A double-blind, placebo-controlled trial of sibutramine for olanzapine-associated weight gain.
OBJECTIVE
Weight gain is commonly observed with olanzapine treatment and can increase the risk for obesity, cardiovascular disease, hypertension, and diabetes mellitus. This study examined the effectiveness of sibutramine, an approved weight loss agent, in overweight and obese subjects taking olanzapine for schizophrenia or schizoaffective disorder.


METHODS
Each subject had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder, had been taking a stable dose of olanzapine for at least 4 months, and had a body mass index of >/=30 kg/m(2) or >/=27 kg/m(2) plus at least one cardiovascular risk factor. In a 12-week double-blind, randomized, placebo-controlled study, 37 subjects received placebo or sibutramine (up to 15 mg/day). For the first 8 weeks all subjects participated in weekly group sessions focused on nutrition and behavioral modification.


RESULTS
The sibutramine and placebo groups had no significant baseline differences on age, gender, education, ethnicity, diagnosis, weight, body mass index, and blood pressure. At week 12 the sibutramine group had significantly greater losses than the placebo group in weight (mean=8.3 lb, SD=2.4, versus mean=1.8 lb, SD=1.6), waist circumference, body mass index, and hemoglobin A(1c). There were no significant differences on most side effects, although the sibutramine group exhibited a mean increase in systolic blood pressure of 2.1 mm Hg (SD=8.5), and anticholinergic side effects and sleep disturbances were at least twice as common in the sibutramine group.


CONCLUSIONS
Sibutramine was an effective and well-tolerated adjunct to behavior modification for weight loss in patients with schizophrenia and schizoaffective disorder being treated with olanzapine.
Henderson
David C
DC
Schizophrenia Program, Weight Center, Endocrine Unit, and Biostatistics Center, Massachusetss General Hospital, Boston, USA. dchenderson@partners.org
Copeland
Paul M
PM
Daley
Tara B
TB
Borba
Christina P
CP
Cather
Corrine
C
Nguyen
Dana D
DD
Louie
Pearl M
PM
Evins
A Eden
AE
Freudenreich
Oliver
O
Hayden
Doug
D
Goff
Donald C
DC
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001067:Appetite Depressants / Q000627:therapeutic use*; D001521:Behavior Therapy; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003503:Cyclobutanes / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009765:Obesity / Q000139:chemically induced* / Q000188:drug therapy* / Q000628:therapy; D000077152:Olanzapine; D010919:Placebos; D011618:Psychotic Disorders / Q000188:drug therapy; D012559:Schizophrenia / Q000188:drug therapy; D012893:Sleep Wake Disorders / Q000139:chemically induced; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D001067:Appetite Depressants; D003503:Cyclobutanes; D010919:Placebos; D001569:Benzodiazepines; D000077152:Olanzapine; C058254:sibutramine