Antidepressants are commonly used in people with dementia to treat symptoms such as depression and anxiety. However, studies suggest that these medications may accelerate cognitive decline, especially at higher doses. While some antidepressants may have beneficial effects on the brain, others may impair cognition. This reinforces the need to carefully evaluate the use of these medications in patients with dementia.
Antidepressants are commonly used in patients with dementia to treat symptoms such as anxiety, depression, aggression, and sleep disorders.
Among the most commonly used options are selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), which are considered first-line treatments for depression because they have fewer side effects than other classes of antidepressants.
However, studies suggest that older adults with depression who use these medications may have a higher risk of developing dementia compared to those who receive psychological therapy.
There is still much uncertainty about the impact of antidepressants on the progression of dementia. For example, tricyclic antidepressants (TCAs) may impair cognition due to their anticholinergic effect, which interferes with the transmission of signals between neurons.
On the other hand, some research suggests that selective serotonin reuptake inhibitors may have a positive effect by stimulating the formation of new neurons and reducing the buildup of toxic proteins associated with Alzheimer's disease.
Some studies suggest that these drugs may slow the progression of mild cognitive impairment to dementia, but the results are still inconclusive.
Many of these studies have limitations, such as short-term follow-up, focusing on specific populations (e.g., only patients with depression rather than patients with dementia), or failing to account for factors such as age, sex, and severity of dementia. Also, differences in effects between classes of antidepressants may be related to the different mechanisms of action of these substances in the brain.
In Sweden, national guidelines recommend sertraline and escitalopram as the preferred options for older people. However, there is evidence that antidepressants may not be as effective in people with dementia, because the brain changes in this condition affect how the body responds to these drugs.
In some situations, dysfunctions in cognitive control in dementia may reduce the effectiveness of selective serotonin reuptake inhibitors.
Another important point is that some antidepressants have anticholinergic effects, which can worsen cognition and increase the risk of falls and mortality, especially in patients with Alzheimer's disease and dementia with Lewy bodies, conditions in which cholinergic transmission is already compromised.
In addition, much of the research on the impact of antidepressants has focused on Alzheimer's disease, with little data on other forms of dementia, such as vascular, frontotemporal, Lewy body and Parkinson's disease-associated dementia.
Long-term studies are difficult to conduct due to high dropout rates and difficulty in follow-up.
Given this knowledge gap, this study was conducted to investigate the long-term impact of antidepressants on cognition, fracture risk and mortality in patients with dementia.
The goal is to better understand how different classes of antidepressants, specific medications and their doses affect the progression of dementia and how individual factors, such as dementia subtype and severity, may modify these effects.
The results may help healthcare professionals make more informed decisions about the use of antidepressants in patients with dementia and guide future research in the area.
To this end, a cohort study was conducted in Sweden, including patients with dementia registered in the national database for cognitive disorders SveDem, between 2007 and 2018. Patients who started taking antidepressants after being diagnosed with dementia were analyzed.
The use of these medications was assessed over time, considering prescriptions made in the six months prior to diagnosis and in subsequent visits. Cognitive performance was measured by the Mini-Mental State Examination (MMSE), a widely used test to assess cognitive function.
The results showed that, among the 18,740 patients analyzed, 22.8% received at least one prescription for an antidepressant. Over the course of the follow-up, almost 12,000 prescriptions were issued, with SSRI antidepressants being the most common class (64.8%).
Antidepressant use and cognitive decline in patients with dementia. Estimated MMSE trajectories between antidepressant use and non-use by dementia subtypes. Abbreviations: SveDem, the Swedish Register for Cognitive Disorders/Dementia; CIs, confidence intervals; MMSE, Mini-Mental State Examination; AD, Alzheimer's disease; Mixed, mixed dementia; VaD, vascular dementia; LBD, Parkinson's disease with dementia and dementia with Lewy bodies; FTD, frontotemporal dementia.
Antidepressant use was associated with more rapid cognitive decline, with the greatest reductions in Mini-Mental State Examination scores observed in patients taking escitalopram, citalopram, sertraline, and mirtazapine.
The impact was strongest among those with severe dementia (baseline Mini-Mental State Examination scores between 0 and 9). Among selective serotonin reuptake inhibitors, escitalopram had the fastest rate of decline compared with sertraline.
A link was also seen between higher doses of selective serotonin reuptake inhibitor antidepressants and higher risks of severe dementia, fractures, and mortality.
In conclusion, this study indicated that the use of antidepressants in patients with dementia may be associated with more rapid cognitive decline. In addition, higher doses of antidepressants were associated with an increased risk of severe dementia, fractures, and death.
These findings highlight the need for close monitoring of antidepressant use in people with dementia and reinforce the importance of carefully evaluating the risks and benefits of these medications in this population.
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Antidepressant use and cognitive decline in patients with dementia: a national cohort study
Minjia Mo, Tamar Abzhandadze, Minh Tuan Hoang, Simona Sacuiu, Pol Grau Jurado, Joana B. Pereira, Luana Naia, Julianna Kele, Silvia Maioli, Hong Xu, Maria Eriksdotter & Sara Garcia-Ptacek
BMC Medicine, volume 23, Article number: 82 (2025)
Abstract:
Dementia is associated with psychiatric symptoms but the effects of antidepressants on cognitive function in dementia are understudied. We aimed to investigate the association between antidepressants and cognitive decline in patients with dementia, and the risk of severe dementia, fractures and death, depending on antidepressant class, drug, and dose. This is a national cohort study. Patients with dementia registered in the Swedish Registry for Cognitive/Dementia Disorders-SveDem from May 1, 2007, until October 16, 2018, with at least one follow-up after dementia diagnosis, and who were new users of antidepressants, were included. Antidepressant use as a time varying exposure defined during the 6 months leading up to dementia diagnosis or each subsequent follow-up. We used linear mixed models to examine the association between antidepressant use and cognitive trajectories assessed by Mini-Mental State Examination (MMSE) scores. We used Cox proportional hazards models to calculate the hazard ratios for severe dementia (MMSE score < 10), fracture, and death. We compared antidepressant classes and drugs, and analyzed dose–response. We included 18740 patients (10 205 women [54.5%]; mean [SD] age, 78.2[7.4] years), of which 4271 (22.8%) received at least one prescription for an antidepressant. During follow-up, a total of 11912 prescriptions for antidepressants were issued, with selective serotonin reuptake inhibitors (SSRI) being the most common (64.8%). Antidepressant use was associated with faster cognitive decline (β (95% CI) = − 0.30(− 0.39, − 0.21) points/year), in particular sertraline (− 0.25(− 0.43, − 0.06) points/year), citalopram (− 0.41(− 0.55, − 0.27) points/year), escitalopram (− 0.76(− 1.09, − 0.44) points/year), and mirtazapine (− 0.19(− 0.34, − 0.04) points/year) compared with non-use. The association was stronger in patients with severe dementia (initial MMSE scores 0–9). Escitalopram showed a greater decline rate than sertraline. Compared with non-use, dose response of SSRIs on greater cognitive decline and higher risks of severe dementia, all-cause mortality, and fracture were observed. In this cohort study, current antidepressant use was associated with faster cognitive decline; furthermore, higher dispensed doses of SSRIs were associated with higher risk for severe dementia, fractures, and all-cause mortality. These findings highlight the significance of careful and regular monitoring to assess the risks and benefits of different antidepressants use in patients with dementia.
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