olanzapine and sibutramine

Metformin (850-1700 mg) plus sibutramine (10-20 mg, n=13) or placebo (n=15) was administered for 12 weeks in olanzapine-treated chronic schizophrenia patients. Weight loss was similar in both groups: -2.8+/-3.2 kg vs. -1.4+/-2.6 kg. Except for preventing a triglyceride increase, the drug combination lacked efficacy for metabolic control in this clinical population.

Topics: Adult; Antipsychotic Agents; Appetite Depressants; Benzodiazepines; Body Mass Index; Chronic Disease; Cyclobutanes; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Male; Metabolic Syndrome; Metformin; Middle Aged; Obesity; Olanzapine; Pilot Projects; Placebos; Schizophrenia; Schizophrenic Psychology; Waist-Hip Ratio; Weight Gain; Weight Loss

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.. 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.. 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.. 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.

Topics: Adult; Antipsychotic Agents; Appetite Depressants; Behavior Therapy; Benzodiazepines; Combined Modality Therapy; Cyclobutanes; Double-Blind Method; Female; Humans; Male; Obesity; Olanzapine; Placebos; Psychotic Disorders; Schizophrenia; Sleep Wake Disorders; Treatment Outcome; Weight Gain

Both olanzapine and sibutramine target serotonergic and noradrenergic neurotransmission and influence body weight, but in opposite ways. The second-generation antipsychotic olanzapine, an antagonist at serotonergic and noradrenergic receptors, frequently induces weight gain as a side-effect, whereas sibutramine, a noradrenaline/serotonin reuptake inhibitor, is known as a weight-reducing agent. To investigate whether altered motivation for palatable food influences the effect of these drugs on body weight, we determined their effects on responding for sucrose pellets under a progressive ratio schedule of reinforcement in rats. We found that a low dose of olanzapine selectively increased responding to sucrose, without affecting free-feeding intake of sucrose. In contrast, sibutramine dose-dependently reduced responding to sucrose and similarly reduced free-feeding intake. Furthermore, coadministration of a dose of sibutramine that failed to affect responding to sucrose when administered alone prevented the increase in motivation by the effective dose of olanzapine. These data show that increased motivation for palatable food is likely to be a significant contributor to olanzapine-induced weight gain. Moreover, the ability of sibutramine to reduce this motivation for palatable food may play an important role in the efficacy of sibutramine as an add-on treatment to counteract olanzapine-induced weight gain.

Topics: Animals; Antipsychotic Agents; Appetite Depressants; Benzodiazepines; Conditioning, Operant; Cyclobutanes; Dose-Response Relationship, Drug; Drug Interactions; Eating; Male; Motivation; Olanzapine; Rats; Rats, Wistar; Reinforcement Schedule

This study focuses on exploring the relationship between changes in appetite or eating behaviors and subsequent weight change for adult patients with schizophrenia or bipolar disorder treated with olanzapine and adjunctive potential weight mitigating pharmacotherapy. The aim is not to compare different weight mitigating agents, but to evaluate patients' characteristics and changes in their eating behaviors during treatment. Identification of patient subgroups with different degrees of susceptibility to the effect of weight mitigating agents during olanzapine treatment may aid clinicians in treatment decisions.. Data were obtained from 3 randomized, double-blind, placebo-controlled, 16-week clinical trials. Included were 158 patients with schizophrenia or bipolar disorder and a body mass index (BMI) > or = 25 kg/m2 who had received olanzapine treatment in combination with nizatidine (n = 68), sibutramine (n = 42), or amantadine (n = 48). Individual patients were analyzed for categorical weight loss > or= 2 kg and weight gain > or = 1 kg. Variables that were evaluated as potential predictors of weight outcomes included baseline patient characteristics, factors of the Eating Inventory, individual items of the Eating Behavior Assessment, and the Visual Analog Scale.. Predictors/correlates of weight loss > or = 2 kg included: high baseline BMI, low baseline interest in food, and a decrease from baseline to endpoint in appetite, hunger, or cravings for carbohydrates. Reduced cognitive restraint, increase in hunger, and increased overeating were associated with a higher probability of weight gain > or = 1 kg.. The association between weight gain and lack of cognitive restraint in the presence of increased appetite suggests potential benefit of psychoeducational counseling in conjunction with adjunctive pharmacotherapeutic agents in limiting weight gain during antipsychotic drug therapy.. This analysis was not a clinical trial and did not involve any medical intervention.

Topics: Adult; Amantadine; Appetite; Benzodiazepines; Bipolar Disorder; Cognition Disorders; Cyclobutanes; Drug Therapy, Combination; Feeding Behavior; Female; Humans; Male; Nizatidine; Olanzapine; Randomized Controlled Trials as Topic; Schizophrenia; Weight Gain; Weight Loss