fluvoxamine and Hyperglycemia

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

Topics: Antidepressive Agents, Second-Generation; Depressive Disorder; Diabetes Mellitus; Female; Fluvoxamine; Humans; Hyperglycemia; Middle Aged

The effects of the selective serotonin reuptake inhibitors, fluoxetine and fluvoxamine, on plasma glucose levels were investigated in mice. Both fluoxetine and fluvoxamine elicited significant hyperglycemia, while a selective noradrenaline reuptake inhibitor maprotiline had no effect. Fluoxetine and fluvoxamine did not change serum insulin levels, although they elicited hyperglycemia. Pretreatment with the serotonin (5-hydroxytryptamine, 5-HT) depleter, p-chlorophenylalanine (pCPA), abolished fluvoxamine-induced hyperglycemia, although pCPA did not affect the fluoxetine-induced glycemic effects. These results suggest that the selective serotonin reuptake inhibitors fluoxetine and fluvoxamine induce hyperglycemia by inhibition of insulin release. Moreover, our findings indicate that the glycemic effects of these drugs are differentially associated with serotonergic mechanisms.

Topics: Animals; Blood Glucose; Enzyme Inhibitors; Fenclonine; Fluoxetine; Fluvoxamine; Hyperglycemia; Insulin; Male; Maprotiline; Mice; Selective Serotonin Reuptake Inhibitors; Time Factors