FDA Alert Outlines Risk of Conventional Antipsychotic Use in Older Patients

In an alert issued June 16, the FDA notified physicians that the agency has directed manufacturers of conventional antipsychotic drugs to add specific warnings about the risk of mortality in elderly patients being treated for dementia-related psychosis to the drugs' package labels. The required warnings would be similar to those added to the prescribing information of atypical antipsychotic drugs in 2005.

FDA officials based this week's action on an analysis of findings from two observational epidemiological studies that examined the risk of death in older Canadian patients who were treated with conventional antipsychotic drugs.

Specifically, a retrospective cohort study involving 27,259 adults ages 66 or older who had a diagnosis of dementia compared the risk for death with use of an atypical antipsychotic versus no antipsychotic. The study also compared the risk for death with use of a conventional antipsychotic versus an atypical antipsychotic. Study investigators found that patients in the first group showed increased mortality as soon as 30 days after treatment onset that persisted through the end of the six-month study period. They also found, however, that conventional antipsychotic use showed a marginally higher risk of death compared with atypical antipsychotic use. The causes of death were not reported in the study.

A second retrospective cohort study involving 37,241 adults ages 65 or older who received conventional or atypical antipsychotic drugs for any reason compared all-cause mortality associated with the use of a conventional antipsychotic to that seen with the use of an atypical antipsychotic for six months. Study investigators found that the risk of death in the conventional antipsychotic group was comparable to, or possibly greater than, the mortality risk in the atypical antipsychotic group. The causes of death with the highest relative risk were cancer and cardiac disease.

The FDA noted that the methodological limitations in these two studies preclude any definitive conclusion that use of conventional antipsychotics carries a greater risk of death than use of atypical antipsychotics. The overall weight of evidence, however, indicates that conventional antipsychotics share the increased risk of death in older patients that had earlier been observed with use of atypical antipsychotics.

In April 2005, FDA officials issued an advisory about the increased risk of mortality in elderly patients taking atypical antipsychotic drugs to treat dementia-related psychosis. At that time, an analyses of 17 placebo-controlled trials involving older adults with dementia-related behavioral disorders showed a risk of death in the drug-treated patients of between 1.6-1.7 times that seen in placebo-treated patients. Although various causes of death were identified, most deaths appeared to result from either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) causes.

Based on the 2005 analysis, the FDA called for manufacturers of atypical antipsychotic drugs to include information about the heightened mortality risk in both a "Boxed Warning" and the "Warnings" section of the drugs’ prescribing information. Now, the prescribing information for all antipsychotic drugs will include the same warnings about this risk.

Physicians can report any unexpected adverse or serious events associated with use of these drugs to the FDA's MedWatch program online or by phone at (800) FDA-1088.