Effect of galcanezumab in women with episodic migraine meeting criteria for menstrually related migraine: A post hoc analysis of EVOLVE-1 and EVOLVE-2.

BACKGROUND: We evaluated galcanezumab for migraine prevention in patients who met International Classification of Headache Disorders, 3rd edition criteria for menstrually related migraine (MRM). METHODS: Patients were identified post hoc from three double-blind, randomized, phase 3 clinical trials in patients with episodic migraine. Patients completed a 1-month prospective baseline period and up to 6 months (EVOLVE-1 and -2, studies pooled) of double-blind treatment with galcanezumab (120 mg/month) or placebo. Menses and headache information were recorded by electronic daily diary. Patients with a migraine attack starting during the 5-day perimenstrual interval (first day of bleeding ± 2 days) for ≥2 of their first three diary-recorded menstrual cycles were categorized as having MRM. The primary efficacy measure was mean change in monthly migraine headache days from baseline, averaged over Months 4 through 6. Response rates, change in monthly perimenstrual migraine headache days, monthly non-perimenstrual migraine headache days, and quality of life were also assessed. RESULTS: Post hoc MRM analysis criteria were met by 462/1133 women (41%). Mean (standard deviation) baseline monthly migraine headache days were 9.7 (±3.1; n = 146) for galcanezumab-treated patients and 9.6 (±2.8; n = 316) for placebo-treated patients. The mean change (standard error [SE]) in migraine headache days over Months 4 through 6 was -5.1 days (±0.39) for galcanezumab versus -3.2 (±0.35) for placebo (p < 0.001). The mean change (SE) in perimenstrual migraine headache days over Months 4 through 6 was -0.75 days (±0.08) for galcanezumab versus -0.49 (±0.07) for placebo (p = 0.004). For migraine headache days outside the perimenstrual period, the mean change in migraine headache days was -4.6 (±0.38) for galcanezumab and -2.8 (±0.33) for placebo (p < 0.001). Improvements in response rates and the Migraine-Specific Quality of Life Questionnaire were also observed over Months 4 through 6. CONCLUSION: Galcanezumab was effective for migraine prevention in women with MRM.

Situational prevention: Pharmacotherapy during periods of increased risk for migraine attacks.

The small molecule calcitonin gene-related peptide receptor antagonists (gepants) are the only drug class with medicines indicated for both the acute and preventive treatment of migraine. Given this dual capacity to both treat and prevent, along with their favorable tolerability profiles and lack of an association with medication-overuse headache, headache specialists have begun to use gepants in ways that transcend the traditional categories of acute and preventive treatment. One approach, called situational prevention, directs patients to treat during the interictal phase, before symptoms develop, in situations of increased risk for migraine attacks. Herein, we present three patients to illustrate scenarios of gepant use for situational prevention. In each case, a gepant was started in anticipation of a period of increased headache probability (vulnerability) and continued for a duration of 1 day to 5 consecutive days. Although this approach may expose patients to medication when headache may not have developed, the tolerability and safety profile and preventive effect of gepants may represent a feasible approach for some patients. Situational prevention is an emerging strategy for managing migraine before symptoms develop in individuals who can identify periods when the probability of headache is high. This paper is intended to increase awareness of this strategy and stimulate future randomized, placebo-controlled trials to rigorously assess this strategy.

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.

Between and within-woman differences in the association between menstruation and migraine days.

OBJECTIVE: To investigate between and within-woman differences in the association between menstruation and migraine days. BACKGROUND: Prior diary studies have shown that at the population level, aggregating across individuals, the odds of migraine increase during the perimenstrual window (from day -2 to day +3, where +1 is the first day of bleeding). These studies have been neither long nor large enough to assess the association between migraine and menses from an individual perspective. Consequently, existing research on menstrual-related migraine has largely overlooked between and within-woman variation that is critical for progressing clinical understanding and practice. METHODS: Intensive longitudinal data for the current study were collected in a digital platform (N1-Headache® ) that tracks individual migraine-related factors daily. Participants for the current study were actively menstruating adult (18+ years old) women who used the platform. Two variables were of primary interest, migraine day (no/yes) and menstrual status (inside or outside the 5-day perimenstrual window). RESULTS: The sample consisted of 203 women with a mean age of 35.6 (SD = 8.7) years. At baseline, the women reported an average of 30.6 (SD = 23.6) headache days over the last 3 months. Analyses were based on a total of 53,302 days (median of 150 per person), 18,520 of which were migraine days (median of 44 per person), and a total of 2,126 menstrual cycles (median of 7 per person). Results showed that the 5-day perimenstrual window was associated with a 34% increase in odds of a migraine day compared to other days (OR = 1.34, 95% CI: 1.23-1.45, p < 0.0001). Importantly, there was between and within-woman variability in the association between menses and migraine days (between-woman variability: p = 0.002; within-woman [between-cycles] variability: p < 0.0001). Exploration of these individual differences demonstrated that relationship between menses and migraine days varied more within-person across cycles than between women. DISCUSSION: This study supports previous research and demonstrates that the odds of migraine days are elevated from day -2 to day +3 of the menstrual cycle. We also show that the effect of menses on migraine days varies more within-woman than between-women. This work provides an initial foundation for better understanding menstrual-related migraine from the perspective of the individual patient.

Evaluation of the 6-item Identify Chronic Migraine screener in a large medical group.

OBJECTIVE: To evaluate the sensitivity and specificity of the 6-item Identify Chronic Migraine screener (ID-CM[6]), designed to improve the detection of chronic migraine (CM). BACKGROUND: CM is often undertreated and underdiagnosed. Survey-based studies have found that approximately 75-80% of people meeting criteria for CM do not report having received an accurate diagnosis. METHODS: This study used claims data of patients enrolled in a large medical group who had at least one medical claim with an International Classification of Diseases 9th/10th revision diagnostic code for migraine in the 12-month prescreening period. The Identify Chronic Migraine survey was administered by e-mail, in-person, or over the telephone to all enrolled patients. A Semi-Structured Diagnostic Interview (SSDI) was administered by telephone by a trained physician. The ID-CM(6) and SSDI classifications of CM status were compared to evaluate sensitivity and specificity of the ID-CM(6) screening tool. RESULTS: The analysis of the ID-CM(6) screening tool included 109 patients, with 65/109 (59.6%) positive for CM based on the SSDI. The mean (standard deviation) age of the patient sample was 49 (15) years and 100/109 (91.7%) were female. Using the SSDI as the diagnostic gold standard, the ID-CM(6) had a sensitivity of 70.8% (46/65) and a specificity of 93.2% (41/44). CONCLUSION: The ID-CM(6) demonstrated acceptable sensitivity and good specificity in determining CM status. The results of this analysis support the real-world utility of the ID-CM(6) as a simple and useful tool to identify patients with CM.

Efficacy and safety of erenumab in women with a history of menstrual migraine.

BACKGROUND: We performed a post hoc, subgroup analysis of a phase 3, randomized, double-blind, placebo-controlled study of erenumab for prevention of episodic migraine (STRIVE) to determine the efficacy and safety of erenumab in women with self-reported menstrual migraine. METHODS: Patients received placebo, erenumab 70 mg, or erenumab 140 mg subcutaneously once monthly during the 6-month double-blind treatment phase of STRIVE. Women who reported history of menstrual migraine and who were ≤ 50 years old were included in the analysis. Endpoints were change from baseline in monthly migraine days (MMD) and monthly acute migraine-specific medication days (MSMD; among patients who took acute migraine-specific medications at baseline), proportion of patients achieving ≥ 50% reduction from baseline in MMD, and incidence of adverse events. RESULTS: Among 814 women enrolled in STRIVE, 232 (28.5%) reported a history of menstrual migraine and were ≤ 50 years old. Of the 232 patients, 214 (92%) had a baseline MMD > 5, suggesting a high proportion of women with attacks outside of the 5-day perimenstrual window (2 days before and 3 days after the start of menstruation). Information on "migraine days" includes (and does not discriminate between) perimenstrual and intermenstrual migraine attacks. Between-group differences from placebo over months 4-6 for erenumab 70 mg and 140 mg were - 1.8 (P = 0.001) and - 2.1 (P < 0.001) days for MMD and - 1.6 (P = 0.002) and - 2.4 (P < 0.001) days for acute MSMD, respectively. The odds of having a ≥ 50% reduction from baseline in MMD over months 4-6 were 2.2 (P = 0.024) and 2.8 (P = 0.002) times greater for erenumab 70 mg and 140 mg, respectively, than for placebo. Erenumab had an overall safety profile comparable to placebo. CONCLUSION: Data from this subgroup analysis of women with menstrual migraine are consistent with data from the overall STRIVE episodic migraine population, supporting the efficacy and safety of erenumab in women who experience menstrual migraine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02456740. Registered 28 May 2015.

Anxiety sensitivity and intentional avoidance of physical activity in women with probable migraine.

INTRODUCTION: Avoidance of physical activity is a common migraine management strategy. Anxiety sensitivity (i.e. fear of anxiety and bodily sensations due to physical, cognitive, or social consequences) is a potential correlate of physical activity avoidance and may strengthen beliefs about physical activity's detrimental effect on migraine. METHOD: Women (n = 100) with probable migraine diagnosis completed an online survey about migraine and physical activity, which included the Anxiety Sensitivity Index-3. RESULTS: Anxiety sensitivity was associated with significantly increased odds of avoiding moderate- and vigorous-intensity physical activity. Anxiety sensitivity, particularly cognitive concerns, was associated with more frequent vigorous and moderate physical activity avoidance. Social concerns about anxiety sensitivity were associated with stronger expected likelihood of vigorous-intensity physical activity as a triggering and worsening factor in migraine. DISCUSSION: Preliminary findings indicate that anxiety sensitivity may contribute to avoidance of moderate and vigorous physical activity and fear-based cognitions about exercise.

Development of a claims-based algorithm to identify potentially undiagnosed chronic migraine patients.

OBJECTIVE: To develop a claims-based algorithm to identify undiagnosed chronic migraine among patients enrolled in a healthcare system. METHODS: An observational study using claims and patient survey data was conducted in a large medical group. Eligible patients had an International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) migraine diagnosis, without a chronic migraine diagnosis, in the 12 months before screening and did not have a migraine-related onabotulinumtoxinA claim in the 12 months before enrollment. Trained clinicians administered a semi-structured diagnostic interview, which served as the gold standard to diagnose chronic migraine, to enrolled patients. Potential claims-based predictors of chronic migraine that differentiated semi-structured diagnostic interview-positive (chronic migraine) and semi-structured diagnostic interview-negative (non-chronic migraine) patients were identified in bivariate analyses for inclusion in a logistic regression model. RESULTS: The final sample included 108 patients (chronic migraine = 64; non-chronic migraine = 44). Four significant predictors for chronic migraine were identified using claims in the 12 months before enrollment: ≥15 versus <15 claims for acute treatment of migraine, including opioids (odds ratio = 5.87 [95% confidence interval: 1.34-25.63]); ≥24 versus <24 healthcare visits (odds ratio = 2.80 [confidence interval: 1.08-7.25]); female versus male sex (odds ratio = 9.17 [confidence interval: 1.26-66.50); claims for ≥2 versus 0 unique migraine preventive classes (odds ratio = 4.39 [confidence interval: 1.19-16.22]). Model sensitivity was 78.1%; specificity was 72.7%. CONCLUSIONS: The claims-based algorithm identified undiagnosed chronic migraine with sufficient sensitivity and specificity to have potential utility as a chronic migraine case-finding tool using health claims data. Research to further validate the algorithm is recommended.

Sleep Disorders Among People With Migraine: Results From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.

OBJECTIVES: We examined the cross-sectional association of sleep apnea and indices of sleep quality with both episodic migraine (EM) and chronic migraine (CM). BACKGROUND: Sleep apnea and abnormal patterns of sleep, such as insomnia, were associated with migraine onset, severity, and progression in previous research. METHODS: The Chronic Migraine Epidemiology & Outcomes Study, a longitudinal study, used a series of web-based surveys to assess migraine symptoms, burden, and patterns of health care utilization. Quota sampling was used from September 2012 to November 2013 to generate a representative sample of the US population. Persons who screened positive for sleep apnea on the Berlin Questionnaire are said to be at "high risk" for sleep apnea. Respondents indicated if they believed that they had sleep apnea, if a physician had diagnosed it, and if and how they were treated. Other aspects of sleep quality were assessed using the Medical Outcomes Study (MOS) Sleep Measures. RESULTS: Of 12,810 eligible respondents with migraine and data on sleep, 11,699 with EM (91.3%) and 1111 with CM (8.7%) provided valid data for this analyses. According to the Berlin Questionnaire, 4739/12,810 (37.0%) were at "high risk" for sleep apnea, particularly persons with CM vs EM (575/1111 [51.8%] vs 4164/11,699 [35.6%]), men vs women (1431/3220 [44.4%] vs 3308/9590 [34.5%]), people with higher body mass index, and older people (all P < .001). Among respondents to the MOS Sleep Measures, persons with CM were more likely to report poor sleep quality than those with EM, including sleep disturbance (mean [SD] values: 53.2 [26.9] vs 37.9 [24.3]), snoring (38.0 [33.9] vs 31.0 [32.1]), shortness of breath (34.9 [29.8] vs 15.3 [20.6]), somnolence (44.1 [23.4] vs 32.2 [21.2]), and less likely to report sleep adequacy (34.0 [24.2] vs 39.2 [22.1]). CONCLUSIONS: Compared with respondents with EM, a larger proportion of those with CM were at "high risk" for sleep apnea and reported poor sleep quality. This reflects an association between CM vs EM and sleep apnea and poor sleep quality; the potential relationships are discussed.

Anxiety Sensitivity as a Risk Indicator for Anxiety, Depression, and Headache Severity in Women With Migraine.

OBJECTIVE: The primary aim of this exploratory study was to assess the relationship between anxiety sensitivity and emotional disorders, migraine characteristics, and migraine-related fear and avoidance behaviors in women with probable migraine. BACKGROUND: Anxiety and depressive disorders are the most frequent comorbid psychiatric conditions in migraine, particularly in women; however, the underlying reasons for these comorbidities are uncertain. Anxiety sensitivity, the tendency to catastrophically appraise anxiety and bodily sensations in terms of their physical, social, or cognitive consequences, is a psychological factor that may contribute to the comorbidity of anxiety and depressive disorders and migraine. It was hypothesized that anxiety sensitivity would be associated with greater migraine severity and psychiatric symptoms. METHOD: Participants were women (n = 100) who screened positive for migraine on the validated IDMigraine Screener participated in an anonymous single-session online survey-based study on migraine. The Anxiety Sensitivity Index-3 total and subscales scores were used to assess anxiety sensitivity. Anxiety and depression symptoms were assessed with the brief Patient Health Questionnaire. RESULTS: On average, anxiety sensitivity was clinically elevated (mean ± SD: 24.0 ± 15.2). Anxiety sensitivity cognitive and social concerns were most strongly correlated with severity of anxiety (r's = .38-.46) and depressive symptoms (r = .35-.39, P's < .001), and all anxiety sensitivity facets were related to fear of head pain (r's = .35-.38, P's < .001). Anxiety sensitivity cognitive concern facet was uniquely related to headache patterns, including longer migraine attack duration (r = .22, P = .029) and pain intensity (r = .24, P = .029), pain-related avoidance, including avoiding movement and more frequent misuse of prescribed or non-prescribed pain medication (r's = .20-.21, P's < .01). CONCLUSIONS: These novel findings indicate that anxiety sensitivity, specifically fearful appraisal of bodily sensations, are linked to both psychiatric symptoms and migraine severity in women. In this cross-sectional study, causal sequence cannot be determined. If anxiety sensitivity leads to more severe pain and psychiatric distress, targeting anxiety sensitivity could lead to better headache outcomes.

Sleep Disorders and Migraine: Review of Literature and Potential Pathophysiology Mechanisms.

Migraine shares a complex and poorly understood relationship with sleep. Patients consistently report poor sleep prior to migraine attacks and during them, identifying poor sleep as a migraine trigger. However, anecdotally, sleep is reported to serve a therapeutic role in terminating headache. Are the associations between migraine and sleep simply the result of various bidirectional relationships? A growing body of evidence suggests there may be a common underlying etiology as well. Our objective was to review studies of sleep and migraine from the last 2 decades utilizing validated subjective and objective measures of sleep and to explore potential mechanisms underlying this complex relationship by incorporating recent advances in neuroscience. We specifically focus on insomnia, obstructive sleep apnea, parasomnias, sleep related movement disorders, and REM sleep related disorders and their relationship to migraine. Parts of brainstem-cortical networks involved in sleep physiology are unintentionally being identified as important factors in the common migraine pathway. Recent discoveries on anatomic localization (the hypothalamus as a key and early mediator in the pathophysiology of migraine), common mediating signaling molecules (such as serotonin and dopamine), and the discovery of a new CNS waste removal system, the glymphatic system, all point to a common pathophysiology manifesting in migraine and sleep problems.

The role of migraine headache severity, associated features and interactions with overweight/obesity in inhibitory control.

AIM OF THE STUDY: While migraine and obesity are related and both conditions are associated with reduced executive functioning, no study has examined whether obesity exacerbates executive dysfunction in migraine. This cross-sectional study examined whether overweight/obesity moderated associations of migraine severity and associated features with inhibitory control, one aspect of executive function. MATERIALS AND METHODS: Women (n = 124) aged 18-50 years old with overweight/obesity body mass index (BMI) = 35.1 ± 6.4 kg/m2 and migraine completed a 28-day smartphone-based headache diary assessing migraine headache severity (attack frequency, pain intensity) and frequency of associated features (aura, photophobia, phonophobia, nausea). They then completed computerized measures of inhibitory control during an interictal (headache-free) period. RESULTS: Participants with higher migraine attack frequency performed worse on the Flanker test (accuracy and reaction time; p < .05). Migraine attack frequency and pain intensity interacted with BMI to predict slower Stroop and/or Flanker Reaction Time (RT; p < .05). More frequent photophobia, phonophobia and aura were independently related to slower RT on the Stroop and/or Flanker tests (p < .05), and BMI moderated the relationship between the occurrence of aura and Stroop RT (p = .03). CONCLUSIONS: Associations of migraine severity and presence of associated features with inhibitory control varied by BMI in overweight/obese women with migraine. These findings warrant consideration of weight status in clarifying the role of migraine in executive functioning.

Sex-related influences in migraine.

Migraine is a common neurological disorder with significantly higher incidence and prevalence in women than men. The presentation of the disease in women is modulated by changes in sex hormones from adolescence to pregnancy and menopause. Yet, the effect of sex influences has often been neglected in both basic and clinical and in clinical management of the disease. In this review, evidence from epidemiological, clinical, animal, and neuroimaging studies on the significance of the sex-related influences in migraine is presented, and the unmet needs in each area are discussed. © 2016 Wiley Periodicals, Inc.

Importance of Pain Acceptance in Relation to Headache Disability and Pain Interference in Women With Migraine and Overweight/Obesity.

BACKGROUND: Pain acceptance involves willingness to experience pain and engaging in valued activities while pain is present. Though pain acceptance could limit both headache-related disability and pain interference in individuals with migraine, few studies have addressed this issue. This study evaluated whether higher levels of total pain acceptance and its two subcomponents, pain willingness and activity engagement, were associated with lower levels of headache-related impairment in women who had both migraine and overweight/obesity. METHODS: In this cross-sectional study, participants seeking weight loss and headache relief in the Women's Health and Migraine trial completed baseline measures of pain acceptance (Chronic Pain Acceptance Questionnaire [CPAQ]), headache-related disability (Headache Impact Test-6), and pain interference (Brief Pain Inventory). Migraine headache frequency and pain intensity were assessed daily via smartphone diary. Using CPAQ total and subcomponent (pain willingness and activity engagement) scores, headache frequency, pain intensity, and body mass index (BMI) as predictors in linear regression, headache-related disability, and pain interference were modeled as outcomes. RESULTS: On average, participants (n = 126; age = 38.5 ± 8.2 years; BMI = 35.3 ± 6.6 kg/m2 ) reported 8.4 ± 4.7 migraine days/month and pain intensity of 6.0 ± 1.5 on a 0-10 scale on headache days. After correcting for multiple comparisons (adjusted α = .008), pain willingness was independently associated with both lower headache-related disability (P < .001; ß = -0.233) and pain interference (P < .001; ß = -0.261). Activity engagement was not associated with headache-related disability (P = .128; ß = -0.138) and pain interference (P = .042; ß = -0.154). CPAQ total score was not associated with headache-related disability (P = .439; ß = 0.066) and pain interference (P = .305; ß = 0.074). Pain intensity was significantly associated with outcomes in all analyses (Ps < .001; ßs 0.343-0.615). CONCLUSIONS: Higher pain willingness, independent of degree of both migraine severity and overweight, is associated with lower headache-related disability and general pain interference in treatment-seeking women with migraine and overweight/obesity. Future studies are needed to clarify direction of causality and test whether strategies designed to help women increase pain willingness, or relinquish ineffective efforts to control pain, can improve functional outcomes in women who have migraine and overweight/obesity.

Psychological Factors Associated With Chronic Migraine and Severe Migraine-Related Disability: An Observational Study in a Tertiary Headache Center.

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.

Sexual Dysfunction in Women With Migraine and Overweight/Obesity: Relative Frequency and Association With Migraine Severity.

BACKGROUND/OBJECTIVE: Previous studies suggest that migraine might be associated with female sexual dysfunction (FSD), although this association may be complicated by overweight/obesity. To disentangle relationships of migraine and obesity with FSD, we examined: (1) FSD rates in women who had migraine and obesity with a matched sample of women with obesity who were free of migraine and (2) associations between indices of migraine severity and FSD in a larger sample of participants with migraine and overweight/obesity, controlling for important confounders. METHODS: Women with migraine and obesity seeking behavioral weight loss treatment to decrease headaches (n = 37) and nonmigraine controls (n = 37) with obesity seeking weight loss via bariatric surgery were matched on age (±5 years), body mass index (BMI; ±3 kg/m2 ), and reported sexual activity during the past month. Both groups completed the Female Sexual Function Index (FSFI), with a validated FSFI-total cutoff score used to define FSD. In participants with migraine and overweight/obesity (n = 105), separate logistic regression models evaluated associations of migraine attack frequency, intensity, and duration with odds of having FSD, controlling for age, BMI, depression, and anxiety. RESULTS: On average, participants and matched controls had severe obesity (BMI = 42.4 ± 3.8 kg/m2 ; range = 35-49.9) and were 37.3 ± 7.2 years of age (range = 22-50). FSD rate did not differ between migraine participants and controls (56.8% vs. 54.1%, P = .82). In the larger sample of participants with migraine and overweight/obesity (38.2 ± 7.8 years of age; BMI = 34.8 ± 6.4 [range = 25-50 kg/m2 ]; 8.0 ± 4.3 migraine days/month, maximum pain intensity = 5.9 ± 1.4 on 0-10 scale; average attack duration = 18.3 ± 9.7 hours), FSD was not associated with attack frequency (P = .31), pain intensity (P = .92), or attack duration (P = .35) but was associated with more severe anxiety symptoms (Ps < .017). CONCLUSIONS: Rates of sexual dysfunction did not differ in severely obese women with and without migraine. Moreover, indices of migraine severity were not associated with increased risk of FSD in women with overweight/obesity. Replication of present findings in wider populations of women with migraine and of both normal-weight and overweight/obese status are warranted.

Association Between Obesity and Migraine in Women.

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

Lower inhibitory control interacts with greater pain catastrophizing to predict greater pain intensity in women with migraine and overweight/obesity.

BACKGROUND: Pain catastrophizing (PC) is associated with more severe and disabling migraine attacks. However, factors that moderate this relationship are unknown. Failure of inhibitory control (IC), or the ability to suppress automatic or inappropriate responses, may be one such factor given previous research showing a relationship between higher PC and lower IC in non-migraine samples, and research showing reduced IC in migraine. Therefore, we examined whether lower IC interacts with increased PC to predict greater migraine severity as measured by pain intensity, attack frequency, and duration. METHODS: Women (n = 105) aged 18-50 years old (M = 38.0 ± 1.2) with overweight/obesity and migraine who were seeking behavioral treatment for weight loss and migraine reduction completed a 28-day smartphone-based headache diary assessing migraine headache severity. Participants then completed a modified computerized Stroop task as a measure of IC and self-report measures of PC (Pain Catastrophizing Scale [PCS]), anxiety, and depression. Linear regression was used to examine independent and joint associations of PC and IC with indices of migraine severity after controlling for age, body mass index (BMI) depression, and anxiety. RESULTS: Participants on average had BMI of 35.1 ± 6.5 kg/m2and reported 5.3 ± 2.6 migraine attacks (8.3 ± 4.4 migraine days) over 28 days that produced moderate pain intensity (5.9 ± 1.4 out of 10) with duration of 20.0 ± 14.2 h. After adjusting for covariates, higher PCS total (ß = .241, SE = .14, p = .03) and magnification subscale (ß = .311, SE = .51, p < .01) scores were significant independent correlates of longer attack duration. IC interacted with total PCS (ß = 1.106, SE = .001, p = .03) rumination (ß = 1.098, SE = .001, p = .04), and helplessness (ß = 1.026, SE = .001, p = .04) subscale scores to predict headache pain intensity, such that the association between PC and pain intensity became more positive at lower levels of IC. CONCLUSIONS: Results showed that lower IC interacted with higher PC, both overall and specific subcomponents, to predict higher pain intensity during migraine attacks. Future studies are needed to determine whether interventions to improve IC could lead to less painful migraine attacks via improvements in PC.

Improving the detection of chronic migraine: Development and validation of Identify Chronic Migraine (ID-CM).

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-3ß 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.

Clinical Pain Catastrophizing in Women With Migraine and Obesity.

OBJECTIVE/BACKGROUND: Obesity is related to migraine. Maladaptive pain coping strategies (eg, pain catastrophizing) may provide insight into this relationship. In women with migraine and obesity, we cross-sectionally assessed: (1) prevalence of clinical catastrophizing; (2) characteristics of those with and without clinical catastrophizing; and (3) associations of catastrophizing with headache features. METHODS: Obese women migraineurs seeking weight loss treatment (n = 105) recorded daily migraine activity for 1 month via smartphone and completed the Pain Catastrophizing Scale (PCS). Clinical catastrophizing was defined as total PCS score ≥30. The six-item Headache Impact Test (HIT-6), 12-item Allodynia Symptom Checklist (ASC-12), Headache Management Self-Efficacy Scale (HMSE), and assessments for depression (Centers for Epidemiologic Studies Depression Scale) and anxiety (seven-item Generalized Anxiety Disorder Scale) were also administered. Using PCS scores and body mass index (BMI) as predictors in linear regression, we modeled a series of headache features (ie, headache days, HIT-6, etc) as outcomes. RESULTS: One quarter (25.7%; 95% confidence interval [CI] = 17.2-34.1%) of participants met criteria for clinical catastrophizing: they had higher BMI (37.9 ± 7.5 vs 34.4 ± 5.7 kg/m(2) , P = .035); longer migraine attack duration (160.8 ± 145.0 vs 97.5 ± 75.2 hours/month, P = .038); higher HIT-6 scores (68.7 ± 4.6 vs 64.5 ± 3.9, P < .001); more allodynia (7.0 ± 4.1 vs 4.5 ± 3.5, P < .003), depression (25.4 ± 12.4 vs 13.3 ± 9.2, P < .001), and anxiety (11.0 ± 5.2 vs 5.6 ± 4.1, P < .001); and lower self-efficacy (80.1 ± 25.6 vs 104.7 ± 18.9, P < .001) compared with participants without clinical catastrophizing. The odds of chronic migraine were nearly fourfold greater in those with (n = 8/29.6%) vs without (n = 8/10.3%) clinical catastrophizing (odds ratio = 3.68; 95%CI = 1.22-11.10, P = .021). In all participants, higher PCS scores were related to more migraine days (ß = 0.331, P = .001), longer attack duration (ß = 0.390, P < .001), higher HIT-6 scores (ß = 0.425, P < .001), and lower HMSE scores (ß = -0.437, P < .001). Higher BMI, but not higher PCS scores, was related to more frequent attacks (ß = -0.203, P = .044). CONCLUSIONS: One quarter of participants with migraine and obesity reported clinical catastrophizing. These individuals had more frequent attacks/chronicity, longer attack duration, higher pain sensitivity, greater headache impact, and lower headache management self-efficacy. In all participants, PCS scores were related to several migraine characteristics, above and beyond the effects of obesity. Prospective studies are needed to determine sequence and mechanisms of relationships between catastrophizing, obesity, and migraine.