Antidepressants may increase the speed of cognitive decline
Key takeaways:
- Antidepressants, particularly SSRIs like escitalopram, were tied to a faster cognitive decline.
- Higher dispensed doses of SSRIs also increased the risk for all-cause death and severe dementia.
Current use of antidepressants corresponded with faster cognitive decline in older adults with dementia, a cohort analysis published in BMC Medicine indicated.
The researchers further found that higher dispensed doses of selective serotonin reuptake inhibitors (SSRIs) increased the risk for severe dementia, fractures and mortality from all causes.
“Antidepressants sometimes have sedative or anticholinergic effects, so some cognitive effects were not unexpected,” Sara Garcia-Ptacek, MD, PhD, an assistant professor at the Karolinska Institute in Sweden, told Healio. “What was surprising were the differences between antidepressants and the fact that the cognitive effects were different for different dementia types.”
Comprehensive knowledge about the clinical effects of antidepressants on dementia progression is lacking, according to Garcia-Ptacek and colleagues.
“Tricyclic antidepressants are anticholinergics and negatively impact cognition,” they wrote. “In contrast, a beneficial impact of SSRIs on neurogenesis and pathologic biomarkers, including amyloid burden and tau deposits, has been reported, along with evidence suggesting they may delay the progression from mild cognitive impairment to Alzheimer’s dementia among persons with depression.”
The researchers conducted a national cohort study aimed to further assess the relationship between cognition and antidepressants by analyzing a sample of 18,740 adults with dementia who received at least one prescription for an antidepressant.
The study cohort had been registered in the Swedish Registry for Cognitive/Dementia Disorders-SveDem and included adults (54.5% women) who had at least one follow-up following their dementia diagnosis.
The investigation evaluated antidepressants by drug class and type, while analysis outcomes included cognitive trajectories, severe dementia, fractures and death.
Results showed that antidepressant use corresponded with faster cognitive decline vs. nonuse (B = 0.3 points a year; 95% CI, 0.39 to 0.21), with results being similar between SSRIs (B = 0.39 points a year; 95% CI, 0.5 to 0.28) and other antidepressants (B = 0.2 points a year; 95% CI, 0.35 to 0.05).
These effects “appeared to be more pronounced in patients with more severe dementia,” the researchers wrote.
Among SSRIs, compared with sertraline, those who received escitalopram (B = 0.51 points a year; 95% CI, 0.89 to 0.12) experienced faster cognitive decline while citalopram (B = 0.28 points a year; 95% CI, 0.17-0.39) showed slower decline.
“These differences may influence medication choice for a given patient and may show varied effect on dementia progression,” Garcia-Ptacek and colleagues wrote.
They also reported that antidepressant corresponded with greater risk for all-cause mortality (HR = 1.07; 95% CI, 1.01-1.13) and fractures (HR = 1.18; 95% CI, 1.1-1.26). Compared with non-use, higher dispensed doses of SSRIs increased the risk for severe dementia (HR = 1.35; 95% CI, 1.02-1.8), death from all causes (HR = 1.18; 95% CI, 1.07-1.31), and fracture (HR = 1.25; 95% CI, 1.1-1.43).
The study was observational “and it was not designed to infer causality,” Garcia-Ptacek underlined.
“It is always a good idea to follow up on prescriptions and see how the patient reacts,” she told Healio. “Patients with dementia are cognitively fragile and a number of factors can destabilize them. Tighter control after any changes in medication is often a good idea.”
The next step for research in this area should be to figure out which medication is appropriate for each patient “to move toward more personalized medicine,” Garcia-Ptacek added.
“Our hope is to find something we can repurpose to treat Alzheimer's [disease] but also to detect brain-friendly alternatives among frequently prescribed drugs.”