Aripiprazole for treatment-resistant schizophrenia: Results of a multicenter, randomized, double-blind, comparison study versus perphenazine

John M. Kane*, Herbert Y. Meltzer, William H. Carson, Robert D. McQuade, Ronald N. Marcus, Raymond Sanchez

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

Objective: 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. Method: 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 ≥ 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. Results: 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 (> 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 (≥ 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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)213-223
Number of pages11
JournalJournal of Clinical Psychiatry
Volume68
Issue number2
DOIs
StatePublished - Feb 2007

ASJC Scopus subject areas

  • Psychiatry and Mental health

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