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


METHODS
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.


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 (>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).


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.
Kane
John M
JM
Zucker Hillside Hospital and The Albert Einstein College of Medicine, Glen Oaks, NY 11004, USA. psychiatry@lij.edu
Meltzer
Herbert Y
HY
Carson
William H
WH
McQuade
Robert D
RD
Marcus
Ronald N
RN
Sanchez
Raymond
R
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000068180:Aripiprazole; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D010546:Perphenazine / Q000009:adverse effects / Q000627:therapeutic use*; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011388:Prolactin / Q000097:blood; D011788:Quality of Life; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole; D011388:Prolactin; D010546:Perphenazine