Schizophrenia Symptom Improvements and Adverse Effects

In a systematic review of clinical trials examining risperidone, researchers have found that based on low-quality evidence, the atypical drug risperidone appears more effective than placebo at reducing symptoms of schizophrenia, but similar to typical treatments, it was also associated with serious adverse effects such as parkinsonism.

Raganath D. Rattehalli, MB BS, DPM, MRC Psych, MMedSc, from Logan Hospital in Brisbane, Australia, and colleagues searched the Cochrane Schizophrenia Group Trials Register and registries of clinical trials and identified 15 clinical trials with 2428 participants to include in their review. The studies randomly assigned in- and outpatients with schizophrenia to receive either oral risperidone or placebo.

The researchers found that participants in the risperidone group were generally more likely to achieve significant clinical improvement in mental state (6 randomized clinical trials; n=864; risk ratio [RR], 0.64; 95% CI, 0.52-0.78; very low quality evidence), and this clinical improvement remained even after removing 3 trials with >50% attrition rate from the analysis (3 RCTs; n=589; R,R 0.77; 95% CI, 0.67-0.88).

Participants in the placebo group were less likely to have a clinically significant improvement on Clinical Global Impression scale than those receiving risperidone (4 RCTs; n=594; RR, 0.69; 95% CI, 0.57-0.83; very low quality evidence).

Participants in the risperidone group were also 31% less likely to leave the trials early compared with the placebo group (12 RCTs; n=2261; RR, 0.69; 95% CI, 0.62-0.78; low-quality evidence). However, rates of significant extrapyramidal adverse effects were more likely to occur in the risperidone group (7 RCTs; n=1511; RR, 1.56; 95% CI, 1.13-2.15; very low quality evidence).

“Based on low quality evidence, risperidone appears to be [beneficial] in improving mental state compared with placebo, but it also causes more adverse events [than placebo],” the investigators concluded.

“Firm conclusions are difficult to make based on the results of this review,” wrote Ben Gray, Senior Peer Researcher from the McPin Foundation, in a plain language summary.

“The evidence available was very low quality. Information and data were limited, poorly reported, and probably biased in favour of risperidone. Nearly half of the included trials were funded by drug companies.”

He concluded that better-conducted and better-reported trials could increase the confidence in these findings.