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Child Psychiatrist /Adult Psychiatrist

No Evidence of Dementia, Brain Atrophy With Antidepressant Use

Keypoint: Long-term use of antidepressants is not associated with dementia risk.

Antidepressant medication use is not associated with long-term cognitive decline, brain atrophy, or dementia risk, according to results from a prospective cohort study published in Alzheimer’s and Dementia.


Although antidepressants are used widely and have become more frequently used among older adults, the long-term effects of antidepressant use on cognition and dementia remain uncertain.

To address this knowledge gap, investigators analyzed data from the Rotterdam Study – an ongoing prospective population-based cohort study that began in 1990 and evaluated participants every 4 years at a dedicated research center. The investigators included participants (N=5511) who were 60 years of age and older, attended a follow-up examination at a dedicated research center between 2002 and 2008, and had no indication of cognitive impairment at baseline. All participants underwent cognitive assessments and magnetic resonance imaging (MRI), and the investigators used pharmacy records to identify antidepressant medication use between 1991 and baseline (eg, between 2002 and 2008). The primary outcomes of interest were incident dementia (diagnosed between baseline and 2018), changes in cognition, and brain atrophy.

On average, participants were 70.6 (SD, 7.6) years of age and had a body mass index (BMI) of 27.7 (SD, 4.2) kg/m2. Overall, 57.5% were women, 49.7% used benzodiazepines, 16.7% of participants had used antidepressants in the 10 years before baseline, 4.1% continued to use antidepressants at baseline, and 1.6% used antipsychotic medications. Medication use at baseline was more common among women than men (20.8% vs 11.7%), among individuals with lower education, and among individuals aged 80 years and older than among those aged 45 to 50 years (5.4% vs 2.1%), respectively.

Among the cohort that used antidepressants, 33% only used tricyclic antidepressants (TCAs), 36% used serotonin reuptake inhibitors, 5% used other types, and 25% used a combination of antidepressants.

During a mean follow-up of 10.2 years, 11.6% of individuals developed incident dementia. The investigators found that dementia risk was not significantly associated with overall antidepressant use. However, after stratifying by type of antidepressant, dementia risk was elevated among individuals who had ever used TCAs (adjusted hazard ratio [aHR], 1.36; 95% CI, 1.01-1.83). The increased risk tended to be associated with shorter-term use (aHR, 1.43; 95% CI, 1.00-2.04) and not with longer-term use (aHR, 1.26; 95% CI, 0.78-2.02) of TCAs.

The investigators did not observe a relationship between antidepressant use and cognition at baseline or with a decline in global cognitive performance over time. However, antidepressant use was associated with a slower reduction in Purdue Pegboard Test performance over time (b, 0.010; 95% CI, 0.002-0.018).

Similarly, no relationships between antidepressant use and brain volume at baseline or with changes in brain volume over time were observed.

Study authors concluded, “[A]ntidepressant use was not associated with long-term adverse effects on dementia risk, cognitive decline, or brain atrophy in older individuals without clear signs of cognitive impairment.”

This study may have been limited by excluding individuals with Mini-Mental State Examination (MMSE) scores of less than 26 at baseline.

Note: This article originally appeared on Psychiatry Advisor

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