Aripiprazole augmentation in the management of residual symptoms in clozapine-treated outpatients with chronic schizophrenia: An open-label pilot study.

Objective: The aim of this study was to investigate whether augmentation of clozapine with aripiprazole improves clinically significant residual symptoms in stabilized outpatients with chronic schizophrenia.

Methods: Twenty seven stabilized outpatients meeting criteria for chronic schizophrenia, who had residual symptoms despite clozapine treatment, were assigned to receive oral aripiprazole (15 mg/day) for a period of 16 weeks. Patients remained on clozapine (100-900 mg/day) for at least 12 months, prior to study initiation. Symptoms assessments were made with the Positive and Negative Symptom Scale (PANSS), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Mini-Mental State Examination (MMSE), at baseline and at weeks 4, 8, 12, and 16. The Quality of Life Scale (QLS) was administered at baseline and at week 16.

Results: There was a statistically significant improvement in the mean scores for PANSS (p<0.05), PANSS negative (p<0.001), MADRS (p<0.05), MMSE (p<0.01), and QLS (p<0.05), but not for PANSS positive (p>0.05). Extrapyramidal side effects (as assessed by the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale) did not vary significantly at any point of the study. No statistically significant change was observed in prolactin levels and body weight. Results were similar for the intention-to-treat (n=27) and completer (n=23) groups.

Conclusions: Aripiprazole augmentation in a group of chronic schizophrenic outpatients treated with clozapine led to a substantial improvement in clinically significant residual symptoms, such as negative-depressive symptoms, cognitive impairment and quality of life, without worsening the side effect burden.