Adjunctive fluvoxamine inhibits clozapine-related weight gain and metabolic disturbances.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Lu
Mong-Liang
ML
Department of Psychiatry, Taipei Medical University-Wan Fang Hospital, Taiwan.
Lane
Hsien-Yuan
HY
Lin
Shih-Ku
SK
Chen
Kun-Po
KP
Chang
Wen-Ho
WH
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D003024:Clozapine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D016666:Fluvoxamine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control*; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D001786:Blood Glucose; D002784:Cholesterol; D003024:Clozapine; D016666:Fluvoxamine; D017367:Selective Serotonin Reuptake Inhibitors; D014280:Triglycerides; C058272:norclozapine