February 25, 2025

expert reaction to observational study of antidepressant prescriptions and cognitive decline in people with dementia

An observational study published in BMC Medicine looks at antidepressant use and cognitive decline in people with dementia. 

Prof Tara Spires-Jones, Director of the Centre for Discovery Brain Sciences at the University of Edinburgh, Group Leader in the UK Dementia Research Institute, and President of the British Neuroscience Association said:

“Mo and colleagues’ study examined data from over 18,000 people with dementia enrolled in a Swedish national registry to look for associations between antidepressant use and dementia symptoms.  They observed faster cognitive decline in people with dementia who were taking selective serotonin reuptake inhibitor (SSRI) type antidepressants. This was a large study that looked at data over time, which is a strong design. However, this type of data cannot prove that it was antidepressant use that caused the faster decline.  People who needed antidepressants may have had more aggressive disease or the depression itself could have been affecting disease progression.  It is also worth noting that the effect was not the same for all types of dementia; people with frontotemporal dementia (FTD) did not have accelerated cognitive decline when taking antidepressants. In people with FTD, antidepressants were associated with slightly slower decline. Previous studies have also reported mixed results, highlighting the need for more research before we have a full understanding of the effects of antidepressant use on dementia progression.”

Dr Richard Oakley, Associate Director for Research and Innovation at Alzheimer’s Society, said:  

“This study suggested that antidepressants led to faster rates of memory and thinking decline in people with dementia. But it did not rule out the possibility that the changes were due to the presence of depression rather than antidepressant use, so further research is needed to understand the effects of antidepressants. 

“Alzheimer’s Society wants to see the severity of an individual’s dementia recorded on their primary care records as either mild, moderate or severe. This is especially important as the study shows a decline in memory and thinking skills was stronger in people with more severe dementia who took antidepressants than those who didn’t. 

“It’s vital that regular reviews are carried out when prescribing antidepressants, but recent research showed that less than half of people with a dementia diagnosis had their medication reviewed in the preceding 12 months.  

“Alzheimer’s Society is funding research to better understand depression and anxiety in people living with dementia, how to manage it, and how genetics might be involved.” 

Dr Emma L Anderson, Associate Professor of Epidemiology, University College London, said:

“As the authors themselves acknowledge, there is substantial risk with this study design for confounding by indication, which could explain the results either in part, or entirely. Confounding by indication is where the outcomes we observe are actually due to the underlying reason people take these medications in the first place (e.g. mental health conditions), rather than the medication itself. More robust study designs, which overcome this very important limitation, are needed before such bold conclusions can be made. When based on limited evidence, these claims can be very damaging for public understanding of antidepressants, which we know help millions of people around the world.”

Dr Prasad Nishtala, Reader, University of Bath, said:

“This large population-level study from Sweden uses real-world data and is well-conducted. However, there are some important limitations that should be considered. One major issue is that the severity of depression in dementia patients wasn’t fully accounted for, which has the potential to bias the results. Additionally, there may be a “channelling bias,” meaning that certain antidepressants like citalopram and sertraline might have been more commonly prescribed to patients with severe dementia, which could also bias the results.

“Another key limitation is that the study found only a small change in MMSE (Mini-Mental State Examination) scores, which may not be meaningful in everyday clinical practice. Previous research has shown that older adults taking tricyclic antidepressants can experience faster cognitive decline because these drugs interfere with the activity of acetylcholine—a chemical in our brain critical for maintaining cognition. Even among SSRIs (a common type of antidepressant), some, like paroxetine, are known to have stronger anticholinergic effects that could impact cognition negatively. There is also a problem of “residual confounding”,- meaning there could be other risk factors that can affect cognition, and it is unclear if they have accounted for other anticholinergic drugs like oxybutynin, which many dementia patients take to treat their urinary incontinence. The analyses were done on dispensed data (medication sold by pharmacists), and it is unclear if patients actually took them.

“This study suggests that SSRIs like citalopram and sertraline might also speed up cognitive decline. However, it doesn’t explain how or why this happens at a biological level. Because of these limitations, the study’s findings should be interpreted with caution and ideally replicated using other real-world data sources.”

‘Antidepressant use and cognitive decline in patients with dementia: a national cohort study’ by Minjia Mo et al. was published in BMC Medicine at 01:00 UK time on Tuesday 25^th February. 

DOI: https://doi.org/10.1186/s12916-025-03851-3

Declared interests

Prof Tara Spires-Jones: I have no conflicts with this study but have received payments for consulting, scientific talks, or collaborative research over the past 10 years from AbbVie, Sanofi, Merck, Scottish Brain Sciences, Jay Therapeutics, Cognition Therapeutics, Ono, and Eisai. I am also Charity trustee for the British Neuroscience Association and the Guarantors of Brain and serve as scientific advisor to several charities and non-profit institutions.

Dr Emma L Anderson: I have no declarations or conflicts of interest. 

Dr Prasad Nishtala: I sit on the editorial board for BMC Medicine.