Use of Antidepressants and Dementia in US Veterans: Is There a Risk?

Among United States veterans with major depressive disorder (MDD), the use of antidepressants is not significantly associated an increased risk for Alzheimer disease (AD) or AD-related dementias, according to findings published in Alzheimer’s & Dementia.

Researchers conducted a nationwide retrospective study between January 2000 and June 2022 to assess the relationship between antidepressant exposure and risk for AD and AD-related dementias among veterans diagnosed with MDD. The researchers sourced data from the US Department of Veterans Affairs Corporate Data Warehouse. Veterans aged 55 and older with their first-ever diagnosis of MDD were eligible for inclusion. Drug exposure was defined as a prescription lasting over 3 months.

The primary outcome was time to incident diagnosis of AD or AD-related dementias (ie, Lewy body dementia, vascular dementia, nonspecific dementia). Inverse probability weighted Cox models with time-varying covariates were used in statistical analyses.

A total of 35,200 patients (mean age, 65.4; men, 90.6%; non-Hispanic White, 62.0%) were included in the final analysis, 16,815 (47.8%) of whom were exposed to antidepressants. Prior to receiving a dementia diagnosis, 1944 (5.5%) patients died. A total of 1056 patients received a dementia diagnosis.

The median treatment duration and time from diagnosis to treatment initiation was 4.08 and approximately 2.68 years, respectively. Age, race, ethnicity, smoking status, as well as histories of hypertension, posttraumatic stress disorder, and use of benzodiazepines were the primary drivers of antidepressant exposure.

Overall, current antidepressant exposure vs no exposure was not associated with risk for incident AD or AD-related dementias (adjusted hazard ratio [aHR], 0.93; 95% CI, 0.80-1.08; P =.32).

Similarly, a change in risk for AD or AD-related dementias was not linked to current exposure to any of the following individual antidepressant drug classes:

• selective serotonin reuptake inhibitors: events, n=937; aHR, 0.92; 95% CI, 0.78-1.08; P =.31;
• norepinephrine and dopamine reuptake inhibitor: events, n=524; aHR, 0.81; 95% CI, 0.43-1.50; P =.49;
• serotonin-norepinephrine reuptake inhibitor: events, n=547; aHR, 0.87; 95% CI, 0.54-1.42; P =.58; and,
• noradrenaline and specific serotonergic antidepressants: events, n=527; aHR, 0.89; 95% CI, 0.50-1.59; P =.69.

Study limitations included the young-leaning cohort, small sample size, participants’ potential use of supplemental insurance, inability to examine the effects of combinations of antidepressants on the risk for AD/ADRD, and use of restrictive diagnostic codes to define major depressive disorder and AD/AD-related dementias.

“A possibility for the conflicting results in retrospective studies is that the heightened risk identified in participants on antidepressants may be attributed to depression itself, rather than the result of a potential pharmacological action, so this and other clinical confounding factors need to be taken into account,” the researchers concluded.