Focus on olanzapine.

Abstract

Olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine) is a novel antipsychotic agent of the theinobenzodiazepine class developed by Eli Lilly & Co. It has a pleotrophic pharmacology and affects the dopaminergic, serotonergic, muscarinic and adrenergic systems. The therapeutic advantage of recent antipsychotics (so-called atypical antipsychotics) has been attributed to additional serotonergic effects. Clinical studies and trials suggest that olanzapine is comparable or superior to haloperidol and may be superior to risperidone in terms of efficacy and side-effect profiles. The starting dose of olanzapine is a single dose of 10 mg. The drug reaches peak plasma levels in 5-8 h, and has a half-life of about 35 h, depending on metabolism. The recommended maximum dose is 20 mg daily, but higher doses have been employed. Abnormalities of the QTc interval on ECG are unlikely to occur and so there is no need for a baseline ECG as with sertindole, which has recently been withdrawn. The most common side-effects are somnolence and weight gain. About 40% of patients in clinical trials gain weight--especially if they are on a high starting dose and if they were underweight pre-treatment. Reported evidence to date suggests that olanzapine is relatively less likely to produce sexual dysfunction. In general, weight gain and sexual dysfunction are of great concern to people taking antipsychotics and the side-effect profile of any antipsychotic may affect compliance. Olanzapine's general efficacy and side-effect profile suggest that, unforeseen post-marketing complications notwithstanding, olanzapine deserves a major place in the first-line management of psychotic disorders.