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A drug used to treat agitation in people with dementia is no more effective than a placebo, and might even increase mortality, according to a recent study published in The Lancet. The research has shown that antidepressant mirtazapine offered no improvement in agitation for people with dementia and was possibly more likely to be associated with mortality than no intervention at all.

The study was led by the University of Plymouth in the UK with Prof Iracema Leroi from the Global Brain Health Institute (GBHI), Trinity College Dublin, as coinvestigator on the study. Agitation is a common symptom of dementia, characterised by inappropriate verbal, vocal or motor activity, and often involves physical and verbal aggression. Non-drug patient-centred care is the first intervention that should be offered but, when this doesn’t work, clinicians may move to a drug-based alternative.

Antipsychotics have been proven to increase death rates in those with dementia, along with other poor outcomes, and so mirtazapine has been routinely prescribed. This study was designed to add to the evidence base around its effectiveness. Funded by the National Institute for Health Research (NIHR), the study recruited 204 people with probable or possible Alzheimer’s disease from 20 sites around the UK, allocating half to mirtazapine and half to placebo.

The trial was double-blinded. The results showed that there was no less agitation after 12 weeks in the mirtazapine group than in the control group. There were also more deaths in the mirtazapine group (seven) by week 16 than in the control group (only one), with analysis suggesting this was of marginal statistical significance.

The study is an example of the importance of clinical trials for dementia. Currently, less than 0.5 per cent of people with dementia participate in research in Ireland, despite the need for evidence to address the rapidly increasing impact of dementia on our aging society. The study’s publication coincides with the launch of Dementia Trials Ireland (DTI), a five-year initiative funded by the Irish Health Research Board (HRB) and led by Prof Iracema Leroi and Prof Sean Kennelly, both faculty of GBHI at Trinity College. The aim of DTI is to significantly increase the opportunities for people with dementia to participate in clinical trials in Ireland.

Prof Leroi said: “It is only through conducting robust and high-quality clinical trials for Alzheimer’s disease and other forms of dementia that we can hope to combat this condition which affects so many families in Ireland. It is every patient’s right to participate in research and we therefore have to ensure that they have the opportunity to do so.”

Lead researcher Prof Sube Banerjee, Executive Dean of the Faculty of Health and Professor in Dementia at the University of Plymouth, explained why the results of the study were so surprising, but important. “Dementia affects 46 million people worldwide — a figure set to double over the next 20 years.

Poor life quality is driven by problems like agitation, and we need to find ways to help those affected. This study shows that a common way of managing symptoms is not helpful and could even be detrimental. It’s really important that these results are taken into account and mirtazapine is no longer used to treat agitation in people
with dementia.”