Adjunctive fluvoxamine with clozapine

M. L. Lu

Department of Psychiatry, Taipei Medical University—Wan Fang Hospital, Taipei, Taiwan

H. Y. Lane

Department of Psychiatry, China Medical College Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan

EDITED BY KHALIDA ISMAIL

Declaration of interest

None. Funding was received from the National Science Council and the National Health Research Institutes, Taiwan.

We read with interest the article by Williams et al (2002). The authors summarise treatment options for patients resistant to clozapine monotherapy. However, in the section on combining antidepressants with clozapine, several issues deserve more attention. The authors disagree with utilisation of adjunctive antidepressants to reduce the cost of clozapine treatment. In our recent study (Lu et al, 2000), addition of 50 mg/day fluvoxamine to low-dose (100 mg/day) clozapine could raise the mean plasma clozapine level to over 400 ng/ml to achieve suitable therapeutic ranges. Therefore, concomitant fluvoxamine can reduce clozapine doses and, consequently, costs (Armstrong & Cozza, 2001).

Interestingly, this pharmacokinetic interaction is more pronounced in patients with high cytochrome P450 1A2 activity and at low clozapine plasma concentrations (Olesen & Linnet, 2000). This phenomenon could therefore be used to narrow down the wide interindividual variation in blood clozapine concentrations. Several open trials also demonstrated that coadministration of fluvoxamine could augment clozapine efficacy and curtail plasma norclozapine:clozapine ratios (Wetzel et al, 1998; Lu et al, 2000). Norclozapine has been suggested to be more toxic than its parent compound. Although addition of fluvoxamine to low-dose clozapine was well-tolerated in our pilot study (Lu et al, 2000), further studies are warranted to substantiate its safety and efficacy.

REFERENCES

Armstrong, S. C. & Cozza, K. L. (2001) Consultation—liaison psychiatry drug—drug interactions update. Psychosomatics, 42, 157-159.[Free Full Text]

Lu, M. L., Lane, H. Y., Chen, K. P., et al (2000) Fluvoxamine reduces the clozapine dosage needed in refractory schizophrenic patients. Journal of Clinical Psychiatry, 61, 594-599.

Olesen, O. V. & Linnet, K. (2000) Fluvoxamine—clozapine drug interaction: inhibition in vitro of five cytochrome P450 isoforms involved in clozapine metabolism. Journal of Clinical Psychopharmacology, 20, 35-42.[CrossRef][Medline]

Wetzel, H., Anghclescu, I., Szegedi, A., et al (1998) Pharmacokinetic interactions of clozapine with selective serotonin reuptake inhibitors: differential effects of fluvoxamine and paroxetine in a prospective study. Journal of Clinical Psychopharmacology, 18, 2-9.[CrossRef][Medline]

Williams, L., Newton, G., Roberts, K., et al (2002) Clozapine-resistant schizophrenia: a positive approach. British Journal of Psychiatry, 181, 184-187.[Free Full Text]





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