Agitation, aggression, and psychosis are among the most troublesome behavioral and psychological symptoms of dementia (BPSD) and impair the lives of dementia patients and their caregivers. Atypical antipsychotics have been widely prescribed to improve these BPSD. However, in a number of trials with atypical antipsychotics, a consistent increase in overall mortality has been observed. The US Food and Drug Administration issued a warning for all atypical antipsychotics as a result of a meta-analysis of 17 placebo-controlled clinical trials using various atypical antipsychotics for the treatment of BSPD.
To evaluate this mortality risk specifically for risperidone, 6 phase-2/3 double-blind trials comparing risperidone with placebo were analyzed. Data were obtained from Johnson & Johnson Pharmaceutical Research and Development. Hazard ratios with 95% confidence intervals were calculated to compare the relative mortality risk between patients treated with risperidone and those treated with placebo.
In this meta-analysis, 1721 patients were included. In the pooled sample, the mortality was 4.0% with risperidone versus 3.1% with placebo (relative risk, 1.21; 95% confidence interval, 0.71-2.06) during treatment or within 30 days after treatment discontinuation. The most common adverse events associated with death were pneumonia, cardiac failure or arrest, or cerebrovascular disorder. No relationship was found between risperidone dose and mortality.
In conclusion, this meta-analysis found a nonsignificant increase in mortality during treatment with risperidone in dementia patients. Larger studies would be needed to rule out a small increase in mortality in these patients. Careful assessments of potential benefits and risks should be made before prescribing risperidone for the treatment of BPSD.