Olanzapine for schizophrenia

Olanzapine is an atypical antipsychotic that is reported to be effective without producing the disabling extrapyramidal side effects associated with the older, typical antipsychotic drugs. To determine the clinical effects and safety of olanzapine as compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses. The reviewers undertook electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), The Cochrane Schizophrenia Group's Register (September 1999), EMBASE (1980-1999), MEDLINE (1966-1999), and PsycLIT (1974-1999). References of all identified studies were searched for further trials, and the reviewers contacted relevant pharmaceutical companies and authors of trials. All randomised clinical trials comparing olanzapine to placebo or any antipsychotic treatment for those with schizophrenia or schizophreniform psychoses. Data were independently extracted. For homogeneous dichotomous data the random effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data the reviewers calculated weighted mean differences. Twenty trials are included. Attrition from olanzapine versus placebo studies was so great (olanzapine - 61%, placebo - 73% by six weeks, RR 0.85 CI 0. 7-0.98, NNT 8 CI 5-40) that interpretation of results is problematic. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (RR 0.88 CI 0.8-0.98, NNT 8 CI 5-27), but trial data regarding negative symptoms are equivocal for this comparison. Dizziness and dry mouth were more common in the olanzapine-treated group, and, although not statistically significant, the olanzapine group gained more weight. Data from several small trials are incomplete; but, for the short term outcome of 'no important clinical response', olanzapine seem as effective as typical antipsychotics (n=2778, RR 0.9 CI 0.76-1.06). Brief Psychiatric Rating Scale (BPRS) data tended to be equivocal but Positive and Negative Syndrome Scale (PANSS) rating of total score and negative and positive symptom sub-scores favoured olanzapine. With high attrition in both groups (olanzapine - 36%, typical drug - 49% by 6 weeks, n=2738, RR 0.85 CI 0.66-1.1; olanzapine - 83%, typical drug - 90% by 1 year, n=2738, RR 0.9 CI 0. 86-1.02), the assumptions included in all continuous data are co