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A Claims-Based Approach

Brian C. Lund, PharmD; Paul J. Perry, PhD; John M. Brooks, PhD; Stephan Arndt, PhD

Arch Gen Psychiatry. 2001;58:1172-1176.

Background  Numerous case reports have linked clozapine to the development of diabetes mellitus and hyperlipidemia in patients with schizophrenia. However, investigators have been unable to clearly demonstrate this association when compared with a control group receiving conventional antipsychotics.

Methods  Medical and pharmacy claims from the Iowa Medicaid program were used to compare incidence rates for diabetes, hyperlipidemia, and hypertension in 552 patients receiving clozapine and 2461 patients receiving conventional antipsychotics (eg, haloperidol, chlorpromazine hydrochloride), with the use of a retrospective cohort design. Logistic regression was used to compare incidence rates adjusting for age, sex, and duration of available follow-up.

Results  No significant differences in overall incidence rates for diabetes, hyperlipidemia, or hypertension were observed in patients receiving clozapine vs conventional antipsychotics. However, among younger patients (aged 20-34 years), clozapine administration was associated with a significantly increased relative risk of diabetes (2.5 [95% confidence interval, 1.2-5.4]) and hyperlipidemia (2.4 [95% confidence interval, 1.1-5.2]), but not hypertension (0.9 [95% confidence interval, 0.4-2.0]).

Conclusions  These data suggest that clozapine may not be an independent cause of diabetes or hyperlipidemia, but instead acts as an effect modifier in susceptible populations by increasing weight or affecting insulin secretion and resistance. This finding requires confirmation in other settings and patient populations and with the other atypical antipsychotics (risperidone, olanzapine, and quetiapine fumarate). The potential long-term medical and economic implications of the early induction of diabetes and hyperlipidemia in patients with schizophrenia warrant further study.

From the Division of Clinical and Administrative Pharmacy, College of Pharmacy (Drs Lund, Perry, and Brooks), Department of Psychiatry, College of Medicine (Drs Perry and Arndt), and Department of Biostatistics, College of Public Health (Dr Arndt), University of Iowa, Iowa City.

Corresponding author and reprints: Brian C. Lund, PharmD, University of Iowa, College of Pharmacy, 443 S Pharmacy Bldg, Iowa City, IA 52242-1112 (e-mail: brian-lund{at}uiowa.edu).

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