RESEARCH ARTICLE


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



Alessandra Benedetti§, 1, *, Antonello Di Paolo^, 1, Marianna Lastella^, Francesco Casamassima§, Chiara Candiracci°, Antonella Litta§, Laura Ciofi^, Romano Danesi^, Lorenzo Lattanzi§, Mario Del Tacca, Giovanni Battista Cassano§
1 those Authors equally contributed to the study


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© Benedetti et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies, University of Pisa, Via Roma 57, 56126 Pisa – Italy; Tel: +39-050-835411; Fax: +39-050-21581; E-mail: a.benedetti@med.unipi.it, benedettia@hotmail.it
§ Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies, University of Pisa
^ Department of Internal Medicine, University of Pisa
° Psychiatric Clinic, Polytechnic University of Marche, Ancona


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 (mean 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.

Keywords: Psychotic bipolar disorder, schizoaffective disorder, clozapine, aripiprazole, augmentation, pharmacokinetic interactions.