Older Antipsychotics May Be Riskier in the Elderly

NEW YORK (Reuters Health) - In April, the US Food and Drug Administration issued an advisory that the use of atypical antipsychotics increases mortality in elderly persons with dementia, but now investigators report that conventional antipsychotic medications may be even more dangerous.

"If confirmed," Dr. Philip S. Wang and his co-authors caution in The New England Journal of Medicine for December 1st, "our results suggest that conventional antipsychotic medications may not be safer than atypical agents and should not simply replace atypical drugs that are stopped in response to recent FDA warnings, as may be happening."

The reason the FDA's advisory did not include conventional antipsychotics "is because the FDA did not have enough trial data on them," Wang told Reuters Health. "They didn't say that the old drugs were free of risk, but our concern is that physicians may translate 'lack of data' into meaning 'lack of risk'," the researcher added. "We suspect that some clinicians are simply switching from the new drugs to the old drugs because they don't see the same warning on the old drugs."

Wang's group at Brigham and Women's Hospital in Boston evaluated data from the Pennsylvania Pharmaceutical Assistance Contract for the Elderly, which included Medicare information on patients 65 years of age or older who were treated between 1994 and 2003. Medicare data on mortality were drawn from the Death Master File.

The data included 9,142 patients who began using a conventional antipsychotic drug (such as Haldol or Thorazine) and 13,748 who began using an atypical antipsychotic drug (such as Zyprexa or Seroquel).

In the first 180 days of use, 17.9 percent of those using a conventional agent died, compared with 14.6 percent of those who used an atypical antipsychotic.

The greatest discrepancy in death rates, after accounting for the potential influence of demographic factors, the presence of other illnesses, the use of other medications, hospitalizations and nursing home stays, occurred during the first 40 days of use, when the risk was 56 percent higher in atypical antipsychotic users. For the periods 40 to 79 days and 80 to 180 days after beginning therapy, the increased risk was 37 percent and 27 percent, respectively.

"At this point we only have hypotheses" as to why antipsychotic drugs raise the risk of death, Wang noted. The only clues available are from the FDA's analysis, "in which they found that the most common causes of death were cardiovascular, such as sudden death or heart failure, and infections, primarily pneumonia."

Because there are often no other good alternatives for elderly patients with delirium and dementia, "clearly physicians need to thoughtfully weigh the risks and benefits. Simply switching elderly from newer to older drugs is not a solution," Wang said.

"When patients are started on antipsychotic drugs they should be carefully monitored and any signs of adverse effects or anything problematic should be noted as soon as possible," he advised.

The other issue that his group's study highlights is the need for new trials carried out specifically in elderly patients, he added.

In a related editorial, Dr. Wayne A. Ray, from Vanderbilt University School of Medicine in Nashville, Tennessee, notes that "nonrandomized studies can provide valuable information, as does the thoughtful study by Wang and colleagues."

SOURCE: The New England Journal of Medicine, December 1, 2005.