Association between first-line antidepressant use and risk of dementia in older adults: a retrospective cohort study

Prior studies suggested that antidepressant use is associated with an increased risk of dementia compared to no use, which is subject to confounding by indication. We aimed to compare the dementia risk among older adults with depression receiving first-line antidepressants (i.e., SSRI/SNRI) versus psychotherapy, which is also considered the first-line therapy for depression.

This retrospective cohort study was conducted using the US Medical Expenditure Panel Survey from 2010 to 2019. We included adults aged ≥ 50 years diagnosed with depression who initiated SSRI/SNRI or psychotherapy. We excluded patients with a dementia diagnosis before the first record of SSRI/SNRI use or psychotherapy. The exposure was the patient's receipt of SSRI/SNRI (identified from self-report questionnaires) or psychotherapy (identified from the Outpatient Visits or Office-Based Medical Provider Visits files). The outcome was a new diagnosis of dementia within 2 years (i.e., survey panel period) identified using ICD-9/ICD-10 codes from the Medical Conditions file. Using a multivariable logistic regression model, we reported adjusted odds ratios (aORs) with 95% confidence intervals (CIs). We also conducted subgroup analyses by patient sex, age group, race/ethnicity, severity of depression, combined use of other non-SSRI/SNRI antidepressants, and presence of underlying cognitive impairment.

Among 2,710 eligible patients (mean age = 61 ± 8, female = 69%, White = 84%), 89% used SSRIs/SNRIs, and 11% received psychotherapy. The SSRI/SNRI users had a higher crude incidence of dementia than the psychotherapy group (16.4% vs. 11.8%), with an aOR of 1.36 (95% CI = 1.06-1.74). Subgroup analyses yielded similar findings as the main analyses, except no significant association for patients who were aged < 65 years (1.23, 95% CI = 0.93-1.62), male (1.34, 95% CI = 0.95-1.90), Black (0.76, 95% CI = 0.48-1.19), had a higher PHQ-2 (1.39, 95% CI = 0.90-2.15), and had underlying cognitive impairment (1.06, 95% CI = 0.80-1.42).

Our findings suggested that older adults with depression receiving SSRIs/SNRIs were associated with an increased dementia risk compared to those receiving psychotherapy.