Los Angeles, Oct. 11, 2006 -- Most Alzheimer's patients prescribed antipsychotic drugs for delusions, agitation or aggression do no better than those who take a placebo because so many discontinue the drugs due to significant side effects, according to a major new nationwide study led by Lon Schneider, professor of psychiatry, neurology and gerontology at the Keck School of Medicine of the University of Southern California (USC).
The Phase I results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Alzheimer's Disease Study, funded by the National Institutes of Mental Health, appear in this week's New England Journal of Medicine. The study is highly anticipated, because it provides the first long-term comparative look at the three major antipsychotic drugs now used "off label" to treat difficult symptoms of Alzheimer's disease.
"We thought overall the drugs would show their effectiveness," explains Schneider. "The answer is yes, they are somewhat effective, but overall the efficacy is offset by adverse events that resulted in discontinuing the medication. It was a surprise, in that the expert opinion which drove this study was that these drugs are particularly useful in treating these difficult symptoms."
Almost 3/4 of all Alzheimer's patients suffer delusions or aggression, says Schneider, which makes their care particularly difficult. The study's 421 participants at 42 sites nationwide all had Alzheimer's disease and were experiencing delusions, hallucinations, aggression or agitation that disrupted their daily functioning.
"The findings here look at the time to discontinuation for the antipsychotics versus the placebo, and that time difference reflects the overall effectiveness of the medication. By that measure, the medications were not better than placebo," he explains. "Patients on the medications were more likely to discontinue because of the side effects, offsetting the efficacy."
Side effects from the three antipsychotic medications - olanzapine, quetiapine, and risperidone - ranged from sedation, weight gain and confusion to worsening psychosis.
Almost a quarter of those taking olanzapine quit because of adverse events, as did 18% on risperidone and 16% on quetiapine. Those on all three medications were significantly more likely to discontinue treatment than those who received a placebo.
Ultimately between 77 to 85% of study participants discontinued their medication, either because of adverse side effects or no improvement.
"The results suggest antipsychotic drugs should be prescribed only with some deliberation," says Schneider.
This research represents only Phase I of the $16.9 million CATIE Alzheimer's disease study, says Schneider. In CATIE- designed to resemble real-world prescribing patterns- patients in the study were allowed to switch double-blindly to a second antipsychotic medication or the antidepressant citalopram if they discontinued the first. Future results will show which treatments, if any, are cost effective and will help improve symptoms, quality of life, and functioning, as well as caregiver burden, thereby delaying nursing home placement.
Lon S. Schneider, Pierre N. Tariot, Karen S. Dagerman, Sonia M. Davis, John K. Hsaio, M. Saleem Ismail, Barry D. Lebowitz, Constantine G. Lyketsos, J. Michael Ryan, T. Scott Stroup, David L. Sultzer, Daniel Weintraub and Jeffrey A. Lieberman for the CATIE-AD Study Group, "Effectiveness of Atypical Antipsychotic Drugs In Patients With Alzheimer's Disease," New England Journal of Medicine, October 12, 2006, Volume 344, Number 15
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