title: Augmentation of clozapine with aripiprazole in severe psychotic bipolar and schizoaffective disorders: a pilot study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: those Authors equally contributed to the study.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Benedetti
authors.forename: Antonello
authors.initials: A
authors.lastname: Di Paolo
authors.forename: Marianna
authors.initials: M
authors.lastname: Lastella
authors.forename: Francesco
authors.initials: F
authors.lastname: Casamassima
authors.forename: Chiara
authors.initials: C
authors.lastname: Candiracci
authors.forename: Antonella
authors.initials: A
authors.lastname: Litta
authors.forename: Laura
authors.initials: L
authors.lastname: Ciofi
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Lattanzi
authors.forename: Mario
authors.initials: M
authors.lastname: Del Tacca
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Cassano