Alzheimer's drugs raise death risk

A newer class of drugs used to treat behavioral disorders in patients with Alzheimer's disease and other dementias boosts risks for death slightly, and the same might be true of older anti-psychotic medications, a new study finds.

But the study's authors stress that the drugs' effects on mortality are relatively small.

"This is not a paper about, 'these drugs kill,"' says lead researcher Dr. Lon S. Schneider of the University of Southern California, Los Angeles. His team's report on a number of controlled trials of "atypical anti-psychotic drugs" appears in the Oct. 19 issue of The Journal of the American Medical Association.

Properly used, the drugs' benefits might outweigh the increased risk of death in some cases, says Schneider, who is professor of psychiatry, neurology and gerontology at USC.

The report came as no surprise, since the U.S. Food and Drug Administration had issued a warning about the risk in April, asking that a boxed warning be added to drug labeling. "But the FDA warning was without supporting documentation," Schneider says.

"This meta-analysis provides the documentation."

Schneider and his colleagues studied the results of 15 trials, nine of them unpublished, which compared outcomes in dementia patients treated with one of four antipsychotic drugs -- aripiprazole (brand-named Abilify), olanzapine (Zyprexa), quetiapine (Seroquel) and risperidone (Risperdal) -- to outcomes in patients given a placebo. The trials, which included more than 5,000 patients in total, lasted an average of between 10 to 12 weeks.

Patients receiving one of the four medications had a 3.5 percent death rate compared to 2.3 percent for those who got a placebo over the trial period, Schneider's team found.

The patients in those trials were frail and elderly, Schneider notes, and so the studies might be showing "a general effect when one treats frail, elderly people with any of a variety of drugs." He says that switching to other drugs, such as antidepressants, might be a mistake because there is no evidence that they can control the aggression, delusions and other symptoms experienced by the patients.

Evidence regarding the possible danger of older anti-psychotic drugs is borderline, Schneider says, and comes from two studies of a single drug, haloperidol, in which the increased risk of death did not reach the level of statistical significance.

Schneider says that, instead of abandoning these beneficial anti-psychotic medications, "physicians have to know and consider, when they treat patients, the potential benefits and adverse effects. They need to be cautious and weigh those potential benefits against the risk."

The study does answer one key question, says Dr. Peter V.

Rabins, a professor of psychiatry at Johns Hopkins Medical Institutions and co-author of an accompanying editorial.

"There was a question before this about whether the risk was limited to specific drugs," he says. "This study makes it pretty clear that it exists for all the drugs."

Like Schneider, Rabins says physicians had to balance benefit against risk when deciding about prescribing the drugs. "Unless they are clearly effective, they should be discontinued after two or three months," he says.

Pharmaceutical companies that market the drugs "need to be more forthcoming in releasing these data," Rabins says. "The authors of the paper did not have access to the cause of death.

Pharmaceutical companies have that information. Only if they communicate it can we find the cause of death."

(The HealthDay Web site is at http://www.HealthDay.com.)