Trinity College Dublin: Common antidepressant should no longer be used to treat people with dementia

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 new 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. Professor Iracema Leroi from the Global Brain Health Institute (GBHI), Trinity College Dublin, is a co-investigator 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 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-blind; meaning that neither the researcher nor the study participants knew what they were taking.

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 importance of clinical trials in Ireland
The study is an example of the importance of clinical trials for dementia. Currently, less than 0.5% 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 5-year initiative funded by the Irish Health Research Board (HRB) and led by Professor Iracema Leroi and Professor 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.

By growing Ireland’s capacity and capability to deliver dementia-related trials, and by increasing the number of people participating in trials, DTI aims to prevent/slow progression to dementia for those at risk, and to improve quality of life for people with dementia.

Professor 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 Professor 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.

This study has added important information to the evidence base, and we look forward to investigating further treatments that may help to improve people’s quality of life.

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