Combination of clozapine and ziprasidone in treatment-resistant schizophrenia: an open clinical study

OBJECTIVES: Therapeutic options for patients with treatment-resistant schizophrenia are limited. In such patients, combined application of atypical antipsychotic drugs is an often-used strategy. The authors tested the hypothesis that the combination of ziprasidone and clozapine would lead to an improvement in this patient group. METHODS: Nine patients with treatment-resistant schizophrenia participated in this open clinical trial and received a combination regimen of ziprasidone and clozapine. Patients had to have remained on a stable dose of clozapine for at least 6 months to ensure a reasonable opportunity to respond to clozapine monotherapy. Clinical status was evaluated at baseline, and at 3 and 6 months' follow-up using the Brief Psychiatric Rating Scale (BPRS). RESULTS: All patients completed the 6-month combination treatment. The mental state of 7 patients (77.8%) was improved and there was a significant reduction in the mean BPRS score over the 6 months treatment. The coadministration of ziprasidone in clozapine-treated patients did not result in a corresponding increase in side effects. The combination allowed a 18% reduction of the daily clozapine dose. CONCLUSION: The combined application of clozapine and ziprasidone follows a neurobiologic rationale and appears to be safe and well tolerated without increasing the risk of side effects.