Lipton, Richard B.

Abstract Objectives To summarize the baseline methods for the Migraine in America Symptoms and Treatment (MAST) Study and evaluate gender differences in sociodemographics and headache features; consultation and diagnosis patterns; and patterns of acute and preventive treatment use for migraine among study participants. Background The MAST Study is a longitudinal, internet‐based panel study of symptoms, approaches to management, and unmet treatment needs among US adults with migraine. This analysis focuses on the initial cross‐sectional survey, conducted beginning in 2016, and is intended to update results from earlier national epidemiologic surveys of people with migraine in the United States. Methods Respondents to the MAST Study were recruited from a US nationwide online research panel. Stratified random sampling identified a representative cohort of adults (aged ≥18 years). We administered a validated diagnostic screener based on modified ICHD‐3 beta criteria to identify individuals with migraine averaging at least 1 monthly headache day (MHD) over the previous 3 months. A baseline assessment evaluated sociodemographic and headache features, patterns of consultation and diagnosis, and use of acute and preventive medications for migraine. Frequency data and chi‐square contrasts ( P < .05) were used to compare respondents based on gender. Results Baseline survey data (N = 95,821) identified 18,353 respondents who met criteria for migraine, including 15,133 (women n = 11,049, men n = 4084) reporting at least 1 MHD for the preceding 3 months. The mean age of the sample was 43.1 (13.6) years; 73.0% of respondents were women, and 81.0% were Caucasian. Compared with men, women were younger (46.1 vs 42.0 years; P < .001); had more MHDs (5.6 vs 5.3; P < .001); and were more likely to report moderate or severe headache‐related disability (45.9% vs 35.8%; P < .001) and cutaneous allodynia (43.7% vs 29.5%; P < .001). The lifetime rate of medical consultation for headache was 79.8% overall and slightly higher in women than in men. Women were more likely than men to have been diagnosed with migraine (48.3% vs 38.8%, P < .001). While 95.1% of people with migraine currently used acute treatment, the majority (58.9%) used over‐the‐counter (OTC) drugs to the exclusion of prescription drugs, while 11.3% used exclusively prescription drugs, and 20.5% used both. Among acute prescription medication users, women were more likely than men to take triptans (17.7% vs 14.3%, P < .001), while men were more likely than women to take opioids (14.5% vs 9.2%, P < .001). Oral formulations were used predominately (92.7% of the medication users), but men were more likely to use nasal sprays (13.6% vs 9.4%, P < .001) and injectables (7.9% vs 3.4%, P < .001). Men (14.5%) were also significantly more likely than women (10.4%) to be taking daily oral preventive medication ( P < .001). Conclusions The MAST Study identified a large sample of women and men with migraine from a sampling frame that broadly resembles the US population. Low participation rate increases the risk of response bias, however, comparisons with Census data and prior population studies for the demographic and headache characteristics of the current sample suggest that findings are generalizable to the population of people with migraine. Women had more MHDs than men, and they were more likely to report migraine‐related disability and cutaneous allodynia. The lifetime consultation rate for headache was relatively high, but many with migraine symptoms reported never having received a diagnosis of migraine from a healthcare professional. Acute prescription and preventive migraine treatments are underused. Migraine persists as an underdiagnosed and undertreated public health problem in 2018, and there are many opportunities to improve the diagnosis and treatment of people with this painful, disabling condition.

Objective To evaluate the efficacy and tolerability of single pulse transcranial magnetic stimulation (sTMS) for the preventive treatment of migraine. Background sTMS was originally developed for the acute treatment of migraine with aura. Open label experience has suggested a preventive benefit. The objective of this trial was to evaluate the efficacy and tolerability of sTMS for migraine prevention. Methods The eNeura SpringTMS Post-Market Observational U.S. Study of Migraine (ESPOUSE) Study was a multicenter, prospective, open label, observational study. From December 2014 to March 2016, patients with migraine (n = 263) were consented to complete a 1-month baseline headache diary followed by 3 months of treatment. The treatment protocol consisted of preventive (four pulses twice daily) and acute (three pulses repeated up to three times for each attack) treatment. Patients reported daily headache status, medication use, and device use with a monthly headache diary. The primary endpoint, mean reduction of headache days compared to baseline, was measured over the 28-day period during weeks 9 to 12. The primary endpoint was compared to a statistically-derived placebo estimate (performance goal). Secondary endpoints included: 50% responder rate, acute headache medication consumption, HIT-6, and mean reduction in total headache days from baseline of any intensity. Results Of a total of 263 consented subjects, 229 completed a baseline diary, and 220 were found to be eligible based on the number of headache days. The device was assigned to 217 subjects (Safety Data Set) and 132 were included in the intention to treat Full Analysis Set. For the primary endpoint, there was a −2.75 ± 0.40 mean reduction of headache days from baseline (9.06 days) compared to the performance goal (−0.63 days) ( p < 0.0001). The 50% responder rate of 46% (95% CI 37%, 56%) was also significantly higher ( p < 0.0001) than the performance goal (20%). There was a reduction of −2.93 (5.24) days of acute medication use, headache impact measured by HIT-6, −3.1 (6.4) ( p < 0.0001), and total headache days of any intensity −3.16 days (5.21) compared to the performance goal (−0.63 days) ( p < 0.0001). The most common adverse events were lightheadedness (3.7%), tingling (3.2%), and tinnitus (3.2%). There were no serious adverse events. Conclusions This open label study suggests that sTMS may be an effective, well-tolerated treatment option for migraine prevention. Trial registration number NCT02357381

Background Quality clinical trials form an essential part of the evidence base for the treatment of headache disorders. In 1991, the International Headache Society Clinical Trials Standing Committee developed and published the first edition of the Guidelines for Controlled Trials of Drugs in Migraine. In 2008, the Committee published the first specific guidelines on chronic migraine. Subsequent advances in drug, device, and biologicals development, as well as novel trial designs, have created a need for a revision of the chronic migraine guidelines. Objective The present update is intended to optimize the design of controlled trials of preventive treatment of chronic migraine in adults, and its recommendations do not apply to trials in children or adolescents.

Objective To assess the impact of parental migraine on adolescents (aged 13‐21 years) living within the parental home from the adolescent's perspective. Background Family members are affected by their parent's migraine. We surveyed adolescents on the social, academic, and emotional effects of their parent's migraine. Methods The Chronic Migraine Epidemiology and Outcomes (CaMEO) study was a longitudinal Web‐based study with cross‐sectional modules designed to assess migraine symptoms, severity, frequency, and disability; migraine‐related consulting practices, healthcare utilization, medication use, comorbid health conditions, and family related burden associated with migraine. The Family Burden Module (adolescent version; FBM‐A) from the CaMEO study assessed parents with migraine and adolescent household members (dyads). Adolescents ranged in age from 13‐21 years and were living at home with their parent. The initial FBM‐A survey included 52 items covering five domains, which was refined and reduced by confirmatory factor analysis to 36 items covering four domains. Depression (9‐item Patient Health Questionnaire) and anxiety (7‐item Generalized Anxiety Disorder scale) were assessed. Item responses were stratified by parent migraine status (episodic migraine [EM], <15 headache days/month; chronic migraine [CM], ≥15 headache days/month). Frequencies of activities/events missed because of parental headache were categorized as ≥1 time or ≥4 times/previous 30 days. Results The sample included 1,411 parent‐adolescent dyads (parent with EM, n = 1,243 [88.1%]; parent with CM, n = 168 [11.9%]). Burden due to a parent's migraine was reported in four domains based on 36 items including: Loss of Parental Support and Reverse Caregiving (5 items); Emotional Experience (13 items); Interference with School (4 items); and Missed Activities and Events (14 items). Across domains, perceived burden was greater for adolescents of parents with CM vs EM. Rates of moderate‐to‐severe anxiety symptoms were higher among adolescents of parents with CM (6.2 vs 11.3%, P = .01), while moderate‐to‐severe depression symptom rates were similar (5.5 vs 8.9%, P = .08). More adolescents of CM vs EM parents reported having a headache within the previous 3 months ( P < .001). Conclusions Parental migraine negatively impacts adolescent children, extending our understanding of the family burden of migraine and emphasizing the potential benefit to children of optimizing migraine care.

Objectives To examine the association between vascular pathology and rate of cognitive decline in older adults independent of Alzheimer's disease ( AD ) pathology. Design Prospective cohort study. Setting Community sample. Participants Individuals from the Einstein Aging Study autopsy series (N = 62). Measurements The Blessed Information‐Memory‐Concentration ( BIMC ) test was used to assess global cognitive status. AD pathology was quantified according to Braak stage (<3 vs ≥ 3). Vascular pathology was quantified using a previously reported macrovascular lesion ( MVL ) score. The association between vascular pathology and antemortem rates of cognitive decline adjusted for level of AD pathology was assessed using linear mixed‐effects models. Results Mean age was 81.8 at enrollment and 89.0 at death. Participants with more than two MVL s had faster cognitive decline than those with no MVL s (difference in annual rate of change in BIMC 0.74 points/yr, P = .03). Braak stage was also associated with cognitive decline (difference 0.57 points/yr, P = .03). The difference in rate of cognitive decline between those with more than two MVL s and those free of vascular lesions persisted after adjustment for AD pathology (difference in rate of change in BIMC 0.68 points/yr, P = .04). The effect of vascular pathology on cognitive decline was not significantly different according to AD pathology. Conclusion Vascular brain pathology is associated with rate of cognitive decline after adjusting for level of AD pathology.

Aim The aim of this trial was to evaluate the efficacy and tolerability of ubrogepant (MK-1602), a calcitonin gene-related peptide receptor antagonist (CGRP-RA), for the acute treatment of migraine. Methods This double-blind, placebo-controlled study randomized 834 participants to treat one migraine attack with ubrogepant 1 mg, 10 mg, 25 mg, 50 mg, 100 mg, or placebo in a 1:1 ratio. The co-primary endpoints were pain freedom and headache response at two hours. The first primary hypothesis tested the dose-response trend for two-hour pain freedom using a logistic regression model. Subsequent hypotheses tested the effects of each dose on the co-primary endpoints, using a closed sequential testing procedure to control for multiplicity. Results A total of 527 participants received ubrogepant and 113 received placebo. A positive response trend in the proportion of participants achieving two-hour pain freedom was demonstrated ( p < 0.001). Ubrogepant 100 mg was significantly superior to placebo for two-hour pain freedom (25.5% vs 8.9%) but not for two-hour headache response. Per the prespecified multiplicity strategy, this nonsignificant result precluded further formal hypothesis testing, although the 50 mg and 25 mg doses demonstrated nominal significance over placebo for two-hour pain freedom (unadjusted p < 0.05). Overall, adverse events were similar between ubrogepant and placebo. Conclusion This trial supports ubrogepant’s efficacy and provides further evidence that CGRP-RAs are viable options for the acute treatment of migraine.

Objective To assess the rates and predictors of traversing steps essential to good medical care for chronic migraine, including: (1) medical consultation, (2) accurate diagnosis, and (3) minimal pharmacologic treatment. Candidate predictors included socioeconomic, demographic, and headache‐specific variables. Background Previous research has established that barriers to effective management for episodic migraine include the absence of health insurance, lack of appropriate medical consultation, failure to receive an accurate diagnosis, and not being offered a regimen with acute and preventive treatments. Methods/Design The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, a longitudinal web‐based panel study of migraine, included a cross‐sectional module focused on patterns of and barriers to medical care. Participants eligible for this analysis met the study criteria for chronic migraine, had evidence of headache‐related disability, and provided data on health insurance status. The main outcomes in the current analysis included the proportion of respondents who sought consultation for headache with a designated healthcare professional, self‐reported receiving a diagnosis of chronic or transformed migraine, and received minimal pharmacologic treatment for headache with a focus on prescribed acute and preventive treatments. Results In the CaMEO Study, 80,783 respondents provided study data, 16,789 (20.8% of respondents) met criteria for migraine, and 1476 (8.8% of those with migraine) met chronic migraine criteria. In total, 1254 participants (85.0% of those with chronic migraine) met inclusion criteria for this analysis. Of those, 512 respondents (40.8%) reported currently consulting with a healthcare professional for headache. Odds of consulting increased with increasing age (OR 1.02; 95% CI 1.01–1.03), body mass index (BMI) (OR 1.01; 95% CI 1.00–1.03), migraine‐related disability (OR 1.02; 95% CI 1.00–1.04), and migraine severity (OR 1.16; 95% CI 1.11–1.22) and presence of health insurance (OR 4.61; 95% CI 3.05–6.96). Among those consulting a healthcare professional, 126 (24.6%) received an accurate diagnosis and 56 of those with a correct diagnosis (44.4%) received both acute and preventive pharmacologic treatments; odds of a CM diagnosis were higher for women (OR 1.93; 95% CI 1.03–3.61), those with greater migraine severity (OR 1.25; 95% CI 1.14–1.37), and those currently consulting a specialist (OR 2.38; 95% CI 1.54–3.69). No predictors of receiving appropriate treatment were identified among those currently consulting. Among our sample of people with chronic migraine, only 56 (4.5%) individuals successfully traversed the series of 3 barriers to successful chronic migraine care (ie, consulted a healthcare professional for migraine, received an accurate diagnosis, and were prescribed minimal acute and preventive pharmacologic treatments). Conclusion Our findings suggest that <5% of persons with chronic migraine traversed 3 barriers to receiving care for headache (consultation, diagnosis, and treatment), representing a large unmet need for improving care in this population. Predictors of consulting a healthcare professional included age, having health insurance, greater migraine‐related disability, and greater migraine symptom severity. Among those consulting, predictors of an appropriate diagnosis included consulting a specialist, female sex, and greater migraine severity. Public health efforts are needed to improve outcomes for patients with chronic migraine by a range of interventions and educational efforts aimed at improving consultation rates, diagnostic accuracy, and adherence to minimal pharmacologic treatment.