Risperidone versus placebo for schizophrenia.

backgroundRisperidone is the first new generation antipsychotic drug made available in the market in its generic form.

objectivesTo examine the clinical effects of oral risperidone for people with schizophrenia and schizophrenia-like psychoses in comparison with placebo. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's Register (February 2008), references of all included studies, and contacted industry and authors of included studies for relevant studies and data. SELECTION CRITERIA: Randomised clinical trials comparing oral risperidone with placebo treatments for people with schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Two reviewers independently inspected citations and/or abstracts, ordered papers, re-inspected and assessed the quality of results and extracted data. For dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT), on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). MAIN

resultsOne study (n=599) compared risperidone against placebo but the attrition rate was 60% over a period of six weeks rendering most of the efficacy and global improvement data unusable. The attrition rate was higher for placebo compared with risperidone (n=1363, 10 RCTs, RR 0.70 CI 0.57 to 0.86, NNT 13 CI 9 to 29) and less participants left the trial in the risperidone arm due to lack of efficacy (n=888, 5 RCTs, RR 0.38 CI 0.20 to 0.73, NNT 7 CI 5 to 15). Risperidone was no better than placebo on the CGI global score (n=397, 3 RCTs, RR 0.80 CI 0.55 to 1.15) but significantly more number of participants in risperidone arm had more than 20% reduction in their BPRS/PANSS score (n=856, 7 RCTs, RR 0.43 CI 0.32 to 0.58, NNT 7 CI 6 to 10). Data became considerably more homogeneous (and positive) when the one study independent of industry funding was removed (I(2) 75% to 55%). Despite poor reporting, it is clear that around 24% of all participants receiving either risperidone or placebo developed some form of extrapyramidal effects (n=723, 5 RCTs, RR 1.40 CI 0.93 to 2.10). Three people on risperidone had prolonged QTc (n=198, 1 RCT, RR 7.5 CI 0.4 to 144), more on risperidone gained weight (n=303, 2 RCTs, RR 5.14 CI 1.79 to 14.73, NNH 10 CI 3 to 51) and had a raised prolactin (n=323, 2 RCTs, RR 12.54 CI 5.11 to 30.79, NNH 3 CI 2 to 5). Fewer in the risperidone arm needed an additional psychotropic during the trial period (n=186, 1 RCT, RR 0.62 CI 0.45 to 0.85, NNT 10 CI 7 to 28). AUTHORS'

conclusionsRisperidone appears to have a marginal benefit in terms of clinical improvement compared with placebo in the first few weeks of treatment but data are limited, poorly reported and probably biased in favour of risperidone. The margin of improvement chosen by the researchers as their outcome may not be clinically meaningful. Even after so much use of this drug, we feel that further independent trials can be justified.