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

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.