Antidepressants for Dementia Patients? Time to Rethink

A recent large-scale study has found that certain antidepressants can accelerate cognitive decline in people with dementia. Using data from nearly 19,000 patients in the Swedish Dementia Registry (SveDem), researchers observed that individuals taking antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), experienced a faster rate of cognitive decline compared to those who did not take these medications. The study also found that some antidepressants had a greater impact on memory and cognition than others, with the effects being more pronounced in patients with severe dementia. Additionally, higher doses of these medications were associated with an increased risk of severe dementia, fractures, and death.

The study analyzed 18,740 dementia patients who were newly prescribed antidepressants after their diagnosis. These individuals were followed over time to assess how their cognitive abilities changed, with cognitive function measured using the Mini-Mental State Examination (MMSE). The MMSE is a widely used tool that scores cognitive ability on a scale from 0 to 30, with lower scores indicating more severe cognitive impairment.

The study found that patients who used antidepressants experienced a greater cognitive decline over time compared to non-users. On average, those taking antidepressants had an additional cognitive decline of −0.30 MMSE points per year. This turns out to be significant when played out over a number of years. Points on the MMSE are precious.

The effect varied by the type of antidepressant:

• SSRIs were the most commonly prescribed class (64.8% of all prescriptions) and were associated with the greatest cognitive decline.
• Mirtazapine, an antidepressant with a different mechanism of action, was linked to a smaller decline in cognitive function than SSRIs.
• Tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) did not show a statistically significant impact on cognitive decline.

Among individual antidepressants, the decline in MMSE scores varied:

• Escitalopram, (Lexapro®  SSRI): −0.76 points per year.
• Citalopram (Celexa®  SSRI): −0.41 points per year.
• Sertraline ( Zoloft® SSRI): −0.25 points per year.
• Mirtazapine (Remeron®): −0.19 points per year.

Escitalopram had the strongest association with cognitive decline, while mirtazapine had a more moderate effect.

The study also found that the cognitive impact of antidepressants was stronger in patients with more severe dementia (MMSE scores of 0–9 at baseline). These individuals experienced the fastest decline compared to those with mild or moderate dementia.

The study found a dose-dependent effect, meaning that higher doses of SSRIs were associated with more rapid cognitive decline:

• Lower doses (≤0.5 Defined Daily Dose, DDD): −0.32 MMSE points per year
• Moderate doses (0.5–1.0 DDD): −0.41 MMSE points per year
• Higher doses (>1.0 DDD): −0.42 MMSE points per year

This pattern suggests that the risk of cognitive decline increases with higher daily doses of SSRIs.

In addition to cognitive decline, antidepressant use was linked to higher risks of severe dementia, fractures, and all-cause mortality (meaning death from any cause):

• Severe dementia risk (MMSE <10): Patients taking higher doses of SSRIs had a 35% increased risk of developing severe dementia.
• All-cause mortality: Patients using antidepressants had a 7% higher risk of death.
• Fracture risk: Antidepressant users had an 18% higher risk of fractures. Patients taking higher doses of SSRIs (>1.0 DDD) had an even greater risk of mortality and fractures compared to those on lower doses.

These findings highlight the importance of careful prescribing of antidepressants in dementia patients. Based on these results doctors should be cautious when using SSRIs in dementia patients, especially at higher doses.

For patients who require antidepressants, mirtazapine may be a safer alternative as it was associated with less cognitive decline. Additionally, healthcare providers should consider non-drug interventions for depression in dementia, such as behavioral therapies and caregiver support programs, to reduce the need for antidepressants.

Regular cognitive monitoring is recommended for patients taking antidepressants to track potential declines in memory and function. Lower doses should be preferred whenever possible to reduce risks.

This study provides strong evidence that antidepressants, especially SSRIs, can accelerate cognitive decline in dementia patients, with higher doses leading to greater risks of severe dementia, fractures, and mortality. While treating depression in dementia remains important, doctors should be mindful of the potential negative effects of certain medications and consider alternative treatments when appropriate. Individualized care, dose monitoring, and further research will be crucial in ensuring the best outcomes for patients with dementia.