Reducing antipsychotic-induced weight gain in schizophrenia: A double-blind placebo-controlled study of reboxetine-betahistine combination

Michael Poyurovsky*, Camil Fuchs, Artashez Pashinian, Adva Levi, Ronit Weizman, Abraham Weizman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


Rationale: Combination treatment with reboxetine, a selective norepinephrine reuptake inhibitor, and betahistine, a histamine H1 receptor agonist/H3 antagonist, was developed to produce complementary action in CNS pathways regulating appetite and body weight. In the present placebo-controlled study, we evaluated whether a reboxetine-betahistine combination attenuates olanzapine-induced weight gain in schizophrenia patients. Method: Forty-three inpatients with DSM-IV schizophrenic disorder participated in a randomized double-blind study. Reboxetine (4 mg/day) with betahistine (48 mg/day) (N = 29) or placebo (N = 14) was co-administered with olanzapine (10 mg/day) for 6 weeks. Mental status was assessed at baseline and endpoint with relevant rating scales. Intention-to-treat method was used for statistical analysis. Results: Seven patients in the study group and four in the placebo group discontinued the trial. At the end of the trial, patients in the olanzapine/reboxetine + betahistine group gained significantly less weight than those in the olanzapine/placebo group [2.02 ± 2.37 and 4.77 ± 3.16 kg, respectively; t = 2. 89, degrees of freedom (df) = 41, p = 0.006]. The weight-attenuating effect of this combination was twofold larger than the weight-attenuating effect previously demonstrated with reboxetine alone. Significantly fewer patients in the study group than in the comparison group increased their initial weight by >7 %, the cutoff for clinically significant weight gain [3/29 (10.3 %) and 6/14 (42.9 %), respectively; χ 2 = 6.03, df = 1, p = 0.014]. The reboxetine-betahistine combination was safe and well tolerated. Conclusions: Reboxetine-betahistine combination produces a clinically meaningful attenuation of olanzapine-induced weight gain. These results justify direct comparison between the reboxetine-betahistine combination and reboxetine alone.

Original languageEnglish
Pages (from-to)615-622
Number of pages8
Issue number3
StatePublished - Apr 2013


  • Antipsychotics
  • Betahistine
  • Body mass index
  • Olanzapine
  • Reboxetine
  • Weight gain


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