The Pharmaceutical Journal
Vol 275 No 7378 p680
3 December 2005

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Conventional antipsychotics as likely as atypicals to increase risk of death in elderly, study suggests

Conventional antipsychotic drugs are at least as likely as atypical antipsychotics to increase the risk of death among elderly people, according to the authors of a study published in The New England Journal of Medicine this week (2005;353:2335).

The US Food and Drug Administration issued a public health advisory in April that warned that, compared with placebo, the use of atypical antipsychotics almost doubled the risk of death in elderly patients with dementia.

Philip Wang, department of psychiatry, Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues conducted an observational study with the aim of defining the risk of death among elderly patients starting treatment with conventional antipsychotics compared with those starting atypicals. They analysed data from 22,890 patients aged 65 years and over who had begun receiving a conventional or an atypical antipsychotic drug and compared risk of death within 180 days, less than 40 days, 40 to 79 days and 80 to 180 days of initiation of therapy.

Analyses that adjusted for a number of confounders showed that conventional anti-psychotics were associated with a higher risk of death than atypical antipsychotics at all intervals (<=180 days: relative risk 1.37, 95 per cent confidence interval 1.27–1.49; <40 days: RR 1.56, 1.37–1.78; 40–79 days: RR 1.37, 1.19–1.59; 80 to 180 days: RR 1.27, 1.14–1.41). The greatest increase in risk occurred with higher doses and during the first 40 days after initiation of therapy, say the researchers.

They also looked at subgroups of patients, defined by the presence or absence of dementia and residency in a nursing home, and found that the risk of death within 180 days was higher with conventional antipsychotics in all subgroups.

“On average, for every 100 patients treated with a conventional antipsychotic drug instead of an atypical agent, there would be seven additional deaths,” they say. “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, as may be happening.” They suggest that well defined studies specifically involving the elderly are needed to define optimal care.