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. 2025 Mar;33(3):287-304.
doi: 10.1016/j.jagp.2024.08.015. Epub 2024 Sep 6.

A Systematic Review of Antidepressants and Psychotherapy Commonly Used in the Treatment of Late Life Depression for Their Effects on Cognition

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A Systematic Review of Antidepressants and Psychotherapy Commonly Used in the Treatment of Late Life Depression for Their Effects on Cognition

J Craig Nelson et al. Am J Geriatr Psychiatry. 2025 Mar.

Abstract

Cognitive dysfunction is common in late life depression (LLD) and is a major risk factor for dementia. Recent studies show limited improvement in cognition with commonly employed treatments for LLD, contradicting the notion that cognition "returns to normal" with treatment. However, findings differ with the treatments used. The aim of this study is to perform a systematic review of studies of antidepressants and psychotherapies commonly employed in LLD to determine their effects on cognition, particularly processing speed, memory, and executive function. We searched for trials of acute phase treatment, in nondemented individuals 60 years and older with unipolar nonpsychotic Major Depressive Disorder, that assessed cognitive performance with neuropsychological tests before and after treatment. We compared the magnitude of change in cognition by examining within group effect sizes. Six antidepressant trials and two psychotherapy trials (both using Problem Solving Therapy)(PST) provided relatively comparable data that allowed for quantitative comparison. Nine other antidepressant trials provided descriptive findings. Sertraline and vortioxetine had significant positive effects on processing speed and memory. Duloxetine had significant effects on memory. The most selective SRIs-citalopram and escitalopram-had minimal effects on cognition and citalopram had adverse effects in depression nonresponders. PST had modest effects on processing speed and no effect on memory. Effects of practice and improvement in depression on cognition are examined. In all but one study, cognition was a secondary outcome and various quality indicators (e.g. blinding cognitive assessment to treatment) were often not reported. As a consequence, these findings must be considered preliminary.

Keywords: Late life depression; and psychotherapy; antidepressants; cognitive dysfunction.

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Conflict of interest statement

DISCLOSURES During the past 2 years JCN has received research support from National Institute of Mental Health; consultation fees from Biohaven, Clexio, Johnson and Johnson, Novartis, and Otsuka; and royalties from UpToDate. JG reports no conflicts with any product mentioned or concept discussed in this article. RSM has received research support from the National Institute of Mental Health, National Institute of Aging, Johnson and Johnson, and Janssen Research and Development LLC.

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