Metabolic risk during antipsychotic treatment

Background: Compared with the general population, individuals with schizophrenia demonstrate an increased prevalence of obesity, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD). Increased adiposity is associated with decreases in insulin sensitivity leading to an increased risk of hyperglycemia and hyperlipidemia. Antipsychotic medications can increase adiposity, and a range of evidence from case reports, observational studies, retrospective database analyses, and controlled experimental studies (including randomized clinical trials) suggests that treatment with antipsychotic medications may be associated with an increased risk for insulin resistance, hyperglycemia, dyslipidemia, and T2DM. Objective: This article reviews current evidence for the hypothesis that treatment with antipsychotic medications may be associated with increased risks for weight gain, insulin resistance, hyperglycemia, dyslipidemia, and T2DM, and examines the relationship of adiposity to medical risk. Methods: Relevant publications were identified through a search of MEDLINE from 1975 to the present using the primary search parameters diabetes or hyperglycemia or glucose or insulin or lipids and antipsychotic. Meeting abstracts and earlier nonindexed articles concerning antipsychotic-associated weight gain and metabolic disturbance were also reviewed. Key studies in this emerging literature were summarized, including case reports, observational studies, retrospective database analyses, and controlled experimental studies. Results: Individual antipsychotic medications are associated with different degrees of treatment-induced increases in body weight and adiposity, ranging from modest effects (<2 kg) with amisulpride, ziprasidone, and aripiprazole to clinically significant increases with olanzapine (4-10 kg). In addition to strong evidence concerning the effect of adiposity on insulin sensitivity in nonpsychiatric populations, increased adiposity in patients with schizophrenia has been associated with decreases in insulin sensitivity; this and other effects may contribute to increases in plasma glucose concentrations and lipid levels. Conclusion: Metabolic changes in psychiatric patients who receive antipsychotic agents can contribute to the development of the metabolic syndrome and increase the risk for T2DM and CVD. Copyright (C) 2004 Excerpta Medica, Inc.