Starr L. Grundy

The effectiveness of olanzapine in treatment-refractory schizophrenia when patients are nonresponsive to or unable to tolerate clozapine

OBJECTIVE This multicenter, open-label study was designed to assess the efficacy and tolerability of olanzapine in patients with chronic schizophrenia who are resistant to therapy with classic neuroleptic agents and are either not responsive to or unable to tolerate clozapine. METHODS Patients received olanzapine orally once daily for 18 weeks at doses ranging from 5 to 25 mg. The primary efficacy measure was change in the total score on the Positive and Negative Syndrome Scale (PANSS) from baseline to end point. Secondary efficacy measures were the total score on the Brief Psychiatric Rating Scale (BPRS); the PANSS positive, negative, general psychopathology, and mood subscores; and the Clinical Global Impression improvement score. Also recorded were spontaneously reported adverse events; extrapyramidal symptoms (assessed by the Abnormal Involuntary Movement Scale, Simpson-Angus Scale, and Barnes Akathisia Scale); vital signs; and clinical laboratory test results. RESULTS Forty-eight patients were treated with olanzapine; of these, 45 were assessable over the full 18-week study period. Total scores on the PANSS and BPRS were reduced from baseline by an average of 17.7 (14.2%) and 9.8 points (20.2%), respectively. Eighteen patients (40.0%) experienced a treatment response, defined as a reduction in PANSS total score of > or = 20%. A total of 25 patients (55.6%) achieved a similar reduction in BPRS total score. Significant reductions were seen in both the positive and negative symptom scores on the PANSS (P < 0.001). Olanzapine was well tolerated, with minimal treatment-emergent adverse events or clinically relevant changes in vital signs or clinical laboratory test results. No clinically significant blood dyscrasias were observed in olanzapine-treated patients, including those who had discontinued clozapine because of treatment-associated leukopenia or neutropenia. CONCLUSION The results of this study suggest that olanzapine may be of benefit in patients who are refractory to or unable to tolerate clozapine.

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

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.

Olanzapin: kardiales Sicherheitsprofil anhand präklinischer und klinischer EKG-Daten

Fur Neuroleptika konnten Unterschiede bei kardiovaskularen Nebenwirkungen nachgewiesen werden [1]. Wie die vorliegende EKG-Analyse zeigt, ist das atypische Neuroleptikum Olanzapin im Hinblick auf QTc-Effekte mit am vertraglichsten [2].