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.

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.

Predictors of treatment-response to caffeine combination products, acetaminophen, acetylsalicylic acid (aspirin), and nonsteroidal anti-inflammatory drugs in acute treatment of episodic migraine.

OBJECTIVE: To identify predictors of acute treatment optimization for migraine with "over-the-counter" (OTC) or prescription nonsteroidal anti-inflammatory drugs (NSAIDs) as well as other widely used OTCs including acetaminophen, caffeine combination products (CCP), and acetylsalicylic acid (ASA, aspirin) among people with episodic migraine and to develop models that predict treatment response to each class of OTCs. BACKGROUND: Efficacy of acute OTC medications for migraine varies greatly. Identifying predictors of treatment response to particular classes of medication is a step toward evidence-based personalized therapy. METHODS: For this prediction model development study, we used data from 2224 participants from the American Migraine Prevalence and Prevention (AMPP) study who were aged ≥18 years, met criteria for migraine, had <15 monthly headache days, and reported being on monotherapy for acute migraine attacks with one of the following classes medications: CCP (N = 711), acetaminophen (N = 643), ASA (N = 110), and prescription or OTC NSAIDs (N = 760). The primary outcome measures of treatment optimization were adequate 2-h pain freedom (2hPF) and adequate 24-h pain relief (24hPR), which were defined by responses of half the time or more to the relevant items on the Migraine Treatment Optimization Questionnaire-6. RESULTS: The mean (SD) age of the participants was 46.2 (13.1) years, 79.4% (1765/2224) were female, 43.7% (972/2224) reported adequate 2hPF, and 46.1% (1025/2224) reported adequate 24hPR. Those taking CCP had better 2hPF and 24PR outcomes. For those taking NSAIDs, better outcomes were associated with lower average pain intensity (2hPF: odds ratio [OR] 0.89, 95% confidence interval [CI] 0.80-0.99; 24PR: OR 0.86, 95% CI 0.77-0.96), cutaneous allodynia (2hPF: OR 0.92, 95% CI 0.89-0.96; 24PR: OR 0.91, 95% CI 0.87-0.95), depressive symptoms (2hPF: OR 0.95, 95% CI 0.92-0.98; 24PR: OR 0.95, 95% CI 0.91-0.99), and Migraine Disability Assessment Scale (MIDAS) grade (2hPF: OR 0.76, 95% CI 0.64-0.90; 24PR: OR 0.79, 95% CI 0.65-0.95). Adequate 2hPF for those taking CCP was associated with male gender (OR 1.83, 95% CI 1.21-2.77), lower average pain intensity (OR 0.80, 95% CI 0.70-0.91), lower cutaneous allodynia (OR 0.94, 95% CI 0.90-0.97), and lower Migraine Symptom Severity Scale Score (MSSS; OR 0.91, 95% CI 0.86-0.97). Adequate 24hPR for those taking CCP was associated with lower average pain intensity (OR 0.85, 95% CI 0.75-0.96), lower cutaneous allodynia (OR 0.92, 95% CI 0.89-0.96), and lower MIDAS grade (OR 0.81, 95% CI 0.68-0.96). Participants who were married (OR 1.51, 95% CI 1.05-2.19), had lower average pain intensity (OR 0.79, 95% CI 0.70-0.89), lower MSSS (OR 0.93, 95% CI 0.88-0.99), less depression (OR 0.96, 95% CI 0.93-0.99), and lower MIDAS grade (OR 0.72, 95% CI 0.59-0.87) had adequate 2hPF after taking acetaminophen. Participants who were married (OR 1.50, 95% CI 1.02-2.21), had lower pain intensity (OR 0.78, 95% CI 0.69-0.88), less depression (OR 0.95, 95% CI 0.91-0.98) and lower MIDAS grade (OR 0.53, 95% CI 0.42-0.67) had higher 24hPR following use of acetaminophen. A lower MSSS was the only factor associated with higher 2hPF and 24PR after using ASA (OR 0.78, 95% CI 0.67-0.92 and OR 0.79, 95% CI 0.67-0.93). Predictive models had modest performance in identifying responders to each class of OTC. CONCLUSION: A large subgroup of people with migraine had an inadequate response to their usual acute OTC migraine treatment 2- and 24-h after dosing. These findings suggest a need to improve OTC treatment for some and to offer prescription acute medications for others. Predictive models identified several factors associated with better treatment-response in each OTC class. Selecting OTC treatment based on factors predictive of treatment optimization might improve patient outcomes.

Psychiatric Characteristics of Students Who Make Threats Toward Others at School.

OBJECTIVE: While studies have focused on identifying potential school shooters, little is known about the mental health and other characteristics of students who make threats. This study aimed to describe these students and factors prompting psychiatric interventions and treatment recommendations. METHOD: Child and adolescent psychiatry threat assessment evaluations of 157 consecutive school-referred youths in grades K-12 between 1998 and 2019 were reviewed for demographics, reasons for referral, nature of threat, psychiatric diagnosis, and psychiatric and educational recommendations. Predictors of recommendations for psychiatric interventions were modeled using multivariable logistic regression as a function of above-mentioned covariates. RESULTS: Mean (SD) age of referred students was 13.37 (2.79) years; 88.5% were male; 79.7%, White; 11.6%, Hispanic; 10.1%, Black; 2.5%, Asian. Of students, 51.6% were receiving special education services. Verbal threat was made by 80%, and 29.3% brought a weapon to school. History included being bullied in 43.4%, traumatic family events in 52.2%, physical abuse in 5.1%, sexual abuse in 5.7%, and verbal abuse in 36.3%. Frequently encountered psychiatric diagnoses were attention-deficit/hyperactivity, learning, depressive, anxiety, and autism spectrum disorders, usually in combinations. History of medication treatment was reported in 79 (50.3%) and psychotherapeutic interventions in 57 (36.3%). Recommendations to return the student to their prior schools were made for 63.1%. Recommendations for psychotherapy were made for 79.9%, medication for 88.5%, and both for 70.1%. Therapeutic school setting or psychiatric hospitalization was more likely recommended (with statistical significance) with a prior threat history (odds ratio [OR] 5.47, 95% CI 1.91-15.70), paranoid symptoms (OR 5.72, 95% CI 1.55-21.14, p = .009), autism spectrum disorders (OR 3.45, 95% CI 1.32-9.00), mood disorder (OR 5.71, 95% CI 1.36-23.96), personality disorder (OR 9.47, 95% CI 1.78-50.55), or with psychotherapy recommendation (OR 4.84, 95% CI 1.08-21.75). CONCLUSION: Students who make threats have diverse psychiatric profiles and warrant treatments. A trauma and/or abuse history is common. Evaluations of youths who make threats need to go beyond simply assessing the threat itself and should include identifying underlying psychiatric problems. Psychiatric evaluation of students who issue threats of any type can lead to revelations about psychiatric diagnoses and crucial treatment and educational recommendations. DIVERSITY & INCLUSION STATEMENT: The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Optimized Acute Treatment of Migraine Is Associated With Greater Productivity in People With Migraine: Results From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.

OBJECTIVE: This study aimed to ascertain whether level of optimization of acute treatment of migraine is related to work productivity across the spectrum of migraine. METHODS: Data were from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, an internet-based longitudinal survey. Respondents with migraine who reported full-time employment and use of ≥1 acute prescription medication for migraine were included. We determined relationships among lost productive time (LPT; measured with the Migraine Disability Assessment Scale), acute treatment optimization (Migraine Treatment Optimization Questionnaire- ), and monthly headache days (MHDs). RESULTS: There was a direct relationship between LPT and MHD category. Greater acute treatment optimization was associated with lower total LPT, less absenteeism, and less presenteeism within each MHD category. CONCLUSIONS: Optimizing acute treatment for migraine may reduce LPT in people with migraine and reduce indirect costs.

Predictors of treatment-response to acute prescription medications in migraine: Results from the American Migraine Prevalence and Prevention (AMPP) Study.

OBJECTIVE: To identify predictors of acute treatment optimization with prescription drugs among people with episodic migraine. METHODS: A total of 2896 individuals from the American Migraine Prevalence and Prevention study were included in this study. The primary outcome measures of treatment optimization were 2-h pain freedom (2hPF) and 24-h pain relief (24hPR), which were defined by responses to the Migraine Treatment Optimization Questionnaire-6 (mTOQ-6). We identified predictors of 2hPF and 24hPR in response to triptans, butalbital combination medications (BCMs), and opioids. RESULTS: PARTICIPANTS: were on average 47.3 years old (SD=12.0), 85.6 % were female, and 88.4 % were white, 46.9 % of participants reported 2hPF and 49.5 % reported 24hPR with their "usual acute treatment". The odds of adequate 2hPF response were reduced in men and those with higher average headache pain intensity, higher migraine symptom severity scores, presence of cutaneous allodynia, and depression. Adequate 24hPR was associated with being married, but declined in those with higher-than-average average headache pain intensity and frequency, greater disability, presence of cutaneous allodynia, and depression. Among participants reporting acute monotherapy, individuals taking triptans were more likely to have adequate treatment response in comparison with those taking BCMs (2hPF: OR=1.86, 95 %CI 1.42-2.42; 24hPR: OR=2.26, 95 %CI 1.73-2.96) and opioids (2hPF: OR=2.39, 95 %CI 1.94-2.96; 24hPR: OR=2.78, 95 %CI 2.24-3.44). There was no significant difference in response to treatment between the subsample taking BCMs and opioid users. CONCLUSION: Almost half of study respondents were not optimized on their usual prescription acute migraine treatment(s). Predictive models identified several features associated with treatment optimization.

Predictive models for determining treatment response to nonprescription acute medications in migraine: Results from the American Migraine Prevalence and Prevention Study.

OBJECTIVE: To identify predictors of acute treatment response for nonprescription (over-the-counter [OTC]) medications among people with migraine and develop improved models for predicting treatment response. BACKGROUND: Pain freedom and sustained pain relief are important priorities in the acute treatment of migraine. OTC medications are widely used for migraine; however, it is not clear which treatment works best for each patient without going through the trial and error process. METHODS: A prediction model development study was completed using the 2006 American Migraine Prevalence and Prevention Study survey, from participants who were aged ≥18, met criteria and headache day frequency for episodic migraine, did not take prescription medication for migraine, and used ≥1 of the following acute migraine medication classes: acetaminophen, aspirin, NSAIDs, or caffeine containing combination products (CCP). Two items from the Migraine Treatment Optimization Questionnaire were used to evaluate treatment response, adequate 2-h pain freedom (2hPF) and 24-h pain relief (24hPR), which were defined by a response to treatment ≥half the time at 2 h and 24 h post treatment, respectively. We identified predictors of adequate treatment response and developed models to predict probability of treatment response to each medication class. RESULTS: The sample included 3852 participants (3038 [79.0%] females) with an average age of 45.0 years (SD = 12.8). Only 1602/3852 (41.6%) and 1718/3852 (44.6%) of the participants reported adequate 2hPF and 24hPR, respectively. Adequate treatment-response was significantly predicted by lower average headache pain intensity, less cutaneous allodynia, and lower depressive symptom scores. Lower migraine symptom severity was predictive of adequate 2hPF and fewer monthly headache days was predictive of adequate 24hPR. Among participants reporting OTC monotherapy (n = 2168, 56.3%) individuals taking CCP were more likely to have adequate 2hPF (OR = 1.55, 95% CI 1.23-1.95) and 24hPR (OR = 1.79, 95% CI 1.18-1.88) in comparison with those taking acetaminophen. Predictive models were modestly predictive of responders to OTC medications (c-statistics = 0.65; 95% CI 0.62-0.68). CONCLUSION: These results show that response to acute migraine treatments is not optimized in the majority of people with migraine treating with OTC medications. Predictive models can improve our ability to choose the best therapeutic option for individuals with episodic migraine and increase the proportion of patients with optimized response to treatments.

Medication Overuse and Headache Burden: Results From the CaMEO Study.

OBJECTIVE: To estimate the relative frequency of acute medication overuse (AMO) among people with episodic migraine and chronic migraine, to characterize the types of acute medications overused for migraine, and to identify factors associated with AMO. METHODS: We analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study (ClinicalTrials.gov, NCT01648530), a cross-sectional and longitudinal internet study that included a systematic sampling of the US population. From September 2012 to November 2013, the CaMEO Study respondents participated in different modules to collect data on the clinical course of migraine, family burden, barriers to care, endophenotypes, and comorbidities. Among people who met the criteria for migraine consistent with the International Classification of Headache Disorders, third edition (ICHD-3), we evaluated types and frequency of medications used for headache/migraine, selected comorbidities, and emergency department (ED) and urgent care (UC) use. AMO was defined by days per month of medication use as specified by ICHD-3 criteria for medication overuse headache (MOH) without the requirement for ≥15 monthly headache days (MHDs). Nested, multivariable binary logistic regression modeling was used to identify factors associated with an increased risk of AMO. RESULTS: Of 16,789 CaMEO respondents with migraine, 2,975 (17.7%) met the AMO criteria. Approximately 67.9% (2,021/2,975) of AMO respondents reported <15 MHDs. Simple analgesics, combination analgesics, and opioids were the medication classes most commonly overused. Factors associated with AMO in the final multivariable logistic regression model included ≥15 MHDs, moderate to severe disability, severe migraine interictal burden, use of preventive medication, and an ED/UC visit for headache within 6 months. CONCLUSIONS: Approximately two-thirds of respondents with AMO reported <15 MHDs and therefore did not meet the criteria for MOH. Those with AMO had greater disease burden and increased ED/UC utilization relative to people with migraine but not AMO.

Barriers to care in episodic and chronic migraine: Results from the Chronic Migraine Epidemiology and Outcomes Study.

OBJECTIVE: To assess rates of and factors associated with traversing fundamental barriers to good medical outcomes and pharmacologic care in individuals with episodic migraine (EM) and chronic migraine (CM), including socioeconomic status and race. BACKGROUND: Barriers to good outcomes in migraine include the lack of appropriate medical consultation, failure to receive an accurate diagnosis, not being offered a regimen with acute and preventive pharmacologic treatments (if indicated), and not avoiding medication overuse. METHODS: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study was a longitudinal Internet-based survey. Respondents who met criteria for migraine consistent with the International Classification of Headache Disorders, 3rd edition, had a Migraine Disability Assessment score ≥ 6, and provided health insurance coverage status were included in this analysis. Successfully traversing each barrier to care and the effects of sociodemographic characteristics were examined. RESULTS: Among 16,789 respondents with migraine, 9184 (54.7%; EM: 7930; CM: 1254) were eligible. Current headache consultation was reported by 27.6% (2187/7930) of EM and 40.8% (512/1254) of CM respondents. Among consulters, 75.7% (1655/2187) with EM and 32.8% (168/512) with CM were accurately diagnosed. Among diagnosed consulters, 59.9% (992/1655) with EM and 54.2% (91/168) with CM reported minimally appropriate acute and preventive pharmacologic treatment. Among diagnosed and treated consulters, in the EM group 31.8% (315/992) and in the CM group 74.7% (68/91) met medication overuse criteria. Only 8.5% (677/7930) of EM and 1.8% (23/1254) of CM respondents traversed all four barriers. Higher income was positively associated with likelihood of traversing each barrier. Blacks and/or African Americans had higher rates of consultation than other racial groups. Blacks and/or African Americans and multiracial people had higher rates of acute medication overuse. CONCLUSIONS: Efforts to improve care should focus on increasing consultation and diagnosis rates, improving the delivery of all appropriate guideline-based treatment, and avoidance of medication overuse.

Demographics, Headache Features, and Comorbidity Profiles in Relation to Headache Frequency in People With Migraine: Results of the American Migraine Prevalence and Prevention (AMPP) Study.

BACKGROUND: Migraine is typically divided into 2 headache frequency denominated categories, episodic migraine (EM) and chronic migraine (CM). Characterizing more narrow headache day frequency groups may be of value for better understanding the broad range of migraine experience and making treatment decisions. OBJECTIVE: To characterize the impact and burden of migraine in 4 monthly headache day (MHD) categories. METHODS: Respondents to the American Migraine Prevalence and Prevention Study 2005 survey who met criteria for migraine were categorized into low frequency episodic migraine (LFEM) 0-3, moderate frequency episodic migraine (MFEM) 4-7, high frequency episodic migraine (HFEM) 8-14, and CM with ≥15 headache days per month. Data including sociodemographics, headache features and symptomology, comorbidities, cutaneous allodynia, and severe migraine-related disability were compared among groups. We combined the low- and medium-frequency EM groups (L/MFEM) and compared them with the HFEM group in 1 set of models and compared the HFEM and CM groups in a second set of models. Binary logistic regression, linear regression, and ordered logistic regression were used depending upon the variable type and adjusted for sociodemographics. RESULTS: Among 11,603 eligible respondents with migraine, 67.7% (7860/11,603) were categorized with LFEM, 17.7% (2051/11,603) with MFEM, 7.8% (898/11,603) with HFEM, and 6.8% (794/11,603) with CM. The mean age was 46 (SD 13.7), 80.2% (9301/11,603) were female, and 90.0% (10,187/11,323) were White, 6.9% were Black (784/11,323), and 3.1% (352/11,323) were identified as Other race(s). Individuals with HFEM differed from L/MFEM on a wide range of sociodemographic variables in the categories of headache features, disability, and comorbidities while few differences were found when modeling HFEM vs CM. In comparison with L/MFEM and HFEM, the HFEM group was more likely to have severe disability (P < .001 OR = 1.74 [1.42, 2.15]), chronic pain (P ≤ .007 OR = 1.35 [1.09, 1.69]), arthritis (P = .001 OR = 1.44 [1.15, 1.80]), high cholesterol (P = .005, OR = 1.37 [1.10, 1.70]), ulcers (P = .016, OR = 1.44 [1.07, 1.93]), and depression (Patient Health Questionnaire [PHQ-9]) (P < .001 OR = 1.50 [1.22, 1.84]). CONCLUSION: While rates of migraine symptoms, headache impact and disability, and comorbidities generally increased with increases in MHD frequency, respondents with HFEM and CM were remarkably similar on a broad range of variables including sociodemographics, disability/impact, and comorbidities. There were many more significant differences between the HFEM and L/MFEM groups on the same variables. Future work should use empirical strategies to identify naturally occurring groups and possibly reconsider the boundary between CM and HFEM.

Characterizing opioid use in a US population with migraine: Results from the CaMEO study.

OBJECTIVE: To determine the prevalence of and risk factors associated with opioid use in the treatment of migraine, we examined demographics and clinical characteristics of 867 individuals who reported using opioids for the treatment of migraine. METHODS: We analyzed data from the CaMEO study (Chronic Migraine Epidemiology and Outcomes), a cross-sectional, longitudinal, Internet study, to compare sociodemographics, clinical characteristics, and migraine burden/disability of opioid users vs nonusers. Covariates were entered as categorical or continuous variables. Factors associated with opioid use were identified using nested, multivariable binary logistic regression models. RESULTS: Of 2,388 respondents with migraine using prescription medications for acute treatment, 36.3% reported that they currently used or kept on hand opioid medications to treat headaches. Current opioid users had significantly more comorbidities, greater headache-related burden, and poorer quality of life than nonusers. Regression models revealed factors significantly associated with opioid use, including male sex, body mass index, allodynia, increasing monthly headache frequency, Total Pain Index score (excluding head, face, neck/shoulder), anxiety, depression, ≥1 cardiovascular comorbidity, and emergency department/urgent care use for headache in the past 6 months. Self-reported physician-diagnosed migraine/chronic migraine was associated with significantly decreased likelihood of opioid use. CONCLUSIONS: Of respondents who were using acute prescription medications for migraine, more than one-third used or kept opioids on hand, contrary to guidance. This analysis could not distinguish risk factors from consequences of opioid use; thus further research is needed to guide the development of strategies for reducing the inappropriate use of opioids in migraine.

Characterization of Acute Prescription Migraine Medication Use: Results From the CaMEO Study.

OBJECTIVE: To characterize self-reported use of acute prescription medication for migraine in a sample representing the US population. PATIENTS AND METHODS: Data were obtained from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study. The CaMEO Study is an Internet-based cross-sectional longitudinal survey administered between September 17, 2012, and November 19, 2013. Demographic characteristics, migraine-related disability, symptom severity, quality of life, and psychiatric comorbidity profiles were evaluated. RESULTS: Data from 13,624 respondents were analyzed, including 3121 (22.9%) self-reported current users of acute prescription medication for migraine, 1719 (12.6%) previous/discontinued users, and 8784 (64.5%) who had never used acute prescription medication for migraine. Mean ± SD monthly headache frequency was 7.3±7.1 days for current users, 5.6±6.6 days for those who discontinued, and 3.9±4.9 days for respondents who never used acute prescription medication for migraine. Current users experienced the highest degree of migraine-related disability based on Migraine Disability Assessment scores and the highest levels of migraine symptom severity based on Migraine Symptom Severity Scale scores. Current users also had the highest scores on the depression and anxiety questionnaires. The most commonly reported prescription medications used or "kept on hand" by current users were triptans (47.2%; 1474 of 3121), opioids (37.3%; 1164 of 3121), nonsteroidal anti-inflammatory drugs (31.9%; 997 of 3121), and barbiturates (12.8%; 399 of 3121), with many people reporting more than 1 medication. CONCLUSION: Despite reporting moderate to severe migraine-related disability and impairment, many people with migraine have never used acute prescription migraine medication. The burden related to migraine is great, especially among individuals currently using acute prescription medication for migraine.

Comorbid and co-occurring conditions in migraine and associated risk of increasing headache pain intensity and headache frequency: results of the migraine in America symptoms and treatment (MAST) study.

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.

The Effect of Psychiatric Comorbidities on Headache-Related Disability in Migraine: Results From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.

OBJECTIVE: To examine the influences of depression and anxiety on headache-related disability in people with episodic migraine or chronic migraine. BACKGROUND: Depression and anxiety are common comorbidities in people with migraine, especially among those with chronic migraine. METHODS: This cross-sectional analysis of data from the longitudinal, internet-based Chronic Migraine Epidemiology and Outcomes Study assessed sociodemographic and headache features, and headache-related disability (Migraine Disability Assessment Scale). Four groups were defined based on scores from validated screeners for depression (9-item Patient Health Questionnaire) and anxiety (7-item Generalized Anxiety Disorder Scale): depression alone, anxiety alone, both, or neither. RESULTS: Respondents (N = 16,788) were predominantly women (74.4% [12,494/16,788]) and white (84.0% [14,044/16,788]); mean age was 41 years. Depression was more likely in persons with chronic migraine vs episodic migraine (56.6% [836/1476] vs 30.0% [4589/15,312]; P < .001), as were anxiety (48.4% [715/1476] vs 28.1% 4307/15,312]; P < .001) and coexisting depression and anxiety (42.0% [620/1476] vs 20.8% [3192/15,312]; P < .001). After controlling for headache frequency and other covariates, depression alone, and anxiety alone were associated with 56.0% (rate ratio [RR], 1.56; 95% confidence interval [CI], 1.46-1.66) and 39.0% (RR, 1.39; 95% CI, 1.30-1.50) increased risks of moderate/severe migraine-related disability (both P < .001), respectively; the combination had an even greater effect on risk of moderate/severe disability (79.0% increase; RR, 1.79; 95% CI, 1.71-1.87; P < .001). CONCLUSIONS: Depression alone and anxiety alone are associated with greater headache-related disability after controlling for sociodemographic and headache features. Coexisting depression and anxiety are more strongly associated with disability than either comorbidity in isolation. Interventions targeting depression and anxiety as well as migraine itself may improve headache-related disability in people with migraine.

Migraine progression in subgroups of migraine based on comorbidities: Results of the CaMEO Study.

OBJECTIVE: To test the hypothesis that statistically defined subgroups of migraine (based on constellations of comorbidities and concomitant conditions; henceforth comorbidities), previously identified using Chronic Migraine Epidemiology and Outcomes (CaMEO) Study data, differ in prognosis, as measured by rates of progression from episodic migraine (EM) to chronic migraine (CM). METHODS: The onset of CM was assessed up to 4 times over 12 months in individuals with EM and ≥1 comorbidity at baseline, based on constellations of comorbidities (comorbidity classes). The "fewest comorbidities" class served as reference. Individuals completing ≥1 follow-up survey from the web-based CaMEO Study were included. Covariates included sociodemographic variables and headache characteristics. Sex, income, cutaneous allodynia, and medication overuse were modeled as binary variables; age, body mass index, headache-related disability (Migraine Disability Assessment [MIDAS]), and Migraine Symptom Severity Scale as continuous variables. CM onset was assessed using discrete time analysis. RESULTS: In the final sociodemographic model, all comorbidity classes had significantly elevated hazard ratios (HRs) for risk of progression to CM from EM, relative to fewest comorbidities. HRs for CM onset ranged from 5.34 (95% confidence interval [CI] 3.89-7.33; p ≤ 0.001) for most comorbidities to 1.53 (95% CI 1.17-2.01; p < 0.05) for the respiratory class. After adjusting for headache covariates independently, each comorbidity class significantly predicted CM onset, although HRs were attenuated. CONCLUSIONS: Subgroups of migraine identified by comorbidity classes at cross-section predicted progression from EM (with ≥1 comorbidity at baseline) to CM. The relationship of comorbidity group to CM onset remained after adjusting for indicators of migraine severity, such as MIDAS. CLINICALTRIALSGOV IDENTIFIER: NCT01648530.

Discontinuation of Acute Prescription Medication for Migraine: Results From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.

OBJECTIVE: This analysis assessed migraine-related burden and treatment decisions in Chronic Migraine Epidemiology and Outcomes (CaMEO) Study survey respondents who stopped taking acute prescription medications for migraine. BACKGROUND: Migraine is a common yet underdiagnosed and undertreated neurological disease often associated with significant disability. Acute prescription medications are underused, in part because patients discontinue treatment. Rates and reasons for discontinuing acute prescription medications require exploration. METHODS: The CaMEO Study is a longitudinal, Internet-based survey that identified and followed people who met modified ICHD-3 migraine criteria. For this analysis, eligible respondents had used acute prescription medication for migraine in the past but no longer used or kept these treatments on hand (discontinued users). Respondents who reported discontinuing acute prescription treatment answered questions about length of time since last use and reasons for stopping. Reasons for discontinuing were thematically summarized. Monthly headache day frequency, Migraine Disability Assessment (MIDAS), Patient Health Questionnaire 9-item depression screener, Generalized Anxiety Disorder 7-item screener, and the 12-item Allodynia Symptom Checklist were also assessed. RESULTS: Of 13,624 respondents with migraine, 4840 (35.5%) had ever used acute prescription medications and 1719 (35.5%) of those were discontinued users. Discontinued users had a mean (SD) age of 42.1 (14) years, and 1348/1719 (78.4%) were female. Monthly headache frequency of 0-4 days was reported by 1073/1719 (62.4%) of respondents, 5-9 days by 322/1719 (18.7%), 10-14 days by 135/1719 (7.9%), and ≥15 days by 189/1719 (11.0%). Two-thirds (1160/1719 [67.5%]) of discontinued users reported a receiving migraine (or chronic migraine) diagnosis from a doctor or other health professional in the past. Although all had spoken to a doctor about their headaches, 1504/1719 (87.5%) had stopped having their headaches managed or treated by a doctor for at least 12 months. Only 1 in 5 discontinued users reported being able to work or function normally with a headache, and 717/1719 (41.7%) had moderate to severe disability (MIDAS). Among the most commonly reported reasons for prescription medication discontinuation were switching to non-prescription pain medication (782/1719 [45.5%]), as well as concerns about prescription medication efficacy (484/1719 [28.2%]) and tolerability (428/1719 [24.9%]). Nearly half of respondents who reported either efficacy or tolerability concerns had moderate to severe disability. CONCLUSIONS: People with migraine who discontinue acute prescription medication have a high level of unmet treatment need. The majority cannot work or function normally with headaches, with 646/1719 (37.6%) of discontinued users reporting 5 or more headache days per month.

Unmet Acute Treatment Needs From the 2017 Migraine in America Symptoms and Treatment Study.

OBJECTIVES: To characterize unmet treatment needs in a sample of Migraine in America Symptoms and Treatment (MAST) Study participants using oral, acute prescription migraine medications. BACKGROUND: The MAST Study is a 2017 study of US adults with migraine that profiles current treatment patterns and identifies and quantifies unmet treatment needs. METHODS: Cross-sectional data from an online survey of US adults meeting ICHD-3 beta criteria for migraine. For inclusion in this paper, respondents self-reported a history of 3 or more monthly headache days (MHDs) in the past 3 months and at least 1 MHD in the past 30 days, and current use of orally administered acute prescription medication for headache. Three domains of unmet need were identified: inadequate treatment response (ie, inadequate 2-hour pain freedom, recurrence within 24 hours of initial relief), demanding attack characteristics (rapid onset of attack, headache associated with sleep), and unique patient characteristics (opioid or barbiturate overuse, cardiovascular comorbidity). Sociodemographics, oral medication use, and coexisting conditions and symptoms (ie, level of treatment optimization, psychological symptoms, attack-related cutaneous allodynia, and migraine symptom severity) were assessed for each domain and by the number of unmet need domains. RESULTS: Overall, 15,133 respondents met inclusion criteria, 26.0% (3930/15,133) reported current use of oral acute prescription medication to treat headache. Eligible participants had a mean age of 45.0 years, 73.6% [2892/3930] were women and 81.1% [3186/3930]) were White. A total of 95.8% (3765/3930) of respondents had at least 1 unmet acute treatment need; 89.5% (3516/3930) reported demanding attack characteristics, 74.1% (2912/3930) reported inadequate treatment response, and 16.1% (634/3930) presented with unique patient characteristics. Common areas of unmet need were rapid headache onset (65.3% [2567/3930]), moderate to severe disability (55.6% [2187/3930]), inadequate 2-hours pain freedom (49.0% [1892/3930]), and headache recurrence within 24 hours (38.0% [1493/3930]). An increasing number of unmet treatment need domains was associated with worsening psychological symptoms, attack-related cutaneous allodynia and migraine symptom severity. CONCLUSION: Nearly all MAST Study respondents using acute oral prescription medications for migraine reported at least 1 unmet treatment need. As unmet needs increased, so did coexisting conditions and symptom severity.

Life With Migraine: Effects on Relationships, Career, and Finances From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.

OBJECTIVE: To assess the effects of migraine on important life domains and compare differences between respondents with episodic and chronic migraine and between sexes. BACKGROUND: Migraine is associated with a substantial personal and societal burden and can also affect the interpersonal dynamics, psychological health and well-being, and financial stability of the entire family of the person with migraine. METHODS: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study is a prospective, longitudinal, Web-based survey study undertaken between September 2012 and November 2013 in a systematic U.S. sample of people meeting modified International Classification of Headache Disorders, 3rd edition migraine criteria: 19,891 respondents were invited to complete the Family Burden Module, which assessed the perceived impact of migraine on family relationships and life, career and finances, and overall health. Respondents were stratified by episodic migraine (<15 headache days/month) and chronic migraine (≥15 headache days/month) and sex for comparisons. RESULTS: A total of 13,064 respondents (episodic migraine: 11,944 [91.4%]; chronic migraine: 1120 [8.6%]) provided valid data. Approximately 16.8% of respondents not currently in a romantic relationship (n = 536 of 3189) and 17.8% of those in a relationship but not living together (n = 236 of 1323) indicated that headaches had contributed to relationship problems. Of those in a relationship and living together (n = 8154), 3.2% reported that they chose not to have children, delayed having children or had fewer children because of migraine (n = 260; episodic migraine: n = 193 of 7446 [2.6%]; chronic migraine: n = 67 of 708 [9.5%]; P < .001). Of individuals responding to career/finance items (n = 13,061/13,036), 32.7% indicated that headaches negatively affected ≥1 career area (n = 4271; episodic migraine: n = 3617 of 11,942 [30.3%]; chronic migraine: n = 654 of 1119 [58.4%]), and 32.1% endorsed worry about long-term financial security due to migraine (n = 4180; episodic migraine: n = 3539 of 11,920 [29.7%]; chronic migraine: n = 641 of 1116 [57.4%]). CONCLUSIONS: Migraine can negatively affect many important aspects of life including marital, parenting, romantic and family relationships, career/financial achievement and stability, and overall health. Reported burden was consistently greater among those with chronic migraine than among people with episodic migraine; however, few differences were seen between the sexes.