We read with interest the article by Williams et al (Reference Williams, Newton and Roberts2002). 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 (Reference Lu, Lane and ChenLu 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 (Reference Armstrong and CozzaArmstrong & Cozza, 2001).

Interestingly, this pharmacokinetic interaction is more pronounced in patients with high cytochrome P450 1A2 activity and at low clozapine plasma concentrations (Reference Olesen and LinnetOlesen & 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 (Reference Wetzel, Anghclescu and SzegediWetzel et al, 1998; Reference Lu, Lane and ChenLu 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 (Reference Lu, Lane and ChenLu et al, 2000), further studies are warranted to substantiate its safety and efficacy.