Common Mood Medications May Speed Up Mental Decline in Dementia Patients

Widely prescribed antidepressants appear to accelerate cognitive decline in people with dementia, according to a new large-scale Swedish study that could alter treatment approaches for millions of patients worldwide.

The research, published February 25 in BMC Medicine, tracked nearly 19,000 people with dementia over several years and found that those taking antidepressants experienced faster deterioration in cognitive function compared to patients not receiving these medications.

“Depressive symptoms can both worsen cognitive decline and impair quality of life, so it is important to treat them. Our results can help doctors and other healthcare professionals choose antidepressants that are better adapted for patients with dementia,” says Sara Garcia Ptacek, researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, and the study’s last author.

Not All Drugs Perform Equally

The researchers examined data from Sweden’s national dementia registry, comparing cognitive trajectories between patients who received antidepressants and those who did not. Of the 18,740 participants, about 23 percent were prescribed antidepressants during the study period.

Particularly concerning was the discovery that certain commonly prescribed medications appeared more problematic than others. The SSRI escitalopram was associated with the fastest cognitive decline, followed by the SSRIs citalopram and sertraline. Mirtazapine, which works through a different mechanism, showed less negative cognitive impact than escitalopram.

The study represents one of the most comprehensive analyses to date of how different antidepressant medications affect cognitive function in dementia patients, with researchers from Karolinska Institutet and Sahlgrenska University Hospital in Gothenburg following patients’ cognitive development over time.

Clinical Implications

These findings highlight the delicate balancing act clinicians face when treating depression in dementia patients. Untreated depression can significantly worsen quality of life and potentially accelerate cognitive decline itself. Yet this study suggests the very medications used to address depression might contribute to faster cognitive deterioration.

The research team noted that while they can observe this association, they cannot yet definitively determine whether the cognitive impairment stems from the medications themselves or from the underlying depressive symptoms they’re designed to treat.

Higher doses of selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed class of antidepressants, were linked to increased risks of developing severe dementia, experiencing fractures, and higher mortality rates. This dose-response relationship—where higher medication doses correlate with worse outcomes—strengthens the case for a causal connection rather than mere coincidence.

A Closer Look at the Research

The study draws its strength from Sweden’s comprehensive healthcare registries, which allowed researchers to track participants over extended periods while accounting for numerous factors that might influence cognitive outcomes.

During the follow-up period, researchers documented a total of 11,912 antidepressant prescriptions among study participants. SSRIs were by far the most common, accounting for about 65 percent of all prescriptions.

Beyond the medication class, the specific drug choice appeared to matter significantly. Direct comparisons between medications revealed that patients taking escitalopram experienced more rapid cognitive decline than those on sertraline, while citalopram showed comparatively less impact than previously thought.

The study’s design allowed researchers to analyze not just the presence of medication but also dosage effects. Higher doses consistently correlated with faster cognitive decline, particularly for SSRIs and other antidepressants.

Personalized Treatment Approaches

The findings point toward the need for more individualized treatment approaches. The research team plans to investigate whether certain patient groups, such as those with specific dementia types or biomarkers, respond better or worse to different antidepressants.

“The goal is to find these subgroups to create more individualised care,” says Sara Garcia Ptacek.

This nuanced approach could help clinicians navigate the complex risk-benefit calculations when treating depression in dementia patients. Rather than avoiding antidepressants entirely, doctors might opt for medications with less cognitive impact or carefully titrate doses to minimize potential harm.

Broader Context

Dementia affects approximately 55 million people worldwide, with nearly 10 million new cases diagnosed annually. Depression frequently co-occurs with dementia, affecting up to 50 percent of patients at some point during their illness.

Antidepressants are widely prescribed to address not only depression but also anxiety, aggression, and sleep disturbances in dementia patients. These medications typically work by modulating neurotransmitters in the brain, particularly serotonin and norepinephrine.

While the study raises important questions about antidepressant use in dementia, experts caution that patients should not discontinue prescribed medications without consulting their healthcare providers. The risks of untreated depression must be carefully weighed against the potential cognitive impacts highlighted in this research.

Future Directions

The study represents an important step toward more tailored treatment approaches, but many questions remain unanswered. The researchers acknowledge that their observational study design cannot definitively establish causation, though the consistent patterns observed across different analyses strengthen their findings.

Moving forward, the research team hopes to identify specific patient characteristics that might predict better or worse responses to different medications. Such precision would allow clinicians to better match patients with the most appropriate treatments, minimizing risks while maximizing benefits.

The study was funded by several organizations, including the Swedish Research Council, Region Stockholm, the Swedish Dementia Research Foundation, the Alzheimer’s Foundation and New Innovative Roads Call – a private initiative from the Leif Lundblad family and others.

As our understanding of the complex interplay between dementia, depression, and medication effects continues to evolve, studies like this one provide critical guidance for improving care for one of our most vulnerable patient populations.