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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. [ABSTRACT FROM AUTHOR]

Objective: To assess the utility of the novel patient‐identified (PI) most bothersome symptom (MBS) measure from PROMISE‐2, a phase 3 trial of eptinezumab for the preventive treatment of chronic migraine. Background: Relief of bothersome migraine symptoms can influence satisfaction with treatment and therapeutic persistence. Understanding the impact of preventive treatment on a PI‐MBS could improve clinical decision‐making. Methods: In PROMISE‐2, patients with chronic migraine received eptinezumab 100, 300 mg, or placebo administered intravenously every 12 weeks for up to 2 doses (n = 1072). PI‐MBS was an exploratory outcome requiring each patient to self‐report their MBS in response to an open‐ended question. At baseline and week 12, patients rated overall improvement in PI‐MBS. The relationships among PI‐MBS at week 12 and change in monthly migraine days (MMDs) from baseline to month 3 (weeks 9–12), Patient Global Impression of Change at week 12, and changes from baseline to week 12 in the 6‐item Headache Impact Test total, EuroQol 5‐dimensions 5‐levels visual analog scale, and 36‐item Short‐Form Health Survey component scores were assessed. Results: Treatment groups had similar baseline characteristics and reported a total of 23 unique PI‐MBS, most commonly light sensitivity (200/1072, 18.7%), nausea/vomiting (162/1072, 15.1%), and pain with activity (147/1072, 13.7%). Improvements in PI‐MBS at week 12 correlated with changes in MMDs (ρ = −0.49; p < 0.0001) and other patient‐reported outcomes. Controlling for changes in MMDs, PI‐MBS improvement predicted other patient‐reported outcomes in expected directions. The magnitude of the standardized mean differences between placebo and active treatment for PI‐MBS were 0.31 (p < 0.0001 vs. placebo) and 0.54 (p < 0.0001 vs. placebo) for eptinezumab 100 and 300 mg, respectively. Conclusions: Improvement in PI‐MBS at week 12 was associated with improvement in other patient‐reported outcome measures, and PI‐MBS may be an important patient‐centered measure of treatment benefits in patients with chronic migraine. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of fremanezumab in patients with chronic migraine (CM) and moderate to severe depression. Background: Fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene–related peptide, has been approved for the preventive treatment of migraine in adults. CM and depression are highly comorbid. Methods: The 12‐week, Phase 3 HALO trial randomized patients with CM to fremanezumab quarterly (675 mg/placebo/placebo), fremanezumab monthly (675/225/225 mg), or placebo. Post hoc analyses evaluated the effects of fremanezumab in patients with moderate to severe depression (baseline 9‐item Patient Health Questionnaire sum score ≥10) on monthly number of headache days of at least moderate severity; monthly migraine days; Patient Global Impression of Change (PGIC); 6‐item Headache Impact Test (HIT‐6) scores; and depression. Results: For the 219/1121 (19.5%) patients with moderate to severe depression at baseline, fremanezumab was associated with a significant reduction in monthly number of headache days of at least moderate severity for active treatment versus placebo (least‐squares mean change ± standard error for quarterly dosing: −5.3 ± 0.77; for monthly dosing: −5.5 ± 0.72; and for placebo: −2.2 ± 0.81; both p < 0.001). More patients achieved a ≥50% reduction in headache days of at least moderate severity with fremanezumab (quarterly: 31/78 [39.7%]; monthly: 39/96 [40.6%]) than placebo (9/67 [13.4%]; both p < 0.001). Compared with placebo, fremanezumab improved PGIC and HIT‐6 scores. Conclusions: Fremanezumab demonstrated efficacy in the preventive treatment of CM and reduced headache impact in patients with comorbid depression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Migraine is a common and often debilitating neurological disease. It can be divided into episodic and chronic subforms based on the number of monthly headache days. Because only a subset of individuals with episodic migraine (EM) progress to chronic migraine (CM) over any given time period, understanding the factors that predict the new onset of CM or "migraine progression" may provide insights into the mechanisms, pathophysiology, prevention, and treatment of CM. In this review, we identify and summarize studies that report risk factors associated with the new onset of CM or related chronic headache diagnoses, group these risk factors and report the strength of evidence for the identified risk factors. Objective: To conduct a systematic review of studies that identify risk factors for the new onset of CM or related chronic headache diagnoses such as transformed migraine (TM) and chronic daily headache (CDH). Methods: Herein we summarize the findings of studies of risk factors associated with the new onset of CM/TM, CDH, or related diagnoses from the English language literature published before March 2018. The PubMed database was searched for relevant studies. Longitudinal studies with follow‐up data and case‐control studies were included in this qualitative synthesis. We report methodology, analytic criteria, and results for each manuscript and for the parent study. Next, we review the strength of evidence for each of the identified risk factors using a modified version of AB Hill's criteria for causation and rank evidence as fair, moderate, or strong. We categorized risk factors as nonmodifiable, modifiable and based on putative mechanisms. We further categorized risk factors into sociodemographics, lifestyle factors and habits, headache features, comorbid and concomitant diseases and conditions and pharmacologic treatment‐related. Finally, we review theories of the pathophysiology underlying the development of new onset chronic migraine or increasing attack frequency. Results: The PubMed search yielded 1870 records after duplicates were removed. Nine additional records were identified through expert consultation and other methods (eg, citations found as references in manuscripts identified in the literature review and through communication with the authors of manuscripts included in the review). The 1879 manuscripts were screened against the inclusion and exclusion criteria and 109 were found to be potentially eligible. Of 109 full‐text articles, 17 studies were identified as meeting the prespecified criteria based on the consensus of all authors. Of the 17 full texts, 13 were longitudinal cohort studies and 4 were case‐controlled studies. We found strength of evidence ranging from fair to strong for the identified risk factors. The strongest data were found for increased headache day frequency, depression, and medication overuse/high‐frequency use. Risk factors for new onset CM and CDH in children and adolescents were similar to those identified in adults. Conclusions: A range of risk factors for the new onset of CM/TM, CDH, or related chronic headache diseases were identified with the strongest data supporting increased headache day frequency, acute medication overuse/high‐frequency use and depression, which are potentially modifiable risk factors. Modifiable risk factors may provide targets for intervention. The lack of strong evidence or any evidence does not imply that there is not a relationship between a particular risk factor and new onset CM or related disease; but may indicate little or no research or that research did not have sufficient methodological rigor. In addition, it is likely that additional risk factors exist which have not yet been identified. Putative factors include pro‐inflammatory states and pro‐thrombotic states. Development of central sensitization and increased activation of the trigeminal nociceptive pathways may be drivers of the new onset of CM or CDH. Future research may include the systematic testing of interventions targeting modifiable risk factors to determine if progression can be prevented as well as continued exploration of the benefits of treating these risk factors among people with CM in an effort to increase rates of remission. Future work should also consider the natural fluctuations in headache day frequency and examine progression in terms of continuous definitions rather than or in addition to a dichotomous boundary. [ABSTRACT FROM AUTHOR]

Objective: To assess physician‐patient communication and identify the frequency of use of specific communication techniques by analyzing recordings of routinely scheduled medical encounters for patients with clinician‐identified chronic migraine. Background: Chronic migraine is an under‐diagnosed, under‐treated, and highly burdensome disease. Effective medical communication is integral to optimal medical care, including providing accurate diagnoses, creating effective treatment plans, and enhancing patient adherence. Communication patterns during office visits may be a target for intervention to improve outcomes for people with chronic migraine. Design: This was a prospective, observational study based on analysis of audio recordings collected during neurologist‐patient chronic migraine dialogues. Methods: Twenty neurologists from a US neurology panel maintained by Verilogue, Inc., a research organization specializing in healthcare dialogues, were invited to identify patients with chronic migraine and record clinical encounters with their patients. Both new patient visits and follow‐up visits were included in this analysis. Neurologist‐patient dialogues were audio‐recorded, anonymized, transcribed, and analyzed by a sociolinguist for the presence of prespecified communication parameters, strategies, and specific language indicative of optimal migraine‐related medical care. Results: Fourteen out of the 20 invited neurologists (70.0%) accepted the study invitation and recorded 35 encounters with patients eligible for the study. The patient sample was 91.4% female (n = 32/35), with a mean age of 46 years. On average, there were 17 headache‐related questions per visit; 82.0% of questions were closed‐ended (n = 369/450). Headache/migraine frequency was elicited in 77.1% of the dialogues (n = 27/35), but headache days per month was assessed in only a single dialogue. Only one neurologist utilized the ask‐tell‐ask technique. Headache‐related disability was discussed in 22.9%of the dialogues (n = 8/35), with only one using open‐ended questions. None of the dialogues discussed ictal vs interictal headache‐related disability. Chronic migraine was mentioned in 8.6% of dialogues (n = 3/35) and treatment plans were discussed in 37.1% of the dialogues (n = 13/35). Conclusions: Results from this preliminary study showed that the majority of the neurologist‐chronic migraine patient dialogues did not assess elements crucial for diagnosis and treatment (eg, headache days per month and headache related disability) or use standard communication techniques (eg, open‐ended questions, ask‐tell‐ask). We recommend intervention studies designed to assess the benefits of improved communication on diagnostic accuracy, treatment decisions, and patient reported outcomes. [ABSTRACT FROM AUTHOR]

Objective: To identify natural subgroups of people with migraine based on profiles of comorbidities and concomitant conditions, hereafter referred to as comorbidities. Background: Migraine is a heterogeneous disease. Identifying natural subgroups (endophenotypes) may facilitate biological and genetic characterization and the development of personalized treatment. Methods: The Chronic Migraine Epidemiology and Outcomes Study is a prospective web‐based survey study designed to characterize the course of migraine and related comorbidities in a systematic US sample of people with migraine. Respondents were asked if they ever had a specific comorbidity and, if present, whether the comorbidity was confirmed/diagnosed by a “doctor”; 62 comorbidities were available for analysis. Latent class analysis (LCA) modeling determined the optimal number of classes and a parsimonious set of comorbidities. Results: Of the 12,810 respondents with migraine, 11,837 reported ≥1 comorbidity and were included in this analysis. After statistical analysis and clinical judgment reduced the number of comorbidities, we selected an 8‐class model based on 22 comorbidities. Each class had a distinct pattern summarized as follows: Class 1, Most Comorbidities; Class 2, Respiratory/Psychiatric; Class 3, Respiratory/Pain; Class 4, Respiratory; Class 5, Psychiatric; Class 6, Cardiovascular; Class 7, Pain; Class 8, Fewest Comorbidities. The distribution of individuals across models was variable, with one‐third of respondents in Class 8 (Fewest Comorbidities) and <10% in Class 1 (Most Comorbidities). Demographic and headache characteristics, not used in assigning class membership, varied across classes. For example, comparing Class 1 (Most Comorbidities) and Class 8 (Fewest Comorbidities), Class 1 had a greater proportion of individuals with severe disability (Migraine Disability Assessment grade IV; 48.1% vs 22.3% of overall individuals) and higher rates of allodynia (67.6% vs 47.0%), medication overuse (36.4% vs 15.0%), chronic migraine (23.1% vs 9.1%), and aura (40.1% vs 28.8%). Conclusions: LCA modeling identified 8 natural subgroups of persons with migraine based on comorbidity profiles. These classes show differences in demographic and headache features not used to form the classes. Subsequent research will assess prognostic and biologic differences among the classes. [ABSTRACT FROM AUTHOR]

Objective To evaluate the relationships among modifiable psychological factors and chronic migraine and severe migraine-related disability in a clinic-based sample of persons with migraine. Background Evidence evaluating relationships between modifiable psychological factors and chronic migraine and severe migraine-related disability is lacking in people with migraine presenting for routine clinical care. Methods Adults with migraine completed surveys during routinely scheduled visits to a tertiary headache center. Participants completed surveys assessing chronic migraine (meeting criteria for migraine with ≥15 headache days in the past month), severe migraine disability (Migraine Disability Assessment Scale score ≥ 21), and modifiable psychological factors (depressive symptoms [Patient Health Questionnaire-9], anxious symptoms [Generalized Anxiety Disorder-7], Pain Catastrophizing Scale and Headache Specific Locus of Control). Logistic regression evaluated relationships between modifiable psychological factors and chronic migraine and severe migraine disability. Results Among 90 eligible participants the mean age was 45.0 (SD = 12.4); 84.8% were women. One-third (36.0%) met study criteria for chronic migraine; half of participants (51.5%) reported severe migraine-related disability. Higher depressive symptoms (OR = 1.99, 95% CI = 1.11, 3.55) and chance HSLC (OR = 1.85, 95% CI = 1.13, 1.43) were associated with chronic migraine. Higher depressive symptoms (OR = 3.54, 95%CI = 1.49, 8.41), anxiety symptoms (OR = 3.65, 95% CI = 1.65, 8.06), and pain catastrophizing (OR = 1.95, 95% CI = 1.14, 3.35), were associated with severe migraine-related disability. Conclusions Psychiatric symptoms and pain catastrophizing were strongly associated with severe migraine-related disability. Depression and chance locus of control were associated with chronic migraine. This study supports the need for longitudinal observational studies to evaluate the relationships among naturalistic variation in psychological factors, migraine-related disability, and migraine chronification. [ABSTRACT FROM AUTHOR]

Objective To describe the development of the Impact of Migraine on Partners and Adolescent Children (IMPAC) scale. Background Although existing data and clinical experience suggest that the impact of migraine is pervasive and extends beyond the individual with migraine, no validated tools exist for assessing the impact of migraine on the family. Methods The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study is a longitudinal study of people with migraine in the United States. The Family Burden Module (FBM) of the CaMEO Study contained an item pool of 53 questions derived through literature review, clinician input, and patient focus groups pertaining to the following concepts: impact of migraine on family interpersonal relationships, activities, well-being, finances, and health-related quality of life. Respondents with migraine (ie, probands) were categorized into 4 groups based on household composition: migraine probands with partners/spouses and children (M-PC), migraine probands with partners/spouses only (M-P), migraine probands with child(ren) only (M-C), and migraine probands without a partner/spouse or child(ren) (M-O). The IMPAC scale was developed in 3 steps: (1) exploratory factor analysis and item reduction, (2) bifactor analysis, confirmatory factor analysis, and scoring, and (3) reliability and construct validity analyses. Results The analysis of data from 13,064 respondents to the FBM meeting criteria for migraine yielded a 12-item IMPAC scale, with 4 items applying to all of the groups, 4 more items applying to the groups with partners (M-P and M-PC), and 4 additional items to the groups with children (M-C and M-PC). Item responses can be summed and converted into a scoring system assessing mild (<0.5 SD below mean; IMPAC scale Grade I), moderate (0.5 SD below to <0.5 SD above mean; Grade II), severe (0.5-<1.5 SD above mean; Grade III), and very severe (≥0.5 SD above mean; Grade IV) family impact. Test information curves relating to the IMPAC scale for each household type indicated adequate reliability across a large range of family burden severity (from ∼1 SD below to ∼3 SD above mean) and IMPAC scores showed moderate-to-large correlations with other validated tools (range, ± 0.38-0.52), providing support for construct validity. Conclusions We developed a questionnaire to assess family burden attributed to migraine that is brief, robust, and psychometrically sound, with a simple scoring algorithm that can be applied to various household compositions. This questionnaire may be valuable in research settings to provide quantifiable data on the impact of migraine on family dynamics and in clinical settings to facilitate conversations about family burden as a target and a motivation for better treatment. [ABSTRACT FROM AUTHOR]

Objective To compare the methods and baseline characteristics of the American Migraine Prevalence and Prevention (AMPP) and Chronic Migraine Epidemiology and Outcomes (CaMEO) studies. Background The AMPP and CaMEO studies are the largest longitudinal efforts designed to improve our understanding of episodic and chronic migraine in the United States. The studies have complementary strengths and weaknesses. Methods This analysis compares and contrasts the study methods and participation rates of the AMPP and CaMEO studies. We then compare and contrast baseline results in terms of demographic characteristics, headache features, and disability as measured by the Migraine Disability Assessment Scale (MIDAS) among people with episodic and chronic migraine. Results AMPP and CaMEO sampled from panels constructed to be representative of the US population. The AMPP Study collected data using a mailed questionnaire while CaMEO relied on a web survey methodology. Response rates were higher in AMPP (64.8%) than in CaMEO (16.5%). Both studies assessed headache features using the American Migraine Study/AMPP diagnostic module. Both identified persons with episodic (<15 headache days/month) and chronic migraine (≥15 headache days/month) based on the International Classification of Headache Disorders. AMPP collected data annually over 5 years, while CaMEO collected data quarterly over 15 months. Baseline demographic distribution was generally similar, indicating that each study was broadly representative of the US population. The proportion of persons with migraine who had chronic migraine was similar (AMPP, 6.6%; CaMEO, 8.8%). Respondents had similar median headache frequency (days/month) by sex for chronic migraine (AMPP: men = 21.7, women = 20.0; CaMEO: men = 20.0, women = 20.0) and episodic migraine (AMPP: men = 1.7, women = 2.0; CaMEO: men = 2.0, women = 3.0). Median MIDAS scores were substantially higher in both studies for chronic migraine (severe disability [Grade IV]; AMPP: men = 33.0, women = 45.0; CaMEO: men = 32.0, women = 38.0) than episodic migraine (little/mild disability [Grade I/II]; AMPP: men = 3.0, women = 6.0; CaMEO: men = 4.0, women = 7.0). Rates of moderate/severe disability (Grade III/IV) were substantially higher in both studies for chronic migraine (AMPP: men = 66.9%, women = 78.9%; CaMEO: men = 71.0%, women = 82.6%) than episodic migraine (AMPP: men = 23.0%, women = 31.8%; CaMEO: men = 26.7%, women = 37.9%). More women than men respondents in both studies experienced moderate/severe disability. Conclusions AMPP and CaMEO are longitudinal cohort studies that used different methods, but yielded similar results for demographic features, headache frequency, and headache-related disability. Both studies found more severe headache-related disability in those with chronic versus episodic migraine. [ABSTRACT FROM AUTHOR]

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

Objective The objective of this study was to compare the societal direct and indirect costs of chronic and episodic migraine in the United States. Background Episodic and chronic migraine are distinguished by the frequency of headache-days. Chronic migraine has a greater overall impact on quality of life than does episodic migraine. Individuals with chronic migraine also use more healthcare resources (resulting in higher direct costs) and experience greater decreases in productivity (resulting in higher indirect costs) than those with episodic migraine as shown in the American Migraine Prevalence and Prevention (AMPP) Study. Methods The International Burden of Migraine Study utilized a web-based questionnaire to elicit data on several topics related to the burden of migraine illness, including health resource utilization and productivity losses. Potential survey participants were identified by Synovate Healthcare (Chicago, IL, USA) from a pool of registered panelists from various countries. The panelists were screened online to determine eligibility and to identify individuals with migraine (episodic or chronic), based on reported symptoms. Participants from the United States were divided into episodic and chronic migraine groups, based on reported headache-day per month frequency. Direct and indirect costs were estimated by applying estimated unit costs to reported headache-related productivity losses and resource use. Costs were compared between participants with episodic and chronic migraine. Results Mean [standard deviation] total annual cost of headache among people with chronic migraine ($8243 [$10,646]) was over three times that of episodic migraine ($2649 [$4634], P < .001). Participants with chronic migraine had significantly greater direct medical costs ($4943 [$6382]) and indirect (lost productivity) costs ($3300 [$6907]) than did participants with episodic migraine (direct, $1705 [$3591]; indirect, $943 [$2084]) ( P < .001 for each). Unlike previous findings, direct medical costs constituted the majority of total headache-related costs for both chronic migraine (60.0%, $4943 of $8243) and episodic migraine (64.3%, $1705 of $2649) participants. A large portion of direct medical costs are attributable to pharmaceutical utilization among both chronic migraine (80%, $3925 of 4943) and episodic migraine (70%, $1196 of $1705) participants. Conclusion The results of this study build on previous results of the AMPP Study, demonstrating that headache-related direct, indirect, and total costs are significantly greater among individuals with chronic migraine than with episodic migraine in the United States. [ABSTRACT FROM AUTHOR]

Background The migraine Treatment Optimization Questionnaire ( mTOQ) was developed to assess response to acute treatment in persons with migraine. The original validated form used yes or no response options. Objectives This study aims to (1) assess the psychometric properties of a 6-item version of the mTOQ ( mTOQ-6) using ordinal response options; (2) compare treatment optimization using the revised mTOQ-6 for both episodic and chronic migraine ( EM and CM, respectively); (3) identify demographic, headache, and treatment features associated with treatment optimization. Methods The American Migraine Prevalence and Prevention ( AMPP) Study is a longitudinal, US population-based study. Annual questionnaires were mailed to a sample of 24,000 severe headache sufferers identified by screening a panel constructed to be representative of the US population. The current study included respondents to the 2006 AMPP Study survey who met modified International Classification of Headache Disorders-3 beta criteria for migraine; persons with CM (≥15 HA days/month) or EM (<15 HA days/month) were included. Acute treatment optimization was measured with the mTOQ-6. A single factor latent variable model was used to assess item characteristics. This model was expanded through structural equation models ( SEM) to incorporate a contrast between persons with CM and EM on the scaled treatment optimization scores. We estimated both an unadjusted SEM and a SEM adjusted for demographic features, headache characteristics, and acute treatment. Results Migraine criteria were met by 8612 persons (539 for CM and 8073 for EM) who completed the mTOQ-6 as part of the 2006 AMPP Study survey. When compared, those with CM exhibited worse treatment optimization across all domains of the mTOQ-6. For example, 35.1% of CM and 44.6% of EM respondents reported being pain free at 2 hours 'half the time or more' with their usual migraine medication. Latent variable model parameters indicated excellent psychometric properties of the mTOQ-6. Scaled treatment optimization scores obtained from the unadjusted SEM were significantly lower (indicating worse treatment optimization) for persons with CM (3.25) compared to persons with EM (4.01), b = −0.76, P < .0001; scores remained significantly lower for CM after adjustment with a wide array of demographic and disease severity covariates. Poor treatment optimization was associated with cutaneous allodynia, major depression, and the use of nonsteroidal anti-inflammatory drugs. Better treatment optimization was associated with the use of triptans and preventive medications. Conclusion Estimates of the latent variable scores for the mTOQ-6 revealed persistent low levels of treatment optimization for both EM and CM, though treatment optimization is worse for CM. [ABSTRACT FROM AUTHOR]

Background Though nausea is a cardinal feature of migraine, its influence on migraine progression has not been evaluated. This article aims to evaluate persistent frequent headache-related nausea ( PFN) in persons with episodic migraine ( EM) as a predictor of new onset chronic migraine ( CM). Methods This prospective cohort study uses data from the 2007 and 2008 American Migraine Prevalence and Prevention study surveys to identify subgroups with episodic International Classification of Headache Disorders, 2nd edition defined migraine and either PFN or no or low frequency nausea ( NLFN). PFN was defined by the presence of nausea ≥ half the time in both 2007 and 2008. NLFN was defined by nausea that was present < half the time, rarely or never in both years. Persons were considered CM in 2009 if they met symptom criteria for migraine with headaches ≥15 days per month over the preceding 3 months. Univariate differences in demographics for PFN and NLFN were evaluated with chi-square. Binary logistic regressions were performed hierarchically to assess progression to CM in 2009 as a function of nausea status in 2007 and 2008. The initial model included sociodemographic variables only. Subsequent models added the following variables in a hierarchical manner: migraine symptom severity composite score (to control for the impact of other headache features), headache-related disability, depression, opioid use, and an interaction term for nausea status and opioid use. Odds ratios ( OR) and 95% confidence intervals ( CI) contrasted PFN and NLFN on the rate of progression to CM in 2009. Results There were 3182 respondents with headache symptom and frequency data available for all 3 years of the analysis. PFN was found in 43.7% (1389) of respondents, and 3.4% (47) progressed to CM. NLFN was seen in 27.6% (877) of the EM group, and 1.5% progressed to CM. In comparison with the NLFN group, PFN was more common in females ( P < .001) and Caucasians ( P < .06). PFN was associated with a doubling of the risk of progression to CM after adjusting for sociodemographic variables ( OR 2.09, 95% CI 1.11-3.91, P = .022). Adding the symptom composite score and headache-related disability covariates to the model attenuated the association slightly ( OR 2.00, 95% CI 1.03-3.87, P = .04). With the addition of depression, the association fell just below statistical significance but progression risk with PFN remained at nearly two-fold that of the NLFN group ( OR 1.90, 95% CI 0.98-3.71, P = .059). When opioid use and the nausea by opioid use interaction are added to the final model, the significant effect and the doubling of CM progression risk for those with PFN was retained ( OR 2.24, 95% CI 1.07-4.70, P = .033). Conclusions Persistent frequent nausea is common (43.7%) among persons with episodic migraine. After controlling for sociodemographics, migraine symptom severity, headache-related disability, depression, and opioid medication use, migraineurs with frequent nausea that persisted for 2 years of study were twice as likely to progress to CM compared to those with no or low frequency nausea. The study is limited by self-reports of symptom and headache frequency data and the use of modified diagnostic criteria. Additional prospective research is needed to confirm study findings. Persistent frequent nausea could be a marker for the risk of progression to CM or it could be in the causal pathway. [ABSTRACT FROM AUTHOR]

Objectives Refine the classification of migraine subtypes by applying factor mixture models ( FMM) to a large population sample of people with headache. Background Current classification of primary headache disorders is symptom-based and uses somewhat arbitrary boundaries developed by expert consensus. Symptom profiles and headache frequency are used to distinguish among probable migraine (PM), episodic migraine ( EM), high-frequency episodic migraine ( HFEM), and chronic migraine ( CM). Herein, we used statistical approaches to parse the heterogeneity in the broad group of persons with migraine and test the hypothesis that the groups that emerge differ in prognosis. Methods The American Migraine Prevalence and Prevention study mailed surveys to a sample of 120,000 US households selected to represent the US population in 2004. Follow-up surveys were sent to a random sample of 24,000 respondents with 'severe headache' on an annual basis from 2005 to 2009. People meeting International Classification of Headache Disorders, Second Edition, criteria for migraine were classified as EM (<15 headache days/month) and CM (≥15 headache days/month) based on modified Silberstein- Lipton criteria. The EM group was subdivided into HFEM (10 to 14 headache days/month) and low-frequency episodic migraine ( LFEM; <10 headache days/month). Factor mixture models ( FMM) identified 5 subgroups of migraine (taxa) using data from the 2005 survey on the severity of migraine symptoms, average migraine pain intensity, headache-related disability, cutaneous allodynia and depression, as well as monthly headache and migraine frequency as determinants of class membership. We assessed the validity of these taxa by examining the distribution of clinical diagnoses at cross-section and the rate of CM onset within these groups. Results Data from the 2005 American Migraine Prevalence and Prevention survey were used for the FMM and data from the 2006-2009 surveys were used to assess prognosis of groups defined based on FMM. In total, 12,860 participants were eligible for classification analysis, including 10,162 with LFEM and 601 with HFEM, 1302 with probable migraine, and 795 with CM. Of these, 3152 (24.5%), 1076 (8.4%), 3896 (30.3%), 2251 (17.5%), and 2485 (19.3%) were assigned to Taxons 1, 2, 3, 4, and 5, respectively. Overall, there was a strong association between taxon assignment and clinical diagnosis. As the most prevalent disorder in the sample, EM was the largest contributor to each of the 5 taxa, constituting more than 80% of each group other than Taxon 2. Taxon 2 was enriched with the most severe spectrum of migraine including the highest concentrations of CM (28.4%) and HFEM (22.6%), whereas Taxon 5 represented the least severe end of the migraine spectrum including the lowest concentrations of CM (0%) and HFEM (0.08%). Validity of taxon assignment was tested by the ability of taxon membership to predict clinical course. For Taxon 2, 22% of those free of CM at baseline developed it. For Taxon 5, less than 2% of CM-free Taxon 5 members developed it. Conclusion Statistically based classification using FMM extends traditional clinical syndrome-based diagnosis. FMM can serve as an important tool to parse phenotypic heterogeneity and identify natural migraine subgroups. This approach may improve our ability to diagnosis migraine, to select initial therapy, to predict prognosis, and to discover biomarkers and genes. [ABSTRACT FROM AUTHOR]

Objectives To assess the influence of triptan or nonsteroidal anti-inflammatory drug ( NSAID) use on the likelihood of developing chronic migraine ( CM) among persons with episodic migraine ( EM). Background CM is common in tertiary headache care, and relative to EM, CM is associated with a number of deleterious outcomes, including higher headache-related disability, reduced health-related quality of life, and increased direct and indirect costs. Symptomatic medication use has emerged as an important risk factor for the development of CM. Limited evidence based on a single year of follow up suggests that the association between NSAID and triptan use with the onset of CM varies in a dose-dependent manner that interacts with headache frequency. However, this interaction has never been explicitly studied. Herein, we evaluate results from a large-scale, 5-year, population-based observational study to characterize these relationships and test the hypothesis that NSAID use may modify the effect of triptan use on CM onset. Methods In the American Migraine Prevalence and Prevention ( AMPP) study, 11,249 participants had EM in 2005 and provided up to 5 years of annual follow-up data. We analyzed the characteristics of persons with EM 1 year that predicted new onset CM in the subsequent year, focusing on treatment with NSAIDs and triptans as exposures. These adjacent years of data provide the basis for analysis and are termed 'couplets.' Repeated measures logistic regression with a subject-specific random intercept was used to model the likelihood of transition from EM to CM as a function of NSAID or triptan dose while controlling for a number of covariates including headache features, use of other medications, and the number of couplets per individual. Results The analysis included 9031 individuals with EM contributing up to 5 years of data and up to 4 couplets each. Results indicated that on average, 55% of the participants used NSAIDs in any given year and 2% transitioned to CM over subsequent years. Among the 20% using triptans, 3% per year transitioned to CM. Among persons with less than 10 headache days per month, frequency of NSAID use was associated with dose-dependent reductions in risk of CM onset. Among those with 10-14 headache days per month, increasing days per month of NSAID use was associated with increasing risk of CM onset. Increasing days per month of triptan use was associated with increased risk of transitioning to CM. Combination use of NSAIDs and triptans was not protective against transition to CM, but was also not statistically significantly associated with increased risk of CM onset. Conclusion Triptan use in EM is associated with an increased risk of CM onset that increases with days of medication use. For NSAIDs, effects depend on headache days per month. NSAIDs are protective in individuals with less than 10 headache days per month but associated with increased risk with 10 or more headache days per month. Combining a triptan and NSAID was not associated with a statistically significant increased risk of CM onset, whereas increased risk of CM onset was significantly associated with triptan monotherapy. [ABSTRACT FROM AUTHOR]

Objectives.- To estimate the prevalence and distribution of chronic migraine (CM) in the US population and compare the age- and sex-specific profiles of headache-related disability in persons with CM and episodic migraine. Background.- Global estimates of CM prevalence using various definitions typically range from 1.4% to 2.2%, but the influence of sociodemographic factors has not been completely characterized. Methods.- The American Migraine Prevalence and Prevention Study mailed surveys to a sample of 120,000 US households selected to represent the US population. Data on headache frequency, symptoms, sociodemographics, and headache-related disability (using the Migraine Disability Assessment Scale) were obtained. Modified Silberstein-Lipton criteria were used to classify CM (meeting International Classification of Headache Disorders, second edition, criteria for migraine with a headache frequency of ≥15 days over the preceding 3 months). Results.- Surveys were returned by 162,756 individuals aged ≥12 years; 19,189 individuals (11.79%) met International Classification of Headache Disorders, second edition, criteria for migraine (17.27% of females; 5.72% of males), and 0.91% met criteria for CM (1.29% of females; 0.48% of males). Relative to 12 to 17 year olds, the age- and sex-specific prevalence for CM peaked in the 40s at 1.89% (prevalence ratio 4.57; 95% confidence interval 3.13-6.67) for females and 0.79% (prevalence ratio 3.35; 95% confidence interval 1.99-5.63) for males. In univariate and adjusted models, CM prevalence was inversely related to annual household income. Lower income groups had higher rates of CM. Individuals with CM had greater headache-related disability than those with episodic migraine and were more likely to be in the highest Migraine Disability Assessment Scale grade (37.96% vs 9.50%, respectively). Headache-related disability was highest among females with CM compared with males. CM represented 7.68% of migraine cases overall, and the proportion generally increased with age. Conclusions.- In the US population, the prevalence of CM was nearly 1%. In adjusted models, CM prevalence was highest among females, in mid-life, and in households with the lowest annual income. Severe headache-related disability was more common among persons with CM and most common among females with CM. [ABSTRACT FROM AUTHOR]

Background and purpose: An estimated 2.5–3.1% of people with episodic migraine develop chronic migraine in a year. Several risk factors are associated with an increased risk for this transformation. We conducted a systematic review and meta-analysis to provide quantitative and qualitative data on predictors of this transformation. Methods: An electronic search was conducted for published, prospective, cohort studies that reported risk factors for chronic migraine among people with episodic migraine. Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. Quality of evidence was determined according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Effect estimates were retrieved and summarized using risk ratios. Results: Of 5695 identified publications, 11 were eligible for inclusion. The pooled analysis (GRADE system) found "high" evidence for monthly headache day frequency ≥ 10 (risk ratio = 5.95), "moderate" evidence for depression (risk ratio = 1.58), monthly headache day frequency ≥ 5 (risk ratio = 3.18), and annual household income ≥ $50,000 (risk ratio = 0.65) and "very low" evidence for allodynia (risk ratio = 1.40) and medication overuse (risk ratio = 8.82) in predicting progression to chronic migraine. Conclusions: High frequency episodic migraine and depression have high quality evidence as predictors of the transformation from episodic migraine to chronic migraine, while annual household income over $50,000 may be protective. [ABSTRACT FROM AUTHOR]

Background: Migraine, particularly chronic migraine (CM), is underdiagnosed and undertreated worldwide. Our objective was to develop and validate a self-administered tool (ID-CM) to identify migraine and CM.Methods: ID-CM was developed in four stages. (1) Expert clinicians suggested candidate items from existing instruments and experience (Delphi Panel method). (2) Candidate items were reviewed by people with CM during cognitive debriefing interviews. (3) Items were administered to a Web panel of people with severe headache to assess psychometric properties and refine ID-CM. (4) Classification accuracy was assessed using an ICHD-3β gold-standard clinician diagnosis.Results: Stages 1 and 2 identified 20 items selected for psychometric validation in stage 3 (n = 1562). The 12 psychometrically robust items from stage 3 underwent validity testing in stage 4. A scoring algorithm applied to four symptom items (moderate/severe pain intensity, photophobia, phonophobia, nausea) accurately classified most migraine cases among 111 people (sensitivity = 83.5%, specificity = 88.5%). Augmenting this algorithm with eight items assessing headache frequency, disability, medication use, and planning disruption correctly classified most CM cases (sensitivity = 80.6%, specificity = 88.6%).Discussion: ID-CM is a simple yet accurate tool that correctly classifies most individuals with migraine and CM. Further testing in other settings will also be valuable. [ABSTRACT FROM AUTHOR]

Background: Longitudinal migraine studies have rarely assessed headache frequency and disability variation over a year. Methods: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study is a cross-sectional and longitudinal Internet study designed to characterize the course of episodic migraine (EM) and chronic migraine (CM). Participants were recruited from a Web-panel using quota sampling in an attempt to obtain a sample demographically similar to the US population. Participants who passed the screener were assessed every three months with the Core (baseline, six, and 12 months) and Snapshot (months three and nine) modules, which assessed headache frequency, headache-related disability, treatments, and treatment satisfaction. The Core also assessed resource use, health-related quality of life, and other features. One-time cross-sectional modules measured family burden, barriers to medical care, and comorbidities/endophenotypes. Results: Of 489,537 invitees, we obtained 58,418 (11.9%) usable returns including 16,789 individuals who met ICHD-3 beta migraine criteria (EM (<15 headache days/mo): n = 15,313 (91.2%); CM (≥ 15 headache days/mo): n = 1476 (8.8%)). At baseline, all qualified respondents (n = 16,789) completed the Screener, Core, and Barriers to Care modules. Subsequent modules showed some attrition (Comorbidities/Endophenotypes, n = 12,810; Family Burden (Proband), n = 13,064; Family Burden (Partner), n = 4022; Family Burden (Child), n = 2140; Snapshot (three months), n = 9741; Core (six months), n = 7517; Snapshot (nine months), n = 6362; Core (12 months), n = 5915). A total of 3513 respondents (21.0%) completed all modules, and 3626 (EM: n = 3303 (21.6%); CM: n = 323 (21.9%)) completed all longitudinal assessments. Conclusions: The CaMEO Study provides cross-sectional and longitudinal data that will contribute to our understanding of the course of migraine over one year and quantify variations in headache frequency, headache-related disability, comorbidities, treatments, and familial impact. [ABSTRACT FROM AUTHOR]

Objective: To assess migraine epidemiology in men by examining gender differences in disease presentation, comorbidities, and prognosis.Patients and Methods: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study is a longitudinal survey of US adults with migraine identified by web questionnaire. Data were stratified by gender, collected between September 2012-November 2013, and included sociodemographics, headache features, Migraine Disability Assessment, Migraine Symptom Severity Score, Allodynia Symptom Checklist, and comorbidities. Discrete time hazard models addressed 1-year likelihood of transition from episodic to chronic migraine headache frequency.Results: Of the 16,789 migraine respondents, 4294 were men (25.6%). Compared to women, men were slightly older at onset of their headaches (mean 24.1 vs. 22.3 years) and had fewer headache days/month (4.3 vs. 5.3 days), slightly less severe attacks (Migraine Symptom Severity Score, 21.6 vs. 22.6), reduced frequencies of grade IV Migraine Disability Assessment scores (15.7% vs. 24.1%), allodynia (32.6% vs. 49.7%), chronic migraine (6.5% vs. 9.6%, each p < 0.001), and common comorbidities. Men were less likely to report consulting a doctor for their headaches and receiving a migraine diagnosis if they consulted. Men and women with episodic migraine had similar crude 1-year risk of chronic migraine onset. Controlling for known risk factors (i.e. depression, headache frequency, allodynia), men had greater likelihood of chronic migraine onset at 6, 9, and 12 months (each p < 0.05).Conclusions: Findings confirmed gender differences. Men with migraine generally have less severe attacks and disability and are less likely to receive a diagnosis than women with migraine. Prognostic factors may be better understood for women than men. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To quantify the cost differences and predictors of lost productive time (LPT) in persons with chronic migraine (CM) and episodic migraine (EM). Methods: The American Migraine Prevalence and Prevention (AMPP) study is a US national longitudinal survey of severe headache. Cost estimates were obtained via U.S. Census income data. To elucidate the unique predictors of LPT, the optimal distribution for modeling was determined. Zero inflation models for LPT were predicted from sociodemographics, headache features, characteristics and disability, medication use, and depression. The interaction between headache status and age was the primary effect of interest. Results: The eligible sample included 6329 persons with EM and 374 persons with CM. Men with CM aged 45 to 54 years cost employers nearly $200 per week more than do their EM counterparts. Likewise, for women, costs were higher for CM, with the cost differential between EM and CM being $90 per week. After comprehensive adjustment, increases in LPT with age were significantly higher in CM than in EM (rate ratio 1.03; 95% confidence interval 1.01–1.05). When age was recoded to a decade, metric rates of LPT increased 25% more per decade for CM than for EM (rate ratio 1.25; 95% confidence interval 1.004–1.5). Conclusions: LPT is more costly and increases more rapidly for those with CM than for those with EM as age increases. [Copyright &y& Elsevier]