Original Study| Volume 22, ISSUE 2, P433-439, February 2021

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Antidepressant Use and Progression of Mild to Moderate Alzheimer's Disease: Results from the European ICTUS Cohort



      Neuropsychiatric symptoms (NPS) are a core and troubling feature among patients with Alzheimer disease (AD). Because of growing safety warnings against antipsychotics, the use of antidepressants (ATD) in AD has increased extensively. We investigated the potential long-term associations between ATD exposure and functional and cognitive progression in patients with mild to moderate AD.


      Two-year prospective multicenter cohort ICTUS (Impact of Cholinergic Treatment USe) study with biannual assessments.


      Twenty-nine memory clinics from 12 European countries.


      Community-dwelling patients with mild to moderate AD.


      Global cognitive function was measured using the Mini Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Functional impairment was measured using the Activities of Daily Living (ADL). Assessments were performed biannually for 2 years. Antidepressant exposure was defined by an ATD prescription for a minimum period of 6 months. Linear mixed models were used to study the associations between ATD exposure and cognitive and functional progression.


      Antidepressant exposure was not associated with cognitive decline [MMSE: β-coefficients of the linear mixed models (Coef) = 0.06, 95% confidence interval (CI) −0.65 to 0.76, P = .87; ADAS-Cog: Coef = −13.9, 95% CI −34.80 to 7.03, P = .19] or with functional decline (ADL: Coef = −0.05, 95% CI −0.21 to 0.09, P = .48) at 2-year follow-up. Antipsychotic exposure at baseline was associated with a greater functional decline in the ADL score (Coef = −0.39, 95% CI − 0.68 to 0.10, P < .01).

      Conclusions and Implications

      Antidepressant exposure was not associated with a faster rate of cognitive or functional decline in patients with mild to moderate AD. Antidepressants might be appropriate alternatives to antipsychotics in the management of NPS in mild to moderate AD.


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