Prevalence and burden of migraine in the United States: A systematic review.

BACKGROUND: This study reviewed migraine prevalence and disability gathered through epidemiologic survey studies in the United States conducted over the past three decades. We summarized these studies and evaluated changing patterns of disease prevalence and disability. METHODS: We conducted a systematic review of US studies addressing the prevalence, disability, and/or burden of migraine, including both episodic migraine (EM) and chronic migraine (CM). A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was used in conjunction with the PubMed search engine. Eligible studies were published before February 2022, were conducted in the United States, included representative samples, and used a case definition of migraine based on the International Classification of Headache Disorders (ICHD). The primary measure of disease burden was the Migraine Disability Assessment Scale (MIDAS). The MIDAS measures days lost due to migraine over 3 months in three domains and defines groups with moderate (Grade III) or severe disability (Grade IV) using cut-scores. RESULTS: Of the 1609 identified records, 26 publications from 11 US population-based studies met eligibility criteria. The prevalence of migraine in the population has remained relatively consistent for the past 30 years: ranging from 11.7% to 14.7% overall, 17.1% to 19.2% in women, and 5.6% to 7.2% in men in the studies reviewed. CM prevalence is 0.91% (1.3% among women and 0.5% of men) in adults and 0.8% in adolescents. The proportion of people with migraine and moderate-to-severe MIDAS disability (Grades III-IV), has trended upward across studies from 22.0% in 2005 to 39.0% in 2012, to 43.2% in 2016, and 42.4% in 2018. A consistently higher proportion of women were assigned MIDAS Grades III/IV relative to men. CONCLUSION: The prevalence of migraine in the United States has remained stable over the past three decades while migraine-related disability has increased. The disability trend could reflect changes in reporting, study methodology, social and societal changes, or changes in exacerbating or remediating factors that make migraine more disabling, among other hypotheses. These issues merit further investigation.

Characterizing gaps in the preventive pharmacologic treatment of migraine: Multi-country results from the CaMEO-I study.

OBJECTIVE: To analyze data from the Chronic Migraine Epidemiology and Outcomes-International (CaMEO-I) Study in order to characterize preventive medication use and identify preventive usage gaps among people with migraine across multiple countries. BACKGROUND: Guidelines for the preventive treatment of migraine are available from scientific organizations in various countries. Although these guidelines differ among countries, eligibility for preventive treatment is generally based on monthly headache day (MHD) frequency and associated disability. The overwhelming majority of people with migraine who are eligible for preventive treatment do not receive it. METHODS: The CaMEO-I Study was a cross-sectional, observational, web-based panel survey study performed in six countries: Canada, France, Germany, Japan, the United Kingdom, and the United States. People were invited to complete an online survey in their national language(s) to identify those with migraine according to modified International Classification of Headache Disorders, 3rd edition, criteria. People classified with migraine answered questions about current and ever use of both acute and preventive treatments for migraine. Available preventive medications for migraine differed by country. MHD frequency and associated disability data were collected. The American Headache Society (AHS) 2021 Consensus Statement algorithm was used to determine candidacy for preventive treatment (i.e., ≥3 monthly MHDs with severe disability, ≥4 MHDs with some disability, or ≥6 MHDs regardless of level of disability). RESULTS: Among 90,613 valid completers of the screening survey, 14,492 met criteria for migraine and completed the full survey, with approximately 2400 respondents from each country. Based on the AHS consensus statement preventive treatment candidacy algorithm, averaging across countries, 36.2% (5246/14,492) of respondents with migraine qualified for preventive treatment. Most respondents (84.5% [4431/5246]) who met criteria for preventive treatment according to the AHS consensus statement were not using a preventive medication at the time of the survey. Moreover, 19.3% (2799/14,492) of respondents had ever used preventive medication (ever users); 58.1% (1625/2799) of respondents who reported ever using a preventive medication for migraine were still taking it. Of the respondents who were currently using a preventive medication, 50.2% (815/1625) still met the criteria for needing preventive treatment based on the AHS consensus statement. CONCLUSIONS: Most people with migraine who qualify for preventive treatment are not currently taking it. Additionally, many people currently taking preventive pharmacologic treatment still meet the algorithm criteria for needing preventive treatment, suggesting inadequate benefit from their current regimen.

Impact of headache frequency and preventive treatment failure on quality of life, disability, and direct and indirect costs among individuals with episodic migraine in the United States.

OBJECTIVE: To evaluate unmet needs among individuals with episodic migraine (EM) in the United States (US). BACKGROUND: Data are limited on the impact of headache frequency (HF) and preventive treatment failure (TF) on the burden of migraine in the US. METHODS: A retrospective, cross-sectional analysis of 2019 National Health and Wellness Survey (NHWS) data was conducted from an opt-in online survey that identified respondents (aged ≥18 years) in the US with self-reported physician-diagnosed migraine. Participants were stratified by HF (low: 0-3 days/month; moderate-to-high: 4-14 days/month) and prior preventive TF (preventive naive; 0-1 TF; ≥2 TFs). Comparisons were conducted between preventive TF groups using multivariable regression models controlling for patient demographic and health characteristics. RESULTS: Among individuals with moderate-to-high frequency EM, the NHWS identified 397 with ≥2 TFs, 334 with 0-1 TF, and 356 as preventive naive. The 36-item Short-Form Health Survey (version 2) Physical Component Summary scores were significantly lower among those with ≥2 TFs, at a mean (standard error [SE]) of 41.4 [0.8] versus the preventive-naive 46.8 [0.9] and 0-1 TF 44.5 [0.9] groups; p < 0.001 for both). Migraine Disability Assessment Scale scores were significantly higher in the ≥2 TFs, at a mean (SE) of 37.7 (3.9) versus preventive-naive 26.8 (2.9) (p < 0.001) and 0-1 TF 30.1 (3.3) (p = 0.011) groups. The percentages of time that respondents experienced absenteeism (mean [SE] 21.6% [5.5%] vs. 13.4% [3.6%]; p = 0.022), presenteeism (mean [SE] 55.0% [8.3%] vs. 40.8% [6.5%]; p = 0.015), overall work impairment (mean [SE] 59.4% [5.6%] vs. 45.0% [4.4%]; p < 0.001), and activity impairment (mean [SE] 56.8% [1.0%] vs. 44.4% [0.9%]; p < 0.001) were significantly higher in the ≥2 TFs versus preventive-naive group. Emergency department visits (preventive-naive, p = 0.006; 0-1 TF, p = 0.008) and hospitalizations (p < 0.001 both) in the past 6 months were significantly higher in the ≥2 TFs group. Direct and indirect costs were significantly higher in the ≥2 TFs (mean [SE] $24,026 [3460]; $22,074 [20]) versus 0-1 TF ($10,897 [1636]; $17,965 [17]) and preventive-naive ($11,497 [1715]; $17,167 [17]) groups (p < 0.001 for all). Results were similar in the low-frequency EM group. CONCLUSIONS: In this NHWS analysis, individuals with more prior preventive TFs experienced significantly higher humanistic and economic burden regardless of HF.

Real-world Impact of Fremanezumab on Migraine-Related Health Care Resource Utilization in Patients with Comorbidities, Acute Medication Overuse, and/or Unsatisfactory Prior Migraine Preventive Response.

INTRODUCTION: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide, is indicated for preventive treatment of migraine in adults. Real-world evidence assessing the effect of fremanezumab on migraine-related medication use, health care resource utilization (HCRU), and costs in patient populations with comorbidities, acute medication overuse (AMO), and/or unsatisfactory prior migraine preventive response (UPMPR) is needed. METHODS: Data for this US, retrospective claims analysis were obtained from the Merative® MarketScan® Commercial and supplemental databases. Eligible adults with migraine initiated fremanezumab between 1 September 2018 and 30 June 2019 (date of earliest fremanezumab claim is the index date), had ≥ 12 months of continuous enrollment prior to initiation (preindex period) and ≥ 6 months of data following initiation (postindex period; variable follow-up after 6 months), and had certain preindex migraine comorbidities (depression, anxiety, and cardiovascular disease), potential AMO, or UPMPR. Changes in migraine-related concomitant acute and preventive medication use, HCRU, and costs were assessed pre- versus postindex. RESULTS: In total, 3193 patients met the eligibility criteria. From pre- to postindex, mean (SD) per patient per month (PPPM) number of migraine-related acute medication and preventive medication claims (excluding fremanezumab), respectively, decreased from 0.97 (0.90) to 0.86 (0.87) (P < 0.001) and 0.94 (0.74) to 0.81 (0.75) (P < 0.001). Migraine-related outpatient and neurologist office visits, emergency department visits, and other outpatient services PPPM decreased pre- versus postindex (P < 0.001 for all), resulting in a reduction in mean (SD) total health care costs PPPM from US$541 (US$858) to US$490 (US$974) (P = 0.003). Patients showed high adherence and persistence rates, with mean (SD) proportion of days covered of 0.71 (0.29), medication possession ratio of 0.74 (0.31), and persistence duration of 160.3 (33.2) days 6 months postindex. CONCLUSIONS: Patients with certain migraine comorbidities, potential AMO, and/or UPMPR in a real-world setting had reduced migraine-related medication use, HCRU, and costs following initiation of fremanezumab. Graphical abstract available for this article.

Vaporized Cannabis versus Placebo for Acute Migraine: A Randomized Controlled Trial.

Background: Preclinical and retrospective studies suggest cannabinoids may be effective in migraine treatment. However, there have been no randomized clinical trials examining the efficacy of cannabinoids for acute migraine. Methods: In this randomized, double-blind, placebo-controlled, crossover trial, adults with migraine treated up to 4 separate migraine attacks, 1 each with vaporized 1) 6% Δ9-tetrahydrocannabinol (THC-dominant); 2) 11% cannabidiol (CBD-dominant); 3) 6% THC+11% CBD; and 4) placebo cannabis flower in a randomized order. Washout period between treated attack was ≥1 week. The primary endpoint was pain relief and secondary endpoints were pain freedom and most bothersome symptom (MBS) freedom, all assessed at 2 hours post-vaporization. Results: Ninety-two participants were enrolled and randomized, and 247 migraine attacks were treated. THC+CBD was superior to placebo at achieving pain relief (67.2% vs 46.6%, Odds Ratio [95% Confidence Interval] 2.85 [1.22, 6.65], p=0.016), pain freedom (34.5% vs. 15.5%, 3.30 [1.24, 8.80], p=0.017) and MBS freedom (60.3% vs. 34.5%, 3.32 [1.45, 7.64], p=0.005) at 2 hours, as well as sustained pain freedom at 24 hours and sustained MBS freedom at 24 and 48 hours. THC-dominant was superior to placebo for pain relief (68.9% vs. 46.6%, 3.14 [1.35, 7.30], p=0.008) but not pain freedom or MBS freedom at 2 hours. CBD-dominant was not superior to placebo for pain relief, pain freedom or MBS freedom at 2 hours. There were no serious adverse events. Conclusions: Acute migraine treatment with 6% THC+11% CBD was superior to placebo at 2 hours post-treatment with sustained benefits at 24 and 48 hours.

Harris Poll Migraine Report Card: population-based examination of high-frequency headache/migraine and acute medication overuse.

BACKGROUND: Migraine is a disabling neurologic disease that can fluctuate over time in severity, frequency, and acute medication use. Harris Poll Migraine Report Card was a US population-based survey to ascertain quantifiable distinctions amongst individuals with current versus previous high-frequency headache/migraine and acute medication overuse (HFM+AMO). The objective of this report is to compare self-reported experiences in the migraine journey of adults with HFM+AMO to those who previously experienced HFM+AMO but currently have a sustained reduction in headache/migraine frequency and acute medication use. METHODS: An online survey was available to a general population panel of adults (≥18 years) with migraine per the ID Migraine™ screener. Respondents were classified into "current HFM+AMO" (within the last few months had ≥8 headache days/month and ≥10 days/month of acute medication use; n=440) or "previous HFM+AMO" (previously had HFM+AMO, but within the last few months had ≤7 headache days/month and ≤9 days/month of acute medication use; n=110). Survey questions pertained to demographics, diagnosis, living with migraine, healthcare provider (HCP) communication, and treatment. RESULTS: Participants in the current HFM+AMO group had 15.2 monthly headache days and 17.4 days of monthly acute medication use in last few months compared to 4.2 and 4.1 days for the previous HFM+AMO group, respectively. Overall, current preventive pharmacologic treatment use was low (15-16%; P>0.1 for current vs previous) in both groups. Previous HFM+AMO respondents reported better current acute treatment optimization. More respondents with current (80%) than previous HFM+AMO (66%) expressed concern with their current health (P<0.05). More than one-third of both groups wished their HCP better understood their mental/emotional health (current 37%, previous 35%; P>0.1 for current vs previous) and 47% (current) to 54% (previous) of respondents worried about asking their HCP too many questions (P>0.1 for current vs previous). CONCLUSION: Apart from optimization of acute medication, medical interventions did not significantly differentiate between the current and previous HFM+AMO groups. Use of preventive pharmacological medication was low in both groups. Adults with current HFM+AMO more often had health concerns, yet both groups expressed concerns of disease burden. Optimization of acute and preventive medication and addressing mental/emotional health concerns of patients are areas where migraine care may impact outcomes regardless of their disease burden.

Migraine-Related Stigma and Its Relationship to Disability, Interictal Burden, and Quality of Life: Results of the OVERCOME (US) Study

BACKGROUND AND OBJECTIVES: This population-based analysis characterizes the relative frequency of migraine-related stigma and its cross-sectional relationship to migraine outcomes. We hypothesized that migraine-related stigma would be inversely associated with favorable migraine outcomes across headache day categories. METHODS: OVERCOME (US) is a web-based observational study that annually recruited a demographically representative US sample and then identified people with active migraine using a validated migraine diagnostic questionnaire. It also assessed how frequently respondents experienced migraine-related stigma using a novel 12-item questionnaire (Migraine-Related Stigma, MiRS) that contained 2 factors; feeling that others viewed migraine as being used for Secondary Gain (8 items, α = 0.92) and feeling that others were Minimizing disease Burden (4 items, α = 0.86). We defined 5 groups: (1) MiRS-Both (Secondary Gain and Minimizing Burden often/very often; (2) MiRS-SG (Secondary Gain often/very often); (3) MiRS-MB (Minimizing Burden often/very often); (4) MiRS-Rarely/Sometimes; (5) MiRS-Never. Using MiRS group as the independent variable, we modeled its cross-sectional relationship to disability (Migraine Disability Assessment, MIDAS), interictal burden (Migraine Interictal Burden Scale-4), and migraine-specific quality of life (Migraine Specific Quality of Life v2.1 Role Function-Restrictive) while controlling for sociodemographics, clinical features, and monthly headache day categories. RESULTS: Among this population-based sample with active migraine (n = 59,001), mean age was 41.3 years and respondents predominantly identified as female (74.9%) and as White (70.1%). Among respondents, 41.1% reported experiencing, on average, ≥4 monthly headache days and 31.7% experienced migraine-related stigma often/very often; the proportion experiencing migraine-related stigma often/very often increased from 25.5% among those with <4 monthly headache days to 47.5% among those with ≥15 monthly headache days. The risk for increased disability (MIDAS score) was significant for each MiRS group compared with the MiRS-Never group; the risk more than doubled for the MiRS-Both group (rate ratio 2.68, 95% CI 2.56-2.80). For disability, interictal burden, and migraine-specific quality of life, increased migraine-related stigma was associated with increased disease burden across all monthly headache day categories. DISCUSSION: OVERCOME (US) found that 31.7% of people with migraine experienced migraine-related stigma often/very often and was associated with more disability, greater interictal burden, and reduced quality of life.

The impacts of migraine on functioning: Results from two qualitative studies of people living with migraine.

OBJECTIVE: To describe the impact of migraine on functioning based on comprehensive data collection, analysis, and reporting of patients' experiences. BACKGROUND: Qualitative research conducted to understand patients' perspectives on living with migraine has often focused on narrow topics or specific groups of patients or has been selectively reported. METHODS: Qualitative interviews with 71 participants were conducted during two concept elicitation studies as part of the Migraine Clinical Outcome Assessment System (MiCOAS) project, an FDA grant-funded program designed to develop a core set of patient-centered outcome measures for migraine clinical trials. Participants self-reported being diagnosed with migraine by a healthcare professional and participated in semi-structured qualitative interviews about their experiences with the symptoms and impacts of migraine. Interview transcripts were coded to identify and define concepts, which were then grouped into broad domains based on conceptual similarities. RESULTS: A total of 66 concepts were identified: 12 for physical functioning, 16 for cognitive functioning, 10 for social role functioning, 19 for emotional and psychological functioning, and 9 related to migraine management. Participants described a complex and varied relationship between migraine attack symptoms and impacts on functioning. Impacts from migraine were further influenced by numerous contextual factors, such as people's individual social environments and the level of day-to-day demand for functioning they face. CONCLUSION: Findings showed that migraine impacted individual functioning in multiple ways and the nature of these impacts was dependent on social-contextual factors. The results are being used in the development of core measures designed to improve our understanding of the burden of migraine and the efficacy of migraine therapies. The results also offer new insights and raise new questions about migraine experience that can be used to guide future research.

Pre- and post-headache phases of migraine: multi-country results from the CaMEO - International Study.

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.

Impact of monthly headache days on migraine-related quality of life: Results from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study.

OBJECTIVE: To characterize the direct impact of monthly headache days (MHDs) on health-related quality of life (HRQoL) in people with migraine and the potential mediating effects of anxiety, depression, and allodynia. BACKGROUND: Although the general relationship between increased migraine frequency (i.e., MHDs) and reduced HRQoL is well established, the degree to which reduced HRQoL is due to a direct effect of increased MHDs or attributable to mediating factors remains uncertain. METHODS: Cross-sectional baseline data from participants with migraine who completed the Core and Comorbidities/Endophenotypes modules in the 2012-2013 US Chronic Migraine Epidemiology and Outcomes (CaMEO) study, a longitudinal web-based survey study, were analyzed. The potential contribution of depression, anxiety, and/or allodynia to the observed effects of MHDs on HRQoL as measured by the Migraine-Specific Quality-of-Life Questionnaire version 2.1 (MSQ) was evaluated. RESULTS: A total of 12,715 respondents were included in the analyses. The MSQ domain scores demonstrated progressive declines with increasing MHD categories (B = -1.23 to -0.60; p < 0.001). The observed HRQoL decrements associated with increasing MHDs were partially mediated by the presence of depression, anxiety, and allodynia. The MHD values predicted 24.0%-32.4% of the observed variation in the MSQ domains. Depression mediated 15.2%-24.3%, allodynia mediated 9.6%-16.1%, and anxiety mediated 2.3%-6.0% of the observed MHD effects on the MSQ. CONCLUSIONS: Increased MHD values were associated with lower MSQ scores; the impact of MHDs on the MSQ domain scores was partially mediated by the presence of depression, anxiety, and allodynia. MHDs remain the predominant driver of the MSQ variation; moreover, most of the variation in the MSQ remains unexplained by the variables we analyzed. Future longitudinal analyses and studies may help clarify the contribution of MHDs, comorbidities, and other factors to changes in HRQoL.

Impact of headache frequency and preventive medication failure on quality of life, functioning, and costs among individuals with migraine across several European countries: need for effective preventive treatment.

BACKGROUND: Data are limited regarding the combined impact of headache frequency and failure of preventive medication (efficacy and/or tolerability) on the humanistic/economic burden of migraine. METHODS: A retrospective, cross-sectional analysis of 2020 National Health and Wellness Survey (NHWS) data was conducted. An opt-in online survey identified adults in France, Germany, Italy, Spain, and United Kingdom with self-reported physician-diagnosed migraine. Participants with ≥ 4 monthly headache days (MHDs) were stratified by prior preventive medication use/failure (preventive naive; 0-1 failure; ≥ 2 failures). Quality-of-life and economic outcomes were compared among groups using generalized linear modeling. RESULTS: Among individuals with ≥ 4 MHDs (n = 1106), the NHWS identified 298 (27%) with ≥ 2 failures, 308 (28%) with 0-1 failure, and 500 (45%) as preventive naive. Individuals with ≥ 2 failures versus preventive-naive individuals had significantly lower scores on the 12-Item Short Form Survey Physical Component Summary (42.2 vs 44.1; P < 0.005), numerically higher scores on the Mental Component Summary (39.5 vs 38.5; P = 0.145), significantly higher scores on the Migraine Disability Assessment (39.1 vs 34.0; P < 0.05), and significantly higher prevalence of depression symptoms (62% vs 47%; P < 0.001) and anxiety symptoms (42% vs 31%; P < 0.01). The ≥ 2 failures group versus the preventive-naive group also had significantly more functional impairment as assessed by mean numbers of migraine-specific missed work days (7.8 vs 4.3) and household activities days (14.3 vs 10.6) in the past 6 months (P < 0.001) as well as the prevalence of absenteeism (19% vs 13%), overall work impairment (53% vs 42%), and activity impairment (53% vs 47%) (all P < 0.05). Emergency department visits (0.7 vs 0.5; P = 0.001) and hospitalizations (0.5 vs 0.3; P < 0.001) in the past 6 months were significantly higher in the ≥ 2 failures group versus the preventive-naive group, while indirect costs (€13,720 vs €11,282) and the proportion of individuals with non-adherence during the past 7 days (73% vs 64%) were numerically higher. CONCLUSIONS: Increased burden, quality-of-life impairment, and functional impairment exist among individuals with migraine experiencing ≥ 4 MHDs and more treatment failures. While cause and directionality cannot be determined, these results suggest the need for effective preventive migraine treatments.

Risk factors for migraine disease progression: a narrative review for a patient-centered approach.

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.

Harassment in the headache field: a global web-based cross-sectional survey.

BACKGROUND: Matters of workplace harassment are an important issue. This issue needs to be recognized and studied to prevent occurrences. These important sensitive areas of effective workplace management are increasingly gaining more interest. We aimed to identify the prevalence of workplace sexual, verbal and physical harassment among headache professionals. METHODS: We adopted a cross­sectional exploratory survey approach with quantitative design. The survey was distributed electronically among headache healthcare and research professionals globally through the International Headache Society (IHS). RESULTS: Data were obtained from 579 respondents (55.3%; 320/579 women). A large percentage of respondents (46.6%; 270/579) had experienced harassment; specifically, 16.1% (93/578) reported sexual harassment, 40.4% (234/579) verbal harassment and 5.5% (32/579) physical harassment. Women were almost seven times more likely to experience sexual harassment compared to men (odds ratio = 6.8; 95% confidence interval = 3.5-13.2). Although women did also more frequently report other types of harassment, this was not statistically significant (odds ratio = 1.4; 95% confidence interval = 1.0-2.0). CONCLUSIONS: Lifetime exposure to workplace harassment is prevalent among headache professionals, especially in women. The present study uncovers a widespread issue and calls for strategies to be implemented for building a healthy and safe workplace environment.

The Exploration of Cannabis and Cannabinoid Therapies for Migraine.

PURPOSE OF REVIEW: There is increasing interest in the use of cannabis and cannabinoid therapies (CCT) by the general population and among people with headache disorders, which results in a need for healthcare professionals to be well versed with the efficacy and safety data. In this manuscript, we review cannabis and cannabinoid terminology, the endocannabinoid system and its role in the central nervous system (CNS), the data on efficacy, safety, tolerability, and potential pitfalls associated with use in people with migraine and headache disorders. We also propose possible mechanisms of action in headache disorders and debunk commonly held myths about its use. RECENT FINDINGS: Preliminary studies show that CCT have evidence for the management of migraine. While this evidence exists, further randomized, controlled studies are needed to better support its clinical use. CCT can be considered an integrative treatment added to mainstream medicine for people with migraine who are refractory to treatment and/or exhibit disability and/or interest in trying these therapies. Further studies are warranted to specify appropriate formulation, dosage, and indication(s). Although not included in guidelines or the AHS 2021 Consensus Statement on migraine therapies, with the legalization of CCT for medical or unrestricted use across the USA, recent systematic reviews highlighting the preliminary evidence for its use in migraine, it is vital for clinicians to be well versed in the efficacy, safety, and clinical considerations for their use. This review provides information which can help people with migraine and clinicians who care for them make mutual, well-informed decisions on the use of cannabis and cannabinoid therapies for migraine based on the existing data.

Chronic Migraine Epidemiology and Outcomes - International (CaMEO-I) Study: Methods and multi-country baseline findings for diagnosis rates and care.

BACKGROUND: The Chronic Migraine Epidemiology and Outcomes-International study provides insight into people with migraine in multiple countries. METHODS: This cross-sectional, observational, web-based cohort study was conducted in Canada, France, Germany, Japan, United Kingdom, and United States. An initial Screening Module survey solicited general healthcare information from a representative sample and identified participants with migraine based on modified International Classification of Headache Disorders-3 criteria; those with migraine completed a detailed survey based on validated migraine-specific assessments. RESULTS: Among 90,613 people who correctly completed the screening surveys, 76,121 respondents did not meet the criteria for migraine, while 14,492 did. Among respondents with migraine, mean age ranged from 40 to 42 years. The median number of monthly headache days ranged from 2.33 to 3.33 across countries, while the proportion of respondents with moderate-to-severe disability (measured by Migraine Disability Assessment) ranged from 30% (Japan) to 52% (Germany). The proportion of respondents with ≥15 monthly headache days ranged from 5.4% (France) to 9.5% (Japan). Fewer than half of respondents with migraine in each country reported having received a migraine diagnosis. CONCLUSION: These results demonstrated high rates of migraine-related disability and underdiagnosis of migraine across six countries. This study will characterize country-level burden, treatment patterns, and geographical differences in care.

Priority acute and preventive migraine treatment benefits: Results of the Migraine Clinical Outcome Assessment System (MiCOAS) qualitative study of people living with migraine.

BACKGROUND: There is renewed emphasis on including patients in determining, defining, and prioritizing outcomes for migraine treatment. OBJECTIVES: To obtain insights directly from people living with migraine on their priorities for treatment. METHODS: A total of 40 qualitative interviews were conducted as part of the Migraine Clinical Outcome Assessment System project, a United States Food and Drug Administration grant-funded program to develop a core set of patient-centered outcome measures for migraine clinical trials. Interviews included a structured exercise in which participants rank-ordered pre-defined lists of potential benefits for acute and preventive migraine therapy. The 40 study participants who reported being diagnosed with migraine by a clinician ranked the benefits and explained their rationale. RESULTS: Study participants consistently ranked either pain relief or absence of pain as their top priority for acute treatment. Relief/absence of other migraine symptoms and improved functioning were also prioritized. For preventive treatment, participants prioritized reductions in migraine frequency, symptom severity, and attack duration. Few differences were found between participants with episodic migraine and those with chronic migraine. However, participants with chronic migraine ranked "increased predictability of attacks" much higher than those with episodic migraine. Participants' rankings were influenced by prior expectations and experiences of migraine treatments, which caused many participants to deprioritize desired benefits as unrealistic. Participants also identified several additional priorities, including limited side-effects and reliable treatment efficacy in both acute and preventive treatments. CONCLUSION: The results showed the participants prioritized treatment benefits aligned with existing core clinical outcomes used in migraine research, but also valued benefits that are not typically assessed, such as predictability. Participants also deprioritized important benefits when they believed treatment was unlikely to deliver those outcomes.

Validation and meaningful within-patient change in work productivity and activity impairment questionnaire (WPAI) for episodic or chronic migraine.

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.

Patient-reported experiences with migraine-related cognitive symptoms: Results of the MiCOAS qualitative study.

OBJECTIVES: To capture patients' perspectives on migraine-related cognitive symptoms during pre-headache, headache, post-headache, and interictal periods. BACKGROUND: Migraine-related cognitive symptoms are reported by people with migraine both during and between attacks. Associated with disability, they are increasingly viewed as a priority target for treatment. The Migraine Clinical Outcome Assessment System (MiCOAS) project is focused on developing a patient-centered core set of outcome measures for the evaluation of migraine treatments. The project focuses on incorporating the experience of people living with migraine and the outcomes most meaningful to them. This includes an examination of the presence and functional impact of migraine-related cognitive symptoms and their perceived impact on quality of life and disability. METHODS: Forty individuals with self-reported medically diagnosed migraine were recruited via iterative purposeful sampling for semi-structured qualitative interviews conducted using audio-only web conferencing. Thematic content analysis was performed to identify key concepts around migraine-related cognitive symptoms. Recruitment continued until concept saturation was achieved. RESULTS: Participants described symptoms consistent with migraine-related deficits in language/speech, sustained attention, executive function, and memory that manifest during pre-headache (36/40 [90%] reported ≥1 cognitive feature), headache (35/40 [88%] reported ≥1 cognitive feature), post-headache (27/40 [68%] reported ≥1 cognitive feature), and interictal periods (13/40 [33%] reported ≥1 cognitive feature). Among participants reporting cognitive symptoms during pre-headache, 32/40 (81%) endorsed 2-5 cognitive symptoms. Findings were similar during the headache phase. Participants reported language/speech problems consistent with, for example, impairments in receptive language, expressive language, and articulation. Issues with sustained attention included fogginess, confusion/disorientation, and trouble with concentration/focus. Deficits in executive function included difficulty processing information and reduced capacity for planning and decision-making. Memory issues were reported across all phases of the migraine attack. CONCLUSIONS: This patient-level qualitative study suggests that cognitive symptoms are common for persons with migraine, particularly in the pre-headache and headache phases. These findings highlight the importance of assessing and ameliorating these cognitive problems.

Changes in migraine interictal burden following treatment with galcanezumab: Results from a phase III randomized, placebo-controlled study.

OBJECTIVE: To evaluate changes in interictal burden with galcanezumab versus placebo in patients with episodic (EM) or chronic migraine (CM). BACKGROUND: The disruptive effects of migraine occur both during attacks (ictal period) and between attacks (interictal period), affecting work, school, family, and social life. Migraine clinical trials typically assess ictal burden endpoints, neglecting interictal burden. METHODS: CONQUER was a 3-month, double-blind study that randomized adult patients with EM or CM who had experienced failure of two to four standard-of-care migraine preventive medication categories to receive monthly galcanezumab (n = 232) or placebo (n = 230), followed by 3 months of open-label galcanezumab. The mean change in interictal burden, a secondary objective, was measured using the four-item Migraine Interictal Burden Scale (MIBS-4). The total score for MIBS-4 can range from zero to 12, with scores ≥5 indicating severe interictal burden. Post hoc analyses evaluated shifts in MIBS-4 severity categories and item-level improvement. RESULTS: The MIBS-4 total score indicated severe interictal burden at baseline (mean [SD]: all patients, 5.5 [3.5]; EM, 5.0 [3.4]; CM, 6.2 [3.5]). Reductions in the MIBS-4 score were significantly greater with galcanezumab versus placebo at Month 3 (mean [SE]: all patients -1.9 [0.2] vs. -0.8 [0.2], p < 0.0001; EM, -1.8 [0.3] vs. -1.1 [0.3], p = 0.033; CM, -1.8 [0.4] vs. -0.3 [0.4], p < 0.001), with further improvement at Month 6 after all patients had received galcanezumab (mean [SE]: all patients, -2.4 [0.2] vs. -2.0 [0.2]; EM, -2.3 [0.3] vs. -2.2 [0.3]; CM, -2.1 [0.4] vs. -1.5 [0.4]). The percentage of patients with severe interictal burden decreased substantially for the galcanezumab-treated patients, from 59% (137/232) at baseline to 27% (58/217) at Month 6 (EM from 51% [70/137] to 23% [30/131]; CM from 71% [67/95] to 33% [28/86]). CONCLUSION: In addition to the known efficacy of galcanezumab in the ictal period, these findings suggest treatment with galcanezumab results in a significant reduction in interictal burden.

Longitudinal assessment of comorbidities and co-occurring conditions in adolescents with migraine: A secondary analysis of the National Longitudinal Study of Adolescent to Adult Health (Add Health).

OBJECTIVE: To investigate the links between adolescent migraine and comorbid and co-occurring conditions using a large, nationally representative longitudinal study. BACKGROUND: Comorbidities and co-occurring conditions play an important role in the clinical treatment of individuals with migraine. Research in this area has focused largely on the adult population using cross-sectional data, but less is known about adolescents and how conditions may co-occur over time from a broader developmental perspective. The goals of this manuscript were to empirically evaluate the associations between adolescent migraine and several linked conditions and explore the relative timings of onset of these conditions from adolescence to adulthood. METHODS: Data came from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a school-based study of the health-related behaviors and conditions of adolescents. The present study examined data from Wave 1 (W1, study years: 1994-1995), Wave 4 (W4, study years: 2008-2009), and Wave 5 (W5, study years: 2016-2018). Analyses and visual plots were used to evaluate potential links between parent-reported adolescent migraine status (PR-AdMig) at W1 and 15 medical conditions identified based on self-reported medical diagnoses (SR-MDs) at W4 and W5. Based on prior literature in adults, we identified 11 conditions predicted to be associated with PR-AdMig and four conditions predicted not to be associated with PR-AdMig. The analyses were exploratory and post hoc. RESULTS: The total sample size pooling over all analyses was n = 13,786, but the wave-specific sample sizes differed due to missing data (W4 analyses, n = 12,692; W5 analyses, n = 10,340); 7243/13,786 (unweighted: 52.5%; weighted: 50.5%) of participants were female, 7640/13,786 (unweighted: 55.4%; weighted: 68.6%) were White, and 1580/13,786 (unweighted: 11.5%; weighted: 12.0%) had PR-AdMig. The average ages were 15.8 years at W1, 28.7 years at W4, and 37.8 years at W5. Findings showed that PR-AdMig was associated with anxiety/panic disorder (W4: PR-AdMig vs. Control weighted %: 17.1% vs. 12.6%, unadjusted odds ratio [OR] = 1.43, 95% confidence interval [CI] 1.18-1.74, p = 0.0003; W5: 31.6% vs. 22.4%, OR = 1.60, 95% CI 1.28-2.02, p < 0.0001), asthma/chronic bronchitis/emphysema (W4: 20.0% vs. 14.7%, OR = 1.45, 95% CI 1.20-1.76, p < 0.001; W5: 21.0% vs. 14.6%, OR = 1.55, 95% CI 1.25-1.94, p < 0.001), attention deficit hyperactivity disorder (W4: 8.3% vs. 5.4%, OR = 1.58, 95% CI 1.18-2.10, p = 0.002), depression (W4: 23.7% vs. 15.4%, OR = 1.71, 95% CI 1.43-2.04, p < 0.0001; W5: 33.8% vs. 25.1%, OR = 1.53, 95% CI 1.22-1.90, p < 0.001), epilepsy/seizure disorder (W4: 2.2% vs. 1.2%, OR = 1.84, 95% CI 1.23-2.76, p = 0.004), migraine (W4: 38.8% vs. 11.9%, OR = 4.7, 95% CI 4.1-5.5, p < 0.001), post-traumatic stress disorder (W4: 4.1% vs. 2.8%, OR = 1.45, 95% CI 1.01-2.08, p = 0.042; W5: 11.3% vs. 7.1%, OR = 1.67, 95% CI 1.27-2.20, p < 0.001), and sleep apnea (W5: 11.0% vs. 7.6%, OR = 1.51, 95% CI 1.15-1.98, p = 0.003). Among theoretically unlinked conditions, only hepatitis C at W4 was shown to have a relationship with adolescent onset migraine (0.7% vs. 0.2%, OR = 3.63, 95% CI 1.32-10.0, p = 0.013). Visual plots suggested that the retrospective, self-report timing of onset of specific subsets of co-occurring conditions tended to group together over time. CONCLUSIONS: Consistent with the existing headache literature, results showed that adolescent migraine was associated with other medical and psychological conditions and visual plots suggested that there may be developmental patterns in the occurrence of migraine with other related conditions.