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Are Migraine and Bipolar Disorders Comorbid Phenomena?: Findings From a Pharmacoepidemiological Study Using the Norwegian Prescription Database

Oedegaard, Ketil J. MD*†; Dilsaver, Steven C. MD; Hundal, Øivind PhD; Riise, Trond PhD; Lund, Anders MD*†; Akiskal, Hagop S. MD¶#; Fasmer, Ole B. MD*†

Journal of Clinical Psychopharmacology: December 2011 - Volume 31 - Issue 6 - p 734-739
doi: 10.1097/JCP.0b013e318235f4e9
Original Contributions

Objectives: Clinical, epidemiological, and, recently, genome-wide linkage and genome-wide association studies suggest migraine and bipolar disorder are comorbid phenomena. The objective of this study was to determine whether there is also evidence that this comorbidity exists by virtue of there being a positive relationship between the prescription of medications used to treat migraine and mood-stabilizing agents using the National Norwegian Prescription Database.

Methods: Data allowing ascertainment of the concurrence of prescriptions for migraine and mood-stabilizing agents were gleaned from the Norwegian Prescription Database for calendar year 2006, covering the total population (N = 4,640,219). Results were obtained using logistic regression analyses and were expressed by odds ratios (ORs).

Results: A total of 81,225 persons (1.8% of the population) received medications for migraine and 19,517 (0.45%) received a mood-stabilizing agent for a bipolar disorder; 843 persons received both types of medications. The OR expressing the relationship between the concurrent use of both categories of medications was 2.55 (95% confidence interval [CI], 2.38-2.73, P < 0.001, z score = 26.44), significant for all mood stabilizers (lithium: OR = 1.82 [95% CI, 1.58-2.10], P < 0.001, z score = 8.31; carbamazepine: OR = 2.48 [95% CI, 2.01-3.06], P < 0.001, z score = 8.42; valproic acid: OR = 2.26 [95% CI, 1.89-2.70], P < 0.001, z score = 8.96; and lamotrigine: OR = 3.50 [95% CI, 3.14-3.90], P < 0.001, z score = 22.68). The association was significantly higher for men (OR = 3.16 [95% CI, 2.74-3.66], P < 0.001, z score = 15.53) than for women (OR = 2.21 [95% CI, 2.04-2.39], P < 0.001, z score = 19.61) and was most pronounced in younger age groups and for lamotrigine.

Conclusions: There was a strong positive association between the prescription of medications used to treat migraine and mood-stabilizing agents. This is compatible with the hypothesis that migraine and bipolar disorders are associated with one another.

From the *Moodnet Research Group, Haukeland University Hospital; †Department of Clinical Medicine, Section of Psychiatry, University of Bergen, Bergen, Norway; ‡Comprehensive Doctors Medical Group, Arcadia, CA; §Apotekene Vest HF Bergen; ∥Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway; ¶Department of Psychiatry, VA San Diego Healthcare System; and #Department of Psychiatry, University of California, San Diego, CA.

Received November 16, 2010; accepted after revision June 28, 2011.

Reprints: Ketil J. Oedegaard, MD, Moodnet Research Group, Haukeland University Hospital, and Department of Clinical Medicine, Section of Psychiatry, University of Bergen, Norway, PB 23 Sandviken, N-5812 Bergen, Norway (e-mail:

This work was supported by an unrestricted grant from MoodNet, Norwegian Regional Health Department - West.

© 2011 Lippincott Williams & Wilkins, Inc.