Olanzapine. A review of its pharmacological properties and therapeutic efficacy in the management of schizophrenia and related psychoses

Abstract

Olanzapine is a thienobenzodiazepine derivative which displays efficacy in patients with schizophrenia and related psychoses. It has structural and pharmacological properties resembling those of the atypical antipsychotic clozapine and an improved tolerability profile compared with the classical antipsychotic haloperidol. In several large, well controlled trials in patients with schizophrenia or related psychoses, olanzapine generally 5 to 20 mg/day was at least as effective as haloperidol (5 to 20mg) and more so than placebo, as assessed by overall rating scales for psychoses. Olanzapine improved negative symptoms to a greater extent than haloperidol in 2 of 3 comparative trials, including the largest trial. Efficacy of olanzapine has a rapid onset (within 1 to 2 weeks). Its clinical benefits appear to be maintained for treatment periods of up to 1 year, as shown by analysis of the extension phase of several trials demonstrating decreased probability of hospitalisation over this period compared with haloperidol. Preliminary data suggest the drug may also improve quality of life. Olanzapine was associated with significantly fewer adverse movement disorders (e.g. akathisia, dystonia, hypertonia, extrapyramidal symptoms) than haloperidol. There have been no reports of agranulocytosis (as occurs with clozapine) or any other haemotoxicity attributed to olanzapine, and the drug has shown minimal effect on prolactin levels. Transient increases in levels of hepatic transaminases seem to be clinically important. The only events recorded more frequently during olanzapine than during haloperidol therapy were weight gain, dry mouth and increased appetite. Although the antipsychotic activity of olanzapine has been well demonstrated. Its efficacy in refractory schizophrenia and its place relative to other atypical antipsychotics remain to be determined. Nevertheless, if the long term tolerability profile of olanzapine is confirmed, the drug should provide a valuable therapeutic alternative in the management of schizophrenia and related psychoses.