CGRP Monoclonal Antibodies May Be Beneficial for Migraine Prevention
BOSTON—A new class of drugs for the prevention of chronic and episodic migraine demonstrated promising results in recent phase II and phase III trials. Data for four humanized calcitonin gene–related peptide (CGRP) monoclonal antibodies—eptinezumab, erenumab, fremanezumab, and galcanezumab—were presented at the 59th Annual Scientific Meeting of the American Headache Society. Previous research has long implicated CGRP (which is elevated in jugular vein blood during acute migraine and cluster headaches) in disease pathophysiology. Recent advances in molecular neuroscience have helped shed further light on the pathogenic mechanisms and possible targets for treatment.
Eptinezumab
In a phase II study, a single infusion of eptinezumab (which Alder BioPharmaceuticals is developing under the name ALD403) reduced the number of migraine days per month, as well as the number of migraines classified as severe, in patients with chronic migraine. Of the four drugs presented at the meeting, eptinezumab was the only one to have an IV mode of delivery.
“We used International Classification of Headache Disorders 3 criteria to define chronic migraine, which is at least 15 headache days per month, of which eight must be migraine-like,” said Jeffrey T. L. Smith, MD, Senior Vice President of Translational Medicine at Alder BioPharmaceuticals in Bothell, Washington. “Patients also had to have a history of migraine for a year or more.” 
On average, the patients included in this multisite study were slightly younger than 40. Most patients were women, and the average number of migraine days was between 16.2 and 16.5. After a one-month run-in period, patients were randomized to receive placebo or one of four doses of eptinezumab (ie, 300 mg, 100 mg, 30 mg, or 10 mg).
Reporting 12-week data from the 48-week trial, Dr. Smith and colleagues found that significantly more patients taking the 300-mg (33%) and 100-mg (31%) doses of eptinezumab reached the primary end point of a 75% reduction from baseline in migraine days, compared with patients who received placebo (21%). Differences in patients taking the 30-mg and 10-mg doses (28% and 27%, respectively) were not statistically significant. “Overall, approximately half of patients treated with eptinezumab experienced a 50% reduction in migraine days versus 41% of patients on placebo,” Dr. Smith added. Eptinezumab was well tolerated, and no serious adverse events were reported.
Post hoc analyses indicated that of the migraines that were not eliminated as a result of treatment, the percentage classified as severe was significantly reduced from baseline in each of the eptinezumab groups, compared with placebo. Also, fewer patients in the eptinezumab groups than in the placebo group experienced a migraine within the first 24 to 48 hours after infusion. “Although the post hoc results are exploratory, these findings are important as well,” said Dr. Smith. “Other things are happening besides the reduction in migraine frequency that may be of benefit.”
Erenumab
A registration, pivotal study on erenumab for chronic migraine prevention was reported at the meeting. “Unlike eptinezumab, fremanezumab, and galcanezumab, which are monoclonal antibodies against the CGRP ligand, erenumab is an anti-CGRP receptor monoclonal antibody,” said Stewart J. Tepper, MD, Professor of Neurology at the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire. Amgen is developing this antibody. 
In the 12-week randomized controlled trial, patients were enrolled in the US and around the world, Dr. Tepper noted. He and his colleagues included patients who had 15 or more headache days per month with at least eight days of migraine per month. Patients were excluded if they had experienced treatment failure with more than three classes of preventive agents. Mean age was 40, about 80% of patients were women, and roughly half of patients had previously experienced treatment failure with at least two preventive agents.
A total of 667 patients were randomized 3:2:2 to placebo, erenumab (70 mg), or erenumab (140 mg). Treatment was given monthly via subcutaneous injection. The primary end point was change from baseline in monthly migraine days (MMD). Secondary end points included at least a 50% reduction in MMD, change from baseline in acute migraine-specific medication days, and cumulative headache hours.
In both erenumab groups, patients experienced a mean 6.6-day reduction in MMD from a baseline of 18.0 days, which was significantly different, compared with the 4.2-day reduction seen in the placebo group. Furthermore, a significantly greater proportion of patients in the 70-mg and 140-mg groups (40% and 41%, respectively) experienced at least a 50% reduction in MMD, compared with the placebo group (23%). For the secondary end points, both erenumab groups had significantly greater reductions in acute migraine-specific medication days versus placebo. However, the difference in the reduction of cumulative headache hours did not reach statistical significance. “We speculated that this was because headache hours is a relatively variable end point, and it is collected in differing ways, with wide confidence intervals,” Dr. Tepper said.
The safety profile for both erenumab groups and the placebo group was similar. “No serious adverse events were reported by more than one patient in any treatment arm, and no serious adverse events were considered related to treatment,” he said.
Another erenumab trial enrolled patients with episodic migraine. Randomization was stratified by region and current and prior migraine preventive medication, said Daniel Mikol, MD, PhD, Executive Medical Director of Neuroscience Development at Amgen in Thousand Oaks, California. Patients included in the phase III study could be taking a single concomitant migraine preventive therapy. “Patients could have also failed previous preventive therapies due to poor tolerability or lack of efficacy,” he said. “There was no limit regarding the number of previous failures due to poor tolerability. With regard to lack of efficacy, patients could have no therapeutic response to two or fewer preventive therapies.”
Adults with episodic migraine (n = 955) were randomized 1:1:1 to monthly subcutaneous injections of placebo, erenumab (70 mg), or erenumab (140 mg) for 24 weeks. The primary end point was change from baseline in MMD from weeks 13 to 24. Secondary end points included achievement of 50% or more reduction in MMD, change in mean acute migraine-specific medication days, and changes in mean physical impairment and impact on everyday activity scores, as measured by the Migraine Physical Function Impact Diary, a novel patient-reported instrument, Dr. Mikol explained.
Subjects had a mean of 8.3 MMD at baseline. This measurement was reduced by 3.2, 3.7, and 1.8 days in the 70-mg, 140-mg, and placebo groups, respectively—a statistically significant difference in favor of the erenumab groups. Statistically superior results for erenumab 70 mg and 140 mg over placebo also were seen in the secondary end points of > 50% response (43%, 50%, and 27%, respectively), reduction from baseline in monthly acute migraine-specific medication days (1.1, 1.6, and 0.2), improved physical impairment score from baseline (4.2, 4.8, and 2.5), and improved everyday activity scores from baseline (5.5, 5.9, and 3.3).
“The safety profiles for erenumab were similar to that of placebo,” Dr. Mikol said. “Specifically, 63% of patients on placebo had adverse events, compared with 56% to 57% of patients in the erenumab groups. Serious adverse events and adverse events leading to treatment discontinuation were low in frequency and balanced across the groups.”
Galcanezumab
The efficacy, tolerability, and safety of galcanezumab, an investigational drug for the treatment of episodic migraine, was assessed in a six-month phase III study called EVOLVE-2. In this study, patients with episodic migraine experienced four to 14 migraine headache days per month with or without aura. “Our patient population had a mean age of about 40, and most [participants] were Caucasian women,” said Robert Conley, MD, Distinguished Lilly Scholar of Neuroscience at Eli Lilly and Company (the developer of galcanezumab) in Indianapolis. 
“Half of our subjects were from North America, a quarter from Europe, and a quarter from the rest of the world.” Subjects had a 20-year migraine history on average and a mean of nine headache days per month at baseline, he noted. “In addition, two-thirds had been on prior preventive treatment, and they had relatively severe levels of disease.”
After screening 1,700 patients for the study, Dr. Conley and colleagues randomized 914 patients 1:1:2 to subcutaneous injection of galcanezumab (120 mg/month), galcanezumab (240 mg/month), or placebo. “There was about an 87% completion rate for the galcanezumab groups and an 83% completion rate in the placebo group. The higher number of dropouts in the placebo group was due to lack of efficacy,” said Dr. Conley. The primary end point was change from baseline in MMD at the end of six months. Secondary end points were percentages of patients with 50%, 75%, and 100% response rates; reduction in MMD requiring acute migraine medication; change in function score on the Migraine-Specific Quality of Life Questionnaire (MSQ); and change in the Patient Global Impression of Severity (PGI-S) rating.
After adjusting for multiplicity, the investigators found statistically significant differences between placebo and the galcanezumab arms in the primary end point. Mean reductions in headache days were 4.29 in the 120-mg group and 4.18 in the 240-mg group. Patients in the placebo group experienced a reduction of 2.28 days. “We looked at the early effects of treatment and found statistically significant improvements within a few days of injection that persisted over time,” Dr. Conley said.
In addition, statistically significant differences between galcanezumab and placebo were observed for all secondary end points. “In the 120-mg and 240-mg treatment groups, 59.3% and 56.5%, respectively, had at least a 50% reduction in monthly headache days, which was significantly different from placebo, but not different from each other,” said Dr. Conley. “We also saw that approximately one-third of patients in the galcanezumab arms experienced 75% response rates, which is double that seen in the placebo group. The 100% response rate was 11.5% to 13.8% in the treated groups—again, not a significant difference between them, but significantly different from placebo.” The change in the MSQ function score and the PGI-S rating averaged for months 4, 5, and 6 were significantly improved in the galcanezumab arms, compared with the placebo arm.
For most of the safety parameters, there were no significant differences between either dose of galcanezumab and placebo. However, the rates of injection-site reactions and pruritus were significantly higher for both drug doses, compared with placebo. Injection-site erythema was significantly higher in the 240-mg dose only.
Fremanezumab
“The phase III trial for fremanezumab in chronic migraine investigated a flexible dose for a quarterly and a monthly regimen,” said Ernesto Aycardi, MD, Vice President and Therapeutic Area Head for Migraine and Headache at Teva Pharmaceuticals
The primary end point of this multicenter trial was the mean change from baseline in monthly days of headache of at least moderate severity. The four main secondary end points were the proportion of patients with at least a 50% reduction in headache days, mean change in the number of days using acute headache medication at the end of the 12-week period of the trial, mean change from baseline in the days of at least moderate severity in the first four weeks of the trial, and change in disability scale (HIT-6) score from baseline. In this trial, patients treated with fremanezumab experienced significant improvement, compared with placebo on all primary and secondary end points for both monthly and quarterly dosing regimens.
“The average age of the study population was 41, with an average history of migraine of about 20 years,” Dr. Aycardi said. “All demographic characteristics, including weight, height, and ethnicity, were well balanced between the groups.”
Patients on the monthly regimen had a mean reduction of 4.6 headache days of at least moderate severity, and patients on the quarterly regimen had a reduction of 4.3 headache days of at least moderate severity, which was significantly different from the placebo group (2.5 headache days). Researchers also observed significant differences for each of the four secondary end points in favor of the monthly and quarterly regimens.
“Fremanezumab was well tolerated, compared with placebo,” Dr. Aycardi said. “The most commonly reported adverse event in the study was injection-site pain, with similar rates in the placebo and active groups.”
Dr. Aycardi highlighted how phase II results validated that target in chronic migraine. “With these phase III results, this is confirmed, bringing hope for patients with this disabling condition.”
—Adriene Marshall
Suggested Reading
Durham PL. Calcitonin gene-related peptide (CGRP) and migraine. Headache. 2006;46(Suppl 1):S3–S8.
Reuter U. Anti-CGRP antibodies: a new approach to migraine prevention. Lancet Neurol. 2014;13(9):857-859.
Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16(6):425-434.
BOSTON—A new class of drugs for the prevention of chronic and episodic migraine demonstrated promising results in recent phase II and phase III trials. Data for four humanized calcitonin gene–related peptide (CGRP) monoclonal antibodies—eptinezumab, erenumab, fremanezumab, and galcanezumab—were presented at the 59th Annual Scientific Meeting of the American Headache Society. Previous research has long implicated CGRP (which is elevated in jugular vein blood during acute migraine and cluster headaches) in disease pathophysiology. Recent advances in molecular neuroscience have helped shed further light on the pathogenic mechanisms and possible targets for treatment.
Eptinezumab
In a phase II study, a single infusion of eptinezumab (which Alder BioPharmaceuticals is developing under the name ALD403) reduced the number of migraine days per month, as well as the number of migraines classified as severe, in patients with chronic migraine. Of the four drugs presented at the meeting, eptinezumab was the only one to have an IV mode of delivery.
“We used International Classification of Headache Disorders 3 criteria to define chronic migraine, which is at least 15 headache days per month, of which eight must be migraine-like,” said Jeffrey T. L. Smith, MD, Senior Vice President of Translational Medicine at Alder BioPharmaceuticals in Bothell, Washington. “Patients also had to have a history of migraine for a year or more.”
On average, the patients included in this multisite study were slightly younger than 40. Most patients were women, and the average number of migraine days was between 16.2 and 16.5. After a one-month run-in period, patients were randomized to receive placebo or one of four doses of eptinezumab (ie, 300 mg, 100 mg, 30 mg, or 10 mg).
Reporting 12-week data from the 48-week trial, Dr. Smith and colleagues found that significantly more patients taking the 300-mg (33%) and 100-mg (31%) doses of eptinezumab reached the primary end point of a 75% reduction from baseline in migraine days, compared with patients who received placebo (21%). Differences in patients taking the 30-mg and 10-mg doses (28% and 27%, respectively) were not statistically significant. “Overall, approximately half of patients treated with eptinezumab experienced a 50% reduction in migraine days versus 41% of patients on placebo,” Dr. Smith added. Eptinezumab was well tolerated, and no serious adverse events were reported.
Post hoc analyses indicated that of the migraines that were not eliminated as a result of treatment, the percentage classified as severe was significantly reduced from baseline in each of the eptinezumab groups, compared with placebo. Also, fewer patients in the eptinezumab groups than in the placebo group experienced a migraine within the first 24 to 48 hours after infusion. “Although the post hoc results are exploratory, these findings are important as well,” said Dr. Smith. “Other things are happening besides the reduction in migraine frequency that may be of benefit.”
Erenumab
A registration, pivotal study on erenumab for chronic migraine prevention was reported at the meeting. “Unlike eptinezumab, fremanezumab, and galcanezumab, which are monoclonal antibodies against the CGRP ligand, erenumab is an anti-CGRP receptor monoclonal antibody,” said Stewart J. Tepper, MD, Professor of Neurology at the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire. Amgen is developing this antibody.
In the 12-week randomized controlled trial, patients were enrolled in the US and around the world, Dr. Tepper noted. He and his colleagues included patients who had 15 or more headache days per month with at least eight days of migraine per month. Patients were excluded if they had experienced treatment failure with more than three classes of preventive agents. Mean age was 40, about 80% of patients were women, and roughly half of patients had previously experienced treatment failure with at least two preventive agents.
A total of 667 patients were randomized 3:2:2 to placebo, erenumab (70 mg), or erenumab (140 mg). Treatment was given monthly via subcutaneous injection. The primary end point was change from baseline in monthly migraine days (MMD). Secondary end points included at least a 50% reduction in MMD, change from baseline in acute migraine-specific medication days, and cumulative headache hours.
In both erenumab groups, patients experienced a mean 6.6-day reduction in MMD from a baseline of 18.0 days, which was significantly different, compared with the 4.2-day reduction seen in the placebo group. Furthermore, a significantly greater proportion of patients in the 70-mg and 140-mg groups (40% and 41%, respectively) experienced at least a 50% reduction in MMD, compared with the placebo group (23%). For the secondary end points, both erenumab groups had significantly greater reductions in acute migraine-specific medication days versus placebo. However, the difference in the reduction of cumulative headache hours did not reach statistical significance. “We speculated that this was because headache hours is a relatively variable end point, and it is collected in differing ways, with wide confidence intervals,” Dr. Tepper said.
The safety profile for both erenumab groups and the placebo group was similar. “No serious adverse events were reported by more than one patient in any treatment arm, and no serious adverse events were considered related to treatment,” he said.
Another erenumab trial enrolled patients with episodic migraine. Randomization was stratified by region and current and prior migraine preventive medication, said Daniel Mikol, MD, PhD, Executive Medical Director of Neuroscience Development at Amgen in Thousand Oaks, California. Patients included in the phase III study could be taking a single concomitant migraine preventive therapy. “Patients could have also failed previous preventive therapies due to poor tolerability or lack of efficacy,” he said. “There was no limit regarding the number of previous failures due to poor tolerability. With regard to lack of efficacy, patients could have no therapeutic response to two or fewer preventive therapies.”
Adults with episodic migraine (n = 955) were randomized 1:1:1 to monthly subcutaneous injections of placebo, erenumab (70 mg), or erenumab (140 mg) for 24 weeks. The primary end point was change from baseline in MMD from weeks 13 to 24. Secondary end points included achievement of 50% or more reduction in MMD, change in mean acute migraine-specific medication days, and changes in mean physical impairment and impact on everyday activity scores, as measured by the Migraine Physical Function Impact Diary, a novel patient-reported instrument, Dr. Mikol explained.
Subjects had a mean of 8.3 MMD at baseline. This measurement was reduced by 3.2, 3.7, and 1.8 days in the 70-mg, 140-mg, and placebo groups, respectively—a statistically significant difference in favor of the erenumab groups. Statistically superior results for erenumab 70 mg and 140 mg over placebo also were seen in the secondary end points of > 50% response (43%, 50%, and 27%, respectively), reduction from baseline in monthly acute migraine-specific medication days (1.1, 1.6, and 0.2), improved physical impairment score from baseline (4.2, 4.8, and 2.5), and improved everyday activity scores from baseline (5.5, 5.9, and 3.3).
“The safety profiles for erenumab were similar to that of placebo,” Dr. Mikol said. “Specifically, 63% of patients on placebo had adverse events, compared with 56% to 57% of patients in the erenumab groups. Serious adverse events and adverse events leading to treatment discontinuation were low in frequency and balanced across the groups.”
Galcanezumab
The efficacy, tolerability, and safety of galcanezumab, an investigational drug for the treatment of episodic migraine, was assessed in a six-month phase III study called EVOLVE-2. In this study, patients with episodic migraine experienced four to 14 migraine headache days per month with or without aura. “Our patient population had a mean age of about 40, and most [participants] were Caucasian women,” said Robert Conley, MD, Distinguished Lilly Scholar of Neuroscience at Eli Lilly and Company (the developer of galcanezumab) in Indianapolis.
“Half of our subjects were from North America, a quarter from Europe, and a quarter from the rest of the world.” Subjects had a 20-year migraine history on average and a mean of nine headache days per month at baseline, he noted. “In addition, two-thirds had been on prior preventive treatment, and they had relatively severe levels of disease.”
After screening 1,700 patients for the study, Dr. Conley and colleagues randomized 914 patients 1:1:2 to subcutaneous injection of galcanezumab (120 mg/month), galcanezumab (240 mg/month), or placebo. “There was about an 87% completion rate for the galcanezumab groups and an 83% completion rate in the placebo group. The higher number of dropouts in the placebo group was due to lack of efficacy,” said Dr. Conley. The primary end point was change from baseline in MMD at the end of six months. Secondary end points were percentages of patients with 50%, 75%, and 100% response rates; reduction in MMD requiring acute migraine medication; change in function score on the Migraine-Specific Quality of Life Questionnaire (MSQ); and change in the Patient Global Impression of Severity (PGI-S) rating.
After adjusting for multiplicity, the investigators found statistically significant differences between placebo and the galcanezumab arms in the primary end point. Mean reductions in headache days were 4.29 in the 120-mg group and 4.18 in the 240-mg group. Patients in the placebo group experienced a reduction of 2.28 days. “We looked at the early effects of treatment and found statistically significant improvements within a few days of injection that persisted over time,” Dr. Conley said.
In addition, statistically significant differences between galcanezumab and placebo were observed for all secondary end points. “In the 120-mg and 240-mg treatment groups, 59.3% and 56.5%, respectively, had at least a 50% reduction in monthly headache days, which was significantly different from placebo, but not different from each other,” said Dr. Conley. “We also saw that approximately one-third of patients in the galcanezumab arms experienced 75% response rates, which is double that seen in the placebo group. The 100% response rate was 11.5% to 13.8% in the treated groups—again, not a significant difference between them, but significantly different from placebo.” The change in the MSQ function score and the PGI-S rating averaged for months 4, 5, and 6 were significantly improved in the galcanezumab arms, compared with the placebo arm.
For most of the safety parameters, there were no significant differences between either dose of galcanezumab and placebo. However, the rates of injection-site reactions and pruritus were significantly higher for both drug doses, compared with placebo. Injection-site erythema was significantly higher in the 240-mg dose only.
Fremanezumab
“The phase III trial for fremanezumab in chronic migraine investigated a flexible dose for a quarterly and a monthly regimen,” said Ernesto Aycardi, MD, Vice President and Therapeutic Area Head for Migraine and Headache at Teva Pharmaceuticals
The primary end point of this multicenter trial was the mean change from baseline in monthly days of headache of at least moderate severity. The four main secondary end points were the proportion of patients with at least a 50% reduction in headache days, mean change in the number of days using acute headache medication at the end of the 12-week period of the trial, mean change from baseline in the days of at least moderate severity in the first four weeks of the trial, and change in disability scale (HIT-6) score from baseline. In this trial, patients treated with fremanezumab experienced significant improvement, compared with placebo on all primary and secondary end points for both monthly and quarterly dosing regimens.
“The average age of the study population was 41, with an average history of migraine of about 20 years,” Dr. Aycardi said. “All demographic characteristics, including weight, height, and ethnicity, were well balanced between the groups.”
Patients on the monthly regimen had a mean reduction of 4.6 headache days of at least moderate severity, and patients on the quarterly regimen had a reduction of 4.3 headache days of at least moderate severity, which was significantly different from the placebo group (2.5 headache days). Researchers also observed significant differences for each of the four secondary end points in favor of the monthly and quarterly regimens.
“Fremanezumab was well tolerated, compared with placebo,” Dr. Aycardi said. “The most commonly reported adverse event in the study was injection-site pain, with similar rates in the placebo and active groups.”
Dr. Aycardi highlighted how phase II results validated that target in chronic migraine. “With these phase III results, this is confirmed, bringing hope for patients with this disabling condition.”
—Adriene Marshall
Suggested Reading
Durham PL. Calcitonin gene-related peptide (CGRP) and migraine. Headache. 2006;46(Suppl 1):S3–S8.
Reuter U. Anti-CGRP antibodies: a new approach to migraine prevention. Lancet Neurol. 2014;13(9):857-859.
Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16(6):425-434.
BOSTON—A new class of drugs for the prevention of chronic and episodic migraine demonstrated promising results in recent phase II and phase III trials. Data for four humanized calcitonin gene–related peptide (CGRP) monoclonal antibodies—eptinezumab, erenumab, fremanezumab, and galcanezumab—were presented at the 59th Annual Scientific Meeting of the American Headache Society. Previous research has long implicated CGRP (which is elevated in jugular vein blood during acute migraine and cluster headaches) in disease pathophysiology. Recent advances in molecular neuroscience have helped shed further light on the pathogenic mechanisms and possible targets for treatment.
Eptinezumab
In a phase II study, a single infusion of eptinezumab (which Alder BioPharmaceuticals is developing under the name ALD403) reduced the number of migraine days per month, as well as the number of migraines classified as severe, in patients with chronic migraine. Of the four drugs presented at the meeting, eptinezumab was the only one to have an IV mode of delivery.
“We used International Classification of Headache Disorders 3 criteria to define chronic migraine, which is at least 15 headache days per month, of which eight must be migraine-like,” said Jeffrey T. L. Smith, MD, Senior Vice President of Translational Medicine at Alder BioPharmaceuticals in Bothell, Washington. “Patients also had to have a history of migraine for a year or more.”
On average, the patients included in this multisite study were slightly younger than 40. Most patients were women, and the average number of migraine days was between 16.2 and 16.5. After a one-month run-in period, patients were randomized to receive placebo or one of four doses of eptinezumab (ie, 300 mg, 100 mg, 30 mg, or 10 mg).
Reporting 12-week data from the 48-week trial, Dr. Smith and colleagues found that significantly more patients taking the 300-mg (33%) and 100-mg (31%) doses of eptinezumab reached the primary end point of a 75% reduction from baseline in migraine days, compared with patients who received placebo (21%). Differences in patients taking the 30-mg and 10-mg doses (28% and 27%, respectively) were not statistically significant. “Overall, approximately half of patients treated with eptinezumab experienced a 50% reduction in migraine days versus 41% of patients on placebo,” Dr. Smith added. Eptinezumab was well tolerated, and no serious adverse events were reported.
Post hoc analyses indicated that of the migraines that were not eliminated as a result of treatment, the percentage classified as severe was significantly reduced from baseline in each of the eptinezumab groups, compared with placebo. Also, fewer patients in the eptinezumab groups than in the placebo group experienced a migraine within the first 24 to 48 hours after infusion. “Although the post hoc results are exploratory, these findings are important as well,” said Dr. Smith. “Other things are happening besides the reduction in migraine frequency that may be of benefit.”
Erenumab
A registration, pivotal study on erenumab for chronic migraine prevention was reported at the meeting. “Unlike eptinezumab, fremanezumab, and galcanezumab, which are monoclonal antibodies against the CGRP ligand, erenumab is an anti-CGRP receptor monoclonal antibody,” said Stewart J. Tepper, MD, Professor of Neurology at the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire. Amgen is developing this antibody.
In the 12-week randomized controlled trial, patients were enrolled in the US and around the world, Dr. Tepper noted. He and his colleagues included patients who had 15 or more headache days per month with at least eight days of migraine per month. Patients were excluded if they had experienced treatment failure with more than three classes of preventive agents. Mean age was 40, about 80% of patients were women, and roughly half of patients had previously experienced treatment failure with at least two preventive agents.
A total of 667 patients were randomized 3:2:2 to placebo, erenumab (70 mg), or erenumab (140 mg). Treatment was given monthly via subcutaneous injection. The primary end point was change from baseline in monthly migraine days (MMD). Secondary end points included at least a 50% reduction in MMD, change from baseline in acute migraine-specific medication days, and cumulative headache hours.
In both erenumab groups, patients experienced a mean 6.6-day reduction in MMD from a baseline of 18.0 days, which was significantly different, compared with the 4.2-day reduction seen in the placebo group. Furthermore, a significantly greater proportion of patients in the 70-mg and 140-mg groups (40% and 41%, respectively) experienced at least a 50% reduction in MMD, compared with the placebo group (23%). For the secondary end points, both erenumab groups had significantly greater reductions in acute migraine-specific medication days versus placebo. However, the difference in the reduction of cumulative headache hours did not reach statistical significance. “We speculated that this was because headache hours is a relatively variable end point, and it is collected in differing ways, with wide confidence intervals,” Dr. Tepper said.
The safety profile for both erenumab groups and the placebo group was similar. “No serious adverse events were reported by more than one patient in any treatment arm, and no serious adverse events were considered related to treatment,” he said.
Another erenumab trial enrolled patients with episodic migraine. Randomization was stratified by region and current and prior migraine preventive medication, said Daniel Mikol, MD, PhD, Executive Medical Director of Neuroscience Development at Amgen in Thousand Oaks, California. Patients included in the phase III study could be taking a single concomitant migraine preventive therapy. “Patients could have also failed previous preventive therapies due to poor tolerability or lack of efficacy,” he said. “There was no limit regarding the number of previous failures due to poor tolerability. With regard to lack of efficacy, patients could have no therapeutic response to two or fewer preventive therapies.”
Adults with episodic migraine (n = 955) were randomized 1:1:1 to monthly subcutaneous injections of placebo, erenumab (70 mg), or erenumab (140 mg) for 24 weeks. The primary end point was change from baseline in MMD from weeks 13 to 24. Secondary end points included achievement of 50% or more reduction in MMD, change in mean acute migraine-specific medication days, and changes in mean physical impairment and impact on everyday activity scores, as measured by the Migraine Physical Function Impact Diary, a novel patient-reported instrument, Dr. Mikol explained.
Subjects had a mean of 8.3 MMD at baseline. This measurement was reduced by 3.2, 3.7, and 1.8 days in the 70-mg, 140-mg, and placebo groups, respectively—a statistically significant difference in favor of the erenumab groups. Statistically superior results for erenumab 70 mg and 140 mg over placebo also were seen in the secondary end points of > 50% response (43%, 50%, and 27%, respectively), reduction from baseline in monthly acute migraine-specific medication days (1.1, 1.6, and 0.2), improved physical impairment score from baseline (4.2, 4.8, and 2.5), and improved everyday activity scores from baseline (5.5, 5.9, and 3.3).
“The safety profiles for erenumab were similar to that of placebo,” Dr. Mikol said. “Specifically, 63% of patients on placebo had adverse events, compared with 56% to 57% of patients in the erenumab groups. Serious adverse events and adverse events leading to treatment discontinuation were low in frequency and balanced across the groups.”
Galcanezumab
The efficacy, tolerability, and safety of galcanezumab, an investigational drug for the treatment of episodic migraine, was assessed in a six-month phase III study called EVOLVE-2. In this study, patients with episodic migraine experienced four to 14 migraine headache days per month with or without aura. “Our patient population had a mean age of about 40, and most [participants] were Caucasian women,” said Robert Conley, MD, Distinguished Lilly Scholar of Neuroscience at Eli Lilly and Company (the developer of galcanezumab) in Indianapolis.
“Half of our subjects were from North America, a quarter from Europe, and a quarter from the rest of the world.” Subjects had a 20-year migraine history on average and a mean of nine headache days per month at baseline, he noted. “In addition, two-thirds had been on prior preventive treatment, and they had relatively severe levels of disease.”
After screening 1,700 patients for the study, Dr. Conley and colleagues randomized 914 patients 1:1:2 to subcutaneous injection of galcanezumab (120 mg/month), galcanezumab (240 mg/month), or placebo. “There was about an 87% completion rate for the galcanezumab groups and an 83% completion rate in the placebo group. The higher number of dropouts in the placebo group was due to lack of efficacy,” said Dr. Conley. The primary end point was change from baseline in MMD at the end of six months. Secondary end points were percentages of patients with 50%, 75%, and 100% response rates; reduction in MMD requiring acute migraine medication; change in function score on the Migraine-Specific Quality of Life Questionnaire (MSQ); and change in the Patient Global Impression of Severity (PGI-S) rating.
After adjusting for multiplicity, the investigators found statistically significant differences between placebo and the galcanezumab arms in the primary end point. Mean reductions in headache days were 4.29 in the 120-mg group and 4.18 in the 240-mg group. Patients in the placebo group experienced a reduction of 2.28 days. “We looked at the early effects of treatment and found statistically significant improvements within a few days of injection that persisted over time,” Dr. Conley said.
In addition, statistically significant differences between galcanezumab and placebo were observed for all secondary end points. “In the 120-mg and 240-mg treatment groups, 59.3% and 56.5%, respectively, had at least a 50% reduction in monthly headache days, which was significantly different from placebo, but not different from each other,” said Dr. Conley. “We also saw that approximately one-third of patients in the galcanezumab arms experienced 75% response rates, which is double that seen in the placebo group. The 100% response rate was 11.5% to 13.8% in the treated groups—again, not a significant difference between them, but significantly different from placebo.” The change in the MSQ function score and the PGI-S rating averaged for months 4, 5, and 6 were significantly improved in the galcanezumab arms, compared with the placebo arm.
For most of the safety parameters, there were no significant differences between either dose of galcanezumab and placebo. However, the rates of injection-site reactions and pruritus were significantly higher for both drug doses, compared with placebo. Injection-site erythema was significantly higher in the 240-mg dose only.
Fremanezumab
“The phase III trial for fremanezumab in chronic migraine investigated a flexible dose for a quarterly and a monthly regimen,” said Ernesto Aycardi, MD, Vice President and Therapeutic Area Head for Migraine and Headache at Teva Pharmaceuticals
The primary end point of this multicenter trial was the mean change from baseline in monthly days of headache of at least moderate severity. The four main secondary end points were the proportion of patients with at least a 50% reduction in headache days, mean change in the number of days using acute headache medication at the end of the 12-week period of the trial, mean change from baseline in the days of at least moderate severity in the first four weeks of the trial, and change in disability scale (HIT-6) score from baseline. In this trial, patients treated with fremanezumab experienced significant improvement, compared with placebo on all primary and secondary end points for both monthly and quarterly dosing regimens.
“The average age of the study population was 41, with an average history of migraine of about 20 years,” Dr. Aycardi said. “All demographic characteristics, including weight, height, and ethnicity, were well balanced between the groups.”
Patients on the monthly regimen had a mean reduction of 4.6 headache days of at least moderate severity, and patients on the quarterly regimen had a reduction of 4.3 headache days of at least moderate severity, which was significantly different from the placebo group (2.5 headache days). Researchers also observed significant differences for each of the four secondary end points in favor of the monthly and quarterly regimens.
“Fremanezumab was well tolerated, compared with placebo,” Dr. Aycardi said. “The most commonly reported adverse event in the study was injection-site pain, with similar rates in the placebo and active groups.”
Dr. Aycardi highlighted how phase II results validated that target in chronic migraine. “With these phase III results, this is confirmed, bringing hope for patients with this disabling condition.”
—Adriene Marshall
Suggested Reading
Durham PL. Calcitonin gene-related peptide (CGRP) and migraine. Headache. 2006;46(Suppl 1):S3–S8.
Reuter U. Anti-CGRP antibodies: a new approach to migraine prevention. Lancet Neurol. 2014;13(9):857-859.
Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16(6):425-434.
Triptans, Antidepressants, and Serotonin Syndrome: How Real Is the Risk?
BOSTON—The incidence of serotonin syndrome ranged from 0.02% to 0.04% among all patients who were coprescribed triptans and an SSRI/SNRI during any calendar year from 2001 to 2014, according to a study presented at the 59th Annual Scientific Meeting of the American Headache Society. “Our data do not suggest a clinically meaningful risk of serotonin syndrome in patients coprescribed triptans with SSRI/SSNI antidepressants,” said Yulia Y. Orlova, MD, a clinical fellow at the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston. 
Serotonin syndrome is a drug-induced group of symptoms that can be life-threatening. In 2006, the FDA issued an advisory concerning the risk of serotonin syndrome with concomitant use of triptans and SSRI/SNRI antidepressants. Since then, pharmacy systems and other decision support systems routinely have issued safety alerts when coprescription occurs. “However, all published reports of serotonin syndrome in patients receiving triptans alone or in combination with an SSRI/SNRI are case reports or case series that lack a denominator, so the true risk remains unknown,” said Dr. Orlova on behalf of her study collaborators.
Dr. Orlova and colleagues conducted a population-based study. For each year from 2001 to 2014, they used the Partners Healthcare System Research Patient Data Registry to identify patients receiving coprescriptions. The registry is a centralized data warehouse with clinical information about more than 6.5 million patients. The ICD-9 code for serotonin syndrome (333.99) is not reported separately in the database, but is part of a broader category of “other extrapyramidal diseases and abnormal movement disorders.” The researchers conservatively assumed that all reports of diagnostic code ICD-9 333.99 might represent serotonin syndrome. Among those patients receiving coprescriptions in the database, the researchers searched for those with the 333.99 code. The research team then reviewed detailed medical records to determine whether those patients met Sternbach or Hunter criteria for serotonin toxicity, or both, during the year in which concomitant prescription of a triptan antimigraine medication and SSRI/SNRI antidepressant may have occurred.
Over the 14-year study period, nearly 48,000 patients were prescribed triptans. Among these patients, about 19,000 were also coprescribed SSRI or SNRI antidepressants. A total of 229 received an ICD-9 diagnosis of 333.99. Detailed chart review revealed 17 cases where serotonin syndrome was reported as part of the differential diagnosis, past medical history, or main diagnosis. Seven of the 17 patients met Sternbach criteria (0.04% of all coprescription cases), four met Hunter criteria (0.02% of all coprescription cases), and all of the latter also satisfied Sternbach criteria.
Triptan use was reported in close temporal relation to the onset of symptoms in two cases. One case, involving eletriptan, was self-reported by the patient and recorded by the physician in the medical record. Chart information for this case did not allow assessment of whether the case met diagnostic criteria. The second case satisfied both sets of criteria for serotonin syndrome and involved the use of rizatriptan, although the onset of symptoms preceded rizatriptan use.
BOSTON—The incidence of serotonin syndrome ranged from 0.02% to 0.04% among all patients who were coprescribed triptans and an SSRI/SNRI during any calendar year from 2001 to 2014, according to a study presented at the 59th Annual Scientific Meeting of the American Headache Society. “Our data do not suggest a clinically meaningful risk of serotonin syndrome in patients coprescribed triptans with SSRI/SSNI antidepressants,” said Yulia Y. Orlova, MD, a clinical fellow at the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston.
Serotonin syndrome is a drug-induced group of symptoms that can be life-threatening. In 2006, the FDA issued an advisory concerning the risk of serotonin syndrome with concomitant use of triptans and SSRI/SNRI antidepressants. Since then, pharmacy systems and other decision support systems routinely have issued safety alerts when coprescription occurs. “However, all published reports of serotonin syndrome in patients receiving triptans alone or in combination with an SSRI/SNRI are case reports or case series that lack a denominator, so the true risk remains unknown,” said Dr. Orlova on behalf of her study collaborators.
Dr. Orlova and colleagues conducted a population-based study. For each year from 2001 to 2014, they used the Partners Healthcare System Research Patient Data Registry to identify patients receiving coprescriptions. The registry is a centralized data warehouse with clinical information about more than 6.5 million patients. The ICD-9 code for serotonin syndrome (333.99) is not reported separately in the database, but is part of a broader category of “other extrapyramidal diseases and abnormal movement disorders.” The researchers conservatively assumed that all reports of diagnostic code ICD-9 333.99 might represent serotonin syndrome. Among those patients receiving coprescriptions in the database, the researchers searched for those with the 333.99 code. The research team then reviewed detailed medical records to determine whether those patients met Sternbach or Hunter criteria for serotonin toxicity, or both, during the year in which concomitant prescription of a triptan antimigraine medication and SSRI/SNRI antidepressant may have occurred.
Over the 14-year study period, nearly 48,000 patients were prescribed triptans. Among these patients, about 19,000 were also coprescribed SSRI or SNRI antidepressants. A total of 229 received an ICD-9 diagnosis of 333.99. Detailed chart review revealed 17 cases where serotonin syndrome was reported as part of the differential diagnosis, past medical history, or main diagnosis. Seven of the 17 patients met Sternbach criteria (0.04% of all coprescription cases), four met Hunter criteria (0.02% of all coprescription cases), and all of the latter also satisfied Sternbach criteria.
Triptan use was reported in close temporal relation to the onset of symptoms in two cases. One case, involving eletriptan, was self-reported by the patient and recorded by the physician in the medical record. Chart information for this case did not allow assessment of whether the case met diagnostic criteria. The second case satisfied both sets of criteria for serotonin syndrome and involved the use of rizatriptan, although the onset of symptoms preceded rizatriptan use.
BOSTON—The incidence of serotonin syndrome ranged from 0.02% to 0.04% among all patients who were coprescribed triptans and an SSRI/SNRI during any calendar year from 2001 to 2014, according to a study presented at the 59th Annual Scientific Meeting of the American Headache Society. “Our data do not suggest a clinically meaningful risk of serotonin syndrome in patients coprescribed triptans with SSRI/SSNI antidepressants,” said Yulia Y. Orlova, MD, a clinical fellow at the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston.
Serotonin syndrome is a drug-induced group of symptoms that can be life-threatening. In 2006, the FDA issued an advisory concerning the risk of serotonin syndrome with concomitant use of triptans and SSRI/SNRI antidepressants. Since then, pharmacy systems and other decision support systems routinely have issued safety alerts when coprescription occurs. “However, all published reports of serotonin syndrome in patients receiving triptans alone or in combination with an SSRI/SNRI are case reports or case series that lack a denominator, so the true risk remains unknown,” said Dr. Orlova on behalf of her study collaborators.
Dr. Orlova and colleagues conducted a population-based study. For each year from 2001 to 2014, they used the Partners Healthcare System Research Patient Data Registry to identify patients receiving coprescriptions. The registry is a centralized data warehouse with clinical information about more than 6.5 million patients. The ICD-9 code for serotonin syndrome (333.99) is not reported separately in the database, but is part of a broader category of “other extrapyramidal diseases and abnormal movement disorders.” The researchers conservatively assumed that all reports of diagnostic code ICD-9 333.99 might represent serotonin syndrome. Among those patients receiving coprescriptions in the database, the researchers searched for those with the 333.99 code. The research team then reviewed detailed medical records to determine whether those patients met Sternbach or Hunter criteria for serotonin toxicity, or both, during the year in which concomitant prescription of a triptan antimigraine medication and SSRI/SNRI antidepressant may have occurred.
Over the 14-year study period, nearly 48,000 patients were prescribed triptans. Among these patients, about 19,000 were also coprescribed SSRI or SNRI antidepressants. A total of 229 received an ICD-9 diagnosis of 333.99. Detailed chart review revealed 17 cases where serotonin syndrome was reported as part of the differential diagnosis, past medical history, or main diagnosis. Seven of the 17 patients met Sternbach criteria (0.04% of all coprescription cases), four met Hunter criteria (0.02% of all coprescription cases), and all of the latter also satisfied Sternbach criteria.
Triptan use was reported in close temporal relation to the onset of symptoms in two cases. One case, involving eletriptan, was self-reported by the patient and recorded by the physician in the medical record. Chart information for this case did not allow assessment of whether the case met diagnostic criteria. The second case satisfied both sets of criteria for serotonin syndrome and involved the use of rizatriptan, although the onset of symptoms preceded rizatriptan use.
Is Chronic Migraine More Common in the MS Population?
BOSTON—At Island Neurological Associates in Plainview, New York, researchers uncovered a prevalence of chronic migraine among their population of patients with multiple sclerosis (MS) that was higher than would be expected in the general population. They reported their results at the 59th Annual Scientific Meeting of the American Headache Society. “Since migraine as a whole is generally accepted to occur in about 12% of the population, it appears that our MS patient prevalence of 21% significantly exceeds this [prevalence],” said Ira Turner, MD, a headache subspecialist at the Long Island facility. Similarly, “chronic migraine is thought to occur in 1% to 2% of the general population, but [it occurs] in 7% of our MS population,” Dr. Turner said. 
Observing that MS and migraine are both chronic neurologic conditions in which inflammatory processes play an important role, Dr. Turner and colleagues sought evidence for increased migraine prevalence in the MS population. “Anecdotally, it has been our experience that there is a comorbidity of headache disorders in our MS patient population,” Dr. Turner said.
The investigators conducted a retrospective review of the electronic medical record (EMR) system at their community-based Comprehensive MS Center and Center for Headache Care and Research. They reviewed the EMR for all patients with a diagnosis of any form of MS. The EMR was then queried to determine which of the patients with MS had any headache diagnosis listed as a comorbidity. Those headache diagnoses were then reviewed and separated into those that met ICHD
The researchers found 610 active patients with a diagnosis of MS. Of these, 139 (23%) also had a headache diagnosis listed in the EMR as a comorbidity. Migraine without aura was coded in 62 patients (10%), migraine with aura in 26 (4%), and chronic migraine in 45 (7%). Combining these diagnoses yielded a prevalence of comorbid migraine of 21% in the MS population studied. Episodic cluster headache was diagnosed in one patient, tension-type headache in two patients, and nonspecific headache in four patients. The prevalence of these three diagnoses was less than 1% each.
“While there is a potential bias caused by our practice having both an MS center and a headache center, this increased prevalence seems to be of great interest and would appear to warrant further investigation,” Dr. Turner said.
—Glenn S. Williams
BOSTON—At Island Neurological Associates in Plainview, New York, researchers uncovered a prevalence of chronic migraine among their population of patients with multiple sclerosis (MS) that was higher than would be expected in the general population. They reported their results at the 59th Annual Scientific Meeting of the American Headache Society. “Since migraine as a whole is generally accepted to occur in about 12% of the population, it appears that our MS patient prevalence of 21% significantly exceeds this [prevalence],” said Ira Turner, MD, a headache subspecialist at the Long Island facility. Similarly, “chronic migraine is thought to occur in 1% to 2% of the general population, but [it occurs] in 7% of our MS population,” Dr. Turner said.
Observing that MS and migraine are both chronic neurologic conditions in which inflammatory processes play an important role, Dr. Turner and colleagues sought evidence for increased migraine prevalence in the MS population. “Anecdotally, it has been our experience that there is a comorbidity of headache disorders in our MS patient population,” Dr. Turner said.
The investigators conducted a retrospective review of the electronic medical record (EMR) system at their community-based Comprehensive MS Center and Center for Headache Care and Research. They reviewed the EMR for all patients with a diagnosis of any form of MS. The EMR was then queried to determine which of the patients with MS had any headache diagnosis listed as a comorbidity. Those headache diagnoses were then reviewed and separated into those that met ICHD
The researchers found 610 active patients with a diagnosis of MS. Of these, 139 (23%) also had a headache diagnosis listed in the EMR as a comorbidity. Migraine without aura was coded in 62 patients (10%), migraine with aura in 26 (4%), and chronic migraine in 45 (7%). Combining these diagnoses yielded a prevalence of comorbid migraine of 21% in the MS population studied. Episodic cluster headache was diagnosed in one patient, tension-type headache in two patients, and nonspecific headache in four patients. The prevalence of these three diagnoses was less than 1% each.
“While there is a potential bias caused by our practice having both an MS center and a headache center, this increased prevalence seems to be of great interest and would appear to warrant further investigation,” Dr. Turner said.
—Glenn S. Williams
BOSTON—At Island Neurological Associates in Plainview, New York, researchers uncovered a prevalence of chronic migraine among their population of patients with multiple sclerosis (MS) that was higher than would be expected in the general population. They reported their results at the 59th Annual Scientific Meeting of the American Headache Society. “Since migraine as a whole is generally accepted to occur in about 12% of the population, it appears that our MS patient prevalence of 21% significantly exceeds this [prevalence],” said Ira Turner, MD, a headache subspecialist at the Long Island facility. Similarly, “chronic migraine is thought to occur in 1% to 2% of the general population, but [it occurs] in 7% of our MS population,” Dr. Turner said.
Observing that MS and migraine are both chronic neurologic conditions in which inflammatory processes play an important role, Dr. Turner and colleagues sought evidence for increased migraine prevalence in the MS population. “Anecdotally, it has been our experience that there is a comorbidity of headache disorders in our MS patient population,” Dr. Turner said.
The investigators conducted a retrospective review of the electronic medical record (EMR) system at their community-based Comprehensive MS Center and Center for Headache Care and Research. They reviewed the EMR for all patients with a diagnosis of any form of MS. The EMR was then queried to determine which of the patients with MS had any headache diagnosis listed as a comorbidity. Those headache diagnoses were then reviewed and separated into those that met ICHD
The researchers found 610 active patients with a diagnosis of MS. Of these, 139 (23%) also had a headache diagnosis listed in the EMR as a comorbidity. Migraine without aura was coded in 62 patients (10%), migraine with aura in 26 (4%), and chronic migraine in 45 (7%). Combining these diagnoses yielded a prevalence of comorbid migraine of 21% in the MS population studied. Episodic cluster headache was diagnosed in one patient, tension-type headache in two patients, and nonspecific headache in four patients. The prevalence of these three diagnoses was less than 1% each.
“While there is a potential bias caused by our practice having both an MS center and a headache center, this increased prevalence seems to be of great interest and would appear to warrant further investigation,” Dr. Turner said.
—Glenn S. Williams
Patient Satisfaction With Prophylactic Migraine Medications
BOSTON—Effectiveness and tolerability were the key factors influencing patients’ satisfaction with prophylactic migraine medications, according to a study presented at the 59th Annual Scientific Meeting of the American Headache Society. “There is an unmet need for treatments that have better efficacy and tolerability profiles than existing prophylactic migraine medications,” said lead author Marci Clark, PharmD, Director of Patient-Centered Outcomes Assessment at RTI Health Solutions in Ann Arbor, Michigan, on behalf of her study collaborators. 
To gain insight into reasons for patient satisfaction or dissatisfaction with prophylactic migraine medications and identify medication characteristics that would increase patient satisfaction with future prophylactic migraine medications, the researchers recruited study participants from research facilities in Charlotte, North Carolina; St. Louis, Missouri; Southfield, Michigan; and Tampa, Florida. Individuals were eligible to participate if they met the following self-reported criteria: age 18 to 55, physician diagnosis of migraine for 12 or more months, current or prior experience taking one or more prescription prophylactic migraine medication in the past six months, experiencing four or more migraine headache days per month, and further classification as having episodic or chronic migraine (based on the headache/migraine days reported). Individual discussions with all participants were conducted by two experienced interviewers.
Forty participants were recruited and interviewed; 36 met all eligibility criteria. Twenty-one participants met the criteria for episodic migraine, 15 met the criteria for chronic migraine, and four participants, who were current migraineurs, were unable to be classified as having episodic or chronic migraine. Participants provided feedback on 20 prescription prophylactic migraine medications. The most commonly used current or prior migraine prophylactics were topiramate (n = 27), amitriptyline (n = 6), propranolol (n = 6), onabotulinumtoxinA (n = 5), and zonisamide (n = 3).
In general, medication effectiveness and tolerability were the most influential factors on patient satisfaction or dissatisfaction with their prophylactic migraine medications. Lack of efficacy, cited by 56% of respondents, was the most frequently reported reason for participants’ dissatisfaction with their medications. Regarding tolerabilit
Among those who were satisfied with their prophylactic migraine medications, decreased migraine frequency was the most common reason for their satisfaction (65%), followed by decreased migraine severity or intensity, which was reported by 28% of participants.
The most frequently reported desirable characteristics of a new prophylactic migraine medication that would increase participants’ satisfaction were related to the medication’s ability to decrease the frequency and severity or intensity of migraines. Nausea (36%), weight gain (26%), dizziness/light-headedness (23%), drowsiness/grogginess (15%), and memory loss, including the ability to remember words and speak clearly (13%), are side effects that patients reported that they do not want to see in a new or future prophylactic migraine medication.
BOSTON—Effectiveness and tolerability were the key factors influencing patients’ satisfaction with prophylactic migraine medications, according to a study presented at the 59th Annual Scientific Meeting of the American Headache Society. “There is an unmet need for treatments that have better efficacy and tolerability profiles than existing prophylactic migraine medications,” said lead author Marci Clark, PharmD, Director of Patient-Centered Outcomes Assessment at RTI Health Solutions in Ann Arbor, Michigan, on behalf of her study collaborators.
To gain insight into reasons for patient satisfaction or dissatisfaction with prophylactic migraine medications and identify medication characteristics that would increase patient satisfaction with future prophylactic migraine medications, the researchers recruited study participants from research facilities in Charlotte, North Carolina; St. Louis, Missouri; Southfield, Michigan; and Tampa, Florida. Individuals were eligible to participate if they met the following self-reported criteria: age 18 to 55, physician diagnosis of migraine for 12 or more months, current or prior experience taking one or more prescription prophylactic migraine medication in the past six months, experiencing four or more migraine headache days per month, and further classification as having episodic or chronic migraine (based on the headache/migraine days reported). Individual discussions with all participants were conducted by two experienced interviewers.
Forty participants were recruited and interviewed; 36 met all eligibility criteria. Twenty-one participants met the criteria for episodic migraine, 15 met the criteria for chronic migraine, and four participants, who were current migraineurs, were unable to be classified as having episodic or chronic migraine. Participants provided feedback on 20 prescription prophylactic migraine medications. The most commonly used current or prior migraine prophylactics were topiramate (n = 27), amitriptyline (n = 6), propranolol (n = 6), onabotulinumtoxinA (n = 5), and zonisamide (n = 3).
In general, medication effectiveness and tolerability were the most influential factors on patient satisfaction or dissatisfaction with their prophylactic migraine medications. Lack of efficacy, cited by 56% of respondents, was the most frequently reported reason for participants’ dissatisfaction with their medications. Regarding tolerabilit
Among those who were satisfied with their prophylactic migraine medications, decreased migraine frequency was the most common reason for their satisfaction (65%), followed by decreased migraine severity or intensity, which was reported by 28% of participants.
The most frequently reported desirable characteristics of a new prophylactic migraine medication that would increase participants’ satisfaction were related to the medication’s ability to decrease the frequency and severity or intensity of migraines. Nausea (36%), weight gain (26%), dizziness/light-headedness (23%), drowsiness/grogginess (15%), and memory loss, including the ability to remember words and speak clearly (13%), are side effects that patients reported that they do not want to see in a new or future prophylactic migraine medication.
BOSTON—Effectiveness and tolerability were the key factors influencing patients’ satisfaction with prophylactic migraine medications, according to a study presented at the 59th Annual Scientific Meeting of the American Headache Society. “There is an unmet need for treatments that have better efficacy and tolerability profiles than existing prophylactic migraine medications,” said lead author Marci Clark, PharmD, Director of Patient-Centered Outcomes Assessment at RTI Health Solutions in Ann Arbor, Michigan, on behalf of her study collaborators.
To gain insight into reasons for patient satisfaction or dissatisfaction with prophylactic migraine medications and identify medication characteristics that would increase patient satisfaction with future prophylactic migraine medications, the researchers recruited study participants from research facilities in Charlotte, North Carolina; St. Louis, Missouri; Southfield, Michigan; and Tampa, Florida. Individuals were eligible to participate if they met the following self-reported criteria: age 18 to 55, physician diagnosis of migraine for 12 or more months, current or prior experience taking one or more prescription prophylactic migraine medication in the past six months, experiencing four or more migraine headache days per month, and further classification as having episodic or chronic migraine (based on the headache/migraine days reported). Individual discussions with all participants were conducted by two experienced interviewers.
Forty participants were recruited and interviewed; 36 met all eligibility criteria. Twenty-one participants met the criteria for episodic migraine, 15 met the criteria for chronic migraine, and four participants, who were current migraineurs, were unable to be classified as having episodic or chronic migraine. Participants provided feedback on 20 prescription prophylactic migraine medications. The most commonly used current or prior migraine prophylactics were topiramate (n = 27), amitriptyline (n = 6), propranolol (n = 6), onabotulinumtoxinA (n = 5), and zonisamide (n = 3).
In general, medication effectiveness and tolerability were the most influential factors on patient satisfaction or dissatisfaction with their prophylactic migraine medications. Lack of efficacy, cited by 56% of respondents, was the most frequently reported reason for participants’ dissatisfaction with their medications. Regarding tolerabilit
Among those who were satisfied with their prophylactic migraine medications, decreased migraine frequency was the most common reason for their satisfaction (65%), followed by decreased migraine severity or intensity, which was reported by 28% of participants.
The most frequently reported desirable characteristics of a new prophylactic migraine medication that would increase participants’ satisfaction were related to the medication’s ability to decrease the frequency and severity or intensity of migraines. Nausea (36%), weight gain (26%), dizziness/light-headedness (23%), drowsiness/grogginess (15%), and memory loss, including the ability to remember words and speak clearly (13%), are side effects that patients reported that they do not want to see in a new or future prophylactic migraine medication.
Patient Satisfaction With Prophylactic Migraine Medications
BOSTON—Effectiveness and tolerability were the key factors influencing patients’ satisfaction with prophylactic migraine medications, according to a study presented at the 59th Annual Scientific Meeting of the American Headache Society. “There is an unmet need for treatments that have better efficacy and tolerability profiles than existing prophylactic migraine medications,” said lead author Marci Clark, PharmD, Director of Patient-Centered Outcomes Assessment at RTI Health Solutions in Ann Arbor, Michigan, on behalf of her study collaborators.
To gain insight into reasons for patient satisfaction or dissatisfaction with prophylactic migraine medications and identify medication characteristics that would increase patient satisfaction with future prophylactic migraine medications, the researchers recruited study participants from research facilities in Charlotte, North Carolina; St. Louis, Missouri; Southfield, Michigan; and Tampa, Florida. Individuals were eligible to participate if they met the following self-reported criteria: age 18 to 55, physician diagnosis of migraine for 12 or more months, current or prior experience taking one or more prescription prophylactic migraine medication in the past six months, experiencing four or more migraine headache days per month, and further classification as having episodic or chronic migraine (based on the headache/migraine days reported). Individual discussions with all participants were conducted by two experienced interviewers.
Forty participants were recruited and interviewed; 36 met all eligibility criteria. Twenty-one participants met the criteria for episodic migraine, 15 met the criteria for chronic migraine, and four participants, who were current migraineurs, were unable to be classified as episodic or chronic migraine. Participants provided feedback on 20 prescription prophylactic migraine medications. The most commonly used current or prior migraine prophylactics were topiramate (n = 27), amitriptyline (n = 6), propranolol (n = 6), onabotulinumtoxinA (n = 5), and zonisamide (n = 3).
In general, medication effectiveness and tolerability were the most influential factors on patient satisfaction or dissatisfaction with their prophylactic migraine medications. Lack of efficacy, cited by 56% of respondents, was the most frequently reported reason for participants’ dissatisfaction with their medications. Regarding tolerability, 51% of participants reported that a particular side effect was the most dissatisfying characteristic of their medication. The most bothersome side effects reported by participants were memory loss (n = 6), dizziness or light-headedness (n = 5), tiredness/drowsiness/grogginess/sluggishness (n = 5), nausea (n = 3), and dry mouth (n = 2).
Among those who were satisfied with their prophylactic migraine medications, decreased migraine frequency was the most common reason for their satisfaction (65%), followed by decreased migraine severity or intensity, which was reported by 28% of participants.
The most frequently reported desirable characteristics of a new prophylactic migraine medication that would increase participants’ satisfaction were related to the medication’s ability to decrease the frequency and severity or intensity of migraines. Nausea (36%), weight gain (26%), dizziness/light-headedness (23%), drowsiness/grogginess (15%), and memory loss, including the ability to remember words and speak clearly (13%), are side effects that patients reported that they do not want to see in a new or future prophylactic migraine medication.
BOSTON—Effectiveness and tolerability were the key factors influencing patients’ satisfaction with prophylactic migraine medications, according to a study presented at the 59th Annual Scientific Meeting of the American Headache Society. “There is an unmet need for treatments that have better efficacy and tolerability profiles than existing prophylactic migraine medications,” said lead author Marci Clark, PharmD, Director of Patient-Centered Outcomes Assessment at RTI Health Solutions in Ann Arbor, Michigan, on behalf of her study collaborators.
To gain insight into reasons for patient satisfaction or dissatisfaction with prophylactic migraine medications and identify medication characteristics that would increase patient satisfaction with future prophylactic migraine medications, the researchers recruited study participants from research facilities in Charlotte, North Carolina; St. Louis, Missouri; Southfield, Michigan; and Tampa, Florida. Individuals were eligible to participate if they met the following self-reported criteria: age 18 to 55, physician diagnosis of migraine for 12 or more months, current or prior experience taking one or more prescription prophylactic migraine medication in the past six months, experiencing four or more migraine headache days per month, and further classification as having episodic or chronic migraine (based on the headache/migraine days reported). Individual discussions with all participants were conducted by two experienced interviewers.
Forty participants were recruited and interviewed; 36 met all eligibility criteria. Twenty-one participants met the criteria for episodic migraine, 15 met the criteria for chronic migraine, and four participants, who were current migraineurs, were unable to be classified as episodic or chronic migraine. Participants provided feedback on 20 prescription prophylactic migraine medications. The most commonly used current or prior migraine prophylactics were topiramate (n = 27), amitriptyline (n = 6), propranolol (n = 6), onabotulinumtoxinA (n = 5), and zonisamide (n = 3).
In general, medication effectiveness and tolerability were the most influential factors on patient satisfaction or dissatisfaction with their prophylactic migraine medications. Lack of efficacy, cited by 56% of respondents, was the most frequently reported reason for participants’ dissatisfaction with their medications. Regarding tolerability, 51% of participants reported that a particular side effect was the most dissatisfying characteristic of their medication. The most bothersome side effects reported by participants were memory loss (n = 6), dizziness or light-headedness (n = 5), tiredness/drowsiness/grogginess/sluggishness (n = 5), nausea (n = 3), and dry mouth (n = 2).
Among those who were satisfied with their prophylactic migraine medications, decreased migraine frequency was the most common reason for their satisfaction (65%), followed by decreased migraine severity or intensity, which was reported by 28% of participants.
The most frequently reported desirable characteristics of a new prophylactic migraine medication that would increase participants’ satisfaction were related to the medication’s ability to decrease the frequency and severity or intensity of migraines. Nausea (36%), weight gain (26%), dizziness/light-headedness (23%), drowsiness/grogginess (15%), and memory loss, including the ability to remember words and speak clearly (13%), are side effects that patients reported that they do not want to see in a new or future prophylactic migraine medication.
BOSTON—Effectiveness and tolerability were the key factors influencing patients’ satisfaction with prophylactic migraine medications, according to a study presented at the 59th Annual Scientific Meeting of the American Headache Society. “There is an unmet need for treatments that have better efficacy and tolerability profiles than existing prophylactic migraine medications,” said lead author Marci Clark, PharmD, Director of Patient-Centered Outcomes Assessment at RTI Health Solutions in Ann Arbor, Michigan, on behalf of her study collaborators.
To gain insight into reasons for patient satisfaction or dissatisfaction with prophylactic migraine medications and identify medication characteristics that would increase patient satisfaction with future prophylactic migraine medications, the researchers recruited study participants from research facilities in Charlotte, North Carolina; St. Louis, Missouri; Southfield, Michigan; and Tampa, Florida. Individuals were eligible to participate if they met the following self-reported criteria: age 18 to 55, physician diagnosis of migraine for 12 or more months, current or prior experience taking one or more prescription prophylactic migraine medication in the past six months, experiencing four or more migraine headache days per month, and further classification as having episodic or chronic migraine (based on the headache/migraine days reported). Individual discussions with all participants were conducted by two experienced interviewers.
Forty participants were recruited and interviewed; 36 met all eligibility criteria. Twenty-one participants met the criteria for episodic migraine, 15 met the criteria for chronic migraine, and four participants, who were current migraineurs, were unable to be classified as episodic or chronic migraine. Participants provided feedback on 20 prescription prophylactic migraine medications. The most commonly used current or prior migraine prophylactics were topiramate (n = 27), amitriptyline (n = 6), propranolol (n = 6), onabotulinumtoxinA (n = 5), and zonisamide (n = 3).
In general, medication effectiveness and tolerability were the most influential factors on patient satisfaction or dissatisfaction with their prophylactic migraine medications. Lack of efficacy, cited by 56% of respondents, was the most frequently reported reason for participants’ dissatisfaction with their medications. Regarding tolerability, 51% of participants reported that a particular side effect was the most dissatisfying characteristic of their medication. The most bothersome side effects reported by participants were memory loss (n = 6), dizziness or light-headedness (n = 5), tiredness/drowsiness/grogginess/sluggishness (n = 5), nausea (n = 3), and dry mouth (n = 2).
Among those who were satisfied with their prophylactic migraine medications, decreased migraine frequency was the most common reason for their satisfaction (65%), followed by decreased migraine severity or intensity, which was reported by 28% of participants.
The most frequently reported desirable characteristics of a new prophylactic migraine medication that would increase participants’ satisfaction were related to the medication’s ability to decrease the frequency and severity or intensity of migraines. Nausea (36%), weight gain (26%), dizziness/light-headedness (23%), drowsiness/grogginess (15%), and memory loss, including the ability to remember words and speak clearly (13%), are side effects that patients reported that they do not want to see in a new or future prophylactic migraine medication.
Mindfulness May Alleviate Chronic Migraine Associated With Medication Overuse
Mindfulness training is as effective as prophylactic medications for treating chronic migraine associated with medication overuse (CM-MO), according to research published online ahead of print February 4 in the Journal of Headache and Pain. 
“Our results further suggest that a mindfulness-based treatment may be comparable to standard pharmacologic prophylaxis with regard to relevant primary outcomes such as headache frequency reduction and reduction in the consumption of acute medications,” said Licia Grazzi, MD, a neurologist at Istituto Neurologico Carlo Besta in Milan.
Research has suggested that mindfulness may be beneficial for headache. Previous studies, however, have been limited by inadequate consideration of several significant end points in chronic headache, such as frequency of headache and consumption of medications for acute headache management, said the authors.
To address these limitations, Dr. Grazzi and colleagues conducted an exploratory clinical trial that compared conventional prophylactic pharmacologic treatment with a mindfulness-based treatment for patients diagnosed with CM-MO. Researchers hypothesized that the mindfulness-based approach would be as effective as conventional prophylactic treatment.
Eligible participants were between ages 18 and 65 and had been diagnosed with CM-MO according to the International Classification of Headache Disorders, third edition (beta version), and had presented for treatment at the Headache Center of the Istituto Neurologico Carlo Besta between February 2014 and June 2015. In addition, participants had a history of chronic migraine for at least 10 years that was associated with overuse of triptans and nonsteroidal anti-inflammatory drugs for a minimum of the past five years.
All patients completed a five-day medication withdrawal program and were encouraged to exercise at least 45 minutes twice a week, to stay properly hydrated, and to consume three meals every day.
Participants were separated into two groups. In one group, patients were treated with prophylactic medications. In the second group, patients participated in a mindfulness-based training that consisted of six weekly sessions of guided mindfulness. Patients were invited to practice mindfulness training for seven to 10 minutes per day. At each follow-up visit, the Headache Impact Test, the Migraine Disability Assessment, the State and Trait Anxiety Inventory, and the Beck Depression Inventory were administered. Patients also kept headache diaries.
A total of 44 patients participated in the study. The average age was 44.5, the average headache frequency per month was 20.5, and the average monthly medication intake was 18.4 pills. Overall, data indicated a similar improvement over time in the mindfulness group and pharmacologic prophylaxis group for headache frequency, use of medication, Migraine Disability Assessment, Headache Impact Test, and Beck Depression Inventory. No changes on State and Trait Anxiety Inventory were reported. Both groups had significant and equivalent proportions of participants who achieved at least 50% reduction of headaches, compared with baseline. The majority of patients in each group no longer satisfied criteria for chronic migraine.
“Our findings support the value of conducting further … well-controlled studies (incorporating random assignment, larger sample sizes, and checks on integrity of treatment),” said Dr. Grazzi. “[Such studies] are warranted to more fully explore the benefits, boundaries, and mechanisms of action for mindfulness in treating chronic migraine by itself and when it is complicated by medication overuse and medical or psychological comorbidities.”
—Erica Tricarico
Suggested Reading
Grazzi L, Sansone E, Raggi A, et al. Mindfulness and pharmacological prophylaxis after withdrawal from medication overuse in patients with chronic migraine: an effectiveness trial with a one-year follow-up. J Headache Pain. 2017;18(1):15.
Mindfulness training is as effective as prophylactic medications for treating chronic migraine associated with medication overuse (CM-MO), according to research published online ahead of print February 4 in the Journal of Headache and Pain.
“Our results further suggest that a mindfulness-based treatment may be comparable to standard pharmacologic prophylaxis with regard to relevant primary outcomes such as headache frequency reduction and reduction in the consumption of acute medications,” said Licia Grazzi, MD, a neurologist at Istituto Neurologico Carlo Besta in Milan.
Research has suggested that mindfulness may be beneficial for headache. Previous studies, however, have been limited by inadequate consideration of several significant end points in chronic headache, such as frequency of headache and consumption of medications for acute headache management, said the authors.
To address these limitations, Dr. Grazzi and colleagues conducted an exploratory clinical trial that compared conventional prophylactic pharmacologic treatment with a mindfulness-based treatment for patients diagnosed with CM-MO. Researchers hypothesized that the mindfulness-based approach would be as effective as conventional prophylactic treatment.
Eligible participants were between ages 18 and 65 and had been diagnosed with CM-MO according to the International Classification of Headache Disorders, third edition (beta version), and had presented for treatment at the Headache Center of the Istituto Neurologico Carlo Besta between February 2014 and June 2015. In addition, participants had a history of chronic migraine for at least 10 years that was associated with overuse of triptans and nonsteroidal anti-inflammatory drugs for a minimum of the past five years.
All patients completed a five-day medication withdrawal program and were encouraged to exercise at least 45 minutes twice a week, to stay properly hydrated, and to consume three meals every day.
Participants were separated into two groups. In one group, patients were treated with prophylactic medications. In the second group, patients participated in a mindfulness-based training that consisted of six weekly sessions of guided mindfulness. Patients were invited to practice mindfulness training for seven to 10 minutes per day. At each follow-up visit, the Headache Impact Test, the Migraine Disability Assessment, the State and Trait Anxiety Inventory, and the Beck Depression Inventory were administered. Patients also kept headache diaries.
A total of 44 patients participated in the study. The average age was 44.5, the average headache frequency per month was 20.5, and the average monthly medication intake was 18.4 pills. Overall, data indicated a similar improvement over time in the mindfulness group and pharmacologic prophylaxis group for headache frequency, use of medication, Migraine Disability Assessment, Headache Impact Test, and Beck Depression Inventory. No changes on State and Trait Anxiety Inventory were reported. Both groups had significant and equivalent proportions of participants who achieved at least 50% reduction of headaches, compared with baseline. The majority of patients in each group no longer satisfied criteria for chronic migraine.
“Our findings support the value of conducting further … well-controlled studies (incorporating random assignment, larger sample sizes, and checks on integrity of treatment),” said Dr. Grazzi. “[Such studies] are warranted to more fully explore the benefits, boundaries, and mechanisms of action for mindfulness in treating chronic migraine by itself and when it is complicated by medication overuse and medical or psychological comorbidities.”
—Erica Tricarico
Suggested Reading
Grazzi L, Sansone E, Raggi A, et al. Mindfulness and pharmacological prophylaxis after withdrawal from medication overuse in patients with chronic migraine: an effectiveness trial with a one-year follow-up. J Headache Pain. 2017;18(1):15.
Mindfulness training is as effective as prophylactic medications for treating chronic migraine associated with medication overuse (CM-MO), according to research published online ahead of print February 4 in the Journal of Headache and Pain.
“Our results further suggest that a mindfulness-based treatment may be comparable to standard pharmacologic prophylaxis with regard to relevant primary outcomes such as headache frequency reduction and reduction in the consumption of acute medications,” said Licia Grazzi, MD, a neurologist at Istituto Neurologico Carlo Besta in Milan.
Research has suggested that mindfulness may be beneficial for headache. Previous studies, however, have been limited by inadequate consideration of several significant end points in chronic headache, such as frequency of headache and consumption of medications for acute headache management, said the authors.
To address these limitations, Dr. Grazzi and colleagues conducted an exploratory clinical trial that compared conventional prophylactic pharmacologic treatment with a mindfulness-based treatment for patients diagnosed with CM-MO. Researchers hypothesized that the mindfulness-based approach would be as effective as conventional prophylactic treatment.
Eligible participants were between ages 18 and 65 and had been diagnosed with CM-MO according to the International Classification of Headache Disorders, third edition (beta version), and had presented for treatment at the Headache Center of the Istituto Neurologico Carlo Besta between February 2014 and June 2015. In addition, participants had a history of chronic migraine for at least 10 years that was associated with overuse of triptans and nonsteroidal anti-inflammatory drugs for a minimum of the past five years.
All patients completed a five-day medication withdrawal program and were encouraged to exercise at least 45 minutes twice a week, to stay properly hydrated, and to consume three meals every day.
Participants were separated into two groups. In one group, patients were treated with prophylactic medications. In the second group, patients participated in a mindfulness-based training that consisted of six weekly sessions of guided mindfulness. Patients were invited to practice mindfulness training for seven to 10 minutes per day. At each follow-up visit, the Headache Impact Test, the Migraine Disability Assessment, the State and Trait Anxiety Inventory, and the Beck Depression Inventory were administered. Patients also kept headache diaries.
A total of 44 patients participated in the study. The average age was 44.5, the average headache frequency per month was 20.5, and the average monthly medication intake was 18.4 pills. Overall, data indicated a similar improvement over time in the mindfulness group and pharmacologic prophylaxis group for headache frequency, use of medication, Migraine Disability Assessment, Headache Impact Test, and Beck Depression Inventory. No changes on State and Trait Anxiety Inventory were reported. Both groups had significant and equivalent proportions of participants who achieved at least 50% reduction of headaches, compared with baseline. The majority of patients in each group no longer satisfied criteria for chronic migraine.
“Our findings support the value of conducting further … well-controlled studies (incorporating random assignment, larger sample sizes, and checks on integrity of treatment),” said Dr. Grazzi. “[Such studies] are warranted to more fully explore the benefits, boundaries, and mechanisms of action for mindfulness in treating chronic migraine by itself and when it is complicated by medication overuse and medical or psychological comorbidities.”
—Erica Tricarico
Suggested Reading
Grazzi L, Sansone E, Raggi A, et al. Mindfulness and pharmacological prophylaxis after withdrawal from medication overuse in patients with chronic migraine: an effectiveness trial with a one-year follow-up. J Headache Pain. 2017;18(1):15.