title: Reducing antipsychotic-induced weight gain in schizophrenia: a double-blind placebo-controlled study of reboxetine-betahistine combination.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: Research Unit, Tirat Carmel Mental Health Center, POB 9, Tirat Carmel 30200, Israel. poyurovs@tx.technion.ac.il
authors.forename: Michael
authors.initials: M
authors.lastname: Poyurovsky
authors.forename: Camil
authors.initials: C
authors.lastname: Fuchs
authors.forename: Artashez
authors.initials: A
authors.lastname: Pashinian
authors.forename: Adva
authors.initials: A
authors.lastname: Levi
authors.forename: Ronit
authors.initials: R
authors.lastname: Weizman
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001621:Betahistine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D017442:Histamine Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000077152:Olanzapine; D000077593:Reboxetine; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects*; D055815:Young Adult
chemical_list: D018759:Adrenergic Uptake Inhibitors; D014150:Antipsychotic Agents; D017442:Histamine Agonists; D009025:Morpholines; D001569:Benzodiazepines; D000077593:Reboxetine; D000077152:Olanzapine; D001621:Betahistine