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Clozapine-associated diabetes
E Koller1, B Schneider, K Bennett
1Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20857, USA.
The American Journal of Medicine
|December 19, 2001
Summary
Clozapine, an antipsychotic, is linked to new-onset diabetes and worsening of existing diabetes. Many cases occurred within six months of starting clozapine, with some improving after drug discontinuation.
Area of Science:
- Pharmacovigilance
- Endocrinology
- Psychiatry
Background:
- Clozapine is a widely used antipsychotic medication.
- Reports of diabetes mellitus associated with clozapine therapy have increased.
- The precise risks and characteristics of clozapine-associated diabetes remain unclear.
Purpose of the Study:
- To investigate the risk and characteristics of diabetes mellitus in patients treated with clozapine.
- To analyze spontaneous adverse event reports of hyperglycemia associated with clozapine.
Main Methods:
- A descriptive epidemiologic study was conducted.
- Data were collected from the Food and Drug Administration MedWatch surveillance program (1990-2001) and pooled with published cases.
- Key parameters included diabetes documentation, severity, onset, patient demographics, and response to drug withdrawal.
Main Results:
- 384 reports of hyperglycemia were identified, with 242 new-onset diabetes cases and 54 exacerbations of pre-existing diabetes.
- Most cases occurred within 6 months of clozapine initiation, with a mean patient age of 40 years.
- Severe outcomes included 80 cases of metabolic acidosis/ketosis and 25 deaths; 46 patients improved after clozapine discontinuation or dose reduction.
Conclusions:
- A causal relationship between clozapine and diabetes mellitus is suggested.
- The temporal association, patient demographics, and reversibility upon drug withdrawal support this link.
- Clozapine-associated diabetes can range from mild glucose intolerance to severe diabetic ketoacidosis or hyperosmolar coma.
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