FGAs Not Necessarily Safer Than SGAs in Elderly

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 Quality.

Higher Stroke Risk With SGAs

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 Web site.

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.

Antipsychotics for Elderly Still Popular

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 posted at<www3.interscience.wiley.com/journal/121371905/abstract>. 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>.▪