Mirtazapine did not improve agitation symptoms

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.

The research, led by the University of Plymouth and involving the University of Exeter, published in The Lancet, 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.  

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.

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 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,” he said.

“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.”

Collaborator Professor Paul Francis, of the University of Exeter, said: “This is an incredibly important aspect of the evidence base to establish what really works for people with dementia, and what could cause them harm. It’s disappointing when a seemingly promising drug is proven not to be effective in controlling a distressing symptom often present in people living with dementia. It should spur scientists and clinicians to redouble their efforts to understand mechanisms underlying agitation and identify new approaches that will work.”

Dr Richard Oakley, Head of Research at Alzheimer’s Society said:“Unnecessary prescribing of antipsychotics to people with dementia is dangerous and associated with a higher risk of death, which is why we’ve been campaigning hard to reduce levels since the late 90s, saving tens of thousands of lives. The gold star treatments for agitation don’t involve drugs and are tailored to the person – like arts and crafts or movement to music. In recent years antidepressants – like mirtazapine – have been considered a fallback if non-drug approaches don’t work.

“While only a small study, these results suggest a rethink is needed. Not only was the drug ineffective at reducing agitation, it was associated with more deaths, suggesting mirtazapine should be avoided in Alzheimer’s – and research carried out to understand its effects in other types of dementia.”

The full study, entitled Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trial, is available to view in The Lancet.

Date: 21 October 2021