Most Alzheimer’s patients given an atypical antipsychotic for delusions, agitation or aggression have no benefit versus placebo because so many discontinue drug use due to significant side effects, according to an article in the October 12 issue of the New England Journal of Medicine.

The widely anticipated new study was led by Lon Schneider, MD, professor of psychiatry, neurology and gerontology at the Keck School of Medicine of the University of Southern California.

The Phase I results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Alzheimer’s Disease Study was funded by the National Institutes of Mental Health and provides the first long-term comparative look at the three major antipsychotic drugs now used to treat difficult symptoms of Alzheimer’s disease.

“We thought overall the drugs would show their effectiveness,” said 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 three fourths 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 function.

“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 explained. “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.

Twenty-four percent of patients taking olanzapine quit because of adverse events, as did 18 percent on risperidone and 16 percent on quetiapine. Only 5 percent of placebo patients discontinued their medication due to intolerability.

Ultimately between 77 percent and 85 percent of 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,” said 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.