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

Abstract

Background: Migraine has many presumed comorbidities which have rarely been compared between samples with and without migraine. Examining the association between headache pain intensity and monthly headache day (MHD) frequency with migraine comorbidities is novel and adds to our understanding of migraine comorbidity.

Methods: The MAST Study is a prospective, web-based survey that identified US population samples of persons with migraine (using modified International Classification of Headache Disorders-3 beta criteria) and without migraine. Eligible migraine participants averaged ≥1 MHDs over the prior 3 months. Comorbidities "confirmed by a healthcare professional diagnosis" were endorsed by respondents from a list of 21 common cardiovascular, neurologic, psychiatric, sleep, respiratory, dermatologic, pain and medical comorbidities. Multivariable binary logistic regression calculated odds ratios (OR) and 95% confidence intervals for each condition between the two groups adjusting for sociodemographics. Modeling within the migraine cohort assessed rates of conditions as a function of headache pain intensity, MHD frequency, and their combination.

Results: Analyses included 15,133 people with migraine (73.0% women, 77.7% White, mean age 43 years) and 77,453 controls (46.4% women, 76.8% White, mean age 52 years). People with migraine were significantly (P < 0.001) more likely to report insomnia (OR 3.79 [3.6, 4.0]), depression (OR 3.18 [3.0, 3.3]), anxiety (OR 3.18 [3.0 3.3]), gastric ulcers/GI bleeding (OR 3.11 [2.8, 3.5]), angina (OR 2.64 [2.4, 3.0]) and epilepsy (OR 2.33 [2.0, 2.8]), among other conditions. Increasing headache pain intensity was associated with comorbidities related to inflammation (psoriasis, allergy), psychiatric disorders (depression, anxiety) and sleep conditions (insomnia). Increasing MHD frequency was associated with increased risk for nearly all conditions and most prominent among those with comorbid gastric ulcers/GI bleeding, diabetes, anxiety, depression, insomnia, asthma and allergies/hay fever.

Conclusions: In regression models controlled for sociodemographic variables, all conditions studied were reported more often by those with migraine. Whether entered into the models separately or together, headache pain intensity and MHD frequency were associated with increased risk for many conditions. Future work is required to understand the causal sequence of relationships (direct causality, reverse causality, shared underlying predisposition), the potential confounding role of healthcare professional consultation and treatment, and potential detection bias.

Keywords: Comorbidities; Epidemiology; Headache frequency; Headache pain intensity; Migraine; Sociodemographics.

Conflict of interest statement

SM and PS are employed by Dr. Reddy’s Laboratories; RBL, DCB, MLR, TJS, and DWD were paid consultants of Dr. Reddy’s Laboratories.

DCB has received grant support and honoraria from Allergan, Amgen, Avanir, Biohaven, Eli Lilly, Novartis and Promius/Dr. Reddys. She has not been paid by any company for work writing manuscripts, or writing or presenting abstracts, posters or platforms. She serves on the editorial boards of Current Pain and Headache Reports, the Journal of Headache and Pain, Pain Medicine News, and Pain Pathways magazine.

DWD: Consulting: Amgen, University Health Network, Daniel Edelman Inc., Autonomic technologies, Axsome, Allergan, Alder, Biohaven, Charleston Laboratories, Promius, Eli Lilly, eNeura, Neurolief, Novartis, Ipsen, Impel, Satsuma, Supernus, Theranica, Teva, WL Gore, Nocira, XoC, Zosano, Upjohn (Division of Pfizer), Pieris, Revance, Equinox, Salvia, Amzak Health. Honoraria: Foresite Capital, ZP Opco, Oppenheimer, Association of Translational Medicine, Healthlogix, Medicom Worldwide, Medlogix Communications, Mednet, Electrocore, Miller Medical, PeerView, WebMD Health/Medscape, Chameleon, Academy for Continued Healthcare Learning, Sun Pharma (India), Universal meeting management, Haymarket, Global Scientific Communications, Global Life Sciences, Global Access Meetings, UpToDate (Elsevier), Oxford University Press, Cambridge University Press, Wolters Kluwer Health. Research Support: Department of Defense, National Institutes of Health, Henry Jackson Foundation, Sperling Foundation, American Migraine Foundation, and Patient Centered Outcomes Research Institute (PCORI). Stock Options/Shareholder/Patents/Board of Directors: Aural analytics, Healint, Theranica, Second Opinion/Mobile Health, Epien (Options/Board), Nocira, Matterhorn/Ontologics (Options/Board), King-Devick Technologies (Options/Board), Precon Health (Options/Board). Patent 17189376.1–1466:vTitle: Botulinum Toxin Dosage Regimen for Chronic Migraine Prophylaxis.

MLR, KMF, and RB are employees of Vedanta Research, which has received support funded by Allergan, Amgen, Colucid, Eli Lilly, NuPathe, Novartis, Ortho-McNeil and the National Headache Foundation.

TJS received research support from the American Migraine Foundation, Henry Jackson Foundation, National Institutes of Health, Patient-Centered Outcomes Research Institute, US Department of Defense, and Amgen. Within the past 12 months, he has served as a consultant or advisory board member for Alder, Allergan, Amgen, Avanir, Biohaven, Dr. Reddy’s, Eli Lilly, Equinox, Ipsen Bioscience, Novartis, Teva, and XoC Pharmaceuticals. He holds stock options in Aural Analytics, Nocira, and Second Opinion. He serves as an Associate Editor for Headache and Cephalalgia.

RBL has received grant support from the National Institutes of Health, the National Headache Foundation, and the Migraine Research Fund. He serves as consultant, serves as an advisory board member, or has received honoraria from Alder, Allergan, American Headache Society, Autonomic Technologies, Biohaven, Eli Lilly, eNeura Therapeutics, Merck, Novartis, Pfizer, and Teva, Inc. He receives royalties from Wolff’s Headache, 8th Edition (Oxford University Press, 2009). He holds stock options in eNeura Therapeutics and Biohaven.

Figures

Fig. 1

Relative odds of migraine (and 95% CI) vs. migraine free controls for each comorbid condition*. *Adjusted for sociodemographic characteristics (age, gender, Hispanic origin, race, marital status, employment, household income). Reference group is the non-migraine cohort. GI = gastrointestinal; OR = odds ratio; TIA = transient ischemic attack

Fig. 2

Among persons with migraine the odds ratios (and 95% CI) for each comorbid cardiovascular condition*. *Fully adjusted models with sociodemographic characteristics (age, gender, Hispanic origin, race, marital status, employment, household income), headache pain intensity and headache frequency. Reference groups are low headache pain intensity for headache pain intensity and low frequency headache (1–4 MHDs) for headache frequency

Fig. 3

Among persons with migraine the odds ratios (and 95% CI) for each comorbid neurologic condition*. *Fully adjusted models with sociodemographic characteristics (age, gender, Hispanic origin, race, marital status, employment, household income), headache pain intensity and headache frequency. Reference groups are low headache pain intensity for headache pain intensity and low frequency headache (1–4 MHDs) for headache frequency

Fig. 4

Among persons with migraine the odds ratios (and 95% CI) for each comorbid general medical condition*. Fully adjusted models with sociodemographic characteristics (age, gender, Hispanic origin, race, marital status, employment, household income), headache pain intensity and headache frequency. Reference groups are low headache pain intensity for headache pain intensity and low frequency headache (1–4 MHDs) for headache frequency

Fig. 5

Among persons with migraine the odds ratios (and 95% CI) for comorbid psychiatric and sleep conditions*. Fully adjusted models with sociodemographic, characteristics (age, gender, Hispanic origin, race, marital status, employment, household income), headache pain intensity and headache frequency. Reference groups are low headache pain intensity for headache pain intensity and low frequency headache (1–4 MHDs) for headache frequency

Fig. 6

Among persons with migraine the odds ratios (and 95% CI) for comorbid respiratory and dermatologic conditions*. *Fully adjusted models with sociodemographic characteristics (age, gender, Hispanic origin, race, marital status, employment, household income), headache pain intensity and headache frequency. Reference groups were low headache pain intensity for headache pain intensity and low frequency headache (1–4 MHDs) for headache frequency

Fig. 7

Among persons with migraine the odds ratios (and 95% CI) for each comorbid pain condition*. *Fully adjusted models with sociodemographic characteristics (age, gender, Hispanic origin, race, marital status, employment, household income), headache pain intensity and headache frequency. Reference groups are low headache pain intensity for headache pain intensity and low frequency headache (1–4 MHDs) for headache frequency