Augmentation of Clozapine with Aripiprazole in Severe Psychotic Bipolar and Schizoaffective Disorders: A Pilot Study

Abstract

Aim: To evaluate the efficacy and safety of the augmentation of clozapine with aripiprazole in patients with treatment-resistant schizoaffective and psychotic bipolar disorders in a retrospective manner. Pharmacodynamic and pharmacokinetic interactions between the two drugs were also investigated. Patients: Three men and 4 women (median age 36 and 40 years, respectively) who had mean scores at BPRS and CGI-Severity of 59.1±12.0 and 5.4±0.5, respectively, were treated with clozapine (mean dose 292.9±220.7 mg/day). Patients received an adjunctive treatment with aripiprazole (mea n dose 6.8 ± 3.7 mg/day). Clozapine, norclozapine and aripiprazole plasma levels were measured by means of a high performance liquid chromatograpy with UV detection. Results: Total scores at BPRS decreased significantly (from 59.1±12.0 to 51.1±15.6, p=0.007) after aripirazole augmentation. In particular, the factors "thought disorder" (from 10.4±4.4 to 9.0±4.5, p=.047) and "anergia" (from 10.0±2.7 to 8.0±2.4, p=.018) significantly improved. Concomitant administration of aripiprazole and clozapine did not result in an increase in side effects over the period of treatment. Dose-normalized plasma levels of both clozapine and norclozapine and the clozapine/norclozapine metabolic ratio in all patients did not vary as well. Conclusion: The augmentation of clozapine with aripirazole was safe and effective in severe psychotic schizoaffective and bipolar disorders which failed to respond to atypical antipsychotics. A possible pharmacokinetic interaction between clozapine and aripiprazole does not account for the improved clinical benefit obtained after aripiprazole augmentation. © Benedetti et al.