Weight Gain from Novel Antipsychotic Drugs: Need for Action Alan I. Green, M.D., Jayendra K. Patel, M.D., Robert M. Goisman, M.D., David B. Allison, Ph.D., and George Blackburn, M.D., Ph.D. Abstract: Obesity is common in schizophrenia, and people with schizophrenia appear to be at increased risk for certain obesity-related conditions, such as type 2 diabetes and cardio- vascular disease. Antipsychotic drugs, used chronically to con- trol symptoms of schizophrenia, are associated with often- substantial weight gain, a side effect that is a special concern with the latest generation of highly effective “novel” agents. That the most effective (e.g., novel) antipsychotic medications lead to substantial weight gain presents the field with a critical public health problem. Although preliminary data have been reported regarding the beneficial use of behavior therapy pro- grams for short-term weight control in patients with schizo- phrenia, the available data are quite limited, and there are no data regarding the long-term beneficial effects of these pro- grams in this population. The obesity field recently has devel- oped programs emphasizing “lifestyle changes” (e.g., diet, ex- ercise, and problem-solving skills) to successfully manage weight in patients without schizophrenia. Such programs can be adapted for patients with schizophrenia through the use of highly structured and operationalized modules emphasizing medication compliance, social skills development, and partici- pation in outpatient programs. Moreover, these programs can potentially be combined with the use of adjunctive pharmaco- therapy to maximize and maintain weight loss. The field must solve the paradox that some of our most effective medications for schizophrenia produce substantial weight gain and its as- sociated troubling health risks. © 2000 Elsevier Science Inc. Introduction Schizophrenia is a tragic and devastating mental illness that usually manifests in young people on the threshold of adulthood [1]. The disease, which has a lifetime prevalence of 1% worldwide, extracts a high toll in morbidity (60% of patients receive disability benefits within the first year after onset) [2] and mortality (the suicide rate is 10%) [3,4]. Antipsychotic medications are an integral part of the therapeutic program for most individuals with schizophrenia, and the new generation of “novel” antipsychotics are particularly helpful for many pa- tients with this and other psychotic disorders. To derive maximum benefit from these antipsychotic agents, however, patients must be able to tolerate their side effects and take them as prescribed. One untoward side effect of many antipsychotic drugs, especially the newer “novel” or “atypical” antipsychotics, is often-substantial weight gain [5–9]. Studies suggest that 40% to 80% of patients taking antipsychotic medication experience weight gain that exceeds ideal body weight by 20% or greater [10,11]. This noticeable and unwanted side effect may undermine compliance and thus predis- pose patients to relapse, in addition to increasing obesity-related comorbidities and health risks [5,11–13]. That the most effective (e.g., novel) antipsychotic medications lead to substantial weight gain presents the field with a critical public health problem. This article will initially provide an overview of the topic of weight gain in patients treated with the novel an- tipsychotic agents. Then, after reviewing the limited data regarding approaches to the prevention of such weight gain, we will present one possible strategy for an approach to treatment in this area. Commonwealth Research Center (A.I.G.), and the Massachu- setts Mental Health Center (A.I.G., J.K.P., R.M.G.), Harvard Medical School Department of Psychiatry (A.I.G., J.K.P., R.M.G.) Boston, Massachusetts; the Division of Nutrition, Beth Israel Deaconess Medical Center (G.B.), Harvard Medical School De- partment of Surgery (G.B.) Boston, Massachusetts; and the Obe- sity Research Center, St. Lukes/Roosevelt Hospital, Columbia University College of Physicians and Surgeons (D.B.A.) New York, New York. Address reprint requests to: Dr. Alan I. Green, Common- wealth Research Center, 74 Fenwood Road, Boston, MA 02115. General Hospital Psychiatry 22, 224 –235, 2000 224 © 2000 Elsevier Science Inc. All rights reserved. ISSN 0163-8343/00/$–see front matter 655 Avenue of the Americas, New York, NY 10010 PII S0163-8343(00)00081-5