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NEUROLOGY

Risk of Cerebrovascular Events Associated with Antidepressant Use in Patients with Depression: A Population-Based, Nested Case-Control Study

Research Associate of Pharmacoepidemiology and Pharmacoeconomics, Department of Pharmacy Practice and Administrative Sciences, School of Pharmacy, University of Cincinnati Medical Center, Cincinnati, OH

Jeff J Guo, PhD

Associate Professor of Pharmacoepidemiology and Pharmacoeconomics, Department of Pharmacy Practice and Administrative Sciences, School of Pharmacy, University of Cincinnati Medical Center

Hong Li, PhD MPH

Group Director, Outcomes Research, Asia Pacific, Bristol-Myers Squibb Co., Singapore

Lawson Wulsin, MD

Professor, Department of Psychiatry, College of Medicine, University of Cincinnati Medical Center

Nick C Patel, PharmD PhD

Assistant Professor, College of Pharmacy, University of Georgia; Department of Psychiatry, Medical College of Georgia, Augusta, GA

Reprints: Dr. Chen, Department of Pharmacy Practice and Administrative Sciences, School of Pharmacy, University of Cincinnati Medical Center, 3225 Eden Ave., Cincinnati, OH 45267, fax 513/558-4372, yance{at}email.uc.edu

BACKGROUND: Given the widespread use of antidepressants and the negative consequence of cerebrovascular events (CVEs), an evaluation of the risk of CVEs associated with antidepressants is warranted.

OBJECTIVE: To examine the association between the use of an antidepressant and risk of CVEs among patients diagnosed with depression.

METHODS: A case-control study was performed using a managed care medical claims database from 1998 through 2002. A total of 1086 cases with CVEs were identified and matched with 6515 controls by age, sex, and the year of the index date of depression. Case patients were categorized by stroke type: hemorrhagic stroke, ischemic stroke, and other CVEs. Diagnoses of depression, CVEs, and other medical comorbidities were identified based on International Classification of Diseases, Ninth Revision, codes. Patients were defined as current users (antidepressant ended 30 days before CVE), recent users (31-60 days before CVE), past users (61-90 days before CVE), and remote/nonusers (91 days before CVE or nonuse). Cox proportional hazards regression analysis was conducted to estimate the risk of CVEs associated with antidepressant use.

RESULTS: A 24% increased risk of a CVE was noted in patients with current exposure to selective serotonin-reuptake inhibitors (SSRIs; adjusted hazard ratio [HR] 1.24; 95% CI 1.07 to 1.44), 34% increased risk for current exposure to tricyclic antidepressants (HR 1.34; 95% CI 1.10 to 1.62), and 43% increased risk for current exposure to other antidepressants (HR 1.43; 95% CI 1.21 to 1.69). The risk of ischemic stroke in current SSRI users was significantly higher (HR 1.55; 95% CI 1.00 to 2.39) compared with remote/nonusers.

CONCLUSIONS: Current users of antidepressants may be at increased risk of a CVE. Clinicians should consider the relationship of antidepressants with the occurrence of CVEs when determining the risk-benefit profile of pharmacologic treatment in patients with depression, particularly those with existing risk factors for a CVE.

Key Words: antidepressants, case-control study, cerebrovascular events, depression

Published Online, January 22, 2008. www.theannals.com, DOI 10.1345/aph.1K369