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Atypical Antipsychotics: Lower Risk in Elderly

December 6, 2005

Among elderly people, atypical antipsychotics appear to be link with a lower risk of death, compared with so-called conventional antipsychotics, according to new data.

This finding is particularly significant, arriving in the wake of a US Food and Drug Administration (FDA) "black box" warning earlier this year stating that atypical agents-e.g., Risperdal (risperidone) and Zyprexa (olanzapine)-were associated with a higher risk of death among elderly people with dementia.

"Numerically, it looks as if the older agents actually have a greater risk," said pharmaco-epidemiologist Philip Wang, MD, DrPH, of Brigham and Women's Hospital in Boston.

The recent analysis of data was in the 1 December issue of the New England Journal of Medicine(NEJM) online and reported by MedPage Today on 30 November 2005.

Which Drug Class Is Safest?

The FDA's study, which analyzed randomized controlled trials that included over 5,100 patients, revealed that patients receiving atypical agents had an approximately 65% higher risk of death, compared with patients receiving placebo.

In Dr Wang et al's retrospective cohort study, which included 22,890 patients, the researchers found that conventional antipsychotics-e.g., Thorazine (chlorpromazine) and Haldol (haloperidol)-were associated with a "significantly higher adjusted risk of death" compared with atypical agents.

However, in an interview Dr Wang reportedly said that clinicians should not assume "lack of warning means lack of risk" and thus switch their patients off atypical antipsychotic drugs.

"Don't assume that either medication class is safe," he said, according to MedPage Today.

The FDA appears to be thinking along similar lines, as their announcement of the black box warning noted that they were considering a similar warning for conventional antipsychotics, but that supportive data were limited.

The Recent Study

To help provide the needed data, Dr Wang and colleagues reviewed data from patients with drug insurance benefits in Pennsylvania who began receiving either conventional or atypical antipsychotic medication between 1994 and 2003.

After adjusting for various potentially confounding factors, Wang et al found that the conventional antipsychotic agents were associated with a higher risk of death, compared with atypical agents, for all time-periods up to 180 days after starting drug therapy.

Overall, use of any conventional antipsychotic was associated with a relative mortality risk of 1.37, compared with atypical antipsychotic agents.

The study was deemed "thoughtful," by pharmaco-epidemiologist Wayne Ray, PhD, of Vanderbilt in Nashville, who wrote an accompanying article in the same issue of the NEJM. Dr Ray pointed out that Dr Wang et al's study was not a randomized controlled trial, which would provide the most reliable data.

However, in the absence of randomized trials, Dr Wang and colleagues' investigation provides valuable information likely to be of "keen interest to patients and their physicians," wrote Dr Ray.

"We're well aware that our data are not from an experiment," Dr. Wang said, according to MedPage Today. Nonetheless, "we see a risk that's remarkably similar to what was observed [by the FDA for atypical agents].

Dr Wang also noted that it is "critical to remember" that their study population consisted of frail, elderly people receiving treatment for a range of indications that includes psychosis and dementia. The increased risks apparent from this study and the FDA's analysis do not arise among younger patients being treated for psychosis.

"This absolutely has something to do with the vulnerability of frail elderly patients," Dr Wang added, although the cause of the higher mortality remains unknown.

Posted: December 2005