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Previous studies have provided equivocal evidence of antidepressant use on subsequent cognitive impairment; this could be due to inconsistent modeling approaches. Our goals are methodological and clinical. We evaluate the impact of statistical modeling approaches on the associations between antidepressant use and risk of Mild Cognitive Impairment (MCI) in older adults with depression.    Methods  716 participants were enrolled. Our primary analysis employed a time-dependent Cox proportional hazards model. We also implemented two fixed-covariate proportional hazards models—one based on having  ever  used antidepressants during follow-up, and the other restricted to  baseline  use only.    Results  Treating antidepressant use as a time-varying covariate, we found no significant association with incident MCI (HR = 0.92, 95% CI: 0.70, 1.20). In contrast, when antidepressant use was treated as a fixed covariate, we observed a significant association between having  ever  used antidepressants and lower risk of MCI (HR = 0.40, 95% CI: 0.28, 0.56). However, in the  baseline-use  only model, the association was non-significant (HR = 0.84, 95% CI: 0.60, 1.17).    Discussion  Our results were dependent upon statistical models and suggest that antidepressant use should be modeled as a time-varying covariate. Using a robust time-dependent analysis, antidepressant use was not significantly associated with incident MCI among cognitively normal persons with depression.

Estimating associations between antidepressant use and incident mild cognitive impairment in older adults with depression