medwireNews: Antidepressant use, particularly higher doses of selective serotonin reuptake inhibitors (SSRIs), may hasten cognitive decline in people with dementia, suggest findings from a Swedish cohort study.
“The findings may inform clinical care and contribute to future research, providing insights for primary care practitioners and specialists involved in dementia healthcare,” observe Minjia Mo (Karolinska Institutet, Stockholm) and colleagues.
The researchers identified 18,740 individuals with incident diagnosed dementia from the Swedish Registry for Cognitive/Dementia Disorders between 2007 and 2018, 54.5% of whom were women. The participants had a mean age of 78.2 years, no known diagnosis of depression, and their baseline Mini–Mental State Examination (MMSE) score was a mean of 22.1 out of 30 points, where a high score indicates better cognitive function.
Over an average 4.3 years per person (total 80,737 person–years) of follow-up, 11,912 prescriptions for antidepressants were given, with 22.8% of patients receiving at least one prescription.
SSRIs were the most common class prescribed, at 64.8%, followed by tricyclic antidepressants (TCAs) and serotonin norepinephrine reuptake inhibitors (SNRIs), at a respective 2.2% and 2.0%. Other types of antidepressants made up the remaining 31.0%.
First antidepressant use in the 6 months prior to diagnosis of any dementia or afterwards was associated with a significantly faster cognitive decline than no use with an estimated 3.0-point greater reduction in MMSE score per year, after taking into account potential confounding factors such as age, sex, type of dementia, MMSE score at diagnosis, comorbidities, and the use of other medications.
The results were “largely similar” and statistically significant for diagnoses of Alzheimer’s disease and mixed dementia, vascular dementia, and other types of dementias, excluding frontotemporal dementia and dementia with Lewy bodies, the investigators report.
The antidepressants most associated with cognitive decline were the SSRIs escitalopram, citalopram, sertraline, and the tetracyclic antidepressant mirtazapine, with statistically significant estimated average annual decreases in MMSE scores versus no use of 0.76, 0.41, 0.25, and 0.19, respectively. However, the researchers note that for all of these antidepressants the effect “appears to be lower than the minimum clinically significant change in MMSE score of 1–3 points.”
When compared directly with sertraline, escitalopram was found to be associated with a significant 0.51-point greater decline in estimated MMSE score per year.
Mo and team point out that in subgroup analyses the detrimental effect of antidepressant use on cognitive decline “appeared to be more pronounced in patients with more severe dementia.”
They found that the annual decline in MMSE score among severe dementia patients with a baseline score of 0–9 points was 1.51 points versus no use, compared with declines of 0.19–0.29 points among those with higher scores.
In addition to increased cognitive decline, antidepressant use in the full study population, compared with no use, was associated with a significant 7% higher risk for all-cause mortality and an 18% higher risk for fracture.
And the risks for these outcomes as well as that of severe dementia were found to be dose dependent, particularly for SSRIs, where a defined daily dose (the average amount usually prescribed) of SSRI above 1.0, compared with no antidepressant use, significantly increased the risk for all-cause mortality, fracture, and severe dementia by 18%, 25%, and 35%, respectively.
The study authors caution that their study “cannot distinguish whether these findings are due to the antidepressants or the underlying psychiatric indication.”
Nevertheless, they conclude that “[t]hese findings highlight the significance of careful and regular monitoring to assess the risks and benefits of different antidepressants [used] in patients with dementia.”
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