A Randomized Placebo-Controlled Trial of Risperidone for the Treatment of Aggression, Agitation, and Psychosis of Dementia

Background: This randomized, double-blind, placebo-controlled trial examined the efficacy and safety of risperidone in the treatment of aggression, agitation, and psychosis in elderly nursing-home patients with dementia.

Method: Elderly patients with a DSM-IV diagnosis of dementia of the Alzheimer’s type, vascular dementia, or a combination of the 2 (i.e., mixed dementia) and significant aggressive behaviors were randomized to receive, for a period of 12 weeks, a flexible dose of either placebo or risperidone solution up to a maximum of 2 mg/day. Outcome measures were the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer’s Disease (BEHAVE-AD) rating scale, and the Clinical Global Impression of Severity (CGI-S) and of Change (CGIC) scales.

Results: A total of 345 patients were randomized to treatment with risperidone or placebo, and 337 patients received at least one dose of study drug. The trial was completed by 67% of patients in the placebo group and 73% of patients in the risperidone group. The mean ± SE dose of risperidone was 0.95 ± 0.03 mg/day. The primary endpoint of the study, the difference from baseline to endpoint in CMAI total aggression score, showed a significant reduction in aggressive behavior for risperidone versus placebo (p < .001). A similar improvement was also seen for the CMAI total non-aggression subscale (p < .002) and for the BEHAVE-AD total (p < .001) and psychotic symptoms subscale (p = .004). At endpoint, the CGI-S and the CGI-C scores indicated a significantly greater improvement with risperidone compared with placebo (p < .001). Overall, 94% and 92% of the risperidone and placebo groups, respectively, reported at least 1 adverse event. Somnolence and urinary tract infection were more common with risperidone treatment, whereas agitation was more common with placebo. There was no significant difference in the number of patients who reported extrapyramidal symptoms between the risperidone (23%) and placebo (16%) groups.

Conclusion: Treatment with low-dose (mean = 0.95 mg/day) risperidone resulted in significant improvement in aggression, agitation, and psychosis associated with dementia.