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.

The longitudinal relation of inflammation to incidence of vasomotor symptoms.

OBJECTIVE: Vasomotor symptoms (VMS), the most frequently reported symptoms during the menopausal transition, have been associated with inflammation. Whether inflammation is a risk factor for or a consequence of VMS remains unclear. The objectives of these analyses were to determine if elevated proinflammatory marker levels were associated with increased incident VMS in women without VMS at baseline and whether these associations varied by menopause transition stage or race/ethnicity. METHODS: We used longitudinal data on incident VMS, high-sensitivity C-reactive protein (hs-CRP; n = 1,922) and interleukin-6 (IL-6; n = 203) from 13 follow-up visits in the Study of Women's Health Across the Nation, which included five racial/ethnic groups of midlife women. We performed multivariable discrete-time survival analyses to determine adjusted hazard ratios (aHRs) for the association of these proinflammatory markers with incident VMS in women without VMS at baseline. RESULTS: We found no significant associations of incident VMS with dichotomized hs-CRP (>3 vs ≤3 mg/L) at baseline, concurrent or prior visit (aHRs, 1.04-2.03) or IL-6 (>1.44 vs ≤1.44 pg/mL) at visit 1, concurrent or prior visit (aHRs, 0.67-1.62), or continuous hs-CRP or IL-6 values over 13 follow-up visits (with nonsignificant adjusted increased hazards ranging from 0% to 2%). CONCLUSIONS: Our results showed no significant association of the proinflammatory biomarkers, hs-CRP or IL-6, either concurrently or with subsequent incident VMS, indicating that inflammation was unlikely to be a risk factor for VMS. Thus, clinical treatments directed at reducing inflammation would be unlikely to reduce the occurrence of VMS.

The importance of an early onset of migraine prevention: an evidence-based, hypothesis-driven scoping literature review.

Recently approved migraine preventive therapies facilitate rapid control of migraine activity, potentially improving patients' lives and minimizing the societal burden of migraine. This review synthesizes available evidence on rates and timing of early onset of migraine prevention and identifies patient-level outcomes related to early onset prevention. This evidence-based scoping review identified all available clinical trial evidence regarding the early onset of prevention of migraine, under the hypothesis 'Patients with migraine (episodic or chronic) report additional benefits when receiving an approved migraine preventive treatment that demonstrates an early onset of prevention'. Early onset of prevention was defined as migraine preventive benefits within 30 days post-administration. PubMed, EMBASE, and CINAHL were searched for publications between 1988 and 2020. Overall, 16 publications described 18 studies. All studies were conducted in approved treatments [four anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies and one chemodenervation agent] in patients with episodic/chronic migraine; no publications were identified for traditional oral agents for early migraine prevention. Compared to placebo, erenumab (three studies) reduced weekly migraine days within 1 week; fremanezumab (six studies) increased reports of no headache of at least moderate severity on Day 1 and significantly reduced migraine frequency within 1 week; galcanezumab (three studies) significantly reduced the mean number of patients with migraine beginning Day 1 and each day of the first week; eptinezumab (four studies) significantly reduced migraine attack likelihood on Day 1 by > 50% versus baseline; and onabotulinumtoxinA (two studies) reduced headache and migraine days within 1 week. Four publications described function, disability, and quality of life improvements as early as Week 4; none reported cost-benefit. Anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab) and a chemodenervation agent (onabotulinumtoxinA) provide clinically relevant benefits during the first treatment week. Literature describing clinically relevant benefits regarding early onset of prevention in patients with migraine is limited.

Pain in midlife women: a growing problem in need of further research.

More than 10% of American adults experience some level of daily pain, and nearly 40 million (17.6%) experience episodes of severe pain annually. Women are particularly impacted by both episodic and chronic pain with higher prevalence and a greater level of pain-related disability compared to men. Midlife is a critical period for women during which the frequency of pain complaints begins to increase. Although pain is known to be influenced and controlled by sex hormones, it has not been widely recognized as a symptom of the menopausal transition outside of the menopause research community. The recent thematic series in this journal has specifically highlighted pain related conditions including rheumatoid arthritis, migraine and abdominal pain for which the significance among midlife women is not typically recognized. The studies presented in this thematic series present a small fraction of relevant, understudied questions regarding pain and its impact on women in midlife. Addressing the gaps in knowledge will require longitudinal studies that consider the emergence of pain symptomatology in relation to midlife trajectories of other symptoms and health determinants, as well as further study of new and emerging therapies.

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.

Reliabilities of Intra-Individual Mean and Intra-Individual Variability of Self-Reported Pain Derived From Ecological Momentary Assessments: Results From the Einstein Aging Study.

An individual's pain experiences vary substantially over time. Though variability in pain may be an important metric which usually predicts health consequences, research on the measurement of pain variability estimates is lacking among older adults. We aimed to examine the reliabilities of both intra-individual mean (IIM) and intra-individual variability (IIV) of pain assessed using ecological momentary assessments (EMA) among racially diverse, systematically recruited community dwelling cohort of older adults. Participants (N = 311, age = 70-91) completed a 14-day EMA protocol which included self-reports of pain intensity, pain interference with activities, and pain interference with concentration multiple times a day. Over a 2-week period, we found excellent reliabilities for both pain IIM (.99), and pain IIV (≥.90). We also found that we need 5 to 6 days to achieve good reliability (.8) for pain IIV, suggesting that a shorter protocol may be used to reduce participants' burden among the current sample, although caution is required when using this result to determine EMA study designs among different samples. Future studies are required to examine the associations of various EMA pain metrics with different health outcomes among older adults to facilitate the detection of underlying mechanisms linking pain to health as a prelude to interventions. PERSPECTIVE: Mean levels and variability in pain intensity, pain interference with activities, and pain interference with concentration can be reliably measured to be linked with various health outcomes in older adults. Future studies including these pain metrics will assess the natural history, the consequences, and effects of intervention of pain.

Headache in Women.

PURPOSE OF REVIEW: Women are greatly overrepresented among patients seeking treatment for symptoms of headache pain in general and migraine in particular. Understanding the presentation of headache in women in relation to hormonal changes both during the menstrual cycle and throughout the life span is essential for appropriate diagnosis and treatment. RECENT FINDINGS: Although perimenstrual migraine attacks are generally without aura, the diagnosis of migraine with aura has been added to the headache classification for menstrual migraine to account for women with the diagnosis of migraine with aura who experience menstrual migraine attacks. Emerging knowledge regarding the differences between menstrual and nonmenstrual attacks, the variability of attack triggering within and between women, and the response of women with menstrually related migraine to new migraine drug classes is contributing to better understanding and more effective treatment of these particularly burdensome and refractory attacks. Given the burden of migraine, almost one-fourth of women with migraine avoid or delay pregnancy. Women who experience migraine during pregnancy are more likely to have a hypertensive disorder and stroke during pregnancy and/or delivery and the postpartum period. Treatment of headache in general and migraine in particular in pregnancy is challenging because of fetal and maternal risks; however, a 2021 systematic review suggests that triptans and low-dose aspirin may not be associated with fetal/child adverse effects and could be more strongly considered for headache treatment in pregnancy. SUMMARY: Headache in general and migraine in particular are extraordinarily common in women of reproductive age and fluctuate with hormonal changes and phases of life. Improved knowledge of the epidemiology, pathophysiology, and response to treatment of perimenstrual attacks is essential for more effective response to this most burdensome headache type. Treatment of headache in pregnancy remains challenging.

Naturalistic assessment of patterns and predictors of acute headache medication use among women with comorbid migraine and overweight or obesity.

Given the potential for obesity to complicate migraine treatment outcomes, there is a need to understand patterns and correlates of acute medication use among individuals with this comorbidity. Experience sampling methodology (ESM) was used to characterize patterns of acute medication use among those with migraine and overweight/obesity and to examine individual and momentary factors related to medication use (both migraine-specific and nonspecific medications). Women with migraine and overweight/obesity (N = 170) seeking behavioral migraine treatment completed questionnaires followed by 28 days of daily ESM headache diaries. Participants used medications to treat 71.9% of attacks, 20% of which were treated with migraine-specific medications. Participants were more likely to use medication in the context of longer and more severe attacks that started earlier in the day. Presence of aura and greater work-related pain interference uniquely related to migraine-specific medication use. Questionnaire-assessed factors were not related to medication use, although older age and higher educational attainment related to more frequent use. A substantial proportion of attacks were left untreated, suggesting unmet treatment needs in this population. Results also suggest that ESM-assessed factors are more salient correlates of medication use compared to questionnaires. Additional investigation of barriers to medication use is needed.

Obesity may contribute to more severe migraine symptoms and negatively impact migraine treatment outcomes. The present study aimed to understand patterns of acute medication use among 170 women with migraine and obesity who were seeking behavioral migraine treatment. Data were collected in participants' natural environment using experience sampling methodology, during which participants reported daily migraine symptoms for 4 weeks. Approximately, 30% of attacks were not treated with any medications, and one in five attacks (i.e., 20%) was treated with migraine-specific medication. Participants were more likely to use medication during longer and more severe attacks that started earlier in the day. Participants were also more likely to use migraine-specific medication when attacks were precipitated by an aura and associated with work-related pain interference. Questionnaire-assessed factors were not related to medication use, although older age and higher educational attainment related to more frequent use. In general, these results also suggest that naturalistically assessed factors are more salient correlates of medication use compared to questionnaires. Additional investigation of barriers to medication use is needed among younger individuals and those of lower socioeconomic status.

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.

The impact of midlife on migraine in women: summary of current views.

Migraine is three times more common in women than in men and is the 4th leading cause of disability in women. Onset of migraine increases at menarche, with peaks in prevalence in the late 30s, and a rapid decline after menopause. While the prevalence is highest among women of childbearing age the frequency of headache and burden of migraine frequently worsens during midlife. Abundant population data suggest that hormonal factors may trigger headache attacks and influence onset and remission. The midlife worsening of migraine is attributed to hormonal fluctuations characteristic of the menopausal transition. Drops in estrogen presumably lead to increased migraine attacks at the time of menses as well as during the menopausal transition. During the menopausal transition, recommended approaches include both acute and preventive non-hormonal and hormonal options as well as behavioral approaches. Herein, is a brief review on the presentation of migraine in women across the lifespan, with special emphasis on midlife and the menopausal transition and implications for treatment.

Migraine Patients With Cardiovascular Disease and Contraindications: An Analysis of Real-World Claims Data.

INTRODUCTION: Triptans, the most commonly prescribed acute treatments for migraine attacks are, per FDA labeling, contraindicated in cardiovascular (CV) disease patients and have warnings and precautions for those with CV risk factors. METHODS: Headache specialists, cardiologists, and health economics and outcomes researchers convened to identify diagnostic codes for: (1) CV diseases contraindicating triptans based on FDA labeling; (2) conditions comprising "other significant underlying CV disease"; and (3) CV risk factors included as warnings and precautions for triptans. A retrospective, cross-sectional analysis of commercially insured adult US migraine patients in the 2017 Optum® Clinformatics® Data Mart (CDM) and the 2017 IBM® Watson Health MarketScan® Commercial Claims database was used to estimate the proportion of migraine patients with CV contraindications and warnings and precautions to triptans. RESULTS: Of the 56,662 migraine patients analyzed from Optum CDM, 13.5% had ≥1 CV disease as specified in triptan labeling and an additional 8.5% had ≥1 "other CV disease" judged by the panel to constitute a "significant underlying CV disease" (total: 22.0% migraine patients). Of 176 724 migraine patients analyzed from MarketScan, 12.2% had ≥1 CV disease as specified in the labeling and an additional 8.0% had ≥1 "other significant underlying CV disease" (total: 20.2% of migraine patients). An additional 25.4% and 25.1% of migraine patients had ≥2 CV risk factors in Optum CDM and MarketScan. In total, 47.4% and 45.3% of migraine patients in both databases had a CV disease specified as a contraindication, an "other CV disease" endorsed as significant, or ≥2 CV risk factors identified as warnings and precautions to triptans. CONCLUSIONS: Analyses of more than 230,000 people with migraine showed that ≥20% of commercially insured US migraine patients have a CV condition that specifically contraindicates triptan treatment, and an additional 25% have ≥2 CV risk factors identified as warnings and precautions to triptans.

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.

Treatment effects on pain catastrophizing and cutaneous allodynia symptoms in women with migraine and overweight/obesity.

OBJECTIVE: Pain catastrophizing and cutaneous allodynia represent two risk factors for greater headache-related disability. Yet, there is limited knowledge of the extent to which these risk factors are modifiable and whether nonpharmacological treatment-related changes are associated with migraine improvements. Using data from the Women's Health and Migraine (WHAM) study, a randomized controlled trial that compared effects of behavioral weight loss (BWL) and migraine education (ME) in women with migraine and overweight/obesity, we tested whether: (a) BWL versus ME produced greater changes in pain catastrophizing and allodynia from baseline across posttreatment and follow-up time points, and (b) whether these improvements were associated with improvements in headache disability. METHOD: Women (N = 110) were randomly assigned to 16 weeks of either BWL or ME and assessed at baseline, posttreatment, and follow up (32 weeks). Multilevel mixed effects modeling tested: (a) for between-groups differences in pain catastrophizing and allodynia changes over time, and (b) associations of changes in pain catastrophizing and allodynia with changes in headache disability, adjusting for migraine severity and weight loss. RESULTS: Both BWL and ME had significant reductions in pain catastrophizing and allodynia from baseline to posttreatment and follow up, and the improvements were comparable across conditions. Reductions in pain catastrophizing and cutaneous allodynia were associated with significant reductions in headache disability, even when controlling for intervention-related improvements in migraine and weight loss. CONCLUSION: Pain catastrophizing and allodynia are not only reduced after nonpharmacologic treatments for migraine, but greater improvements are associated with greater reductions in headache-related disability, independent of migraine severity. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

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.

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.

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.

The Temporal Relationship between Pain Intensity and Pain Interference and Incident Dementia.

BACKGROUND: Chronic pain is common among older adults and is associated with cognitive dysfunction based on cross-sectional studies. However, the longitudinal association between chronic pain and incident dementia in community-based samples is unknown. OBJECTIVE: We aimed to evaluate the association of pain intensity and pain interference with incident dementia in a community-based sample of older adults. METHODS: Participants were 1,114 individuals 70 years of age or older from Einstein Aging Study (EAS), a longitudinal cohort study of community-dwelling older adults in the Bronx County, NY. The primary outcome measure was incident dementia, diagnosed using DSM-IV criteria. Pain intensity and interference in the month prior to first annual visit were measured using items from the SF-36 questionnaire. Pain intensity and pain interference were assessed as predictors of time to incident dementia using Cox proportionate hazards models while controlling for potential confounders. RESULTS: Among participants, 114 individuals developed dementia over an average 4.4 years (SD=3.1) of follow-up. Models showed that pain intensity had no significant effect on time to developing dementia, whereas higher levels of pain interference were associated with a higher risk of dementia. In the model that included both pain intensity and interference as predictors of incident dementia, pain interference had a significant effect on incident dementia, and pain intensity remained non-significant. CONCLUSION: As a potential remediable risk factor, the mechanisms linking pain interference to cognitive decline merit further exploration.

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.

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.