Although regulatory warnings have been issued about the use of
second-generation antipsychotics (SGAs) in elderly patients, recent studies
indicate that first-generation antipsychotics (FGAs) pose similar or possibly
higher risk of death, especially death related to cardiovascular disease.
Evidence also suggests that dementia is associated with a higher risk of
stroke in elderly patients taking antipsychotics.
In a large observational study published in the August 6 Journal of the
American Society for Geriatric Psychiatry, Harvard Medical School
researchers Soko Setoguchi, M.D., Dr.P.H., and colleagues analyzed medical
records and causes of death of 12,882 elderly patients who were started on
FGAs and 24,359 started on SGAs. All subjects were residents of British
Columbia, Canada, from 1996 through 2004 and aged 65 or older.
The researchers found that cardiovascular causes accounted for almost half
(49 percent) of patient deaths within the first 180 days of initiating
treatment with an antipsychotic drug. FGAs were associated with statistically
significantly higher risks than SGAs in terms of all noncancer deaths, with a
hazard ratio of 1.27.
Patients who were started on FGAs had significantly higher risks for
cardiovascular, respiratory (excluding pneumonia), and nervous-system-related
deaths, but not infection- and mental disorder-related deaths, compared with
those initiated on SGAs.
FGAs are considered more likely to prolong the QTc interval and
repolarization in the heart than are SGAs (except for ziprasidone), which may
explain the higher risk of cardiovascular deaths associated with FGAs, the
researchers suggested. The increased risk of respiratory deaths, however, has
not been studied before. They hypothesized that the reason may be that greater"
anticholinergic side effects of [FGAs] in elderly patients with severe
chronic respiratory disorders might cause worsening of symptoms and choking
through drying secretions and difficulty in clearing mucus."
The patients in the study, which looked at deaths from all causes, were on
average about 80 years old when they started taking an antipsychotic drug.
About 10 percent of them had dementia.
The study was funded by the U.S. Agency for Healthcare Research and
Although the risk of death appears to be higher in elderly patients taking
FGAs than in those taking SGAs, SGAs were associated with a higher risk of
stroke than were FGAs in elderly patients, especially those with dementia,
according to a study posted August 28 on the British Medical Journal
The study was conducted by Ian Douglas, M.D., and Liam Smeeth, Ph.D., of
the London School of Hygiene and Tropical Medicine. They analyzed medical data
from the U.K. General Practice Research Database and identified 6,790 patients
who had at least one prescription for an antipsychotic drug and a recorded
incident of stroke between January 1988 and the end of 2002.
Using the patients as their own controls before and after they were
prescribed an antipsychotic drug, the researchers found an increased risk of
stroke associated with antipsychotic use, and this risk was "slightly
higher" in patients given SGAs (risk ratio 2.32 after treatment compared
with before) than FGAs (risk ratio 1.69). In addition, the
antipsychotic-associated risk of stroke in patients with dementia was more
than twice as high as that in patients without dementia.
As in the Canadian study, the patients in this study also had an average
age of approximately 80 at the time they were started on an antipsychotic
drug. Unlike the Canadian sample, however, this study focused on stroke, not
death, and a third of the patients had dementia.
Regulatory agencies in the United States, Canada, and the United Kingdom
have issued warnings about the increased risk of death associated with SGA use
in elderly dementia patients. The warnings are based on epidemiological data.
And the U.S. Food and Drug Administration recently required that the package
inserts for FGAs have the same black-box warning as the SGAs concerning use in
elderly people (Psychiatric News, July 18).
Regulatory agencies began warning physicians and the public about
SGA-associated risks starting in 2002, but elderly patients continued to
receive these medications to treat agitation and other behavioral symptoms, a
group of Canadian researchers found.
Using prescription-drug claims data from the Ontario government's
drug-benefits program, the authors analyzed the number of antipsychotics
prescribed for dementia patients from May 1, 2000, to February 28, 2007. They
found that the number of SGA prescriptions for elderly dementia patients
continued to rise after Health Canada issued three advisories to warn health
care professionals of the associated risks.
Overall, the prescription rates of antipsychotics increased by 20 percent
from September 2002, immediately before the first regulatory warning, to the
end of the study period. The authors concluded that the regulatory warnings
had "limited impact" on physicians' prescribing of
antipsychotics for elderly patients with dementia.
This study was funded by the Canadian Institutes of Health Research and
published in the August 26 Canadian Medical Association Journal.
An abstract of "Potential Causes of Higher Mortality in
Elderly Users of Conventional and Atypical Antipsychotic Medications" is
An abstract of "Exposure to Antipsychotics and Risk of Stroke:
Self-Controlled Case Series Study" is posted at<www.bmj.com/cgi/content/full/337/aug28_2/a1227>.
An abstract of "Effect of Regulatory Warnings on Antipsychotic
Prescription Rates Among Elderly Patients With Dementia: A Population-Based
Time-Series Analysis" is posted at<www.cmaj.ca/cgi/content/abstract/179/5/438>.▪