Attenuation of olanzapine-induced weight gain with reboxetine in patients with schizophrenia: a double-blind, placebo-controlled study.
OBJECTIVE
Since increased norepinephrine availability may account for the weight-reducing effect of appetite suppressants, the authors hypothesized that the addition of the selective norepinephrine reuptake inhibitor reboxetine may prevent or attenuate olanzapine-induced weight gain.


METHODS
Twenty-six patients hospitalized for first-episode DSM-IV schizophrenic disorder participated in the study. In addition to 6 weeks of treatment with olanzapine, 10 mg/day, patients were randomly allocated in a double-blind design to receive either reboxetine, 4 mg/day, (N=13) or placebo (N=13).


RESULTS
Ten patients in each group completed the 6-week trial. Patients given olanzapine and reboxetine demonstrated a significantly lower increase in body weight (mean=2.5 kg, SD=2.7) than those given olanzapine and placebo (mean=5.5 kg, SD=3.1). Significantly fewer patients in the olanzapine/reboxetine group (N=2 of 10) than in the olanzapine/placebo group (N=7 of 10) gained at least 7% of their initial weight, the cutoff for clinically significant weight gain. The addition of reboxetine to olanzapine treatment was safe and well tolerated by the patients. A between-group difference in the reduction of Hamilton depression scale scores was seen that favored the olanzapine/reboxetine group (mean difference=-3.1, SD=1.25).


CONCLUSIONS
The selective norepinephrine reuptake inhibitor reboxetine may reduce olanzapine-induced weight gain in schizophrenia patients, and activation of the adrenergic system may attenuate weight gain induced by atypical antipsychotic agents.
Poyurovsky
Michael
M
Tirat Carmel Mental Health Center, Israel. tyrmichael@matat.health.gov.il
Isaacs
Ilanit
I
Fuchs
Camil
C
Schneidman
Michael
M
Faragian
Sarit
S
Weizman
Ronit
R
Weizman
Abraham
A
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines; D015992:Body Mass Index; D004311:Double-Blind Method; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D000077593:Reboxetine; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects*
D018759:Adrenergic Uptake Inhibitors; D014150:Antipsychotic Agents; D009025:Morpholines; D001569:Benzodiazepines; D010890:Pirenzepine; D000077593:Reboxetine; D000077152:Olanzapine