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

Abstract

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 (CGI-C) 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.

Relationship between antipsychotic drug use and behavioral and psychological symptoms of dementia in old people with cognitive impairment living in geriatric care

“…All these four associated factors, however, raise the question of whether the patients are treated for their own sake, or for that of the staff. In light of the known side-effects and rather serious risks associated with antipsychotic drug use (Brodaty et al, 2003;Katz, 2004), this is an important ethical question, especially because there are alternative ways of managing the behavioral disturbances that might occur in dementia. Non-pharmacological approaches have been used successfully to reduce behavioral disturbances (Rovner et al, 1996;Sloane et al, 2004).…”

“…This might have been expected, as the efficacy of antipsychotic drug treatment, compared to a placebo, for these behavioral disturbances has been proved (Brodaty et al, 2003;De Deyn et al, 1999). The effectiveness of antipsychotic drugs in dementia is, however, modest (Gormley and Howard, 1999).…”

“…The introduction of atypical antipsychotics, such as risperidone and olanzapine, has changed the treatment for this population, as they are more effective in controlling BPSD and have fewer and milder extrapyramidal side-effects (EPS) than conventional antipsychotics (Brodaty et al, 2003;De Deyn et al, 1999). In the USA the atypical antipsychotics have now become a more common treatment for old people with dementia than the conventional drugs (Liperoti et al, 2003).…”

“…In the treatment of frail old people, EPS, sedation and cognitive decline are seen even when atypical antipsychotics are used. It has also been reported that their use incurs an approximately threefold increase in the risk of adverse cerebrovascular events (stroke or transitory ischemic attack) compared to when a placebo drug is administered (Brodaty et al, 2003). A mortality rate of 3.5%, compared to 1.5% for the placebo group, has been seen in clinical trials (Katz, 2004).…”

Psychopharmakologische Behandlungspraxis in Münchener Altenpflegeheimen

“…Neuere Neuroleptika, wie Risperidon und Olanzapin ergeben eine günstigere Nutzen/RisikoAbschätzung Brodaty et al, 2003;Martin et al, 2003). Risperidon wurde im 5 Rahmen des zweiten Konsensustreffens von Vertretern u.a.…”