Aripiprazole for Treatment-Resistant Schizophrenia

Abstract

Treatment-resistant schizophrenia poses a major therapeutic challenge. This multicenter, double-blind, randomized study compared the efficacy and safety of aripiprazole and perphenazine in treatment-resistant patients with schizophrenia. Schizophrenia patients (DSM-IV diagnosis) with a history of antipsychotic resistance underwent 4 to 6 weeks of open-label treatment with olanzapine or risperidone to confirm treatment resistance. Only patients who completed this open-label period and failed to respond (< 20% improvement in Positive and Negative Syndrome Scale [PANSS] total score or a Clinical Global Impressions-Severity of Illness score >or= 4) entered the 6-week, double-blind treatment phase. In all, 300 patients with confirmed treatment resistance were randomly assigned to aripiprazole (15-30 mg/day) or perphenazine (8-64 mg/day). The primary outcome measure was change in PANSS score from baseline. The study was conducted between August 30, 2000, and March 18, 2002. Both aripiprazole and perphenazine treatment were associated with clinically relevant improvements in PANSS total scores from baseline. After 6 weeks, 27% of aripiprazole-treated patients and 25% of perphenazine-treated patients were responders (>or= 30% decrease in PANSS total score or a Clinical Global Impressions-Improvement score of 1 or 2). Perphenazine-treated patients had a higher incidence of extrapyramidal symptom-related adverse events, mean increases (i.e., worsening) in extrapyramidal symptom rating scale scores, and a higher rate of elevated prolactin levels than aripiprazole (57.7% vs. 4.4%, p < .001). Improvements in quality of life considered to be clinically relevant (>or= 20% improvement in Quality of Life Scale score) occurred in 36% of the aripiprazole-treated patients and in 21% of those treated with perphenazine (p = .052). Aripiprazole and perphenazine, at the doses used here, can improve the symptoms of schizophrenia in treatment-resistant patients who have failed to respond to olanzapine or risperidone.