OBJECTIVES To investigate the effect of topiramate on the steady-state plasma concentrations of the second-generation antipsychotics--clozapine, olanzapine, risperidone, and quetiapine--in patients with schizophrenia or bipolar disorder. METHODS Thirty-eight outpatients on long-term treatment with clozapine (250-500 mg/d, n = 10), olanzapine (10-20 mg/d, n = 12), risperidone (3-6 mg/d, n = 9), or quetiapine (200-600 mg/d, n = 7) received adjunctive topiramate, gradually titrated up to a final dosage of 200 mg/d for 6 weeks. Pharmacokinetic assessments were made at baseline and at the end of treatment weeks 4 and 8 at topiramate dosages of 100 and 200 mg/d, respectively. RESULTS Plasma concentrations of clozapine and its metabolite (norclozapine), olanzapine, risperidone and its metabolite (9-hydroxy-risperidone), and quetiapine were not significantly modified during concomitant administration of topiramate. Adjunctive topiramate therapy was well tolerated in all groups. CONCLUSIONS These findings indicate that topiramate, at the dosages recommended for use as a mood stabilizer, does not affect the plasma levels of the new antipsychotics-clozapine, olanzapine, risperidone, and quetiapine.