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 P₄₅₀ (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 µ_test/µ_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.