Antidepressant use and cognitive deficits in older men: addressing confounding by indications with different methods

Antidepressant use has been associated with cognitive impairment in older persons. We sought to examine whether this association might reflect an indication bias.

A total of 544 community-dwelling hypertensive men aged ≥65 years completed the Hopkins Verbal Learning Test at baseline and 1 year. Antidepressant medications were ascertained by the use of medical records. Potential confounding by indications was examined by adjusting for depression-related diagnoses and severity of depression symptoms using multiple linear regression, a propensity score, and a structural equation model (SEM).

Before adjusting for the indications, a one unit cumulative exposure to antidepressants was associated with -1.00 (95% confidence interval [CI], -1.94, -0.06) point lower HVLT score. After adjusting for the indications using multiple linear regression or a propensity score, the association diminished to -0.48 (95% CI, -0.62, 1.58) and -0.58 (95% CI, -0.60, 1.58), respectively. The most clinical interpretable empirical SEM with adequate fit involves both direct and indirect paths of the two indications. Depression-related diagnoses and depression symptoms significantly predict antidepressant use (p < .05). Their total standardized path coefficients on Hopkins Verbal Learning Test score were twice (0.073) or as large (0.034) as the antidepressant use (0.035).

The apparent association between antidepressant use and memory deficit in older persons may be confounded by indications. SEM offers a heuristic empirical method for examining confounding by indications but not quantitatively superior bias reduction compared with conventional methods.