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Clozapine May Impair Glucose Control in Patients With Schizophrenia

Schizophrenic patients taking clozapine are at greater risk of developing abnormal glucose control, according to a new British study.

Previous studies found an association between clozapine treatment and higher insulin levels, suggesting that this drug induces insulin resistance. However, data is lacking with respect to clozapine's effect on glucose-insulin homeostasis.

Oliver D. Howes, MRCPsych, Division of Psychological Medicine, Institute of Psychiatry, London, United Kingdom, and colleagues examined glucose control and insulin sensitivity in 20 schizophrenic patients who were switched to clozapine as the sole antipsychotic.

Upon enrollment, no patient had diabetes mellitus or was receiving treatment for glycaemic control or any other condition associated with glucose intolerance. After baseline assessment, patients received clozapine titrated according to the each patient's clinical response.

Clozapine levels were measured at baseline and at 2 to 4 months using a standard oral glucose tolerance test (GTT) according to World Health Organization (WHO) specifications after 9 hours of fasting. Insulin resistance was evaluated with the homeostasis model assessment method and clozapine levels were measured using high performance liquid chromatography.

Results indicate that 55% of patients developed de novo abnormal glucose tolerance, including one case of diabetes mellitus, 2 cases of impaired fasting hyperglycaemia, and 8 cases of impaired glucose tolerance. The proportion of patients showing abnormal glucose control was significantly increased after clozapine treatment compared to before treatment ((P = .006, McNemar test).

There were significant increases in mean fasting glucose level (0.55 mmol/L change) and mean 2-hour glucose level (1.4 mmol/L change). There was no significant increase in insulin level, insulin resistance level or mean body mass index.

"To our knowledge, this is the first direct evidence that, within 4 months, clozapine treatment results in increased plasma glucose concentrations, independent of changes in insulin resistance or body mass index," the investigators write.

Clinicians will need to weigh the risks associated with hyperglycaemia and diabetes mellitus when deciding to initiate clozapine treatment, they conclude.
Am J Psychiatry 2004 Feb;161:2:361-3.

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