Common antidepressant should no longer be used to treat people with dementia, study says
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 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.”
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.”
"This is a large national randomised controlled trial led by BSMS which also involved over 20 clinical research centres across the UK. Our study tested mirtazapine for the treatment of patients with dementia who present with agitation. The data showed no benefit for mirtazapine with potential for serious side effects. The negative results show again the challenges faced by clinicians in managing behavioural and psychological symptoms of dementia and alert specialists to the potential harm of using commonly available psychotropic medications, especially when efficacy is unproven". Professor Naji Tabet, Director of Centre for Dementia Studies, BSMS
“As a multi centre complex clinical trial - SYMBAD was fully supported by the Joint Clinical Research Office (JCRO) who ensured seamless set up, co-ordination and delivery throughout the three years of the project. It is wonderful to see the fruition of all the hard work across the multiple functions and organisations involved in SYMBAD with this Lancet publication. SYMBAD has produced not only publications and outcomes for patients but also established BSMS as a playing a lead role in the design and delivery of large scale, high quality clinical trials.” Tanya Telling, Joint Clinical Research Office (JCRO)
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.
See this link
The study was co-authored by:
· University of East Anglia, Brighton and Sussex Medical School, LSE, University of Exeter, Birmingham and Solihull Mental Health Foundation NHS Trust, University of Manchester, UCL, Trinity College Dublin, Surrey and Borders Partnership NHS Foundation Trust, Alzheimer’s Society Research Network, University of Cambridge, Cambridge and Peterborough Foundation Trust, Newcastle University. Sussex Partnerhship was pleased to be a site for this study and extends thanks to everyone who took part.
Information provided by University of Plymouth