Brief ReportsA Randomized, Double-Blind, Placebo-Controlled Pilot Study of Betahistine to Counteract Olanzapine-Associated Weight GainBarak, Nir MD; Beck, Yaffa PhD; Albeck, Joseph H. MDAuthor Information From the *Obesity Clinic, Leumit Health Fund, Tel Aviv, Israel; †Private Practice, Tel Aviv Israel; and ‡Private Practice of Psychiatry, Belmont, MA. Received September 26, 2015; accepted after revision February 11, 2016. Reprints: Nir Barak, MD, 130 HaGolan St, Tel Aviv, Israel (email: [email protected]). Journal of Clinical Psychopharmacology: June 2016 - Volume 36 - Issue 3 - p 253-256 doi: 10.1097/JCP.0000000000000489 Buy Metrics Abstract Patients with schizophrenia experience higher rates of obesity and related morbidity and mortality than the general population does. Given preclinical studies revealing the role of histamine H1 receptor in human eating behavior, and the potential of olanzapine to block with this system, we hypothesized that histamine H1 receptor agonists may be beneficial in reducing antipsychotic-associated weight gain. In the present study, 36 patients with a diagnosis of schizophrenia or schizoaffective disorder and treated with olanzapine were randomized to betahistine (48 mg/d) or matching placebo for 16 weeks. Study outcomes were change in body weight from baseline and effect on antipsychotic efficacy of olanzapine. The patients in the betahistine group had less weight gain (−1.95 kg) compared with placebo group (5.6 + 5.5 kg vs 6.9 + 5.6 kg, respectively). Positive and Negative Syndrome Scale Questionnaire showed improvement within each group and that subjects treated with betahistine enjoyed an improvement (reduction) by a mean of 35.7 points, higher when compared with placebo subjects who had a reduction of 26.6 points (P = 0.233). An almost equal amount of subjects in both groups experienced adverse effects during the course of this study (87.5% of betahistine vs 85.0% of placebo-treated subjects). Overall, there were no clinically marked differences in safety signals between both groups. A larger study addressing the weaknesses of this pilot study is warranted. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.