Olanzapine

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.

Olanzapine increases in vivo dopamine and norepinephrine release in rat prefrontal cortex, nucleus accumbens and striatum

“…On the other hand, olanzapine has a favorable sidee¤ect proÞle with minimal extrapyramidal symptoms (EPS), prolactin elevation, sedation induction, and anticholinergic symptoms and no evidence of hematotoxicity (Beasley et al 1996;Fulton and Goa 1997). Thus, olanzapine is believed to be a Þrst-line drug for the treatment of schizophrenia (Meltzer and Fibiger 1996), since the clinical use of the prototype atypical antipsychotic clozapine is limited due to the incidence of agranulocytosis.…”

Y-931, a Novel Atypical Antipsychotic Drug, Is Less Sensitive to Oxidative Phenomena

“…22) Indeed, clozapine is generally administered in the range of 200-900 mg/d, while for olanzapine the usual dose is 10-20 mg/d. Consequently, the low therapeutic plasma concentrations of olanzapine (0.03-0.1 mmol/ l) 23,24) compared to those of clozapine (0.2-1.6 mmol/l) 25) might explain why olanzapine is not frequently associated with agranulocytosis in humans. 820 Vol.…”

“…7) Interestingly, despite the structural similarity between clozapine and olanzapine, no cases of agranulocytosis have been reported with the clinical use of olanzapine. 8) Recently, we reported that Y-931 (8-fluoro-12-(4-methylpiperazin-1-yl)-6H- [1]benzothieno [2,3-b] [1,5]benzodiazepine), [9][10][11] which was developed in our laboratory, showed a pattern of interaction with various neurotransmitter receptors similar to that of clozapine. In addition, Y-931 did not cause catalepsy (a correlate of EPS), despite its potent antagonistic activity of apomorphine-induced hyperlocomotion or conditioned avoidance response (a correlate of antipsychotic effects).…”

Ecstasy-Induced Psychotic Disorder: Six-Month Follow-Up Study

“…Olanzapine is a new antipsychotic drug, one of the socalled atypical antipsychotics, with a favorable tolerance profile, and it has been shown to be effective against both the positive and negative symptoms of schizophrenia [29]. In addition, it has been suggested that olanzapine should be considered as first-choice therapy in the first psychotic episode because of its advantages in both safety and efficacy [30].…”