Search

Objective: To assess rates of traversing barriers to care to access optimal clinical outcomes in people with migraine internationally. Background: People in need of medical care for migraine should consult a health care professional knowledgeable in migraine management, obtain an accurate diagnosis, and receive an individualized treatment plan, which includes scientific society guideline-recommended treatments where appropriate. Methods: The Chronic Migraine Epidemiology and Outcomes-International (CaMEO-I) Study was a cross-sectional, web-based survey conducted from July 2021 through March 2022 in Canada, France, Germany, Japan, the United Kingdom, and the United States (US). Respondents who met modified International Classification of Headache Disorders, 3rd edition, criteria for migraine and had Migraine Disability Assessment Scale (MIDAS) scores of ≥ 6 (i.e., mild, moderate, or severe disability) were deemed to need medical care and were included in this analysis. Minimally effective treatment required that participants were currently consulting a health care professional for headache (barrier 1), reported an accurate diagnosis (barrier 2), and reported use of minimally appropriate pharmacologic treatment (barrier 3; based on American Headache Society 2021 Consensus Statement recommendations). Proportions of respondents who successfully traversed each barrier were calculated, and chi-square tests were used to assess overall difference among countries. Results: Among 14,492 respondents with migraine, 8,330 had MIDAS scores of ≥ 6, were deemed in need of medical care, and were included in this analysis. Current headache consultation was reported by 35.1% (2926/8330) of respondents. Compared with the US, consultation rates and diagnosis rates were statistically significantly lower in all other countries except France where they were statistically significantly higher. Total appropriate treatment rates were also statistically significantly lower in all other countries compared with the US except France, which did not differ from the US. All 3 barriers were traversed by only 11.5% (955/8330) of respondents, with differences among countries (P < 0.001). Conclusions: Of people with migraine in need of medical care for migraine, less than 15% traverse all 3 barriers to care. Although rates of consultation, diagnosis, and treatment differed among countries, improvements are needed in all countries studied to reduce the global burden of migraine. Trial registration: NA. [ABSTRACT FROM AUTHOR]

Background: Atogepant is an oral calcitonin gene–related peptide receptor antagonist approved for the preventive treatment of migraine in adults. These analyses evaluated the proportions of clinical trial participants who experienced sustained responses to atogepant over 12 or 52 weeks of treatment. Methods: These were post hoc analyses of ADVANCE, a 12-week, double-blind, randomized trial of atogepant 10, 30, and 60 mg once daily vs. placebo for the preventive treatment of episodic migraine, and a separate open-label long-term safety (LTS) trial of atogepant 60 mg once daily over 52 weeks. The 60 mg dose of atogepant was used to detect safety issues. An initial response was defined as ≥50%, ≥75%, or 100% reduction from baseline in MMDs in month 1 for ADVANCE or quarter 1 for the LTS trial. The proportions of participants who continued to experience a response above each response-defining threshold through each subsequent month (for ADVANCE) or each quarter (for LTS) were calculated. Results: In ADVANCE, sustained response rates during months 2 and 3 varied with dose and were as follows: 70.8–81.1% following an initial ≥50% response, 47.3–61.9% following an initial ≥75% response, and 34.8–41.7% following an initial 100% response. Of those who experienced an initial ≥75% or 100% response during month 1, more than 79% continued to experience at least a 50% response during both months 2 and 3. During the LTS trial, sustained response rates through quarters 2, 3, and 4 were 84.7% following an initial ≥50% response, 72.6% following an initial ≥75% response, and 37.8% following an initial 100% response. Of those who experienced an initial ≥75% or 100% response during quarter 1, more than 90% continued to experience at least a 50% response through quarters 2, 3, and 4. Conclusion: Over 70% of participants who experienced an initial response with atogepant treatment had a sustained response with continued treatment. Trial registration: ClinicalTrials.gov: NCT03777059 (submitted: December 13, 2018); NCT03700320 (submitted: September 25, 2018). [ABSTRACT FROM AUTHOR]

Introduction: Although acute and preventive treatments for migraine are commonly given in combination, data on the real-world effectiveness of ubrogepant as an acute treatment when used with an anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (with or without onabotulinumtoxinA) are limited. This analysis sought to evaluate the real-world effectiveness, treatment satisfaction, and optimization of ubrogepant for the acute treatment of migraine when used in combination with an anti-CGRP monoclonal antibody, with or without concomitant onabotulinumtoxinA. Methods: This prospective, multiple-attack, open-label, observational study (COURAGE) assessed meaningful pain relief (MPR), return to normal function (RNF), treatment satisfaction, and acute treatment optimization of ubrogepant (50 or 100 mg) when combined with an anti-CGRP monoclonal antibody, onabotulinumtoxinA, or both in adult users of Migraine Buddy, a migraine tracking application. Results: In the ubrogepant and anti-CGRP monoclonal antibody arm (n = 245), following the first ubrogepant-treated attack, 61.6% (151/245) and 80.4% (197/245) of ubrogepant-treated participants achieved MPR at 2 and 4 h post-dose, respectively, and 34.7% (85/245) and 55.5% (136/245) achieved RNF at 2 and 4 h post-dose, respectively. Across up to 10 ubrogepant-treated attacks (N = 1153), MPR was achieved in 51.3% (592/1153) and 73.5% (847/1153) at 2 and 4 h post-dose, respectively. RNF was achieved by 32.2% (371/1153) and 53.2% (613/1153) at 2 and 4 h post-dose. After 30 days, 72.7% (168/231) of participants reported satisfaction (using a 7-point scale) with ubrogepant when used in combination with an anti-CGRP monoclonal antibody, and 79.7% (184/231) of participants achieved acute treatment optimization (defined as moderate-maximum treatment efficacy using the Migraine Treatment Optimization Questionnaire-4). Conclusion: Real-world ubrogepant use with an anti-CGRP monoclonal antibody was associated with MPR, RNF, satisfaction, and acute treatment optimization. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders was developed by WHO to address the worldwide challenges and gaps in provision of care and services for people with epilepsy and other neurological disorders and to ensure a comprehensive, coordinated response across sectors to the burden of neurologic diseases and to promote brain health across life-course. Headache disorders constitute the second most burdensome of all neurological diseases after stroke, but the first if young and midlife adults are taken into account. Despite the availability of a range of treatments, disability associated with headache disorders, and with migraine, remains very high. In addition, there are inequalities between high-income and low and middle income countries in access to medical care. In line with several brain health initiatives following the WHOiGAP resolution, herein we tailor the main pillars of the action plan to headache disorders: (1) raising policy prioritization and strengthen governance; (2) providing effective, timely and responsive diagnosis, treatment and care; (3) implementing strategies for promotion and prevention; (4) fostering research and innovation and strengthen information systems. Specific targets for future policy actions are proposed. The Global Action Plan triggered a revolution in neurology, not only by increasing public awareness of brain disorders and brain health but also by boosting the number of neurologists in training, raising research funding and making neurology a public health priority for policy makers. Reducing the burden of headache disorders will not only improve the quality of life and wellbeing of people with headache but also reduce the burden of neurological disorders increasing global brain health and, thus, global population health. [ABSTRACT FROM AUTHOR]

Background: In individuals with migraine, attacks may increase in frequency, severity, or both. Preventing migraine progression has emerged as a treatment goal in headache subspecialty practice, but there may be less awareness in general neurology or primary care settings where most people with migraine who seek treatment consult. Herein, we review the definition of and risk factors for migraine progression and consider strategies that could reduce its risk. Methods: A group of headache expert healthcare professionals, clinicians, and researchers reviewed published evidence documenting factors associated with increased or decreased rates of migraine progression and established expert opinions for disease management recommendations. Strength of evidence was rated as good, moderate, or based solely on expert opinion, using modified criteria for causation developed by AB Hill. Results: Migraine progression is commonly operationally defined as the transition from ≤ 15 to ≥ 15 monthly headache days among people with migraine; however, this does not necessarily constitute a fundamental change in migraine biology and other definitions should be considered. Established and theoretical key risk factors for migraine progression were categorized into five domains: migraine disease characteristics, treatment-related factors, comorbidities, lifestyle/exogenous factors, and demographic factors. Within these domains, good evidence supports the following risk factors: poorly optimized acute headache treatment, cutaneous allodynia, acute medication overuse, selected psychiatric symptoms, extra-cephalic chronic pain conditions, metabolism-related comorbidities, sleep disturbances, respiratory conditions, former/current high caffeine intake, physical inactivity, financial constraints, tobacco use, and personal triggers as risk factors. Protective actions that may mitigate migraine progression are sparsely investigated in published literature; our discussion of these factors is primarily based on expert opinion. Conclusions: Recognizing risk factors for migraine progression will allow healthcare providers to suggest protective actions against migraine progression (Supplementary Fig. 1). Intervention studies are needed to weight the risk factors and test the clinical benefit of hypothesized mitigation strategies that emerge from epidemiological evidence. [ABSTRACT FROM AUTHOR]

Background: Individuals with migraine frequently experience pre- and post-headache symptoms. This analysis aimed to characterize the relative frequency and burden of pre- and post-headache symptoms in people with migraine using data collected through the Chronic Migraine Epidemiology and Outcomes – International Study. Methods: This cross-sectional, observational, web-based survey was conducted in 2021–2022 in Canada, France, Germany, Japan, the United Kingdom, and the United States. Respondents who met modified International Classification of Headache Disorders, 3rd edition, criteria were offered the opportunity to participate. Information collected included migraine-related disability, depression/anxiety symptoms, cutaneous allodynia, activity limitations, and acute treatment optimization. Respondents indicated how often they had pre- or post-headache symptoms using a 5-point scale, ranging from 0 to 4, with a rating of 2 or higher classified as a pre- or post-headache symptom case. Modeling was used to examine relationships with monthly headache days (MHDs) and activity limitations during pre-headache and post-headache phases. Results: Among a total of 14,492 respondents, pre-headache symptoms were reported by 66.9%, while post-headache symptoms were reported by 60.2%. Both pre-headache and post-headache symptoms were reported by 49.5% of respondents, only pre-headache by 17.4%, only post-headache by 10.7%, and neither pre- nor post-headache symptoms by 22.4%. Compared with respondents who experienced only pre- or post-headache symptoms, respondents who experienced both pre- and post-headache symptoms had the highest rates of 4–7, 8–14, and ≥ 15 monthly headache days (23.1%, 14.1%, and 10.9%, respectively). Of respondents with both pre- and post-headache symptoms, 58.5% reported moderate-to-severe disability, 47.7% reported clinically significant symptoms of depression, 49.0% reported clinically significant symptoms of anxiety, and 63.8% reported cutaneous allodynia with headache (ASC-12). Moderate-to-severe activity limitations were reported during the pre-headache (29.5%) and post-headache phases (27.2%). For all outcomes modeled, after controlling for covariates, having pre-headache symptoms, post-headache symptoms, or both were associated with worse outcomes than having neither. Conclusions: Pre- and post-headache phases of migraine are common, carry unrecognized burden, and may be a target for treatment. [ABSTRACT FROM AUTHOR]

Migraine is a neurologic disease with a complex pathophysiology that can be controlled with current treatment options but not cured. Therefore, treatment expectations are highly variable. The concept of migraine freedom was recently introduced and can mean different things, with some, for example, expecting complete freedom from headache and associated symptoms and others accepting the occasional migraine attack if it does not impact functioning. Therefore, migraine management should be optimized so that patients can have the best opportunity to achieve their optimal treatment goals. With migraine freedom as a goal and, given the complex pathophysiology of migraine and the high incidence of comorbidities among individuals with migraine, treatment with a single modality may be insufficient, as it may not achieve migraine freedom in those with more frequent or disabling attacks. In this clinical perspective article, we have identified four key, partially overlapping principles of multimodal migraine treatment: (1) manage common comorbidities; (2) control modifiable risk factors for progression by addressing medication and caffeine overuse; (3) diagnose and treat secondary causes of headache, if present; and (4) individualize acute and preventive treatments to minimize pain, functional disability, and allodynia. There are many barriers to pursuing migraine freedom, and strategies to overcome them should be optimized. Migraine freedom should be an aspirational goal both at the individual attack level and for the disease overall. We believe that a comprehensive and multimodal approach that addresses all barriers people with migraine face could move patients closer to migraine freedom. [ABSTRACT FROM AUTHOR]

Background: Individuals using onabotulinumtoxinA as a preventive migraine treatment often use acute treatments for breakthrough attacks. Data on real-world effectiveness of the small-molecule calcitonin gene–related peptide (CGRP) receptor antagonist ubrogepant in combination with onabotulinumtoxinA are limited. Methods: COURAGE, a prospective, multiple attack, observational study, evaluated the real-world effectiveness of ubrogepant (50 or 100 mg) for acute treatment of migraine in people receiving onabotulinumtoxinA, an anti-CGRP monoclonal antibody (mAb), or both. This analysis focused only on onabotulinumtoxinA users. The Migraine Buddy app was used to identify eligible participants and track response to treated attacks. For each ubrogepant-treated attack, meaningful pain relief (MPR) and return to normal function (RNF) at 2 and 4 h post-dose over 30 days was assessed. MPR was defined as a level of relief that is meaningful to the participant, usually occurring before the pain is all gone. After 30 days, satisfaction was reported on a 7-point scale and overall acute treatment optimization was evaluated using the migraine Treatment Optimization Questionnaire-4 (mTOQ-4). Results: This analysis included 122 participants who received ubrogepant and onabotulinumtoxinA and reported on 599 ubrogepant-treated attacks. Following the first ubrogepant-treated attack, MPR was achieved in 53.3% of participants 2 h post-dose and in 76.2% of participants 4 h post-dose. RNF was achieved in 25.4% of participants 2 h post-dose and in 45.9% of participants 4 h post-dose. MPR and RNF results were similar across up to 10 ubrogepant-treated attacks. After 30 days, satisfaction with ubrogepant in combination with onabotulinumtoxinA was reported by 69.8% of participants and acute treatment optimization (defined as mTOQ-4 score ≥ 4) was achieved in 77.6%. Conclusions: In this prospective real-world effectiveness study, ubrogepant treatment in onabotulinumtoxinA users with self-identified migraine was associated with high rates of MPR and RNF at 2 and 4 h as well as satisfaction and acute treatment optimization. Although the lack of a contemporaneous control group limits causal inference, these findings demonstrate the feasibility of using a novel, app-based design to evaluate the real-world effectiveness and satisfaction of treatments. [ABSTRACT FROM AUTHOR]

Background: No available studies demonstrate validity and meaningful change thresholds of Work Productivity and Activity Impairment (WPAI) questionnaire in patients with migraine. In this post-hoc analysis, we assessed reliability, validity, responsiveness, and meaningful within-patient change from baseline to Month 3 for Work Productivity and Activity Impairment (WPAI) domain scores in patients with episodic migraine (EM) or chronic migraine (CM). Method: The Phase 3, multicenter, randomized, double-blind, placebo-controlled CONQUER study (NCT03559257, N = 462) enrolled patients with EM or CM who failed two to four categories of prior preventive medication in past ten years. The analyses were performed for WPAI domain scores (absenteeism, presenteeism, overall work productivity, and non-work-related activity impairment). Migraine Specific Quality of Life Questionnaire version 2.1 (MSQv2.1) domain scores (Role Function-Restrictive [RFR] and Role Function-Preventive [RFP]), and monthly migraine headache days were used as anchors. Responder criteria were changes from baseline to Month 3 for each of these anchors and were defined as: increase in MSQ-RFR by ≥ 25.71 points and MSQ-RFP by ≥ 20.00 points and a 50% reduction in monthly migraine headache days. Assessments were performed for overall population, and patients with EM or CM. The meaningful change threshold was determined based on Youden index, Phi coefficient and sensitivity. Results: Of 462 randomized patients, 444 who completed WPAI questionnaire were included in post-hoc analysis. Test–retest reliability over 3 months in a stable subgroup revealed moderate correlations for non-work-related Activity Impairment (ICC = 0.446) presenteeism (ICC = 0.438) and a fair correlation for overall work productivity loss (ICC = 0.360). At baseline, all correlations between WPAI domain scores and continuous anchor variables exceeded recommended threshold of ≥ 0.30, except for WPAI domain scores with number of monthly migraine headache days. Patients achieving pre-specified responsiveness thresholds for monthly migraine headache days, and MSQ-RFP, MSQ-RFR from baseline to Month 3 (responders) showed significant improvements in WPAI domain scores compared with non-responders (P < 0.001). The meaningful change thresholds of -20 (% unit) were identified for WPAI domain scores. Conclusion: In conclusion, WPAI has sufficient validity, reliability, responsiveness, and appropriate interpretation standards to assess the impact of EM or CM on presenteeism and overall work productivity loss and non-work-related activity impairment. Trial registration: NCT number of CONQUER study, NCT03559257. [ABSTRACT FROM AUTHOR]

APOE-ɛ4 risk on Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) differs between race/ethnic groups, presumably due to ancestral genomic background surrounding the APOE locus. We studied whether African and Amerindian ancestry-enriched genetic variants in the APOE region modify the effect of the APOE-ɛ4 alleles on Mild Cognitive Impairment (MCI) in Hispanics/Latinos. We defined African and Amerindian ancestry-enriched variants as those common in one Hispanic/Latino parental ancestry and rare in the other two. We identified such variants in the APOE region with a predicted moderate impact based on the SnpEff tool. We tested their interaction with APOE-ɛ4 on MCI in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) population and African Americans from the Atherosclerosis Risk In Communities (ARIC) study. We identified 5 Amerindian and 14 African enriched variants with an expected moderate effect. A suggestive significant interaction (p-value = 0.01) was found for one African-enriched variant, rs8112679, located in the ZNF222 gene fourth exon. Our results suggest there are no ancestry-enriched variants with large effect sizes of interaction effects with APOE-ɛ4 on MCI in the APOE region in the Hispanic/Latino population. Further studies are needed in larger datasets to identify potential interactions with smaller effect sizes. [ABSTRACT FROM AUTHOR]

Introduction: The objectives of this study were to (1) report long-term health-related quality of life (HRQoL) outcomes among patients using rimegepant preventatively in BHV3000-305 (NCT03732638) open-label extension (OLE) and (2) map Migraine-Specific Quality of Life questionnaire version 2.1 (MSQv2) to EQ-5D-3L utility values over the double-blind treatment (DBT; 0–12 weeks) and the OLE (13–64 weeks) to assess the influence of treatment on these values. Methods: This was a post hoc analysis using data from a rimegepant study for the prevention of migraine (BHV3000-305). Adult patients with migraine took either rimegepant 75 mg or placebo every other day (EOD) during the DBT phase. All patients received rimegepant during the OLE. MSQv2 was measured at baseline, weeks 12, 24, and 64. A validated algorithm was used to map MSQv2 scores to EQ-5D utilities. Results: Baseline data were available for 347 patients treated with placebo and 348 treated with rimegepant in the DBT period, who continued to the OLE. Baseline EQ-5D utilities were similar between trial arms: 0.598 for placebo and 0.614 for rimegepant. EQ-5D improved from baseline to week 12 and utilities increased by + 0.09 for placebo and + 0.10 for rimegepant (p value = 0.011). By 24 weeks, at which point patients who were originally randomized to placebo had received rimegepant 75 mg EOD for 12 weeks, HRQoL measures (MSQv2 and EQ-5D) were similar across groups, demonstrating rapid onset of treatment effect. This HRQoL improvement was durable out to 64 weeks. Conclusion: Compared to placebo, treatment with rimegepant 75 mg was associated with greater improvement in EQ-5D utilities during the 12-week DBT phase. Patients originally randomized to placebo experienced a similar improvement in EQ-5D utilities after switching to rimegepant during the OLE, demonstrating that benefits are realized within 12 weeks of active treatment. This preventive effect was durable out to 64 weeks and was associated with an additional increase in HRQoL over time. Trial Registration: NCT03732638. [ABSTRACT FROM AUTHOR]

Background: Observational studies on the prevalence of premonitory symptoms in people with migraine, preceding the headache pain (or aura) phase, have shown conflicting results. We conducted a systematic review and meta-analysis to estimate the prevalence, and relative frequency among clinic populations, of premonitory symptoms in people with migraine, overall and of the multifarious individual symptoms, and to review the methodologies used to assess them. Methods: We searched PubMed and Embase for studies published from database inception until 31st of May 2022. Two investigators independently screened titles, abstracts, and full texts. We retrieved observational studies that reported the prevalence/relative frequency of one or more premonitory symptoms in people with migraine. Two investigators independently extracted data and assessed risk of bias. Results were pooled using random-effects meta-analysis. Our main outcomes were the percentage of people with migraine who experienced at least one premonitory symptom and the percentages who experienced different individual premonitory symptoms. To describe our outcomes, we used the terms prevalence for data from population-based samples and relative frequency for data from clinic-based samples. We also descriptively and critically assessed the methodologies used to assess these symptoms. Results: The pooled estimated prevalence in population-based studies of at least one premonitory symptom was 29% (95% CI: 8–63; I2 99%) and the corresponding pooled estimated relative frequency in clinic-based studies was 66% (95% CI: 45–82; I2 99%). The data from clinic-based studies only supported meta-analysis of 11 of 96 individual symptoms, with relative frequency estimates ranging from 11 to 49%. Risk of bias was determined as high in 20 studies, moderate in seven, and low in two. Conclusions: The substantial between-study heterogeneity demands cautious interpretation of our estimates. Studies showed wide methodological variations, and many lacked rigor. Overall, the evidence was insufficient to support reliable prevalence estimation or characterization of premonitory symptoms. More data are needed, of better quality, to confirm the existence of a distinctive premonitory phase of migraine, and its features. Methodological guidelines based on expert consensus are a prerequisite. [ABSTRACT FROM AUTHOR]

Background: In controlled clinical trials, compared with placebo, a significantly greater proportion of participants using lasmiditan to treat a migraine attack achieved 2-h pain freedom (PF) and experienced ≥ 1 treatment-emergent adverse event (TEAE). Objective: To better inform clinicians about treatment expectations by evaluating the association between TEAEs and efficacy outcomes after lasmiditan treatment. Methods: Pooled data from SAMURAI, SPARTAN, MONONOFU, and CENTURION were analyzed. A common TEAE (CTEAE) was defined as occurring in ≥ 2% in the overall population. Central nervous system (CNS)-CTEAEs were based on Medical Dictionary for Regulatory Activities. Results: At 2 h, a significantly higher percentage of lasmiditan 200 mg-treated participants who achieved PF experienced ≥ 1 CTEAE than non-responders who continued to experience moderate/severe pain (48.2% vs. 28.7%, respectively). Correspondingly, a significantly higher percentage of lasmiditan 200 mg-treated participants who experienced ≥ 1 CTEAE achieved PF at 2 h than those who did not (39.0% vs. 30.2%, respectively). Similar results were generally observed with individual CNS-CTEAEs, but for non-CNS-CTEAEs, this pattern was less evident or in the opposite direction. No consistent differences were observed for migraine-related functional disability freedom. The percentage of participants with improved patient global impression of change (PGIC) was greater with a CNS-CTEAE versus no CNS-CTEAE. Conclusions: Those who had PF at 2 h were more likely to experience a CNS-CTEAE, and those with CNS-CTEAEs were more likely to experience PF. The occurrence of CTEAEs did not seem to negatively affect disability freedom or PGIC. ClinicalTrials.gov Registration: SAMURAI (NCT02439320), SPARTAN (NCT02605174), MONONOFU (NCT03962738), CENTURION (NCT03670810), ClinicalTrials.gov: NCT02439320, NCT02605174, NCT03962738, NCT03670810 [ABSTRACT FROM AUTHOR]

Introduction: As 5-HT1B receptor agonists, triptans produce vasoconstriction and have cardiovascular contraindications and precautions. Lasmiditan, a selective 5-HT1F receptor agonist, has a low affinity for 5-HT1B receptors, does not cause vasoconstriction, and is free of cardiovascular contraindications and precautions. The objective of this post hoc analysis was to evaluate the efficacy and safety of lasmiditan in patients with and without at least one triptan contraindication. Methods: Patient subgroups, with and without triptan contraindications, were analyzed from pooled patient data from four randomized, double-blind, placebo-controlled clinical trials (SAMURAI, SPARTAN, CENTURION, and MONONOFU). Patients experiencing a single migraine attack of moderate or severe intensity were treated with lasmiditan 50 mg (SPARTAN and MONONOFU only), 100 mg, 200 mg, or placebo, and efficacy data were recorded in an electronic diary. Results: Of 5704 patients, 207 (3.6%) patients had at least one contraindication to triptans. Overall subgroup analysis revealed that the effects of lasmiditan on pain freedom, pain relief, freedom from most bothersome symptom, disability freedom, and Patient Global Impression of Change at 2 h post-dose did not differ in patient groups with and without triptan contraindications. These outcomes generally showed a similar benefit pattern for lasmiditan in both subgroups, with all results being statistically significant in patients without contraindications, and pain relief being statistically significant in patients with contraindications. The safety and tolerability profiles of patients with triptan versus without triptan contraindications were similar, including dizziness in 18.3 to 22.8% and somnolence in 7.9 to 9.9% of patients at the highest dose of lasmiditan. Conclusions: In pooled analyses from four trials, patients with and without triptan contraindications did not differ in their patterns of lasmiditan efficacy. Lasmiditan may be a treatment option in patients with contraindications to triptans. Trial Registration Numbers: SAMURAI, NCT:02439320; SPARTAN, NCT:02605174; CENTURION, NCT:03670810; and MONONOFU, NCT:03962738. [ABSTRACT FROM AUTHOR]

Background: Triptans are the first-line option for the acute treatment of migraine attacks; however, triptans are contraindicated in people with certain underlying cardiovascular risk factors and are associated with inadequate efficacy or poor tolerability in some individuals. Ubrogepant is an oral calcitonin gene–related peptide receptor antagonist approved for the acute treatment of migraine. Methods: This post hoc analysis of the phase 3 ACHIEVE trials examined the impact of ubrogepant on the Functional Disability Scale (FDS), satisfaction with medication, and Patient Global Impression of Change (PGIC) in participants who were self-reported triptan insufficient responders (TIRs), defined as those who are unable to take triptans due to contraindications, tolerability issues, or insufficient efficacy. Responder definitions for the FDS, satisfaction measures, and PGIC were based on qualitative interpretation of the respective response options for the pooled ubrogepant 50 mg and placebo groups. Results: In the pooled analysis population (n = 1799), 451 (25%) participants were TIRs, with most (80%) reporting insufficient efficacy with triptan use. A significantly higher proportion of TIRs treated with ubrogepant vs placebo reported being able to function normally from 2 to 8 h post dose (P < 0.05). Notably, significance was demonstrated at the time of the primary outcome assessments (2 h post dose), where rates of normal function were 38% for ubrogepant vs 29% for placebo (P = 0.048). A greater proportion of TIRs in the ubrogepant arm vs the placebo arm were satisfied with treatment at 2 (33% vs 21%, P = 0.006) and 24 h (58% vs 28%, P < 0.001) and indicated that their migraine improved at 2 h vs placebo (30% vs 18%, P = 0.006). Results were generally similar in the insufficient efficacy subpopulation of TIRs as in the overall TIRs group. Ubrogepant was safe and well tolerated in TIRs, with no new safety signals identified. Conclusions: In people with migraine who are TIRs, individuals treated with ubrogepant had favorable 2-h outcomes, as measured by the FDS, satisfaction with medication, and PGIC, compared with placebo. Trial registration: ClinicalTrials.gov: NCT02828020 (ACHIEVE I), registered July 11, 2016; NCT02867709 (ACHIEVE II), registered August 16, 2016. [ABSTRACT FROM AUTHOR]

Background: PROMISE-1 and PROMISE-2 evaluated the preventive efficacy, tolerability, and safety of eptinezumab, a calcitonin gene-related peptide–targeted monoclonal antibody, in adults with episodic (EM) and chronic migraine (CM), finding significant reductions in migraine frequency. This post hoc analysis compared patient-reported outcomes (PROs), health-related quality of life (HRQoL) and acute medication use in patients with a ≥ 75% migraine responder rate (MRR) after treatment with eptinezumab to patients with a ≥ 50– < 75% MRR. Methods: PROMISE-1 and PROMISE-2 were phase 3, randomized, double-blind, placebo-controlled studies. This analysis included patients from both studies treated with eptinezumab 100 mg or 300 mg who experienced ≥ 75% and ≥ 50–< 75% MRR over Weeks 1–12 (wks1–12). In both studies, HRQoL was measured by the 36-item Short-Form Health Survey (SF-36) and acute medication usage. PROMISE-2 also included the 6-item Headache Impact Test (HIT-6), patient-identified most bothersome symptom (PI-MBS), and Patient Global Impression of Change (PGIC). Results: In PROMISE-1, a total of 115/443 (26.0%; 100 mg, n = 49, 300 mg, n = 66) and 120/443 (27.0%; 100 mg, n = 61, 300 mg, n = 59) eptinezumab-treated patients achieved ≥ 75% and ≥ 50–< 75% MRR over wks1–12, respectively. In PROMISE-2, a total of 211/706 (30.0%; 100 mg, n = 95; 300 mg, n = 116) and 209/706 (29.6%; 100 mg, n = 110, 300 mg, n = 99) eptinezumab-treated patients achieved ≥ 75% and ≥ 50–< 75% MRR over wks1–12, respectively. EM and CM patients with ≥ 75% and ≥ 50–< 75% MRR over wks1–12 showed reduced use of acute headache medication and increased HRQoL to normative levels across SF-36 domains of bodily pain, social functioning, and physical functioning. In CM patients with ≥ 75% and ≥ 50–< 75% MRR over wks1–12, the mean change in HIT-6 total score with eptinezumab (pooled) was − 11.7 and − 7.6, respectively. "Very much" or "much" improvement responses were reported in 41.8% and 16.5% on PI-MBS and 36.2% and 20.0% on PGIC in ≥ 75% and ≥ 50–< 75% MRR, respectively. Conclusion: Eptinezumab treatment induced a ≥ 75% MRR over wks1–12 in the majority of patients. This patient subgroup reported substantial improvements in PROs associated with headache-related life impact and HRQoL, and reductions in acute headache medication use, which were more marked than those in the ≥ 50–< 75% responders. This study supports the clinical meaningfulness of ≥ 75% MRR for patients with either EM or CM. Trial registration: ClinicalTrials.gov identifiers: NCT02559895 (PROMISE-1), NCT02974153 (PROMISE-2). [ABSTRACT FROM AUTHOR]

Background: Demonstrating therapeutic value from the patient perspective is important in patient-centered migraine management. The objective of this study was to investigate the impact of eptinezumab, a preventive migraine treatment, on patient-reported headache impact, acute medication optimization, and perception of disease change when initiated during a migraine attack. Methods: RELIEF was a randomized, double-blind, placebo-controlled trial conducted between 2019 and 2020 in adults with ≥1-year history of migraine and 4–15 migraine days per month in the 3 months prior to screening. Patients were randomized (1:1) to a 30-min infusion of eptinezumab 100 mg or placebo within 1–6 h of a qualifying migraine attack onset. The 6-item Headache Impact Test (HIT-6) and 6-item Migraine Treatment Optimization Questionnaire (mTOQ-6) were administered at baseline and week 4, and the Patient Global Impression of Change (PGIC) at week 4. A post hoc analysis of these measures was conducted in patients who reported headache pain freedom at 2 h after infusion start. Results: Of 480 patients enrolled and treated, 476 completed the study and are included in this analysis. Mean baseline HIT-6 total scores indicated severe headache impact (eptinezumab, 65.1; placebo, 64.8). At week 4, the eptinezumab-treated group demonstrated clinically meaningful improvement in HIT-6 total score compared with placebo (mean change from baseline: eptinezumab, − 8.7; placebo, − 4.5; mean [95% CI] difference from placebo: − 4.2 [− 5.75, − 2.63], P <.0001), with greater reductions in each item score vs placebo (P <.001 all comparisons). Change in HIT-6 total score in the subgroup with 2-h headache pain freedom was − 13.8 for the eptinezumab group compared with − 4.9 for the placebo group. mTOQ-6 total score mean change from baseline favored eptinezumab (change, 2.1) compared with placebo (1.2; mean [95% CI] difference: 0.9 [0.3, 1.5], P <.01). More eptinezumab-treated patients rated PGIC as much or very much improved than placebo patients (59.3% vs 25.9%). Conclusions: When administered during a migraine attack, eptinezumab significantly improved patient-reported outcomes after 4 weeks compared with placebo, with particularly pronounced effects in patients reporting headache pain freedom at 2 h after infusion start. Trial registration: ClinicalTrials.gov Identifier: NCT04152083. November 5, 2019. [ABSTRACT FROM AUTHOR]

Background: Electronic health records (EHR) data can be used to understand population level quality of care especially when supplemented with patient reported data. However, survey non-response can result in biased population estimates. As a case study, we demonstrate that EHR and survey data can be combined to estimate primary care population prescription treatment status for migraine stratified by migraine disability, without and with adjustment for survey non-response bias. We selected disability as it is associated with survey participation and patterns of prescribing for migraine. Methods: A stratified random sample of Sutter Health adult primary care (PC) patients completed a digital survey about headache, migraine, and migraine related disability. The survey data from respondents with migraine were combined with their EHR data to estimate the proportion who had prescription orders for acute or preventive migraine treatments. Separate proportions were also estimated for those with mild disability (denoted "mild migraine") versus moderate to severe disability (denoted mod-severe migraine) without and with correction, using the inverse propensity weighting method, for non-response bias. We hypothesized that correction for non-response bias would result in smaller differences in proportions who had a treatment order by migraine disability status. Results: The response rate among 28,268 patients was 8.2%. Among survey respondents, 37.2% had an acute treatment order and 16.8% had a preventive treatment order. The response bias corrected proportions were 26.2% and 11.6%, respectively, and these estimates did not differ from the total source population estimates (i.e., 26.4% for acute treatments, 12.0% for preventive treatments), validating the correction method. Acute treatment orders proportions were 32.3% for mild migraine versus 37.3% for mod-severe migraine and preventive treatment order proportions were 12.0% for mild migraine and 17.7% for mod-severe migraine. The response bias corrected proportions for acute treatments were 24.8% for mild migraine and 26.6% for mod-severe migraine and the proportions for preventive treatment were 8.1% for mild migraine and 12.0% for mod-severe migraine. Conclusions: In this study, we combined survey data with EHR data to better understand treatment needs among patients diagnosed with migraine. Migraine-related disability is directly related to preventive treatment orders but less so for acute treatments. Estimates of treatment status by self-reported disability status were substantially over-estimated among those with moderate to severe migraine-related disability without correction for non-response bias. [ABSTRACT FROM AUTHOR]

Migraine affects over 40 million Americans and is the world's second most disabling condition. As the majority of medical care for migraine occurs in primary care settings, not in neurology nor headache subspecialty practices, healthcare system interventions should focus on primary care. Though there is grade A evidence for behavioral treatment (e.g., biofeedback, cognitive behavioral therapy (CBT), and relaxation techniques) for migraine, these treatments are underutilized. Behavioral treatments may be a valuable alternative to opioids, which remain widely used for migraine, despite the US opioid epidemic and guidelines that recommend against them. Identifying and removing barriers to the use of headache behavioral therapy could help reduce the disability as well as the personal and social costs of migraine. These techniques will have their greatest impact if offered in primary care settings to the lower socioeconomic status groups at greatest risk for migraine. We review the societal and cultural challenges that impose barriers to optimal use of non-pharmacological treatment services. These barriers include insufficient knowledge of migraine/headache behavioral treatments and insufficient availability of clinicians trained in non-pharmacological treatment delivery; limited access in underserved communities; financial burden; and stigma associated with both headache and mental health diagnoses and treatment. For each barrier, we discuss potential approaches to minimizing its effect and thus enhancing non-pharmacological treatment utilization. Case Example A 25-year-old graduate student with a prior history of headaches in college is attending school in the evenings while working a full-time job. Now, his headaches have significant nausea and photophobia. They are twice weekly and are disabling enough that he is unable to complete homework assignments. He does not understand why the headaches occur on Saturdays when he pushes through all week to get through his examinations that take place on Friday evenings. He tried two different migraine preventive medications, but neither led to the 50% reduction in headache days his doctor had hoped for. His doctor had suggested cognitive behavioral therapy (CBT) before initiating the medications, but he had been too busy to attend the appointments, and the challenges in finding an in-network provider proved difficult. Now with the worsening headaches, he opted for the CBT and by the fifth week had already noted improvements in his headache frequency and intensity. [ABSTRACT FROM AUTHOR]

Introduction: Migraine is a debilitating neurological condition, affecting up to 15% of Americans. Recent estimates from a long-term safety study of rimegepant showed evidence of decreased monthly migraine days (MMD) in people with episodic migraine treated with rimegepant 75 mg. The objective of this study was to characterize migraine-specific quality of life version 2.1 (MSQv2) scores and corresponding mapped EuroQol-5 Dimensions-3 Level (EQ-5D-3L) utility values. Methods: Study participants were randomized into two treatment regimens: individuals with 2–14 MMD received rimegepant 75 mg as needed (PRN), and those with 4–14 MMD at baseline who received rimegepant on a fixed every-other-day schedule plus an as needed dose on days they did not treat (QOD + PRN). MSQv2 was mapped to EQ-5D-3L utilities using a validated algorithm. Outcomes were assessed for the PRN arm at baseline weeks 12, 24, 36, and 52 and for the QOD + PRN arm at baseline and week 12. Results: At baseline, MSQv2 data were available for 1,800 patients: 1,033 with 2–8 MMD in the PRN group, 481 with 9–14 MMD in the PRN group, and 286 with 4–14 MMD in the QOD + PRN group. For all MSQv2 domains as well as mapped utility values, outcomes improved over each study visit. At baseline, EQ-5D-3L utilities were 0.66, 0.63, and 0.65 for the 2–8 MMD PRN, 9–14 MMD PRN, and 4–14 MMD QOD + PRN groups, respectively. At end-of-study, utilities had increased by + 0.09, + 0.10, and + 0.12 for the three groups, respectively (p < 0.001 for all comparisons with baseline). Similar trends in improvement were observed across MSQv2 subdomains; all differences were statistically significant. Conclusions: Rimegepant 75 mg, which has been shown to be associated with reduced MMD, is associated with improvement in MSQv2 domains over time, leading to estimated improvement in EQ-5D-3L utilities. While this improvement was observed in all patient-groups, it was most pronounced in those with higher MMD and those taking rimegepant QOD + PRN. Trial registration: Clinical Trials NCT03266588. [ABSTRACT FROM AUTHOR]

Background: While pain freedom at 2 h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2 h has rarely been explored. Following lasmiditan treatment of a migraine attack with moderate or severe head pain, we contrast those who achieve pain freedom with those who achieve mild pain but not pain freedom 2 h post dosing. Methods: Patient-level data were pooled across studies and treatment arms from two Phase 3 trials comparing lasmiditan and placebo, SAMURAI and SPARTAN. This post hoc analysis assessed freedom from the most bothersome symptom (MBS), freedom from migraine-related functional disability (disability), and improved patient global impression of change (PGIC) in patients who achieved 2 h pain freedom compared to those who experienced 2 h mild pain. Mild pain differs from pain relief which is defined as either mild pain or pain freedom. Results: Patients who achieved 2 h pain freedom (N = 913), in comparison with those with 2 h mild pain (N = 864), were significantly more likely to experience MBS freedom (91.9% vs. 44.9%), disability freedom (87.1% and 13.4%), and improved PGIC (86.5% and 31.5%) (p < 0.001 for all combinations). In addition, more patients who were pain free experienced both 2 h MBS freedom and 2 h functional disability freedom (83.6%) compared to those with mild pain (10.8%; p < 0.001). The proportion of patients with pain freedom who did not achieve either MBS or disability freedom (4.6%) was lower than in patients with mild pain (52.4%). Lastly, 55.2% of patients experienced mild pain before disability freedom compared to 72.1% who experienced pain freedom and disability freedom at the same time. Conclusions: This study demonstrated that, at 2 h post treatment, patients who were pain free were more likely to achieve other outcomes including freedom from their MBS, freedom from migraine-related functional disability, and improved PGIC compared to those with mild pain, confirming that 2 h pain freedom is more robustly associated with other clinical outcomes than the 2 h mild pain endpoint. Trial Registration: SAMURAI (NCT02439320); SPARTAN (NCT02605174). [ABSTRACT FROM AUTHOR]

Objective: To investigate the association of psychiatric and cognitive comorbidities with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (TBI). Methods: A total of 100 patients with persistent PTH attributed to mild TBI and 100 age- and gender-matched healthy controls free of mild TBI were enrolled between July 2018 and June 2019. Quality of sleep was evaluated using the Pittsburgh Sleep Quality Index, while symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Cognitive impairment was evaluated using the Montreal Cognitive Assessment questionnaire, while post-traumatic stress disorder (PTSD) was assessed using the Harvard Trauma Questionnaire. Results: In 100 patients with persistent PTH, 85% reported poor quality sleep, compared with 42% of healthy controls (P < 0.01). The relative frequency of probable to high risk of anxiety was 52% in the persistent PTH group vs. 8% in healthy controls (P < 0.01), while the relative frequency of probable to high risk of depression was 42% in the persistent PTH group vs. 2% in healthy controls (P < 0.01). Furthermore, 27% of the patients with persistent PTH had mild cognitive impairment while 10% had probable PTSD. Conclusions: Poor quality of sleep as well as symptoms suggestive of anxiety and depression were more common in patients with persistent PTH than healthy controls. Clinicians should screen patients with persistent PTH for these comorbidities and develop treatment plans that account for their presence. [ABSTRACT FROM AUTHOR]

The benefits of athletic activity may be attenuated by sport-related head impacts, including soccer-related concussion and subconcussive events. The purpose of this study is to characterize the specific effects of soccer heading on white matter microstructure and cognitive function, independent of concussion, relative to non-athlete controls and relative to active athletes who are not involved in collision sports. 246 amateur soccer players, 72 non-contact/non-collision sports athletes and 110 healthy,non-athlete controls were included in the study, and underwent cognitive testing and 3T diffusion tensor imaging (DTI). Voxelwise linear regression, comparing soccer players and non-contact/non-collision sports athletes healthy,non-athlete controls, identified regions of abnormally low and high fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) in athlete participants. Generalized estimating equations were used to examine the effects of 2 week and 1 year heading exposure quartile on cognitive performance and on the volume of each high and each low DTI parameter. Athletes with no or lower exposure to repetitive heading exhibited greater expression of low RD, greater expression of high FA and better performance on tasks of attention, processing speed, verbal memory, and working memory compared to non-athletes. Soccer players with the highest exposure to repetitive head impacts, however, did not differ significantly from healthy, non-athletes on either micro-structural features or cognitive performance, findings not explained by concussion history or demographic factors. These results are consistent with the notion that beneficial effects of athletic conditioning or training on brain structure and function may be attenuated by exposure to repeated subconcussive head impacts. [ABSTRACT FROM AUTHOR]

Background: Persistent post-traumatic headache (PTH) is a common sequela of mild traumatic brain injury (TBI) and retrospective assessments have found a migraine-like phenotype to be very frequent. This has raised a discussion of shared underlying mechanisms and whether persistent PTH is simply trauma-triggered migraine. Methods: A 28-day prospective diary study with daily entries and acquisition of data on headache characteristics, associated symptoms, and acute medication use. A total of 64 patients with persistent PTH were enrolled from April 2019 to August 2019. Outcomes were the proportion of monthly headache days of any intensity that met the criteria for a migraine-like day or TTH-like day, as well as the corresponding figures for monthly headache days of moderate to severe intensity. Headache phenotypes were initially assigned based on diagnostic evaluation by semi-structured interview, whilst final headache phenotypes were assigned by diary review. Results: After diary review, we found that monthly headache days were exclusively migraine-like in 24 of 64 patients (38%) and exclusively TTH-like days in 8 of 64 patients (13%). Considering only monthly headache days of moderate to severe intensity, the corresponding figures were 35 of 64 patients (55%) for migraine-like days and 8 of 64 patients (13%) for TTH-like days. The following headache phenotypes were assigned based on diary review: chronic migraine-like (n = 47, 73%), combined episodic migraine-like and chronic TTH-like (n = 9, 13%), and 'pure' chronic TTH-like (n = 8, 13%). Conclusions: A migraine-like phenotype is common in patients most adversely affected by persistent PTH, although some patients did have a pure chronic TTH-like phenotype. At minimum, these findings suggest that persistent PTH is – at least in some – not 'trauma-triggered migraine'. [ABSTRACT FROM AUTHOR]

There is substantial biological heterogeneity among older adults with amnestic mild cognitive impairment (aMCI). We hypothesized that this heterogeneity can be detected solely based on volumetric MRI measures, which potentially have clinical implications and can improve our ability to predict clinical outcomes. We used latent class analysis (LCA) to identify subgroups among persons with aMCI (n = 696) enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI), based on baseline volumetric MRI measures. We used volumetric measures of 10 different brain regions. The subgroups were validated with respect to demographics, cognitive performance, and other AD biomarkers. The subgroups were compared with each other and with normal and Alzheimer's disease (AD) groups with respect to baseline cognitive function and longitudinal rate of conversion. Four aMCI subgroups emerged with distinct MRI patterns: The first subgroup (n = 404), most similar to normal controls in volumetric characteristics and cognitive function, had the lowest incidence of AD. The second subgroup (n = 230) had the most similar MRI profile to early AD, along with poor performance in memory and executive function domains. The third subgroup (n = 36) had the highest global atrophy, very small hippocampus and worst overall cognitive performance. The fourth subgroup (n = 26) had the least amount of atrophy, however still had poor cognitive function specifically in in the executive function domain. Individuals with aMCI who were clinically categorized within one group other showed substantial heterogeneity based on MRI volumetric measures. [ABSTRACT FROM AUTHOR]

Objective: To estimate the relative frequency and relative risk of post-traumatic stress disorder (PTSD) attributed to traumatic brain injury (TBI). Data Sources: PubMed and Embase were searched from database inception until January 26, 2019. Study Selection: Two independent investigators screened titles, abstracts, and full texts. We selected studies that included subjects presenting with TBI, and where the number of subjects with TBI and PTSD could be extrapolated. There were no restrictions on study design. Data Extraction and Synthesis: Data were extracted by two independent investigators and results were pooled using random-effects meta-analysis. Results: In civilian populations, relative frequency of PTSD following TBI was 12.2% after 3 months (CI-95 (7.6 to 16.8%) I2 = 83.1%), 16.3% after 6 months (CI-95 (10.2 to 22.4%), I2 = 88.4%), 18.6% after 12 months (CI-95 (10.2 to 26.9%), I2 = 91.5%), and 11.0% after 24 months (CI-95 (0.0 to 25.8%), I2 = 92.0%). Relative risk was 1.67 after 3 months (CI-95 (1.17 to 2.38), P = 0.011, I2 = 49%), 1.36 after 6 months (CI-95 (0.81 to 2.30), P = 0.189, I2 = 34%), and 1.70 after 12 months (CI-95 (1.16–2.50), P = 0.014, I2 = 89%). In military populations, the relative frequency of associated PTSD was 48.2% (CI-95 (44.3 to 52.1%), I2 = 100%) with a relative risk of 2.33 (CI-95 (2.00 to 2.72), P < 0.0001, I2 = 99.9%). Conclusions and Relevance: TBI is a risk factor for PTSD in clinic-based civilian populations. There are insufficient data to assess the relative frequency or relative risk of PTSD in moderate to severe TBI. Due to significant between-study heterogeneity, the findings of our study should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: Migraine has many presumed comorbidities which have rarely been compared between samples with and without migraine. Examining the association between headache pain intensity and monthly headache day (MHD) frequency with migraine comorbidities is novel and adds to our understanding of migraine comorbidity. Methods: The MAST Study is a prospective, web-based survey that identified US population samples of persons with migraine (using modified International Classification of Headache Disorders-3 beta criteria) and without migraine. Eligible migraine participants averaged ≥1 MHDs over the prior 3 months. Comorbidities "confirmed by a healthcare professional diagnosis" were endorsed by respondents from a list of 21 common cardiovascular, neurologic, psychiatric, sleep, respiratory, dermatologic, pain and medical comorbidities. Multivariable binary logistic regression calculated odds ratios (OR) and 95% confidence intervals for each condition between the two groups adjusting for sociodemographics. Modeling within the migraine cohort assessed rates of conditions as a function of headache pain intensity, MHD frequency, and their combination. Results: Analyses included 15,133 people with migraine (73.0% women, 77.7% White, mean age 43 years) and 77,453 controls (46.4% women, 76.8% White, mean age 52 years). People with migraine were significantly (P < 0.001) more likely to report insomnia (OR 3.79 [3.6, 4.0]), depression (OR 3.18 [3.0, 3.3]), anxiety (OR 3.18 [3.0 3.3]), gastric ulcers/GI bleeding (OR 3.11 [2.8, 3.5]), angina (OR 2.64 [2.4, 3.0]) and epilepsy (OR 2.33 [2.0, 2.8]), among other conditions. Increasing headache pain intensity was associated with comorbidities related to inflammation (psoriasis, allergy), psychiatric disorders (depression, anxiety) and sleep conditions (insomnia). Increasing MHD frequency was associated with increased risk for nearly all conditions and most prominent among those with comorbid gastric ulcers/GI bleeding, diabetes, anxiety, depression, insomnia, asthma and allergies/hay fever. Conclusions: In regression models controlled for sociodemographic variables, all conditions studied were reported more often by those with migraine. Whether entered into the models separately or together, headache pain intensity and MHD frequency were associated with increased risk for many conditions. Future work is required to understand the causal sequence of relationships (direct causality, reverse causality, shared underlying predisposition), the potential confounding role of healthcare professional consultation and treatment, and potential detection bias. [ABSTRACT FROM AUTHOR]

Background: Migraine is recognized as the second leading cause of disability globally. Lasmiditan is a novel, selective serotonin 5-HT1F receptor agonist developed for acute treatment of migraine. Here we analyzed effects of lasmiditan on migraine disability assessed with the Migraine Disability Assessment (MIDAS) scale for interim data from a long-term safety study. Methods: Completers of two single-attack parent studies were offered participation in the 1 year GLADIATOR study, that randomized participants to treatment with lasmiditan 100 mg or 200 mg taken as needed for migraine attacks of at least moderate severity. Changes in MIDAS were modeled using a mixed model repeated measures analysis. Results: The sample included 1978 patients who received ≥1 lasmiditan dose and were followed for a median of 288 days. Baseline mean MIDAS scores for the lasmiditan 100-mg and 200-mg groups were 29.4 and 28.9, respectively, indicating severe migraine-related disability. Relative to baseline, MIDAS total scores were significantly lower at 3, 6, 9, and 12 months for both dose groups. At 12 months, changes in MIDAS scores were − 12.5 and − 12.2 for lasmiditan 100 mg and 200 mg, respectively, with 49% and 53% of patients, respectively, achieving at least a 50% decrease in MIDAS total score. Statistically significant improvements were also seen for work and/or school absenteeism and presenteeism, monthly headache days, and mean headache pain intensity at all time points up to 1 year. Findings for patients who completed all visits versus those dropping out early were similar. Responses were generally similar for the lasmiditan 100 mg or 200 mg doses, between subgroups defined based on the number of baseline monthly migraine attacks (≤5 vs. >5), and also between subgroups defined by pain-free response (yes/no) during initial attacks. Conclusions: Long-term treatment with lasmiditan was associated with significant reductions in migraine-related disability, including both work or school absenteeism and presenteeism. The similarity of responses in completers and those who dropped out suggests that selective attrition does not account for the improvements. Benefits were significant at 3 months and maintained through 12 months. Trial registration: clinicaltrials.govNCT02565186; first posted October 1, 2015. [ABSTRACT FROM AUTHOR]

Background: The commercial formulation of sumatriptan nasal spray is an effective option for migraine patients requiring or preferring a non-oral route of drug administration, but its utility is limited by poor absorption and tolerability issues. DFN-02, a new formulation of sumatriptan 10 mg nasal spray, is co-formulated with a permeation enhancer that gives it pharmacokinetics comparable to subcutaneous sumatriptan. As reported previously, DFN-02 was significantly better than placebo on multiple efficacy endpoints at 2 h postdose, including pain freedom, absence of the most bothersome symptom, and pain relief, and its safety and tolerability profiles were excellent.Objective: The objective of this study was to assess the efficacy of acute treatment of migraine with DFN-02, including its effect on migraine-related functional disability and patient satisfaction with treatment.Methods: This was a multicenter, randomized, double-blind, placebo-controlled efficacy and safety study of DFN-02 in adults with episodic migraine. Functional disability and subject satisfaction with treatment were prespecified endpoints, assessed in real-time by subjects, using an electronic diary.Results: In total, 107 subjects were randomized. DFN-02 was significantly superior to placebo for the reduction in functional disability score from predose level at 2 h after treatment (- 1.2 vs. - 0.6, p < 0.001). Subjects treated with DFN-02 were also more likely to be satisfied or very satisfied than subjects treated with placebo at 2 h postdose (70.0% vs. 44.2%, p = 0.027). Using the Patient Perception of Migraine Questionnaire-Revised at 24 h postdose, DFN-02 mean scores were significantly superior to placebo for the subscales of efficacy (65.2 vs. 42.5, p = 0.016) and function (68.9 vs. 42.1, p = 0.001), and for total score (71.0 vs. 56.6, p = 0.016); global medication effectiveness (p = 0.027); and overall satisfaction (p = 0.019). Placebo was significantly better than DFN-02 on the tolerability subscale (94.8 vs. 88.5, p = 0.026). At 24 h postdose, subjects reported significantly higher satisfaction with DFN-02 compared with satisfaction reported pre-randomization regarding their usual migraine medication (p = 0.012).Conclusion: DFN-02 was superior to placebo for the relief of migraine-related functional disability, and provided greater satisfaction than placebo or subjects' usual acute treatment.Trial Registration: ClinicalTrials.gov identifier: NCT02856802. [ABSTRACT FROM AUTHOR]

Accelerated gait decline in aging is associated with many adverse outcomes, including an increased risk for falls, cognitive decline, and dementia. Yet, the brain structures associated with gait speed, and how they relate to specific cognitive domains, are not well-understood. We examined structural brain correlates of gait speed, and how they relate to processing speed, executive function, and episodic memory in three non-demented and community-dwelling older adult cohorts (Overall N = 352), using voxel-based morphometry and multivariate covariance-based statistics. In all three cohorts, we identified gray matter volume covariance patterns associated with gait speed that included brain stem, precuneus, fusiform, motor, supplementary motor, and prefrontal (particularly ventrolateral prefrontal) cortex regions. Greater expression of these gray matter volume covariance patterns linked to gait speed were associated with better processing speed in all three cohorts, and with better executive function in one cohort. These gray matter covariance patterns linked to gait speed were not associated with episodic memory in any of the cohorts. These findings suggest that gait speed, processing speed (and to some extent executive functions) rely on shared neural systems that are subject to age-related and dementia-related change. The implications of these findings are discussed within the context of the development of interventions to compensate for age-related gait and cognitive decline. [ABSTRACT FROM AUTHOR]

To investigate changes in tremor severity over repeated spiral drawings to assess whether learning deficits can be evaluated directly in a limb in essential tremor (ET). A motor learning deficit in ET, possibly mediated by cerebellar pathways, has been established in eye-blink conditioning studies, but not paradigms measuring from an affected, tremulous limb. Computerized spiral analysis captures multiple characteristics of Archimedean spirals and quantifies performance through calculated indices. Sequential spiral drawing has recently been suggested to demonstrate improvement across trials among ET subjects. One hundred and sixty-one ET and 80 age-matched control subjects drew 10 consecutive spirals on a digitizing tablet. Degree of severity (DoS), a weighted, computational score of spiral execution that takes into account spiral shape and line smoothness, previously validated against a clinical rating scale, was calculated in both groups. Tremor amplitude (Ampl), an independent index of tremor size, measured in centimeters, was also calculated. Changes in DoS and Ampl across trials were assessed using linear regression with slope evaluations. Both groups demonstrated improvement in DoS across trials, but with less improvement in the ET group compared to controls. Ampl demonstrated a tendency to worsen across trials in ET subjects. ET subjects demonstrated less improvement than controls when drawing sequential spirals, suggesting a possible motor learning deficit in ET, here captured in an affected limb. DoS improved independently of Ampl, showing that DoS and Ampl are separable motor physiologic components in ET that may be independently mediated. [ABSTRACT FROM AUTHOR]

Early life adversity (ELA) has been associated with pain symptomatology in adulthood, but mechanisms and moderators of these associations are unclear. Using recall based and concurrently assessed self-report data, we examined associations between ELA, mood, sleep, and recent pain intensity and interference, and whether optimism and perceived control weakened these associations in a midlife community sample of diverse adults reporting some ELA. Controlling for demographic variables and BMI, higher levels of ELA were associated with more pain intensity and interference; greater sleep disturbance and negative mood accounted for these associations. When moderation was examined, only the path from sleep disturbance to pain interference was significantly attenuated for those with higher optimism and higher perceived control. These findings suggest that higher levels of ELA may link with pain in adulthood through poorer mood and sleep, and that resilience resources such as optimism and control may buffer some of these pathways. [ABSTRACT FROM AUTHOR]

Purpose Of Review: Migraine is a common and highly disabling condition that is particularly prevalent among women and especially women of reproductive age. The tremendous rise in adiposity in the Western world has led to an epidemic of obesity in women. The particular effects of obesity on women with migraine of various ages are the focus of this review.Recent Findings: Conflicting findings from various studies with different approaches and populations have made challenging definitive conclusions about associations between migraine and obesity. While the association between obesity and migraine frequency has been consistently demonstrated and obesity is considered a risk factor for progression from episodic to chronic migraine, the association between obesity and migraine prevalence is still somewhat debated and appears to be dependent on gender and age, with the most consistent effects observed in women younger than 55 years of age. Association between migraine and obesity is most commonly observed in women of reproductive age. The multimodal changes associated with age and hormonal change in women likely play a role in this relationship, as obesity does not appear to be related to migraine in women over 55 years of age. Future studies focusing on the migraine-obesity relationship in women should examine the effects of age, endogenous hormonal state, and exogenous hormones on migraine and obesity. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the relationship of medial temporal lobe and posterior cingulate cortex (PCC) volumetrics as well as fractional anisotropy of the cingulum angular bundle (CAB) and the cingulum cingulate gyrus (CCG) bundle to performance on measures of verbal memory in non-demented older adults. The participants were 100 non-demented adults over the age of 70 years from the Einstein Aging Study. Volumetric data were estimated from T1-weighted images. The entire cingulum was reconstructed using diffusion tensor MRI and probabilistic tractography. Association between verbal episodic memory and MRI measures including volume of hippocampus (HIP), entorhinal cortex (ERC), PCC and fractional anisotropy of CAB and CCG bundle were modeled using linear regression. Relationships between atrophy of these structures and regional cingulum fractional anisotropy were also explored. Decreased HIP volume on the left and decreased fractional anisotropy of left CAB were associated with lower memory performance. Volume changes in ERC, PCC and CCG disruption were not associated with memory performance. In regression models, left HIP volume and left CAB-FA were each independently associated with episodic memory. The results suggest that microstructural changes in the left CAB and decreased left HIP volume independently influence episodic memory performance in older adults without dementia. The importance of these findings in age and illness-related memory decline require additional exploration. [ABSTRACT FROM AUTHOR]

Results of two recent studies by Messoud Ashina and colleagues demonstrate that infusion of two different potassium channel openers can trigger migraine in humans; one of the compounds also triggered aura in patients diagnosed with migraine with aura. The findings highlight the importance of human experimental models in migraine research. [ABSTRACT FROM AUTHOR]

Background: Studies of the difference between menstrually associated and non-menstrually associated migraine are somewhat controversial. The majority of studies have focused on comparing menstrual to non-menstrual attacks rather than comparing study groups with different migraine diagnoses with respect to menstruation. As there is limited knowledge available on the overall impact and burden of migraine among groups of women with and without menstrually associated migraine our goal was to examine differences between these groups. We hypothesized that there would be greater burden of migraine related to menstruation and headache frequency in a population study across groups of women. Methods: We analyzed data from the American Migraine Prevalence and Prevention (AMPP) Study, a longitudinal, US, population-based study. We included female respondents to the 2009 survey, aged 18 to 60, who met modified ICHD-2 criteria for migraine, were actively menstruating and fit one of three definitions based on the self-reported association of menses and migraine attacks: self-reported predominantly menstrual migraine (MM, attacks that only or predominantly occur at the time of menses), self-reported menstrually-associated migraine (MAM, attacks commonly associated with menses, but that also occur at other times of the month), and self-reported menstrually-unrelated migraine (MUM). These three groups were compared on characteristics and measures of headache impact and burden (Headache Impact Test– 6 item (HIT-6) and Migraine Disability Assessment Scale (MIDAS). Results: There were 1,697 eligible subjects for this study in the following categories: MM (5.5%), MAM (53.8%), or MUM (40.7%). Women with MM had an older age of migraine onset. Those with predominantly menstrually-related attacks (MM) had fewer headache-days but appeared to be more impaired by attacks. HIT-6 and MIDAS scores were significantly higher for both the MM and MAM groups compared with the MUM groups; however, effects were more robust for MM than MAM. Conclusions: Nearly 60% of women with migraine reported an association between migraine and menses. These women reported greater headache impact and migraine-related burden on functioning than those in whom migraines were not related to menstruation. Women with MM were more impaired by attacks while women with MAM had overall highest burden, likely due to experiencing migraines on additional days. [ABSTRACT FROM AUTHOR]

Chronic migraine (CM) and episodic migraine (EM) are part of the spectrum of migraine disorders, but they are distinct clinical entities. Population-based studies have shown that those with CM demonstrate higher individual and societal burden because they are significantly more disabled than those with EM and have greater impaired quality of life both inside and outside the home. Proper diagnosis of both conditions requires clearly defined clinical criteria. Diagnosis enables the initiation of appropriate treatments and risk-factor modification, which ultimately improve functional status and quality of life for persons with migraine. Recognizing that both disorders are on the spectrum of migraine, this review serves as a guide to define the disease state of CM as distinct from EM in terms of clinical, epidemiological, sociodemographic, and comorbidity profiles. [ABSTRACT FROM AUTHOR]

The diagnosis and management of headache disorders in the elderly are challenging. The evaluation of the elderly patient with new-onset or recurrent headache requires a grasp of the heterogeneous set of causes of secondary head pain disorders. Once such aetiologies are excluded, the correct primary headache disordermust be diagnosed. Although tension-type headache is the leading cause of new-onset headache in the elderly, other primary headache disorders such as migraine can manifest in later life, and one disorder, hypnic headache, occurs almost exclusively in the elderly. Primary chronic daily headache persists in elderly patients to a greater extent than the primary episodic headache disorders do. The treatment of elderly patients with primary headache disorders is multifaceted, including acute, prophylactic and at times transitional treatments. Knowledge of drug interactions is particularly important as polypharmacy is the rule. Concomitant illnesses may require adjustments in choice or dose of drugs. In addition, as many acute and preventive treatments are either contraindicated or poorly tolerated in the elderly, modifiable risk factors for headache progression and perpetuation must be addressed. In spite of these treatment complexities, there are numerous opportunities to bring relief to older patients with primary headache disorders from the currently available therapies. New treatment options for elderly patients with headache will soon be available, including acute, prophylactic and interventional techniques. [ABSTRACT FROM AUTHOR]

To estimate the validity of neurological gait evaluations in predicting falls in older adults. We studied 632 adults age 70 and over (mean age 80.6 years, 62% women) enrolled in the Einstein Aging Study whose walking patterns were evaluated by study clinicians using a clinical gait rating scale. Association of neurological gaits and six subtypes (hemiparetic, frontal, Parkinsonian, unsteady, neuropathic, and spastic) with incident falls was studied using generalized estimation equation procedures adjusted for potential confounders, and reported as risk ratio with 95% confidence intervals (CI). Over a mean follow-up of 21 months, 244 (39%) subjects fell. Mean fall rate was 0.47 falls per person year. At baseline, 120 subjects were diagnosed with neurological gaits. Subjects with neurological gaits were at increased risk of falls (risk ratio 1.49, 95% CI 1.11–2.00). Unsteady (risk ratio 1.52, 95% CI 1.04–2.22), and neuropathic gait (risk ratio 1.94, 95% CI 1.07–3.11) were the two gait subtypes that predicted risk of falls. The results remained significant after accounting for disability and cognitive status, and also with injurious falls as the outcome. Neurological gaits and subtypes are independent predictors of falls in older adults. Neurological gait assessments will help clinicians identify and institute preventive measures in older adults at high risk for falls. [ABSTRACT FROM AUTHOR]

Headache associated with moyamoya disease (HAMD) is common in moyamoya disease. However, the characteristics and classification of HAMD are largely unknown. We present a case of a 39-year-old woman with HAMD. To characterize and classify the features of this syndrome, the patient was asked to complete a 4-month diagnostic headache diary. There was a total of 15 ictal days. All episodes were without aura. The headache was more commonly pressing (10/15), mild to moderate in severity (14/15), unchanged by physical activity (11/15), and associated with photophobia (10/15). The International Headache Society Classification was utilized to determine that eight episodes met criteria for probable migraine without aura, while seven episodes met criteria for probable frequent episodic tension-type headache. We identified four other case reports of HAMD with partial descriptions of the characteristics. When combined with our patient, the median age was 34 years old (range 6–49, SD 16). Four were female, while the patient with cluster headache was male. The median time from headache onset to diagnosis with moyamoya disease was 9.5 months (range 0–192, SD 88.0). Headaches were described as migraine with aura in two of five cases, hemiplegic migraine in one of five, and cluster headache in one of five. The highest intensity was described as severe in three of three cases, in which headache intensity was reported. Meanwhile, nausea, vomiting, and photophobia were present in two of three cases, where these features were reported, while nausea without vomiting was seen in one of three cases. In all five cases, patients had other neurological symptoms, such as paresis, seizures, visual disturbances, dysarthria, allodynia, ptosis, and unilateral restless leg syndrome. In conclusion, HAMD can present as migraine without aura. It can be the first presenting symptom of moyamoya disease. The headache features are not diagnostic; hence, early neurovascular imaging should be considered in patients with new onset, refractory migraine-like headache, especially in the setting of other neurological symptoms to exclude underlying moyamoya disease. Further reports using headache diaries are needed to better characterize HAMD as well as to determine whether headache with tension-type features is also part of this condition. [ABSTRACT FROM AUTHOR]

Background: Research indicates that successful migraine assessment and treatment depends on information obtained during patient and healthcare professional (HCP) discussions. However, no studies outline how migraine is actually discussed during clinical encounters.Objective: Record naturally occurring HCP-migraineur interactions, analyzing frequency and impairment assessment, and preventive treatment discussions.Design: HCPs seeing high volumes of migraineurs were recruited for a communication study. Patients likely to discuss migraine were recruited immediately before their normally scheduled appointment and, once consented, were audio- and video-recorded without a researcher present. Separate post-visit interviews were conducted with patients and HCPs. All interactions were transcribed.Participants: Sixty patients (83% female; mean age 41.7) were analyzed. Patients were diagnosed with migraine 14 years and experienced 5 per month, on average.Approach: Transcripts were analyzed using sociolinguistic techniques such as number and type of questions asked and post-visit alignment on migraine frequency and impairment. American Migraine Prevalence and Prevention Study guidelines were utilized.Results: Ninety-one percent of HCP-initiated, migraine-specific questions were closed-ended/short answer; assessments focused on frequency and did not focus on attention on impairment. Open-ended questions in patient post-visit interviews yielded robust impairment-related information. Post-visit, 55% of HCP-patient pairs were misaligned regarding frequency; 51% on impairment. Of the 20 (33%) patients who were preventive medication candidates, 80% did not receive it and 50% of their visits lacked discussion of prevention.Conclusions: Sociolinguistic analysis revealed that HCPs often used narrowly focused, closed-ended questions and were often unaware of how migraine affected patients' lives as a result. It is recommended that HCPs assess impairment using open-ended questions in combination with the ask-tell-ask technique. [ABSTRACT FROM AUTHOR]

Chronic daily headaches (CDHs) refers to primary headaches that happen on at least 15 days per month, for 4 or more hours per day, for at least three consecutive months. The differential diagnosis of CDHs is challenging and should proceed in an orderly fashion. The approach begins with a search for “red flags” that suggest the possibility of a secondary headache. If secondary headaches that mimic CDHs are excluded, either on clinical grounds or through investigation, the next step is to classify the headaches based on the duration of attacks. If the attacks last less than 4 hours per day, a trigeminal autonomic cephalalgia (TAC) is likely. TACs include episodic and chronic cluster headache, episodic and chronic paroxysmal hemicrania, SUNCT, and hypnic headache. If the duration is ≥4 h, a CDH is likely and the differential diagnosis encompasses chronic migraine, chronic tension-type headache, new daily persistent headache and hemicrania continua. The clinical approach to diagnosing CDH is the scope of this review. [ABSTRACT FROM AUTHOR]

It has been suggested that contact point can trigger headache in individuals with migraine. In this article, we review the anatomy of the sinonasal cavity. We then define contact points and discuss the pathophysiology of contact point headaches. We propose a theory to explain the relationship between migraines and contact points. We close by presenting our personal casuistic in the surgical treatment of patients with contact point and refractory headaches. In migraineurs with contact point, surgery may improve the headaches. [ABSTRACT FROM AUTHOR]

Although the influence of age on the prevalence of migraine is well known, the clinical characterization of migraine across the lifespan remains poorly studied. Limited evidence suggests that migraine attacks get shorter and less typical with advancing age. Similar results were found for transformed migraine at different ages. In this article, we first discuss the prevalence and clinical features of episodic migraine. We then discuss the epidemiology and profile of transformed migraine across the lifespan. Clarifying the influence of age on migraine is of importance for clinical diagnosis and treatment. It also may contain clues to evolving disease biology. [ABSTRACT FROM AUTHOR]

This overview of the published epidemiological evidence of migraine helps to identify the size of the public–health problem that migraine represents. It also highlights the need for further epidemiological studies in many parts of the world to gain full understanding of the scale of clinical, economic and humanistic burdens attributable to it. This paper presents some of the work on migraine undertaken by the World Health Organization (WHO) in the Global Burden of Disease study conducted in 2000 and reported in the World Health Report 2001. Migraine was not included in the first Global Burden of Disease 1990. The paper also discussed the measurement of disability attributable to headache disorders using WHO ICF Classification. Using disabilityadjusted life years (DALYs) as a summary measure of population health (which adds disability to mortality), WHO have shown that mental and neurological disorders collectively account for 30.8% of all years of healthy life lost to disability (YLDs) whilst migraine, one amongst these, alone accounts for 1.4% and is in the top 20 causes of disability worldwide. This information is combined with the increasingly widely accepted belief that disability and functioning are relevant parameters for monitoring the health of nations and that there is an increasing need to measure them. WHO's Classification of Functioning, Disability and Health (ICF) provides a model of human functioning and disability, as well as a classification system, that allows us to highlight and measure all dimensions of disability. ICF applied to headache disorders allows comparability with other health conditions as well as evaluation of the role of the environment as a cause of disability amongst people with headache. Migraine causes a large propotion of the non–fatal disease–related burden worldwide.Our kowledge of headache related burden is incomplete and it is necessary to add to it epidemiological studies in many parts of the world and to combine this with measurements of disability using both DALYs and WHO ‘s ICF Classification. The work described here has been the base for the Global Campaign against Headache disorders: "Lifting the Burden", launched in 2004 jointly by WHO, IHS (International Headache Society), WHA (World Headache Alliance) and EHF (European Headache Federation). [ABSTRACT FROM AUTHOR]

Tension-type headache (TTH) is the most prevalent form of primary headache in the general population. In this article, the diagnostic challenges of TTH are discussed. The classification of these headaches according to the second edition of the International Classification of Headache Disorders (ICHD-2) and the main differences between the ICHD-2 and the first edition of the classification (ICHD-1, 1988) are discussed. The typical features of TTH also are highlighted. Finally, the differential diagnosis of episodic and chronic TTH, emphasizing the situations more likely to raise doubts, is discussed. The wide clinical spectrum of TTH frequently challenges the physician's diagnostic acumen. A structured approach to the patient and a better comprehension of this variability of presentation should translate into better quality of care and a more specific diagnosis for TTH sufferers. [ABSTRACT FROM AUTHOR]

Background The physician treating patients with migraine is now able to choose from among seven triptans-almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan. These differ, to greater or lesser degrees, on a range of clinical attributes important for treatment selection. Objective To outline the basic principles of Multiattribute Decision Making (MADM) and describe how one such method-TOPSIS (Technique for Order Preference by Similarity to the Ideal Solution)-can be applied to evaluate the currently available triptans. Methods In an example application, summary data from a recent meta-analysis of 53 published and unpublished placebo-controlled trials of the oral triptans were combined in TOPSIS models with computer-generated attribute importance weights representing the entire range of possible values, That is, the relative performance of the triptans was explored across all logically possible combinations of relative importance of the treatment attributes available from the meta-analysis, and uncertainty was assessed based on the confidence intervals from the meta-analysis. Results When compared across the entire range of values for relative attribute importance, almotriptan, eletriptan and rizatriptan were more similar to a hypothetical ideal triptan and were more likely to appear in the top three closest to the hypothetical ideal, than were naratriptan, sumatriptan, and zolmitriptan. Conclusions Using the TOPSIS model, almotriptan, eletriptan and rizatriptan were more likely to appear in the top three closest to the hypothetical ideal triptan. [ABSTRACT FROM AUTHOR]