Issue 7 / 27 February 2012

NEW research has added to the weight of evidence against the use of antipsychotics in elderly dementia patients, showing some of these drugs are more harmful than others.

The Harvard Medical School study, published in the BMJ, followed a large cohort of nursing home residents who were commenced on any of six different antipsychotic drugs — haloperidol, aripiprazole, olanzapine, quetiapine, risperidone and ziprasidone — for six months. (1)

Of the 75 445 elderly patients, a total of 6598 died within the 6-month study from non-cancer related causes. Patients treated with haloperidol had double the risk of death compared with those taking risperidone, while those taking quetiapine had a reduced risk compared with other antipsychotic users.

The association between haloperidol and mortality was most marked during the first 40 days of treatment, and persisted even after adjusting for dose and the presence of dementia or behavioural disturbances. Almost half the deaths (49%) were recorded as due to circulatory disorders, 10% to brain disorders and 15% to respiratory disorders.

The researchers wrote that although their findings could not prove causality, they did “provide more evidence of the risk of using these drugs in older patients, reinforcing the concept that they should not be used in the absence of clear need”.

“If the clinician faces a situation in which use of these drugs seems inevitable, our findings underscore the importance of always prescribing the lowest possible dose and of closely monitoring patients, especially shortly after the start of treatment”, they wrote.

An accompanying editorial agreed that information on risk must be weighed against the potential benefits of a drug in dealing with aggression in dementia patients. (2)

“This strengthens the argument for avoiding haloperidol on safety grounds. In contrast, there is no high quality evidence that quetiapine is effective for treating neuropsychiatric symptoms in dementia, and the results of the current study should not support its use”, the editorial said.

Australian experts have previously raised similar concerns about antipsychotic drug prescribing in the elderly, as outlined in an article published in the Australian and New Zealand Journal of Psychiatry. (3)

“Despite increasing questions surrounding the risks and benefits of [atypical antipsychotic] use in the elderly, there has been an increase in their use in some aged care facilities, albeit at low doses”, the authors wrote.

Dr David Lie, one of the authors of the article and a clinical affiliate at the Centre for Research in Geriatric Medicine at the University of Queensland, told MJA InSight that with the high prevalence of antipsychotic use in nursing homes and the dangers posed by these drugs, more information was needed on the circumstances under which they are prescribed.

Dr Lie said although there was no easy fix, understanding more about the “social ecology of the prescribing” — who is prescribing, when and why — was necessary to address the problem.

He said a good start would be to support colleagues who work in this area with training, research and guidelines.

“Perhaps some of the money spent on psychotropics in the elderly could be diverted into non-pharmacological approaches, workforce training, early intervention strategies and the like”, he said.

“We also need a wider debate about the quality use of psychotropic medicines in residential care and hospitals, and how we provide health care to people in residential care generally, as we face an exponential rise in dementia numbers over the next two decades”.

Dr Lie said Australian practitioners increasingly favoured risperidone over haloperidol and quetiapine for dementia.

“For Australian doctors, haloperidol is generally already not first choice for dementia, but we need to remember the issue of ceasing haloperidol prescribed for delirium before people leave hospital or reviewing it after transfer to residential care”, he said.

“Once people are put on psychotropics there is a reluctance to stop [the drugs] and they tend to stay on them.”


– Amanda Bryan

1. BMJ 2012; 344: online 24 February
2. BMJ 2012; 344: online 24 February
3. Aust NZ J Psychiatry 2011: 45; 705-708

Posted 27 February 2012

3 thoughts on “Evidence mounts on antipsychotics in elderly

  1. Sue Ieraci says:

    I support the comments above – the use of antipsychotics is, in a way, a marker for difficult behaviour in the demented elderly. The combination of greater longevity and changes in the family structure mean that this is becoming an increasing problem – the burden of care for an agitated, confused or frankly violent dementia patient is enormous – whether on the spouse, child or RACF staff. Certainly we should welcome research on the most effective and safest alternative, but there is no place for indignation about the use of these drugs.

  2. Thinus van Rensburg says:

    A study like this in an overseas journal such as the BMJ does not factor in the local complexities of the risks to these elderly patients in chronically understaffed RACFs. We are forced to weigh up the risks of an aggresive unruly patient to themselves and the other residents, with one or two carers looking after 20 or more residents, against the risk of an antipsychotic casuing a earlier death in a specific demented patient.

  3. Dr Horst Herb says:

    I guess nobody would be worried if the headlines were that people on chemotherapy have a higher risk to die in the next year than those not having it.
    Old people whom we prescribe antipsychotics are usually the ones putting themselves at risk through erratic behaviour, and more often than not are quite ingenuous at being non-compliant with medication regardless of the nursing staff’s best attempts – of course they will have a higher mortality. That excess mortality might even be reduced rather than increased by antipsychotics – bu we don’t know.
    Despite the author’s statement that the results were “adjusted for confounding factors such dementia or behavioural disturbances” I find that hard to believe, given the complexity and individual variance of such problems.

    Hence, we won’t know until we have a good prospective, randomized study with a large enough sample size to accommodate the huge individual variance on risk factors.

    Hence, papers like the presented one sadly do nothing in order to clarify the burning question we have – whether we are doing the right thing by giving or not giving antipsychotic medication to such patients, and if we should give, which one to choose. Such papers just add to the bias and confusion arising in the absence of evidence.

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