Betahistine effects on weight-related measures in patients treated with antipsychotic medications: a double-blind placebo-controlled study

• Published in: Psychopharmacology Vol. 235; no. 12; pp. 3545 - 3558
• Main Authors: Smith, Robert C., Maayan, Lawrence, Wu, Renrong, Youssef, Mary, Jing, Zhihui, Sershen, Henry, Szabo, Victoria, Meyers, Jordan, Jin, Hua, Zhao, Jinping, Davis, John M.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2018; Springer Nature B.V
• Subjects: Adolescent; Adolescents; Adult; Adults; Antagonists; Antipsychotic Agents - adverse effects; Antipsychotic Agents - therapeutic use; Antipsychotics; Appetite; Betahistine - pharmacology; Betahistine - therapeutic use; Biomedical and Life Sciences; Biomedicine; Body Mass Index; Body Weight - drug effects; Body Weight - physiology; Body weight gain; Child; Clozapine; Clozapine - adverse effects; Clozapine - therapeutic use; Double-Blind Method; Double-blind studies; Drug therapy; Female; Histamine; Histamine Agonists - pharmacology; Histamine Agonists - therapeutic use; Humans; Leptin; Male; Neurosciences; Olanzapine; Olanzapine - adverse effects; Olanzapine - therapeutic use; Original Investigation; Patients; Pharmacology/Toxicology; Psychiatry; Psychopathology; Psychotropic drugs; Schizophrenia - blood; Schizophrenia - drug therapy; Side effects; Treatment Outcome; Weight Gain - drug effects; Weight Gain - physiology; Young Adult; Betahistine; Leptin; Weight; BMI; Antipsychotic medication
• ISSN: 0033-3158; 1432-2072; 1432-2072
• DOI: 10.1007/s00213-018-5079-1

Rationale Weight gain during treatment with antipsychotics is a prominent side-effect, especially with some second-generation antipsychotics, such as olanzapine and clozapine, and pharmacological treatments which ameliorate this side-effect are important to investigate. Decreases in histaminergic transmission in the brain induced by antipsychotics may be one of the mechanisms contributing to weight gain. Since betahistine is a histaminergic agonist, it may potentially counteract the weight gain effects of antipsychotics. Method We conducted a double-blind placebo-controlled study to evaluate the effects of 12 weeks of treatment with betahistine ( N  = 29) or placebo ( N  = 22) in adolescents and adults on anthropomorphically measured weight-related parameters, appetite, and fasting glucose-lipid and leptin levels in 51 patients treated with first and/or second-generation antipsychotics who had gained weight during treatment or had high body-mass-index (BMI). Psychopathology and side-effects were also assessed with relevant scales. Results In a sub-group of patients being treated with olanzapine or clozapine ( n  = 26), betahistine was significantly ( P  < .05) better than placebo in preventing increases in weight (3.1 kg less weight gain than placebo), BMI, and waist circumference. Betahistine did not decrease weight or BMI in patients treated with other antipsychotics. There was also no effect of betahistine on preventing weight or BMI gain in the total combined sample of all subjects. Betahistine did not significantly improve appetite or glucose-lipid measures in either subgroup. There were no significant differences in side-effects or psychopathology changes in the betahistine- vs. placebo-treated patients. Conclusions These results suggest that betahistine may potentially be a useful adjunctive drug for decreasing weight gain in patients treated with antipsychotics that are potent histamine antagonists, such as olanzapine or clozapine, but may not be useful for this purpose in patients on other antipsychotic medications. The results justify larger placebo-controlled studies to further confirm these effects before specific recommendations can be made for routine use.