Study Finds Selected Dementia Antipsychotics Raise Death Risks

Nursing home residents over 65 who take certain antipsychotics for dementia are at an increased risk of death, according to a recent study by the Harvard Medical School involving 75,445 patients.

In a paper published on, the study, which was the largest ever undertaken among US nursing home residents, looked at risks of mortality during a six month period.

Specifically, it assessed mortality risks associated with antipsychotics including Bristol-Myers Squibb/Otsuka’s Abilify (aripiprazole), AstraZeneca’s Seroquel (quetiapine), Eli Lilly’s Zyprexa (olanzapine) and Pfizer’s Geodon (ziprasidone), plus Johnson & Johnson’s Haldol (haloperidol) and Risperdal (risperidone).

Within the study, 6,598 died within the six months from non-cancer related causes. The study noted that patients treated with haloperidol had twice the risk of death in comparison to those taking risperidone, while those taking quetiapine had a reduced risk.

The effect of haloperidol was strongest during the first 40 days of treatment which did not alter after dose adjustment. 49% of the deaths were recorded as due to circulatory disorders, 15% to respiratory disorders, and 10% to brain disorders.

The way the recent study was conducted meant that it could not say definitively that certain drugs actually caused more deaths, merely that there was a link between the two.

The authors of the study suggested that not all antipsychotics carry an equal risk of death in elderly populations but “clinicians may want to consider this evidence when evaluating…the best approach to treatment of behavioural problems”.

The US Food and Drug Administration (FDA) in 2005 warned that atypical antipsychotics are associated with an amplified risk of death in elderly patients with dementia, but the BMJ noted that questions still remain on whether risks differ by drugs.

The FDA’s caution was expanded to include conventional antipsychotics in 2008, but the authors concluded by saying  that the use of the drugs is likely to continue as a result of the “continued growth of the dementia population” and the requirement for some form of intervention.

Jenny McCleery from the Oxford NHS Foundation Trust, argued that “the use of any antipsychotic in dementia is undesirable given the increased risk of death and the many other adverse effects of these drugs, in addition to their limited efficacy against target behavioural and psychological symptoms”.

She added that “future research should be pragmatic. It should focus on identifying the key components of non-drug based interventions and on establishing the service structures that can deliver them as simply and efficiently as possible”.

Dr Chris Fox, who researches dementia at the University of East Anglia, commented that “this study provides an interesting insight into the differential harm of these medicines.”

“There is a need to consider duration of use in more acute situations such as severe distress. Is six or 12-week use safe in people with dementia?”

The Department of Health noted that antipsychotic use was “resulting in as many as 1,800 unnecessary deaths per year. This is simply unacceptable.”

The Dementia Action Alliance – which includes the Alzheimer’s Society, Age UK and the Department of Health, called for all antipsychotics prescriptions to be reviewed by the end of March 2012.

Alzheimer’s Research UK’s chief executive Rebecca Wood said the risks of antipsychotics were “well-established” yet “progress has been frustratingly slow” in decreasing their use.

She added that the drugs “should only be used for people with dementia where there is no alternative”.
Dr Anne Corbett, research manager at Alzheimer’s Society, noted that “for a minority of people with dementia antipsychotics should be used, but then only for up to 12 weeks, and under the correct circumstances. For the majority, they do far more harm than good.”

A similar study in 2009, suggested 180,000 people with dementia were taking antipsychotic treatment in the UK, and suggested that the drugs resulted in 1,800 additional deaths.


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