The metabolic effects of antipsychotic medications

Objectives: To review current evidence for the hypothesis that treatment with antipsychotic medications may be associated with increased risks for weight gain, insulin resistance, hyperglycemia, dyslipidemia, and type 2 diabetes mellitus (T2DM) and to examine the relation of adiposity to medical risk. Methods: We identified relevant publications through a search of MEDLINE from the years 1975 to 2006, using the following primary search parameters: "diabetes or hyperglycemia or glucose or insulin or lipids" and "antipsychotic." Meeting abstracts and earlier nonindexed articles were also reviewed. We summarized key studies in this emerging literature, including case reports, observational studies, retrospective database analyses, and controlled experimental studies. Results: Treatment with different antipsychotic medications is associated with variable effects on body weight, ranging from modest increases (for example, less than 2 kg) experienced with amisulpride, ziprasidone, and aripiprazole to larger increases during treatment with agents such as olanzapine and clozapine (for example, 4 to 10 kg). Substantial evidence indicates that increases in adiposity are associated with decreases in insulin sensitivity in individuals both with and without psychiatric disease. The effects of increasing adiposity, as well as other effects, may contribute to increases in plasma glucose and lipids observed during treatment with certain antipsychotics. Conclusion: Treatment with certain antipsychotic medications is associated with metabolic adverse events that can increase the risk for metabolic syndrome and related conditions such as prediabetes, T2DM, and cardiovascular disease.