Double-blind, randomized comparison of olanzapine versus fluphenazine in the long-term treatment of schizophrenia.

ABSTRACT

This study was undertaken to evaluate the efficacy and safety of olanzapine compared with fluphenazine in the treatment of patients who met the Diagnostic and Statistical Manual, fourth edition (DSM-IV) diagnostic criteria for schizophrenia or schizoaffective disorder. This was a long-term (22-week), randomized, double-blind, parallel clinical trial. Sixty patients (mean age, 35.4 years) were randomly assigned to either olanzapine (n=30) or fluphenazine (n=30). They received treatment at three centers in Croatia during a 22-week study period and were assessed weekly for the first 6 weeks and monthly thereafter. Efficacy was measured using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Rating Scale (PANSS) and the Clinical Global Impression (CGI) Severity and Improvement scores. The Hillside Akathisia Scale (HAS), Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), vital signs, laboratory tests, and treatment-emergent adverse events were assessed to evaluate safety. The olanzapine group showed significantly greater mean decreases from baseline to endpoint for BPRS total (-25.8 vs. -16.5, P=.035), PANSS total (-45.7 vs. -29.5, P=.037), PANSS positive (-13.0 vs. -7.9, P=.034), and CGI Severity (-2.2 vs. -1.3, P=.031) scores. The olanzapine group showed greater mean decreases on all measures of extrapyramidal symptoms, significantly so for the SAS (-2.1 vs. 1.9, P=.004) and HAS (-3.4 vs. 2.6, P=.028). Patients in the fluphenazine group experienced a higher incidence of treatment-emergent adverse events (76.7% vs. 50.0%, P=.032). Weight gain was the most frequently reported adverse event in the olanzapine group (16.7% vs. 0.0%, P=.020). Akathisia (30.0% vs. 10.0%, P=.053) and insomnia (20.0% vs. 0.0%, P=.010) appeared most frequent in the fluphenazine group. Daily use of anticholinergics and benzodiazepines were both significantly greater for the fluphenazine group (P=.003 and.04, respectively). No significant changes were observed in vital signs, ECG, or clinical chemistry. The study indicates that olanzapine has advantages in both efficacy and safety compared to fluphenazine; however, the small sample size limits our ability to draw definitive conclusions.