Journal Article

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

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

2013

Overview

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.

• Publisher: Springer-Verlag,Springer
• Subject: Adrenergic Uptake Inhibitors - administration & dosage / Adrenergic Uptake Inhibitors - adverse effects / Adrenergic Uptake Inhibitors - therapeutic use / Adult / Antipsychotic Agents - administration & dosage / Antipsychotic Agents - adverse effects / Antipsychotic Agents - therapeutic use / Antipsychotic drugs / Appetite / Benzodiazepines - administration & dosage / Benzodiazepines - adverse effects / Benzodiazepines - therapeutic use / Betahistine - administration & dosage / Betahistine - adverse effects / Betahistine - therapeutic use / Biomedical and Life Sciences / Biomedicine / Body weight / Central nervous system / Clinical trials / Dosage and administration / Double-Blind Method / Drug therapy / Female / Histamine Agonists - administration & dosage / Histamine Agonists - adverse effects / Histamine Agonists - therapeutic use / Histamine H1 receptors / Humans / Male / Mental disorders / Middle Aged / Morpholines - administration & dosage / Morpholines - adverse effects / Morpholines - therapeutic use / Neuroleptics / Neurosciences / Norepinephrine / Olanzapine / Original Investigation / Pharmacology/Toxicology / Psychiatry / Reboxetine / Schizophrenia / Schizophrenia - drug therapy / Statistical analysis / Treatment Outcome / Weight gain / Weight Gain - drug effects / Young Adult