Atypical Antipsychotic Agents For Alzheimer’s Disease: Risks May Outweigh Benefits

Alzheimer's Disease

Atypical antipsychotic drugs are now common choices for treating delusions, hallucinations, aggression, and agitation in patients with Alzheimer’s disease (AD). These drugs are considered to be at least as effective as haloperidol decan-oate (Haldol, Ortho-McNeil) and other conventional antipsychotic agents, with a lower risk of most adverse effects. However, studies have been relatively sparse and data have been inconsistent, say members of the Clinical Antipsychotic Trials of Intervention Effectiveness Alzheimer’s Disease Study Group. Their own findings suggest that the adverse effects of atypical antipsychotics offset the advantages in patients with AD.

In a multicenter, double-blind, placebo-controlled trial, 421 outpatients with AD and psychosis, aggression, or agitation were randomly assigned to receive olanzapine (Zyprexa generic, Eli Lilly) (mean, 5.5 mg/ day), quetiapine fumarate (Seroquel medication, AstraZeneca) (mean, 56.5 mg/day), risperidone (Generic Risperdal, Janssen) (mean, 1 mg/day), or placebo. Doses were adjusted as needed, and patients were followed for up to 36 weeks. Risperidone and olanzapine doses were within the recommended ranges, and the quetia-pine dose was one-half to one-quarter of that used in two nursing-home trials.

By 12 weeks, improvement was seen in 32% of patients receiving olanzapine, in 29% of those receiving risperidone, 26% of those taking generic quetiapine, and 21% of those receiving placebo. However, 77% to 85% of patients discontinued treatment. Over time, 24% of the olanzapine patients, 18% of the risperidone patients, 16% of the quetiapine patients, and 5% of the placebo patients withdrew from treatment because of adverse events or intolerability.

Sedation was very probable with olan-zapine, which was also associated with increased confusion. Extrapyramidal signs and symptoms with both risperi-done and drug olanzapine were common reasons for stopping treatment.

Patients gained weight with olanza-pine and risperidone tablet and lost weight with placebo. The possibility that anti-psychotic drugs might cause metabolic syndrome in the elderly requires further investigation, the researchers advise.