Quetiapine to Treat Agitation in Dementia: A Randomized, Double-Blind,Placebo-Controlled Study

Abstract

In this 10-week, double-blind, fixed-dose study, elderly institutionalized patients with dementia and agitation were randomized (3:3:2) to quetiapine 200mg/day, 100mg/day, or placebo. The primary endpoint was change in Positive and Negative Syndrome Scale (PANSS)-Excitement Component (EC) scores at endpoint, analysed using last observation carried forward (LOCF) and observed cases (OC) approaches. Other efficacy measures were the Clinical Global Impression of Change (CGI-C), and response rates (percentage with > or =40% reduction [PANSS-EC]; "much" or "very much improved" [CGI-C]), Neuropsychiatric Inventory-Nursing Home version (NPI-NH), and Cohen-Mansfield Agitation Inventory (CMAI). The key safety measure was incidence of adverse events; change in Mini-Mental State Examination (MMSE) was also assessed. Baseline characteristics of 333 participants (quetiapine 200mg/day, n=117; quetiapine 100mg/day, n=124; placebo, n=92) and completion rates (63-65%) were comparable among groups. Compared with placebo, quetiapine 200mg/day was associated with clinically greater improvements in PANSS-EC (LOCF, p=0.065; OC, p=0.014 [ANCOVA]), CGI-C (LOCF, p=0.017; OC, p=0.002 [ANOVA]), and CGI-C response rates (LOCF, p=0.002; OC, p<0.001 [Chi-square test]). Quetiapine 100mg/day did not differentiate from placebo on these measures. There were no between-group differences in NPI-NH or CMAI. Incidences of cerebrovascular adverse events, postural hypotension, and falls were similar among groups. MMSE did not change in any group. Mortality was numerically higher in the quetiapine groups; rates were not statistically different from placebo. The results of this study suggest that quetiapine 200mg/day was effective and well-tolerated for treating agitation associated with dementia. However, caution should be exercised given the concerns regarding increased mortality with atypical antipsychotics in this vulnerable patient population.

Quetiapine treatment for behavioural and psychological symptoms of dementia in Alzheimer's disease patients: a 6‐week, double‐blind, placebo‐controlled study

“…Similar studies in AD (Ballard et al, 2005;Tariot et al, 2006;Zhong et al, 2007) lead to the same conclusion.…”

“…Patients were treated with two fixed doses of quetiapine (100 mg/day and 200 mg/day) or placebo. In a pre-planned subanalysis of patients with Alzheimer's disease, there were significant reductions in the Positive and Negative Syndrome Scale-Excitement Component (the primary endpoint) and CGI-C scores with quetiapine 200 mg/day vs placebo, but not 100 mg/day vs placebo (Zhong et al, 2007).…”

“…This feature of the drug seems to be one of its most important advantages over other SGA in the elderly (Baskys, 2004;Mintzer et al, 2004). Three recent papers (Ballard et al, 2005;Tariot et al, 2006;Zhong et al, 2007), all randomized double blind placebo controlled trials show no benefit of quetiapine over the planned comparisons (haloperidol, rivastigmine or placebo).…”

Pharmacological management of behavioral symptoms associated with dementia

“…A placebo-controlled study did not establish the efficacy of quetiapine at mean daily dose of 100 mg/d for psychotic symptoms, though it showed improvement in secondary measures of agitation [33] . A more recent placebo-controlled study suggests efficacy at 200 mg/d in the treatment of agitation; and the 100 mg/d group did not differentiate from placebo [34] . Another study comparing quetiapine to risperidone showed that low doses (mean doses quetiapine 77 ± 40 mg/d, risperidone 0.9 ± 0.3 mg/d) are equally effective [35] .…”

Tolerability of extended‐release quetiapine fumarate compared with immediate‐release quetiapine fumarate in older patients with Alzheimer's disease with symptoms of psychosis and/or agitation: a randomised, double‐blind, parallel‐group study

“…Thereafter, two randomised, double-blind, placebo-controlled studies showed some benefits of quetiapine IR in older patients with dementia (Tariot et al, 2006;Zhong et al, 2007). Extended-release quetiapine fumarate (quetiapine XR) has subsequently been developed to allow a more convenient once-daily dosing regimen and simpler dose initiation.…”