Antipsychotic medications for the treatment of agitation, aggression, psychosis, and other symptoms of Alzheimer disease (AD) are no better than placebo and may even be harmful, according to a highly publicized study by a team from the University of Southern California Keck School of Medicine. In a statement to the press, the lead author of the study Lon Schneider, MD, professor of psychiatry, neurology, and gerontology at Keck, commented that after 12 weeks participation in a double-blind placebo-controlled trial, no significant differences were seen in symptom improvement in patients taking an antipsychotic drug compared with patients taking placebo. Although Schneider and colleagues conceded that antipsychotic therapy might ameliorate some symptoms in certain patients with AD, adverse effects of the therapy, including confusion, sedation, and parkinsonian symptoms, may offset any benefits.
The double-blind trial was conducted over 5 years at 42 sites and included a total of 421 patients who were randomly selected to receive either olanzapine(Drug information on olanzapine) (Zyprexa; mean dosage, 5.5 mg/d), quetiapine (Seroquel; mean dosage, 56.5 mg/d), risperidone(Drug information on risperidone) (Risperdal; mean dosage, 1.0 mg/d), or placebo. Participants had AD-related dementia characterized by delusions, aggression, hallucinations, or agitation. Patients who responded to therapy continued treatment for up to 36 weeks, and the primary outcome measure was the date of treatment discontinuation.
Researchers determined the risks and benefits of each medication by measuring the amount of time each patient continued therapy before discontinuing for any reason. During the 36-week follow-up period, 82% of patients discontinued their assigned medication. On average, patients discontinued therapy after about 8 weeks, regardless of whether they had been prescribed a drug or placebo.
Some patients had symptomatic improvement with treatment, including 32% treated with olanzapine, 26% treated with quetiapine(Drug information on quetiapine), and 29% treated with risperidone. In comparison, 21% of patients who received placebo also experienced symptomatic improvement. Antipsychotic medications were more often associated with troubling adverse effects than placebo was. Fifteen percent to 24% of those taking antipsychotics discontinued therapy because of adverse effects, while only 5% of those taking placebo did so.
Schneider and colleagues recommend that the use of antipsychotics be restricted to patients in whom clear benefits can be seen.
These results are from the first phase of a large-scale clinical trial funded by the NIH's National Institute of Mental Health. The reference for this article is Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006; 355:1525-1538.