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

Abstract

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

Methods: 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).

Results: 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).

Conclusion: 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.