Alzheimer's patients unresponsive to antipsychotics

By Will Boggs, MD

NEW YORK (Reuters Health) - Second-generation antipsychotic drugs are no better than placebo -- from a cost-benefit viewpoint -- for treating the psychosis and aggression that can develop in Alzheimer disease patients, according to a report in the Archives of General Psychiatry.

"These drugs do not generate enough benefit to justify their cost in this off-label situation," Dr. Robert A. Rosenheck from the VA Connecticut Health Care System, West Haven, Connecticut told Reuters Health. He notes, however, it's not clear how these findings with influence treatment policy for these patients.

Off-label drug use occurs when a physician uses a drug that has regulatory approval to treat one disease, but is used to treat another disease for which the drug has not been studied or has not been thoroughly studied.

Rosenheck and colleagues measured health care costs and health-related quality of life in a cost-benefit analysis of second-generation antipsychotic drugs, including olanzapine (Zyprexa); risperidone (Risperdal), and quetiapine fumarate (Seroquel), in the treatment of 421 patients with Alzheimer disease's and psychosis, aggression or agitation.

The results in the active treatment groups did not differ from those seen in the placebo group or from each other in quality-adjusted life-years gained and according to the results of tests that measure quality of life and dependence.

Patients in the placebo group actually showed significantly higher functioning than patients in each of the second-generation antipsychotic groups on a test that assessed activities of daily living.

While there were no statistically significant differences among the treatment groups in net health benefits, the investigators say, placebo treatment was most often superior to the second-generation antipsychotic drugs on net health benefit analysis, with probabilities ranging from 50 percent to 90 percent."

The total average monthly costs were $1,023 for the placebo group, the report indicates, compared with $1,118 for olanzapine, $1,215 for quetiapine, and $1,092 for risperidone.

"As this study and others have shown, these drugs may offer little clinical efficacy overall when prescribed to patients for agitation and psychosis associated with Alzheimer's disease and showed no overall health economic or effectiveness benefits compared with a strategy that begins with watchful waiting," the authors conclude.

Future research should examine the pharmaceutical and epidemiological affects of these drugs in dementia to identify circumstances under which they might be cost-effective.

"About half of second-generation antipsychotic use is off label," Rosenheck commented. "This is the first rigorous independent cost-effectiveness analysis study of off-label use of second-generation antipsychotics. It did not provide evidence of cost-effectiveness, suggesting other off-label uses need to be studied."

SOURCE: Archives of General Psychiatry, November 2007.