Some Antidepressants May Worsen Dementia

Antidepressants are commonly prescribed to manage depression in dementia patients, but new research from the Karolinska Institute raises concerns about their impact on cognitive health.

Published in BMC Medicine, the study found that certain antidepressants accelerated cognitive decline, while others had a milder effect. These findings highlight the need for more personalized treatment strategies in managing both depression and dementia.

The growing concern over antidepressant use in dementia

Dementia is a neurological condition that currently affects over 55 million people worldwide – a figure expected to double by 2050. Characterized by progressive cognitive decline, dementia not only impairs memory and reasoning but also disrupts mood and behavior, leading to significant challenges for both patients and caregivers.

One of the most troubling aspects of dementia is the prevalence of neuropsychiatric symptoms such as depression, anxiety, aggression and sleep disturbances. To manage these, doctors frequently prescribe antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). However, recent research raises concerns about whether these medications could be doing more harm than good.

“Depressive symptoms can both worsen cognitive decline and impair quality of life, so it is important to treat them,” said corresponding author Dr. Sara Garcia Ptacek, assistant professor in the Department of Neurobiology, Care Sciences and Society at the Karolinska Institute.

Earlier studies have suggested that certain antidepressants might have neuroprotective effects, potentially slowing cognitive decline. Others, however, have linked them to adverse effects such as sedation, increased fall risk and possibly worsening cognitive impairment. Complicating matters further, symptoms of depression and dementia can overlap, making it difficult to determine whether antidepressants are treating a true depressive disorder or merely addressing behavioral symptoms of dementia.

To better understand the impact of antidepressants on cognitive decline in dementia, the team conducted a large observational study using data from the Swedish Dementia Registry (SveDem). The study followed 18,740 patients diagnosed with dementia between 2007 and 2018, tracking their cognitive function over an average period of 4.3 years. Researchers focused on patients who were prescribed antidepressants for the first time up to six months before or after their dementia diagnosis.

The Mini-Mental State Examination (MMSE), a widely used tool that assesses orientation, memory and overall cognitive ability, was used to measure cognitive decline. The analysis compared patients who were prescribed antidepressants to those who were not, tracking changes in MMSE scores over time. The researchers also examined differences between specific antidepressant types and the effect of dosage levels on cognitive decline.

Antidepressant use linked to faster cognitive decline in dementia

Garcia Ptacek and the team observed large differences in how various antidepressants affected cognitive function. Escitalopram, a commonly used SSRI, was associated with the most rapid cognitive decline. Patients experienced a drop of 0.76 MMSE points per year – a steeper decline than any other antidepressant included in the study.

Citalopram and sertraline also contributed to cognitive decline but at slower rates than escitalopram. Mirtazapine, a non-SSRI antidepressant, had a milder impact on cognition compared to SSRIs.

The study found no significant association between SNRIs and cognitive decline, though the researchers cautioned that the study may have been underpowered to detect such an effect.

Additionally, higher doses of SSRIs were linked to an increased risk of developing severe dementia, fractures and mortality, raising further concerns about their long-term use in dementia patients.

The study also observed that men taking antidepressants experienced faster cognitive decline than women.

Why do escitalopram, citalopram and sertraline affect cognition differently?

The varying effects of antidepressants on cognition could be attributed to differences in their mechanisms of action.

SSRIs like escitalopram, citalopram and sertraline increase serotonin levels in the brain, but they may also interfere with other neurotransmitter systems involved in cognition, such as acetylcholine. Some SSRIs have mild anticholinergic effects, which could further contribute to cognitive impairment – particularly in conditions like Alzheimer’s disease, where cholinergic deficits are already present.

Mirtazapine works primarily by blocking certain serotonin and histamine receptors, which might explain its less harmful impact on cognitive decline.

Moving towards personalized treatment

While treating depression in dementia patients is important for their well-being and quality of life, the evidence suggests that some antidepressants may accelerate cognitive decline more than others.

“Our results can help doctors and other healthcare professionals choose antidepressants that are better adapted for patients with dementia,” said Garcia Ptacek.

One of the key uncertainties in this study is whether the cognitive decline observed is caused by the antidepressants themselves or by the underlying depressive symptoms. Depression is known to contribute to cognitive impairment, and in some cases, symptoms resembling depression may actually be part of dementia’s progression rather than a separate disorder. This makes it difficult to fully separate the effects of the disease from the effects of the medication.

To improve treatment strategies, the team now aims to identify patient subgroups who may respond better or worse to certain antidepressants. Future studies will explore whether factors such as dementia type, disease severity or genetic markers can help predict which patients are most vulnerable to antidepressant-related cognitive decline.

Reference: Mo M, Abzhandadze T, Hoang MT, et al. Antidepressant use and cognitive decline in patients with dementia: a national cohort study. BMC Med. 2025;23(1):82. doi: 10.1186/s12916-025-03851-3

This article is a rework of a press release issued by the Karolinska Institute. Material has been edited for length and content.