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Hyperglycemia and Antipsychotic Medications

Dan W. Haupt and John W. Newcomer

Published: January 14, 2001

Article Abstract

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 wasfirst described in psychotic patients prior to the introduction of antipsychotic medications, treatmentwith antipsychotic medications is associated with impaired glucose metabolism, exacerbation of existingtype 1 and 2 diabetes, new-onset type 2 diabetes mellitus, and diabetic ketoacidosis, a severeand potentially fatal metabolic complication. The strength of the association between antipsychoticsand diabetes varies across individual medications, with the largest number of reports for chlorpromazine,clozapine, and olanzapine. Recent controlled studies suggest that antipsychotics can impair glucoseregulation 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 individualagents 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 olanzapinetreatment 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 olanzapinehave also been associated with hypertriglyceridemia, with agents such as haloperidol, risperidone, andziprasidone associated with reductions in plasma triglycerides. Diabetes mellitus is associated withincreased 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 andcardiovascular risk (e.g., myocardial infarction, stroke) begins at glucose levels that are well belowdiabetic or "impaired" thresholds. Increased adiposity and dyslipidemia are additional, independentrisk factors for cardiovascular morbidity and mortality. Patients with schizophrenia suffer increasedmortality due to cardiovascular disease, with presumed contributions from a number of modifiablerisk factors (e.g., smoking, sedentary lifestyle, poor diet, obesity, hyperglycemia, and dyslipidemia).Patients taking antipsychotic medications should undergo regular monitoring of weight and plasmaglucose and lipid levels, so that clinicians can individualize treatment decisions and reduce iatrogeniccontributions to morbidity and mortality.

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