Olanzapine for schizophrenia.

BACKGROUND: 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.

OBJECTIVES: To determine the clinical effects and safety of olanzapine as compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses.

SEARCH STRATEGY: The reviewers undertook electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974-1999) and The Cochrane Schizophrenia Group's Register (October 2000). References of all identified studies were searched for further trials, and the reviewers contacted relevant pharmaceutical companies and authors of trials.

SELECTION CRITERIA: All randomised clinical trials comparing olanzapine to placebo or any antipsychotic treatment for those with schizophrenia or schizophreniform psychoses.

DATA COLLECTION AND ANALYSIS: 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.

MAIN RESULTS: Twenty one 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) and global mental state scores. Although dizziness and dry mouth were reported more frequently in the olanzapine-treated group, this did not reach statistical significance. Tthe olanzapine group gained more weight. When compared to typical antipsychotic drugs, 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 considerable. Participants allocated olanzapine experienced fewer extrapyramidal side effects than people given haloperidol. Weight change data for the short term are not conclusive (n=2455, WMD 0.8kg CI -0.6-2.2) but the three to 12 month results suggest an average gain of four kilograms (n=233, WMD 4 CI 0.3-7.8). It is difficult to distinguish between olanzapine and other atypical drugs, although it may cause fewer extrapyramidal side effects than risperidone (n=339, RR 0.6 CI 0.4-0.9, NNH 8 CI 4-29). Olanzapine did cause more weight gain than its comparators but current data are not statistically significant (3-12 months, n=535, WMD 2.2kg CI -0.6-5). One study (n=180) found no clear differences between olanzapine and clozapine for people with treatment-resistant illness.

REVIEWER'S CONCLUSIONS: The large proportions of participants leaving the studies early, in the large multi-centre trials makes it difficult to draw firm conclusions on clinical effects. For people with schizophrenia olanzapine may offer antipsychotic efficacy with fewer extrapyramidal side effects than typical drugs but more weight gain. Large, long-term randomised trials with participants, interventions and primary outcomes that are familiar to those wishing to help those with schizophrenia are long overdue.