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Background: Two case reports suggest that serum clozapine concentration may increase when risperidone is added to clozapine treatment. However, risperidone is not a significant inhibitor of the most important clozapine metabolising cytochrome P(450) (CYP) enzymes (e.g. CYP1A2)., Objective: To study whether serum clozapine concentrations are affected by risperidone., Methods: Intraindividual comparison of serum clozapine therapeutic drug monitoring data from 18 patients during and without risperidone use., Results: Addition of risperidone (mean +/-SD dose 2.9+/-0.9 mg/day, range 2-4 mg/day) to clozapine treatment (mean clozapine dose 451+/-207 mg/day) did not result in any significant changes in serum clozapine concentration or clozapine concentration/dose (C/D) ratio relative to the values without risperidone (mean clozapine dose 437+/-168 mg/day). During risperidone use mean serum clozapine concentration was 3% (P=0.75) and C/D ratio 8% (P=0.46) lower than without concomitant risperidone. The mean ratio mu(test)/mu(reference) for clozapine C/D ratios was 0.99 (90% CI 0.82-1.15), confidence interval being within the equivalence interval of 0.80-1.25., Conclusions: Risperidone does not affect serum clozapine concentrations to any significant degree.