Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Metabolic syndrome with the atypical antipsychotics Pornpoj Pramyothin a and Lalita Khaodhiar b Introduction It is widely recognized that patients with severe mental illnesses, including schizophrenia, major depressive, and bipolar disorders have higher mortality rate and shorter life expectancy compared to the general population [1–3]. Apart from suicide and accidents, cardiovascular disease is among the leading causes of death among these patients [4,5  ,6]. Metabolic syndrome and its com- ponents, including obesity, glucose intolerance, dyslipi- demia, and hypertension, are highly prevalent among patients with severe mental illnesses [7–9] and have been associated with increased risk of cardiovascular disease [10]. Atypical or second-generation antipsycho- tics (SGAs) have been an important addition to the armamentarium of pharmacologic treatments for schizo- phrenia and other psychiatric disorders. However, they are among the factors implicated in the development of metabolic syndrome in this susceptible population. This review summarizes the recent evidence on metabolic risks associated with SGA, including current recommen- dation for metabolic monitoring, and treatment. Metabolic syndrome and severe mental illnesses The increased risk of cardiovascular disease in patients with severe mental illness is likely to be a composite of unhealthy lifestyle choices (including smoking, physical inactivity, and poor diet [11]), which are common in this population, delayed diagnosis and treatment of hyper- tension, dyslipidemia, and prediabetic states [12,13], and inherent biological risk associated with mental illnesses and its treatment. Multiple observations suggest that mental illness, with schizophrenia in particular, is associated with metabolic abnormality independent of environmental factors or treatment effects. Schizophrenia has been associated with diabetes and abnormal glucose metabolism since a Boston Medical Center and b Boston University School of Medicine, Center for Nutrition and Weight Management, Boston Medical Center, Boston, Massachusetts, USA Correspondence to Lalita Khaodhiar, MD, Assistant Professor of Medicine, Boston University School of Medicine, Center for Nutrition and Weight Management, Boston Medical Center, 88 East Newton Street Robinson Bldg, Suite 4400, Boston, MA 02118, USA Tel: +1 617 638 8638; fax: +1 617 638 8599; e-mail: Lalita.khaodhiar@bmc.org Current Opinion in Endocrinology, Diabetes & Obesity 2010, 17:460–466 Purpose of review Metabolic syndrome and cardiovascular diseases are important causes of morbidity and mortality among patients with severe mental illnesses. Atypical or second-generation antipsychotics (SGAs) are associated with obesity and other components of metabolic syndrome, particularly abnormal glucose and lipid metabolism. This review aims to provide a summary of recent evidence on metabolic risks associated with SGAs, current recommendations for metabolic monitoring, and efficacy of treatment options currently available. Recent findings Studies have identified younger, antipsychotic-naive patients with first-episode psychosis as a population vulnerable to adverse metabolic effects from SGAs. These patients gained more weight and developed evident lipid and glucose abnormalities as soon as 8–12 weeks after treatment initiation. Findings are more striking among children and adolescents. The differential effects of various SGAs are well described, with clozapine and olanzapine associated with the highest metabolic risk. In addition to behavioral therapy, emerging data suggest that pharmacological therapy, most notably metformin, is efficacious in the treatment and possibly prevention of SGA-associated metabolic derangements. Summary More data have become available on the burden from metabolic complications associated with SGAs. New and effective treatment options are required in the near future to improve cardiovascular health in this susceptible population. Keywords antipsychotic, metabolic syndrome, metformin, obesity, psychosis Curr Opin Endocrinol Diabetes Obes 17:460–466 ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins 1752-296X 1752-296X ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/MED.0b013e32833de61c