fluvoxamine and Weight-Gain

Adjunctive fluvoxamine inhibits clozapine metabolism and decreases plasma norclozapine (a toxic metabolite of clozapine) to clozapine ratios. This study aimed to demonstrate the effects of fluvoxamine on clozapine-related weight gain, hyperglycemia, and lipid abnormalities.. Sixty-eight treatment-resistant inpatients with a DSM-IV diagnosis of schizophrenia were randomly assigned to 2 treatment groups for 12 weeks. The monotherapy group (N = 34) received clozapine (< or = 600 mg/day). The coadministration group (N = 34) received fluvoxamine (50 mg/day) plus low-dose clozapine (< or = 250 mg/day). The study was conducted from August 1999 to October 2002.. The 2 groups were similar in demographic data; baseline body weight and body mass index (BMI); baseline serum glucose, triglyceride, and cholesterol levels; and steady-state plasma clozapine concentration. The monotherapy patients (but not the coadministration patients) had significantly higher (p < .05) body weight, BMI, and serum glucose and triglyceride levels after treatment than at baseline. At week 12, the monotherapy patients also had significantly higher glucose (p = .035), triglyceride (p = .041), and norclozapine (p = .009) (and numerically higher cholesterol) levels than the cotreatment patients. The changes in weight and serum glucose and triglyceride levels were significantly correlated (p = .026, p = .005, and p = .028, respectively) with the plasma concentration of norclozapine but not with plasma levels of clozapine.. These results suggest that fluvoxamine cotreatment can attenuate weight gain and metabolic disturbances in clozapine-treated patients. Plasma levels of norclozapine, but not clozapine, are associated with increases in weight and serum glucose and triglyceride levels. Of note, coadministration of fluvoxamine could increase plasma clozapine levels markedly and carry the risk of adverse events. If this combined treatment is applied, conservative introduction with reduced clozapine dosage and careful therapeutic drug monitoring of clozapine concentration is recommended.

Topics: Adolescent; Adult; Antipsychotic Agents; Blood Glucose; Cholesterol; Clozapine; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Hyperglycemia; Hyperlipidemias; Male; Middle Aged; Selective Serotonin Reuptake Inhibitors; Triglycerides; Weight Gain

The effect of extended anti-depressant treatment on weight has been poorly investigated. Also unknown is whether different compounds have differential effects. The aim of the present study was to assess changes in weight in obsessive-compulsive disorder (OCD) patients treated for 2.5 years with clomipramine or selective serotonin reuptake inhibitors.. 138 DSM-IV OCD patients who responded to 6-month acute treatment at the Mood and Anxiety Disorders Unit, Department of Neuroscience, University of Turin, Italy, were followed-up for 2 years while receiving open-label clomipramine, citalopram, fluoxetine, fluvoxamine, paroxetine, or sertraline. Patients were consecutively recruited and followed from May 1998 to March 2003. The mean percentage change in weight was compared for each group, as was the proportion of patients who had a > or = 7% weight increase from baseline.. At the end of the 2.5-year study period, patients had gained a mean of 2.5% of their body weight with respect to baseline (1.58 kg); 14.5% of the total sample experienced a significant (> or = 7%) weight increase. Within each but the fluoxetine treatment group, paired t tests showed a significant increase in weight from baseline to final visit. Analysis of variance showed a significant difference between treatment groups (p = .009), with clomipramine being associated with the highest weight increase and fluoxetine and sertraline with the lowest. A higher proportion of clomipramine-treated patients (34.8%) gained > or = 7% in weight as compared with sertraline and fluoxetine, which accounted for the lowest percentage of patients with a significant weight gain (4.5% and 8.7%, respectively), although this difference was not statistically significant.. Risk of weight gain during extended serotonin reuptake inhibitor treatment for OCD differs depending on which compound is used. The differences among antiobsessive drugs may affect compliance with medication and health risks.

Topics: Adult; Ambulatory Care; Citalopram; Clomipramine; Female; Fluoxetine; Fluvoxamine; Follow-Up Studies; Humans; Male; Obesity; Obsessive-Compulsive Disorder; Paroxetine; Patient Compliance; Prospective Studies; Risk Factors; Selective Serotonin Reuptake Inhibitors; Sertraline; Weight Gain

The effects of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), were studied in normophagic and food-restriction-induced hyperphagic middle-aged Wistar rats. Normophagic intact Wistar rats were given fluvoxamine (100 mg/kg/d, per os (p.o.)) or vehicle for 10 d. Hyperphagic middle-aged Wistar rats were subjected to 10 d of food restriction; they were allowed to refeed for 10 d, with ad libitum food access and administered fluvoxamine (100 mg/kg/d, p.o.) or vehicle during the 10-d refeeding period. Fluvoxamine administration to normophagic middle-aged Wistar rats affected neither their weight nor food intake. However, administration to food-restricted rats showed inhibitory effects of weight gain and food intake during 10 d of refeeding. Fluvoxamine-treated rats showed significantly lower neuropeptide Y (NPY) immunostaining levels in the paraventricular nucleus (PVN) and dorsomedial hypothalamic nucleus (DMH) than untreated controls. Hypophagic and weight-inhibiting effects of fluvoxamine might be mediated via decreased NPY in PVN and DMH. These results suggest that the appetite-controlling effect of fluvoxamine might be responsive to the rats' appetite condition.

Topics: Animals; Antidepressive Agents, Second-Generation; Body Weight; Eating; Fluvoxamine; Hyperphagia; Hypothalamus; Male; Neuropeptide Y; Rats; Rats, Wistar; Weight Gain

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Female; Fluvoxamine; Humans; Olanzapine; Quetiapine Fumarate; Weight Gain