Adjunctive fluvoxamine inhibits clozapine-related weight gain and metabolic disturbances

Mong Liang Lu, Hsien Yuan Lane, Shih K. Lin, Kun P. Chen, Wen H. Chang

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

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. Method: 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 (≤ 600 mg/day). The coadministration group (N = 34) received fluvoxamine (50 mg/day) plus low-dose clozapine (≤ 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 steadystate 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)766-771
Number of pages6
JournalJournal of Clinical Psychiatry
Volume65
Issue number6
DOIs
Publication statusPublished - Jun 2004

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Fluvoxamine
Clozapine
Weight Gain
norclozapine
Triglycerides
Glucose
Serum
Body Mass Index
Body Weight
Weights and Measures
Drug Monitoring
Poisons
Therapeutics
Hypercholesterolemia
Diagnostic and Statistical Manual of Mental Disorders
Hyperglycemia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology

Cite this

Adjunctive fluvoxamine inhibits clozapine-related weight gain and metabolic disturbances. / Lu, Mong Liang; Lane, Hsien Yuan; Lin, Shih K.; Chen, Kun P.; Chang, Wen H.

In: Journal of Clinical Psychiatry, Vol. 65, No. 6, 06.2004, p. 766-771.

Research output: Contribution to journalArticle

Lu, Mong Liang ; Lane, Hsien Yuan ; Lin, Shih K. ; Chen, Kun P. ; Chang, Wen H. / Adjunctive fluvoxamine inhibits clozapine-related weight gain and metabolic disturbances. In: Journal of Clinical Psychiatry. 2004 ; Vol. 65, No. 6. pp. 766-771.
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