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Clozapine Use in Patients With Schizophrenia and the Risk of Diabetes, Hyperlipidemia, and Hypertension
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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