Background: Risperidone is one of a number of 'atypical antipsychotics' which are currently being marketed for the treatment of those with schizophrenia, largely on the basis of claims of improved tolerability and effectiveness compared to much cheaper conventional antipsychotics. The efficacy of risperidone has already been compared to conventional drugs, but it remains unclear how risperidone compares with other atypical antipsychotic drugs such as clozapine.

Objectives: To determine the effects of risperidone compared with other atypical antipsychotic drugs for schizophrenia.

Search strategy: Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 2000), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1999), PSYNDEX (1977-1999) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted.

Selection criteria: All randomised controlled clinical trials that compared risperidone to other atypical antipsychotic treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment.

Data collection and analysis: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, standardised and weighted mean differences were calculated (SMD, WMD). All data were inspected for heterogeneity.

Main results: Nine studies were obtained, comparing risperidone with clozapine (five studies - largely amongst treatment resistant patients); olanzapine (three studies); and amisulpiride (one study). The research was beset by problems of high attrition rates and short term follow up. Clozapine does seem equally acceptable to risperidone in the short term (leaving the study early, n=466, RR 1. 00 CI 0.73-1.37). For most other outcomes wide confidence intervals were obtained, which meant that it was impossible to judge whether the two compounds were equally effective, or whether one was in fact superior to the other. Olanzapine and risperidone seem broadly similar according to numbers of patients responding to treatment (40% reduction in PANSS scores: n=339, RR 1.14, CI 0.99-1.32). Olanzapine caused fewer people to leave the study early (n=404, RR 1. 31 CI 1.06-1.60; NNT 8 CI 4-32) and fewer extrapyramidal side effects (n=339, RR 1.67 CI 1.14-2.46; NNH 8 CI 5-33), although comparative doses of risperidone were higher than those recommended in practice. In one single study (n=228) amisulpiride seemed broadly similar to risperidone in most respects. There were no useful data presented relating to service use and costs. Very few data relating to quality of life were presented.

Reviewer's conclusions: The equivalence of clozapine and risperidone for treatment resistant schizophrenia cannot yet be assumed and there seems to be little to chose between risperidone and both olanzapine and amisulpiride. The research is limited in many respects, and longer term studies measuring clinically important outcomes, including service use and quality of life are needed to judge the comparative value of the various atypical drugs.