The main aim of pharmacotherapy in patients with dementia is to address the behavioral and psychological signs and symptoms (including psychotic features, anxious and depressive features, agitation, aggression, apathy and vegetative disturbances), without causing side effects or exacerbating underlying cognitive impairment. Several studies have demonstrated that atypical antipsychotics are effective in treating these symptoms. A 12-week double-blind trial in 625 patients with Alzheimer’s disease (AD) showed that risperidone (0.5-2 mg/day) improved symptoms of psychosis and aggressive behavior.1 The frequency of extrapyramidal symptoms was significantly greater in patients receiving the higher dose. A follow-up study comparing haloperidol, risperidone and placebo showed no advantage of either active treatment over placebo in the primary analysis, while a secondary analysis showed an effect of risperidone on aggression.2 The first placebo-controlled study of flexible-dose olanzapine in patients with dementia demonstrated no benefit for olanzapine.3 A follow-up, fixed-dose, 6-week study showed benefit of 5 and 10 mg/day, but not 15 mg/day, with side effects including gait disturbance and sedation at all doses.4 In a 52-week, open-label trial of quetiapine (median dose 138 mg/day) in 184 elderly patients with psychosis, improvements in behavioral and psychotic symptoms were observed. 5 A subgroup analysis of this trial, including 78 patients with AD, indicated that quetiapine (100 mg/day) significantly improved hostility symptoms.6 At study end the mean SAS score had decreased and changes in AIMS scores were negligible. These results are generally consistent with data from a placebo-controlled trial of haloperidol versus quetiapine in patients with dementia and psychotic features, in which agitation but not psychosis improved with active treatment versus placebo and there were fewer EPS with quetiapine versus haloperidol and placebo.6 Atypical antipsychotics are efficacious for treatment of agitation and psychosis in dementia and are generally better tolerated than conventional agents. When making individualized therapeutic decisions, the different side-effect profiles of these atypical agents should be considered. References 1. Katz IR, Jeste DV, Mintzer JE, Clyde C, Napolitano J, Brecher M. Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: A randomized, double-blind trial. J Clin Psychiatry 1999; 60: 107-115. 2. De Deyn P, Rabheru K, Rasmussen A, et al. A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology 1999; 53: 946-955. 3. Satterlee WG, Reams SG, Burns PR, et al. A clinical update on olanzapine treatment in schizophrenia and in elderly Alzheimer’s disease patients. Psychopharmacol Bull 1999; 31: 534. 4. Street JS, Clark WS, Gannon KS, et al. Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer’s disease in nursing care facilities: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry 2000; 57: 968-976.
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