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

Patients with schizophrenia suffer from higher rates of obesity and related morbidity and mortality than the general population. Women with schizophrenia are at particular risk for antipsychotic-induced 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-induced 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 (PLA) or naltrexone (NTX) 25mg/day for 8 weeks. The primary outcome measure was change in body weight from baseline. Patients in the NTX group had significant weight loss (−3.40kg) compared to weight gain (+1.37kg) in the PLA group. Mainly non-diabetic subjects lost weight in the naltrexone 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.