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J Clin Psychiatry. 2001;62 Suppl 27:15-26; discussion 40-1.

Hyperglycemia and antipsychotic medications.

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Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA.


Type 2 diabetes mellitus and impaired glucose tolerance are associated with antipsychotic treatment. Risk factors for type 2 diabetes and impaired glucose tolerance include abdominal adiposity, age, ethnic status, and certain neuropsychiatric conditions. While impaired glucose metabolism was first described in psychotic patients prior to the introduction of antipsychotic medications, treatment with antipsychotic medications is associated with impaired glucose metabolism, exacerbation of existing type 1 and 2 diabetes, new-onset type 2 diabetes mellitus, and diabetic ketoacidosis, a severe and potentially fatal metabolic complication. The strength of the association between antipsychotics and diabetes varies across individual medications, with the largest number of reports for chlorpromazine, clozapine, and olanzapine. Recent controlled studies suggest that antipsychotics can impair glucose regulation by decreasing insulin action, although effects on insulin secretion are not ruled out. Antipsychotic medications induce weight gain, and the potential for weight gain varies across individual agents with larger effects observed again for agents like chlorpromazine, clozapine, and olanzapine. Increased abdominal adiposity may explain some treatment-related changes in glucose metabolism. However, case reports and recent controlled studies suggest that clozapine and olanzapine treatment may also be associated with adverse effects on glucose metabolism independent of adiposity. Dyslipidemia is a feature of type 2 diabetes, and antipsychotics such as clozapine and olanzapine have also been associated with hypertriglyceridemia, with agents such as haloperidol, risperidone, and ziprasidone associated with reductions in plasma triglycerides. Diabetes mellitus is associated with increased morbidity and mortality due to both acute (e.g., diabetic ketoacidosis) and long-term (e.g., cardiovascular disease) complications. A progressive relationship between plasma glucose levels and cardiovascular risk (e.g., myocardial infarction, stroke) begins at glucose levels that are well below diabetic or "impaired" thresholds. Increased adiposity and dyslipidemia are additional, independent risk factors for cardiovascular morbidity and mortality. Patients with schizophrenia suffer increased mortality due to cardiovascular disease, with presumed contributions from a number of modifiable risk factors (e.g., smoking, sedentary lifestyle, poor diet, obesity, hyperglycemia, and dyslipidemia). Patients taking antipsychotic medications should undergo regular monitoring of weight and plasma glucose and lipid levels, so that clinicians can individualize treatment decisions and reduce iatrogenic contributions to morbidity and mortality.

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