Antipsychotic drugs increase one-year mortality by 42% in patients with Alzheimer’s disease, according to the Dementia Antipsychotic Withdrawal Trial published in Lancet Neurology.
Clive Ballard and colleagues at King’s College London reached this conclusion after analyzing data from a randomized controlled discontinuation study of 165 Alzheimer’s disease patients living at 4 skilled nursing or long-term care facilities in the UK.
And the mortality gap widened thereafter such that at 42 months, more than twice as many placebo-treated patients survived as those treated with antipsychotics.
The DART findings extend earlier findings that had demonstrated increased mortality in trials with 12-week endpoints.
DART patients were taking one of 5 commonly prescribed antipsychotics for 3 or more months prior to enrollment. They were randomized to receive continued antipsychotic drug therapy for 12 months or a placebo.
The scientists concluded that “the accumulating safety concerns, including the substantial increase in long-term mortality emphasize the urgent need to put an end to unnecessary and prolonged prescribing.”
They recommended replacing antipsychotics with safer alternatives such as psychotherapy or, depending on the syndrome, alternative agents like antidepressants.
The antipsychotic drugs in the London study carry black box warnings cautioning about mortality risk, yet 30% to 60% of dementia patients in North American and European long-term care facilities receive them, according to MedPageToday.
The mechanism by which antipsychotics mediate increased mortality is not known. It’s possible their sedative effects render patients more susceptible to infections and less able to stay fit.