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Risk of Diabetes Mellitus Associated With Atypical Antipsychotic Use Among Patients With Bipolar Disorder: A Retrospective, Population-Based, Case-Control Study

Jeff J. Guo, Ph.D.; Paul E. Keck, Jr., M.D.; Patricia K. Corey-Lisle, Ph.D.; Hong Li, Ph.D.; Dongming Jiang, M.S.; Raymond Jang, Ph.D.; and Gilbert J. L'Italien, Sc.D.

Background: Drug-induced diabetes onset has not been adequately quantified in patients with bipolar disorder, although atypical antipsychotics have been widely used as new mood stabilizers.

Objectives: To quantify the association between atypical antipsychotics and diabetes mellitus.

Method: A retrospective, population-based, case-control study was conducted using the medical claims database from U.S. managed care organizations from January 1, 1998, to December 31, 2002. Nine hundred twenty incident cases of diabetes were matched with 5258 controls by age, sex, and bipolar index month and year. Diabetes cases were identified by either diagnosis of ICD-9 codes or diabetic medications. Patients with diabetes had a minimum 3-month exposure to any medications or at least 3 prescriptions for their bipolar or comorbidity treatment. Cox proportional hazard regression was conducted to assess the risk of diabetes associated with antipsychotic use.

Results: Of 920 cases, 41% received atypical antipsychotics (e.g., olanzapine, risperidone, quetiapine, ziprasidone, clozapine) and 34% received conventional antipsychotics. Compared to patients receiving conventional antipsychotics, the risk of diabetes was greatest among patients taking clozapine (hazard ratio [HR] = 7.0, 95% confidence interval [CI] = 1.7 to 28.9), risperidone (HR = 3.4, 95% CI = 2.8 to 4.2), olanzapine (HR = 3.2, 95% CI = 2.7 to 3.8), and quetiapine (HR = 1.8, 95% CI = 1.4 to 2.4), with controlling covariates of age; sex; duration of follow-up; use of lithium, anticonvulsants, antidepressants, or concomitant drugs; and psychiatric and medical comorbidities.

Conclusion: Development or exacerbation of diabetes mellitus is associated with antipsychotic use in bipolar patients. Metabolic complications are a major issue in patients receiving antipsychotic therapy. Thus, the propensity of an antipsychotic to induce diabetes should be a consideration when selecting an agent for patients with bipolar disorder.

(J Clin Psychiatry 2006;67:1055-1061)

Received Aug. 31, 2005; accepted Jan. 17, 2006. From the College of Pharmacy, University of Cincinnati Medical Center, Cincinnati, Ohio (Drs. Guo and Jang and Mr. Jiang); the Institute for the Study of Health, University of Cincinnati, Cincinnati, Ohio (Dr. Guo); the Department of Psychiatry, University of Cincinnati College of Medicine, and the Mental Health Care Line and General Clinical Research Center, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio (Dr. Keck); and Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Conn. (Drs. Corey-Lisle, Li, and L'Italien).

This project was conducted with research grant support provided by the Bristol-Myers Squibb Pharmaceutical Research Institute.

This study was presented at the European College of Neuropsychopharmacology (ECNP) 18th Conference, Amsterdam, Netherlands, October 22-26, 2005; and the International Conference of Pharmacoepidemiology (ICPE), Nashville, Tenn., August 21-24, 2005.

Dr. Keck is a consultant to or member of the scientific advisory boards of Abbott, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Eli Lilly, Ortho-McNeil, Pfizer, and Shire, and is a principal or co-investigator on research studies sponsored by Abbott, the American Diabetes Association, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, Janssen, Merck, the National Institute of Mental Health, the National Institute of Drug Abuse, Organon, Ortho-McNeil, Pfizer, the Stanley Medical Research Institute, and UCB Pharma. Drs. Corey-Lisle, Li, and L'Italien are employees of Bristol-Myers Squibb. Drs. Guo and Jang and Mr. Jiang report no additional financial or other relationships relevant to the subject of this article.

The opinions and conclusions expressed in this manuscript are solely those of the authors.

Corresponding author and reprints: Jeff J. Guo, Ph.D., Associate Professor of Pharmacoepidemiology and Pharmacoeconomics, University of Cincinnati Medical Center, 3225 Eden Ave., Cincinnati, OH 45267-0004 (e-mail: jeff.guo@uc.edu).

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