The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice.

OBJECTIVE: To incorporate recent research findings, expert consensus, and patient perspectives into updated guidance on the use of new acute and preventive treatments for migraine in adults. BACKGROUND: The American Headache Society previously published a Consensus Statement on the use of newly introduced treatments for adults with migraine. This update, which is based on the expanded evidence base and emerging expert consensus concerning postapproval usage, provides practical recommendations in the absence of a formal guideline. METHODS: This update involved four steps: (1) review of data about the efficacy, safety, and clinical use of migraine treatments introduced since the previous Statement was published; (2) incorporation of these data into a proposed update; (3) review and commentary by the Board of Directors of the American Headache Society and patients and advocates associated with the American Migraine Foundation; (4) consideration of these collective insights and integration into an updated Consensus Statement. RESULTS: Since the last Consensus Statement, no evidence has emerged to alter the established principles of either acute or preventive treatment. Newly introduced acute treatments include two small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists (ubrogepant, rimegepant); a serotonin (5-HT1F ) agonist (lasmiditan); a nonsteroidal anti-inflammatory drug (celecoxib oral solution); and a neuromodulatory device (remote electrical neuromodulation). New preventive treatments include an intravenous anti-CGRP ligand monoclonal antibody (eptinezumab). Several modalities, including neuromodulation (electrical trigeminal nerve stimulation, noninvasive vagus nerve stimulation, single-pulse transcranial magnetic stimulation) and biobehavioral therapy (cognitive behavioral therapy, biofeedback, relaxation therapies, mindfulness-based therapies, acceptance and commitment therapy) may be appropriate for either acute and/or preventive treatment; a neuromodulation device may be appropriate for acute migraine treatment only (remote electrical neuromodulation). CONCLUSIONS: The integration of new treatments into clinical practice should be informed by the potential for benefit relative to established therapies, as well as by the characteristics and preferences of individual patients.

Polypharmacy and comorbidities during pregnancy in a cohort of women with migraine.

OBJECTIVE: To describe longitudinal patterns of medication use throughout pregnancy in women with migraine. METHODS: We used the IBM MarketScan healthcare claims database in the US to create a cohort of pregnancies enrolled between 2011-2015 resulting in live or stillbirth. Migraine headache was identified based on ICD-9-CM diagnosis codes or procedure codes recorded in clinical encounters. Outcomes were patterns of prescriptions filled for medications that may be used to prevent migraine (antiepileptics, antihypertensives, antidepressants) or treat acute episodes (opioids, triptans, acetaminophen) and of other comorbid conditions (hypertension, psychiatric diagnoses, epilepsy). We used group-based multi-trajectory models to cluster women into similar longitudinal patterns of prescription fills. RESULTS: Of 859,501 pregnancies, 8168 had migraine. Within migraineurs, before pregnancy, the most commonly filled prescription was for a triptan (43.2%), followed by opioids (26.7%), acetaminophen (26.2%), antidepressants (24.9%), antiepileptics (18.6%) and antihypertensives (12.3%). Antiepileptics, antidepressants, and triptans were frequently discontinued early in pregnancy with few new users, while antihypertensives were discontinued by some users, but continued or initiated by a minority of users late in pregnancy. Opioids and acetaminophen were used intermittently throughout pregnancy. Comorbidities included hypertension (10.8%), epilepsy (4.7%), depression (14.0%), and anxiety (15.6%). Polypharmacy involving both preventive and acute medications was most common before pregnancy (31.4%) and declined in first trimester (14.7%). In all, 25.9% of women filled prescriptions for two or more acute medications before pregnancy. CONCLUSIONS: Medication use patterns during pregnancy for women with migraine are complex. Patterns of polypharmacy and comorbidity during pregnancy highlight an under-studied area relevant for maternal and child health outcomes.

Neuroimaging for Migraine: The American Headache Society Systematic Review and Evidence-Based Guideline.

OBJECTIVE: To provide updated evidence-based recommendations about when to obtain neuroimaging in patients with migraine. METHODS: Articles were included in the systematic review if they studied adults 18 and over who were seeking outpatient treatment for any type of migraine and who underwent neuroimaging (MRI or CT). Medline, Web of Science, and Cochrane Clinical Trials were searched from 1973 to August 31, 2018. Reviewers identified studies, extracted data, and assessed the quality of the evidence in duplicate. We assessed study quality using the Newcastle-Ottawa Scale. RESULTS: The initial search yielded 2269 publications. Twenty three articles met inclusion criteria and were included in the final review. The majority of studies were retrospective cohort or cross-sectional studies. There were 4 prospective observational studies. Ten studies evaluated the utility of CT only, 9 MRI only, and 4 evaluated both. Common abnormalities included chronic ischemia or atrophy with CT and MRI scanning, and non-specific white matter lesions with MRI. Clinically meaningful abnormalities requiring intervention were relatively rare. Clinically significant neuroimaging abnormalities in patients with headaches consistent with migraine without atypical features or red flags appeared no more common than in the general population. RECOMMENDATIONS: There is no necessity to do neuroimaging in patients with headaches consistent with migraine who have a normal neurologic examination, and there are no atypical features or red flags present. Grade A Neuroimaging may be considered for presumed migraine for the following reasons: unusual, prolonged, or persistent aura; increasing frequency, severity, or change in clinical features, first or worst migraine, migraine with brainstem aura, migraine with confusion, migraine with motor manifestations (hemiplegic migraine), late-life migraine accompaniments, aura without headache, side-locked headache, and posttraumatic headache. Most of these are consensus based with little or no literature support. Grade C.

Migraine: Epidemiology, Burden, and Comorbidity.

Migraine affects an estimated 12% of the population. Global estimates are higher. Chronic migraine (CM) affects 1% to 2% of the global population. Approximately 2.5% of persons with episodic migraine progress to CM. Several risk factors are associated with the progression to CM. There is significant short-term variability in migraine frequency independent of treatment. Migraine is associated with cardiovascular disease, psychiatric disease, and sleep disorders. It is the second most disabling condition worldwide. CM is associated with higher headache-related disability/impact, medical and psychiatric comorbidities, health care resource use, direct and indirect costs, lower socioeconomic status, and health-related quality of life.

Safety Problems With a Transdermal Patch for Migraine: Lessons From the Development, Approval, and Marketing Process.

OBJECTIVE: We sought to analyze publicly available information about patient harm associated with an iontophoretic sumatriptan patch, to identify what went wrong and to suggest ways in which similar problems might be prevented in the future. BACKGROUND: The Zecuity® sumatriptan iontophoretic transdermal system was marketed for acute treatment of migraine. The patch was withdrawn less than 10 months after its introduction because of multiple reports of scarring and burning. As of 2018, the FDA Adverse Event Reporting System public dashboard lists a total of 2889 reports of safety problems with the patch, 904 of which were classified as serious. METHODS: For this narrative review, we examined US Food and Drug Administration documents related to the new drug application for this product and its approval. We searched Clinicaltrials.gov, PubMed, Google, Facebook, Twitter, and Instagram public posts for relevant information relating to the patch, its approval, marketing, and complications. RESULTS: The FDA knew about problems with burns and scarring prior to approval of the product, and turned down the initial new drug application for this reason and because of other quality problems with the patch. The reapplication was approved despite continued concerns of several FDA reviewers about safety. The approval required the manufacturer to comply with enhanced postmarketing safety reporting. However, product information and labeling did not mention the possibility of burns or scarring. Approval was based on 1 clinical trial and 2 open label studies in which reporting of adverse events was suboptimal. The clinical trials had been prospectively registered but outcomes had been changed around the time the trial concluded. Aggressive marketing efforts and social media activity may have contributed to inaccurate perceptions of safety and efficacy, but social media also provided a written and photographic record of burns and other harm suffered by patients who used the patch. CONCLUSIONS: Our review identified several problems with the development, testing, approval, and marketing of the Zecuity patch. To improve the process of developing headache treatments, it is important to consider the lessons that can be drawn from an examination of this high-profile failure of the drug development and regulatory system.

The prevalence and burden of migraine and severe headache in the United States: updated statistics from government health surveillance studies.

BACKGROUND AND OBJECTIVES: The US National Center for Health Statistics, which is part of the Centers for Disease Control, conducts ongoing public health surveillance activities. The US Armed Forces also maintains a comprehensive database of medical information. We aimed to identify the most current prevalence estimates of migraine and severe headache in the United States adult civilian and active duty service populations from these national government surveys, to assess stability of prevalence estimates over time, and to identify additional information pertinent to the burden and treatment of migraine and other severe headache conditions. METHODS: We searched for the most current publicly available summary statistics from the National Ambulatory Medical Care Survey, the National Hospital Ambulatory Medical Care Survey, and the National Health Interview Survey (NHIS). Summary data from the Defense Medical Surveillance System were also obtained, and PubMed was also searched for publications reporting summary statistics based on these studies. Data were abstracted, double-checked for accuracy, and summarized over time periods and as a function of demographic variables. RESULTS: 14.2% of US adults 18 or older reported having migraine or severe headache in the previous 3 months in the 2012 NHIS. The overall age-adjusted 3-month prevalence of migraine in females was 19.1% and in males 9.0%, but varied substantially depending on age. The prevalence of migraine was highest in females 18-44, where the 3-month prevalence of migraine or severe headache was 23.5%. The 3-month prevalence of migraine or severe headache has remained relatively stable over the period of2005-2012, with an average prevalence of 20.2% in females, 9.4% in males, and 14.9% overall [corrected]. During this time, the average female to male sex ratio for migraine or severe headache was 2.17. The unadjusted 1-year prevalence of migraine in active duty US military service members varied from 1% to 1.9% between 1998 and 2010, ranging from 0.7% to 1.2% in males and 3.5% to 6% in females. The 1-year prevalence of "other headache" in this military population ranged from a low of 1.9% in 2003 to a high of 3% in 2010. Headache or pain in the head was the fourth leading cause of visits to the emergency department (ED) in 2009-2010, accounting for 3.1% of all ED visits. Across all ambulatory care settings, migraine accounted for 0.5% of all visits and other headache presentations for 0.4% of all ambulatory care visits. 52.8% of all visits for migraine occurred in primary care settings, 23.2% in specialty outpatient settings, and 16.7% in EDs. In 2010, opioids were administered at 35% of ED visits for headache, while triptans were administered in only 1.5% of visits. CONCLUSIONS: This report summarizes the most recent government statistics on the prevalence and burden of migraine and severe headache in the US civilian and active duty military populations. The prevalence of migraine headaches is high, affecting roughly 1 out of every 7 Americans annually, and has remained relatively stable over the last 8 years. Migraine and headache are leading causes of outpatient and ED visits and remain an important public health problem, particularly among women during their reproductive years.

Migraine and risk of incident diabetes in women: a prospective study.

BACKGROUND: Previous cross-sectional studies evaluating the relationship between diabetes prevalence and migraine status have found conflicting results. We examined the relationship between migraine and incident type 2 diabetes (T2D) in a cohort of adult women. METHODS: Prospective cohort study conducted among participants in the Women's Health Study who provided information on migraine and did not have diabetes at baseline. Our four exposure groups were migraine with aura, migraine without aura, past history of migraine and no history of migraine. Cox proportional hazards models were used to determine the hazard ratio for incident T2D. RESULTS: Among the 38,620 women included in this study, 5062 (13.1%) women had migraine, of whom 2014 (39.8%) reported migraine with aura, and 2087 (5.4%) women had a past history of migraine. During a mean of 14.6 years of follow-up, there were 3032 cases of incident T2D. After adjustment for confounders, the hazard ratio (95% confidence interval) for developing diabetes was 1.06 (0.91-1.24) for women with migraine with aura, 1.01 (0.89-1.16) for women with migraine without aura, and 1.13 (0.98-1.30) for women with a past history of migraine compared with women with no history of migraine. CONCLUSION: Results of this prospective study in women do not support an association between migraine and incident T2D.