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A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Naltrexone to Counteract Antipsychotic-Associated Weight Gain: Proof of Concept

Tek, Cenk MD*; Ratliff, Joseph PhD*; Reutenauer, Erin BA*; Ganguli, Rohan MD; O’Malley, Stephanie S. PhD*

Journal of Clinical Psychopharmacology: October 2014 - Volume 34 - Issue 5 - p 608–612
doi: 10.1097/JCP.0000000000000192
Brief Reports

Patients with schizophrenia experience higher rates of obesity as well as related morbidity and mortality than the general population does. Women with schizophrenia are at particular risk for antipsychotic-associated weight gain, obesity, and related medical disorders such as diabetes and cardiovascular disease. Given preclinical studies revealing the role of the endogenous opioid systems in human appetite and the potential of antipsychotic medications to interfere with this system, we hypothesized that opioid antagonists may be beneficial in arresting antipsychotic-associated weight gain and promoting further weight loss in women with schizophrenia. In the present study, 24 overweight women with a diagnosis of schizophrenia or schizoaffective disorder were randomized to placebo or naltrexone (NTX) 25 mg/d for 8 weeks. The primary outcome measure was a change in body weight from baseline. The patients in the NTX group had significant weight loss (−3.40 kg) compared with weight gain (+1.37 kg) in the patients in the placebo group. Mainly, nondiabetic subjects lost weight in the NTX arm. These data support the need to further investigate the role of D2 blockade in reducing food reward-based overeating. A larger study addressing the weaknesses of this pilot study is currently underway.

From the *Department of Psychiatry, Yale University School of Medicine, New Haven, CT; and †Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada.

Received January 17, 2014; accepted after revision May 19, 2014.

Reprints: Cenk Tek, MD, Department of Psychiatry, Yale School of Medicine, Connecticut Mental Health Center, 34 Park St, 267D, New Haven, CT 06519 (e-mail:

This study was funded by a pilot project grant from Women’s Health Research at Yale. Supported by a NIDDK grant RO1- DK093924 to Dr Tek. The State of Connecticut’s Department of Mental Health and Addiction Services supports all research at the Connecticut Mental Health Center.

© 2014 by Lippincott Williams & Wilkins.