Efficacy of Atypical Antipsychotics in Elderly Patients With Dementia

Pharmacotherapy in patients with dementia aims to improve distressing behavioral and psychologicalsigns of dementia after nonpharmacologic interventions fail, without causing unacceptableside effects or exacerbating underlying cognitive impairment. We review data describing risperidone(3 published placebo-controlled trials), olanzapine (1 abstract regarding a placebo-controlled trial anda published placebo-controlled trial), quetiapine (1 published open-label trial and an abstract regardinga placebo-controlled trial), and aripiprazole (1 abstract regarding a placebo-controlled trial). Forexample, a 12-week study of risperidone in patients with Alzheimer’s disease showed a dose-relatedimprovement in psychosis and agitation. The frequency of extrapyramidal symptoms (EPS) wasalso significantly greater in patients receiving the highest doses. A 6-week study of olanzapineshowed greater improvement than placebo in agitation/aggression and psychosis with doses of 5 and10 mg/day, but not 15 mg/day, with side effects including gait disturbance and sedation at all doses. A52-week, open-label trial of quetiapine (median dose = 138 mg/day) in elderly patients with psychosissuggested good tolerability with apparent behavioral benefit; EPS improved or remained unchangedin most patients. Limited data describing aripiprazole have shown inconclusive evidence regardingrelief of psychosis in elderly patients with Alzheimer’s disease-related dementia, with apparentlygood tolerability over the short term. It appears that, in the aggregate, atypical antipsychotics are efficaciousfor treatment of agitation in dementia, with less clear impact on psychosis, but their tolerabilityprofiles clearly differ. The National Institute of Mental Health-funded Clinical AntipsychoticTrials of Intervention Effectiveness in Alzheimer’s Disease project will provide the first head-to-headcomparisons of atypicals in dementia and will examine possible drug-drug differences between efficacyand effectiveness.