Association between use of short-acting benzodiazepines and migraine occurrence: a nationwide population-based case–control study

Abstract

Aim: To evaluate the association between using benzodiazepines (BZDs) with short- or long-acting durations and migraine occurrence.

Methods: The migraine group comprised 9616 subjects older than 20 years and newly diagnosed with migraine between 2005 and 2011, and the comparison group comprised 38,464 subjects without migraine. The BZDs used in the subjects were dichotomously defined as short-acting (half-life ≤24 h) and long-acting substances. A logistic regression model was used to calculate the odds ratio (OR) of migraine associated with BZD exposure and other diseases.

Results: The adjusted OR of migraine associated with BZD exposure was 1.73 (95% confidence interval [CI] = 1.63–1.84). Either exposure to a short-acting BZD alone or using it combining with a long-acting BZD had significant higher risks of migraine (adjusted OR = 1.69, 95% CI = 1.59–1.80; adjusted OR = 2.06, 95% CI = 1.91–2.24, respectively), whereas only long-acting BZD use was not associated with an increase of migraine. Meanwhile, sleep disorders, anxiety, and stroke were strongly associated with migraine (adjusted OR = 2.00, 1.91, and 1.57, respectively).

Conclusions: We observed a significant increase of migraine occurrence in subjects using short-acting BZDs, either alone or in combination with long-acting ones.

Keywords:

• Benzodiazepine (BZD)
• migraine
• National Health Insurance Research Database (NHIRD)
• population-based study

Transparency

Declaration of funding

This study is supported in part by the Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-133019), China Medical University Hospital, Academia Sinica Taiwan Biobank Stroke Biosignature Project (BM10501010037), NRPB Stroke Clinical Trial Consortium (MOST105-2325-B-039-003), Tseng-Lien Lin Foundation, Taichung, Taiwan, Taiwan Brain Disease Foundation, Taipei, Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.

Author contributions: Conception/design: T.H., C.-H.T. Provision of study materials and patients: C.-H.T. Collection and assembly of data: all authors. Data analysis and interpretation: all authors. Manuscript preparation: all authors. Final approval of manuscript: all authors.

Declaration of financial/other relationships

T.H., Y.-C.W., C.-L.L., and C.-H.T. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgement

This study is supported in part by the Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-133019), China Medical University Hospital, Academia SinicaTaiwan Biobank Stroke Biosignature Project (BM10501010037), NRPB Stroke Clinical Trial Consortium (MOST105-2325-B-039-003), Tseng-Lien Lin Foundation, Taichung, Taiwan, Taiwan Brain Disease Foundation, Taipei, Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds, Japan.