, Volume 235, Issue 12, pp 3545–3558 | Cite as

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

  • Robert C. SmithEmail author
  • Lawrence Maayan
  • Renrong Wu
  • Mary Youssef
  • Zhihui Jing
  • Henry Sershen
  • Victoria Szabo
  • Jordan Meyers
  • Hua Jin
  • Jinping Zhao
  • John M. Davis
Original Investigation



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.


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.


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.


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.


Betahistine Weight BMI Leptin Antipsychotic medication 



This study was supported by a grant from the Stanley Foundation 07TGF-1112; Lawrence Maayan was original PI, and Robert Smith was subsequent PI.

Compliance with ethical standards

Conflict of interest

Investigators report no conflicts of interest relevant to this study. After the study was completed and the original paper submitted, Dr. Smith was asked to be a consultant to Abbot Pharmaceuticals on the development of a combined drug using betahistine.

Supplementary material

213_2018_5079_MOESM1_ESM.docx (361 kb)
ESM 1 (DOCX 360 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Robert C. Smith
    • 1
    • 2
    Email author
  • Lawrence Maayan
    • 3
  • Renrong Wu
    • 4
  • Mary Youssef
    • 5
  • Zhihui Jing
    • 4
  • Henry Sershen
    • 1
    • 2
  • Victoria Szabo
    • 1
  • Jordan Meyers
    • 6
  • Hua Jin
    • 7
  • Jinping Zhao
    • 4
  • John M. Davis
    • 8
  1. 1.Nathan Kline Institute for Psychiatric ResearchOrangeburgUSA
  2. 2.Department of PsychiatryNYU Langone Medical CenterNew YorkUSA
  3. 3.Albany Medical CollegeAlbanyUSA
  4. 4.Department of Psychiatry, the Second Xiangya Hospital, Central South University, Changsha, Hunan, and Mental Health Institute of the Second Xiangya HospitalCentral South UniversityChangshaChina
  5. 5.Harlem Hospital, Columbia UniversityNew YorkUSA
  6. 6.Oregon Health and Science UniversityPortlandUSA
  7. 7.University of California San Diego, Department of Psychiatry, San Diego, and VA San Diego Healthcare SystemSan DiegoUSA
  8. 8.Psychiatric Institute University of IllinoisChicago, Illinois and John Hopkins University Medical SchoolBaltimoreUSA

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