Researchers have determined that elderly demented patients taking
antipsychotic medications face an elevated risk of death regardless of whether
they are taking newer second-generation antipsychotic medications (SGAs) or
older first-generation antipsychotics (FGAs).
In April 2005 the U.S. Food and Drug Administration (FDA) announced it was
asking drug companies who market SGAs to add a black-box warning to the labels
of all SGAs marketed in the United States, cautioning physicians of a higher
risk of death from cerebrovascular events (Psychiatric News, May 6,
2005). At that time, however, the FDA noted only that risk of death associated
with the older medications was "an important issue for future
study."
A group of researchers at Harvard Medical School's Brigham and Women's
Hospital, led by Phillip Wang, M.D., Dr.P.H., an assistant professor of
psychiatry, were alarmed about the potential switching of some elderly
patients off of SGAs and on to FGAs under an unproven notion that they may be
safer.
The Harvard group then sought to define the risk of death in the short term
among elderly patients who were prescribed FGAs, compared with the already
quantified risk of death associated with elderly patients taking SGAs. The
group's report appeared in the December 1, 2005, New England Journal of
Medicine.
Wang and his colleagues undertook a retrospective cohort study involving
22,890 patients aged 65 and older who had drug insurance benefits in
Pennsylvania and were prescribed an antipsychotic medication between January
1, 1994 and December 31, 2003. Patients receiving benefits under the
Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE) program
were either indigent or "near poor."
The researchers identified 9,124 patients who began taking an FGA and
13,724 who began using one of the newer SGAs. Patients prescribed the older,
less-expensive medications were slightly younger and more likely to be male
and non-white compared with those prescribed the newer, more costly drugs.
Patients prescribed the older drugs were less likely to have
cerebrovascular disease, dementia, delirium, psychoses, or other psychiatric
disorders. Those taking the older medications were more likely to have
congestive heart failure, ischemic heart disease, or cancer.
In addition, those taking the older antipsychotics were taking fewer
psychotropic medications as well as a lower total number of medications
altogether. Those on FGAs were also less likely to be hospitalized or stay in
a nursing home in the 180 days preceding the prescribing of their
antipsychotic medication.
Within the first 180 days after the antipsychotic was prescribed, 17.9
percent of those prescribed an FGA died, compared with 14.6 percent of those
who took an SGA. This difference between the two rates was statistically
significant and remained significant even after the team of researchers
adjusted for "a large number of potential confounders" such as
age, sex, date of first prescription, and a propensity scoring adjustment
based on the likelihood of the patient's doctor prescribing FGAs over SGAs or
the reverse.
"The greatest increase in the adjusted risk of death for conventional
as compared with atypical antipsychotic medications," Wang and his
colleagues said, "occurred with higher doses (i.e., greater than the
median) of conventional agents and during the first 40 days after the
initiation of therapy." The differences in the risk of increased death
were also greatest "soon after therapy was initiated; the rates of death
then began converging in subsequent periods."
The researchers concluded that, "If confirmed, 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."
An abstract of "Risk of Death in Elderly Users of Conventional
Versus Atypical Antipsychotic Medications" is posted at<http://content.nejm.org/cgi/content/abstract/353/22/2335>.▪