Risperidone Versus Placebo for Schizophrenia

Background

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

Objectives

To examine the clinical effects and safety 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), inspected references of all included studies, contacted industry, and authors of included studies for relevant studies and data.

Selection Criteria

We included all the randomized 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, reinspected, 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.

Main Results

We found 815 citations but were only able to include 10 studies (42 reports). One study (n = 599) compared risperidone with placebo but the attrition rate was 60% over a period of 6 weeks rendering most of the efficacy and global improvement data unusable. Overall, attrition rate was higher for placebo compared with risperidone (n = 1363, 10 randomized clinical trials (RCTs); RR 0.70, CI 0.57–0.86; NNT 13, CI 9–29) and less people left trials in the risperidone arm due to lack of efficacy (n = 888, 5 RCTs; RR 0.38, CI 0.20–0.73; NNT 7, CI 5–15). Risperidone was no better than placebo on Clinical Global Impression (CGI)-severity (n = 397, 3 RCTs; RR 0.80, CI 0.55–1.15) but significantly more participants in risperidone arms had more than 20% reduction in their Brief Psychiatric Rating Scale (BPRS)/Positive and Negative Syndrome Scale score (n = 856, 7 RCTs; RR 0.43, CI 0.32–0.58; NNT 7, CI 6–10) (figure 1). Data became considerably more homogeneous (and positive) when the one study independent of industry funding was removed (I² 75%–55%). Despite poor reporting, it is clear that around 24% of all participants receiving either risperidone or placebo developed some form of extrapyramidal effect (n = 723, 5 RCTs; RR 1.40, CI 0.93–2.10). Three people on risperidone had prolonged QTc (n = 198, 1 RCT; RR 7.5, CI 0.4–144), more on risperidone gained weight (n = 303, 2 RCTs; RR 5.14, CI 1.79–14.73; NNH 10, CI 3–51), and had raised prolactin levels (n = 323, 2 RCTs; RR 12.54, CI 5.11–30.79; NNH 3, CI 2–5). Fewer in the risperidone arm needed an additional psychotropic during the trial period (n = 186, 1 RCT; RR 0.62, CI 0.45–0.85; NNT 10, CI 7–28) (figure 2). Full version of this review is published on the Cochrane Library.¹

Fig. 1.

Mental State; At Least 20% Reduction on BPRS/Positive and Negative Syndrome Scale Total Score.

Fig. 2.

Global State.

Authors’ Conclusions

Risperidone appears to have a marginal benefit in terms of clinical improvement compared with placebo in the first few weeks of treatment but data are surprisingly limited, poorly reported, and probably biased in favor of risperidone. The margin of improvement chosen by most researchers may not be clinically meaningful. There was very little to choose between risperidone and placebo for outcomes of global state, some efficacy measures and adverse events especially relating to cardiovascular and neurological effects. Although risperidone is widely used, further independent trials can be justified.