Since the early 1950s the mainstay of treatment for schizophrenia has been the typical antipsychotics such as chlorpromazine and haloperidol. Although they are effective in controlling voices and delusions for many people with schizophrenia, they have a smaller effect on symptoms such as apathy and social withdrawal. They also have disabling adverse effects such as tremor, stiffness and slowing of movement. The newer drugs, such as olanzapine, are reputed to have fewer adverse motor effects and are as effective, if not more so, than the older drugs. This review examines the randomised controlled trials of olanzapine compared with placebo, typical and atypical antipsychotic drugs.
Most of the studies in this review were either sponsored by or run by the pharmaceutical companies responsible for the marketing of these drugs. Olanzapine seems to be an effective antipsychotic that produces less adverse effects for movement. It does however tend to cause more weight gain than the older drugs. Its effectiveness appears similar to other atypical drugs and it is not markedly beneficial for apathy, demotivation and social withdrawal.
The large proportion of participants leaving studies early in these trials makes it difficult to draw firm conclusions on olanzapine's clinical effects. For people with schizophrenia it may offer antipsychotic efficacy with fewer extrapyramidal adverse effects than typical drugs, but more weight gain. There is a need for further large, long-term randomised trials with more comprehensive data.
Olanzapine is an atypical antipsychotic reported to be effective without producing disabling extrapyramidal adverse effects associated with older, typical antipsychotic drugs.
To determine the clinical effects and safety of olanzapine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses.
We updated the first search [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)] in October 2004 using the Cochrane Schizophrenia's Group's register of trials. We also searched references of all included studies for further trials, and contacted relevant pharmaceutical companies and authors.
We included all randomised clinical trials comparing olanzapine with placebo or any antipsychotic treatment for people with schizophrenia or schizophreniform psychoses.
We independently extracted data and, for homogeneous dichotomous data, calculated the random effects relative risk (RR), the 95% confidence intervals (CI) and the number needed to treat (NNT) on an intention-to-treat basis. For continuous data we calculated weighted mean differences.
Fifty five trials are included (total n>10000 people with schizophrenia). Attrition from olanzapine versus placebo studies was >50% by six weeks, leaving interpretation of results problematic. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (any dose, 2 RCTs n=418, RR 0.88 CI 0.8 to 0.1, NNT 8 CI 5 to 27). Although dizziness and dry mouth were reported more frequently in the olanzapine-treated group, this did not reach statistical significance. The olanzapine group gained more weight.
When compared with typical antipsychotic drugs, data from several small trials are incomplete. With high attrition in both groups (14 RCTs, n=3344, 38% attrition by six weeks, RR 0.81 CI 0.65 to 1.02) the assumptions included in all data are considerable. For the short term outcome of 'no important clinical response', olanzapine seems as effective as typical antipsychotics (4 RCTs, n=2778, RR 0.90 CI 0.76 to 1.06). People allocated olanzapine experienced fewer extrapyramidal adverse effects than those given typical antipsychotics. Weight change data for the short term are not statistically significant but results between three to 12 months suggest a clinically important average gain of four kilograms for people given olanzapine (4 RCTs, n=186, WMD 4.62, CI 0.6 to 8.64).
Twenty three percent of people in trials of olanzapine and other atypical drugs left by eight weeks; 48% by three to12 months (11 RCTs, n=1847, RR 0.91 CI 0.82 to 1.00). There is little to choose between the atypicals, although olanzapine may cause fewer extrapyramidal adverse effects than other drugs in this category. Olanzapine produces more weight gain than other atypicals with some differences reaching conventional levels of statistical significance (1 RCT, n=980, RR gain at 2 years 1.73 CI 1.49 to 2.00, NNH 5 CI 4 to 7). There are very few data for people with first episode illness (1 RCT, duration 6 weeks, n=42). For people with treatment-resistant illness there were no clear differences between olanzapine and clozapine (4 RCTs, n=457).