A new study published in BMC Medicine finds that antidepressants are associated with faster cognitive decline in people with dementia. Escitalopram (Lexapro) was the antidepressant associated with the most severe cognitive decline, followed by citalopram (Celexa).
The study, led by Minjia Mo of the Karolinska Institutet in Stockholm, additionally finds that high doses of SSRIs were linked to increased risk of death, fractures, and severe dementia. The authors note that while antidepressants were linked to lower cognitive test scores, these lower scores were most typically not considered clinically significant.
Despite antidepressants not being approved to treat dementia or its behavioral symptoms, a 2020 study published in JAMA found that nearly half (49.8%) of dementia patients were prescribed these drugs. The current findings call into question the narrative that these drugs can be safely prescribed to people with dementia as well as the ethics of practitioners writing these prescriptions despite broad knowledge that “antidepressant use in dementia is not only ineffective but potentially harmful.”
The authors write:
“In this nationwide cohort study, we found that the current use of antidepressants was associated with faster cognitive decline in patients with dementia compared with non-use, and this association was driven mainly by patients with severe dementia. Higher dispensed doses of SSRIs were associated with more cognitive decline during follow-up, and higher risk of severe dementia, fracture, and all-cause mortality.”
The goal of the current research was to investigate how different antidepressants and varying doses affect cognitive decline in dementia patients. Additionally, the authors wanted to explore how dementia severity, subtypes, and other medications affect links between antidepressants and cognitive decline.
The authors used data from the Swedish Registry for Cognitive/Dementia Disorders. This database stores primary care and specialist memory clinic information on demographics, diagnostic processes, and cognitive and mortality outcomes. The authors also used records from the Swedish Prescribed Drug Register to establish the dispensation of medications and the Cause of Death Registry for data on causes and dates of death.
To be included in the current study, service users had to be diagnosed with dementia and registered in the Swedish Registry for Cognitive/Dementia Disorders between May 1, 2007, and October 16, 2018. Service users were excluded if they had missing information on the mini-mental state exam (MMSE), if they had been prescribed an antidepressant more than six months before their dementia diagnosis, or if they were taking multiple antidepressants. Service users were also excluded if they had no follow-ups after their initial dementia diagnosis. In total, 18,740 service users were included in the current research.
Service users were considered to be exposed to antidepressants if they had been prescribed an antidepressant up to six months before their dementia diagnosis or at any follow-up exam. For the purposes of analysis, the authors divided antidepressants into four categories: SNRIs, SSRIs, tricyclics, and others.
Antidepressant Prescriptions
22.8% of participants were prescribed at least one antidepressant. SSRIs were the most commonly prescribed class and accounted for 64.8% of antidepressant prescriptions. 31% of antidepressant prescriptions were classed as ‘other’,’2.2% as tricyclics, and 2% as SNRIs. Citalopram, sertraline, escitalopram, venlafaxine (SSRIs), mirtazapine (other), and amitriptyline (tricyclic) accounted for 99% of all antidepressant prescriptions.
Antidepressants and Cognitive Decline by Dementia Subtype
Overall, antidepressant use was linked to an increased rate of cognitive decline of -0.30 points per year on the MMSE (scored 0 – 30 points) compared to non-use. Antidepressant use was not linked to increased cognitive decline in Parkinson’s disease with dementia/dementia with Lewy bodies (LBD) or frontotemporal dementia (FTD). Antidepressant use was linked to increased rates of cognitive decline in three subtypes of dementia:
- Alzheimer’s disease and mixed dementia (-0.28 points per year on the MMSE)
- Vascular dementia (-0.27)
- Other dementias (-0.34)
Antidepressant Class, Specific Drugs, and Cognitive Decline
SNRIs and tricyclic antidepressants were not associated with increased cognitive decline. Compared to non-use, SSRIs (-0.39 points per year on the MMSE), and ‘other’ antidepressants (-0.20) were linked to increased cognitive decline. Four of the six most prescribed antidepressants were associated with cognitive decline in the current research:
- Citalopram (-0.41 points per year on the MMSE)
- Sertraline (-0.25)
- Escitalopram (-0.76)
- Mirtazapine (-0.19)
Higher doses of SSRIs and ‘other’ antidepressants were associated with faster cognitive decline. The authors note that the declines in MMSE scores associated with antidepressant use in the current study were below the 1-point threshold considered clinically significant.
Other Factors Associated with Increased Cognitive Decline
Cognitive decline was especially sharp in dementia patients who took antidepressants and were male, had lower baseline MMSE scores, and did not use anxiolytics or hypnotics. Service users who were taking antidepressants and had low initial MMSE scores had the highest rates of increased cognitive decline (-1.51 points per year on the MMSE). Service users under 78 years old and those diagnosed with frontotemporal dementia showed the slowest rates of cognitive decline when taking antidepressants.
Antidepressants, Severe Dementia, Fracture, and Death
Antidepressant use was linked to a 7% increased risk of death and an 18% increased risk of fracture in dementia patients. Higher doses of antidepressants were associated with an 18% increased risk of death, a 25% increased risk of fracture, and a 35% increased risk of severe dementia.
The authors acknowledge several limitations to the current research. It’s possible that the increased cognitive decline observed in the current work could be related to depression rather than to antidepressants. Clinical diagnoses of depression were obtained through specialized care facilities, which typically deal with more severe cases. More mild cases of depression may have been overlooked. The authors did not have information on depression severity. Actual intake of antidepressants was not measured, only whether prescriptions were filled. As dementia severity can affect rates of cognitive decline, some of the accelerated decline observed in the current work could have been due to increased dementia severity rather than antidepressant use.
Past research has found that antidepressant use is linked to an increased risk of dementia. Anticholinergic drugs, like antidepressants and antipsychotics, have been linked to cognitive decline and a 50% increased risk of dementia. Elderly service users taking multiple medications are at increased risk of cognitive decline. One study found that elderly service users who had COVID and took psychiatric drugs were at a tripled risk of dementia.
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Mo, M., Abzhandadze, T., Hoang, M. T., Sacuiu, S., Jurado, P. G., Pereira, J. B., Naia, L., Kele, J., Maioli, S., Xu, H., Eriksdotter, M., & Garcia-Ptacek, S. (2025). Antidepressant use and cognitive decline in patients with dementia: A national cohort study. BMC Medicine, 23(1). (Link)
