Cognitive Outcomes After Antidepressant Pharmacotherapy for Late-Life Depression: A Systematic Review and Meta-Analysis.

Objective: The authors evaluated whether treatment of late-life depression (LLD) with antidepressants leads to changes in cognitive function.
Methods: A systematic review and meta-analysis of prospective studies of antidepressant pharmacotherapy for adults age 50 or older (or mean age of 65 or older) with LLD was conducted. MEDLINE, EMBASE, and PsycInfo were searched through December 31, 2022. The primary outcome was a change on cognitive test scores from baseline to after treatment. Secondary outcomes included the effects of specific medications and the associations between changes in depressive symptoms and cognitive test scores. Participants with bipolar disorder, psychotic depression, dementia, or neurological disease were excluded. Findings from all eligible studies were synthesized at a descriptive level, and a random-effects model was used to pool the results for meta-analysis.
Results: Twenty-two studies were included. Thirteen of 19 studies showed an improvement on at least one cognitive test after antidepressant pharmacotherapy, with the most robust evidence for the memory and learning (nine of 16 studies) and processing speed (seven of 10 studies) domains and for sertraline (all five studies). Improvements in depressive symptoms were associated with improvement in cognitive test scores in six of seven relevant studies. The meta-analysis (eight studies; N=493) revealed a statistically significant overall improvement in memory and learning (five studies: effect size=0.254, 95% CI=0.103-0.404, SE=0.077); no statistically significant changes were seen in other cognitive domains. The evaluated risk of publication bias was low.
Conclusion: Antidepressant pharmacotherapy of LLD appears to improve certain domains of cognitive function, particularly memory and learning. This effect may be mediated by an improvement in depressive symptoms. Studies comparing individuals receiving pharmacotherapy with untreated control participants are needed.
Competing Interests: Dr. Blumberger has received research support from Brain Canada, CIHR, NIH, and the Temerty Family Foundation through the CAMH Foundation and the Campbell Family Research Institute; he has received research support and in-kind equipment support and was the site principal investigator for investigator-initiated and sponsor-initiated studies for BrainsWay; he has received in-kind equipment support from MagVenture for investigator-initiated studies; he has received medication supplies for an investigator-initiated trial from Indivior; and he has served on advisory boards for Janssen and Welcony. Dr. McAndrews has received grant support from CIHR, the Ontario Brain Institute, and the Weston Brain Institute. Dr. Pollock has received research support from the Alzheimer’s Drug Discovery Foundation, the Alzheimer’s Society of Canada, Brain Canada, BrightFocus Foundation, the CAMH Foundation and Discovery Fund, the Canadian Consortium on Neurodegeneration in Aging, the Centre for Aging and Brain Health Innovation, CIHR, the Garfield Weston Foundation, Genome Canada, National Institute of Aging, the Ontario Brain Institute, the Peter and Shelagh Godsoe Endowed Chair in Late-Life Mental Health, and the Weston Brain Institute; he has received honoraria from the American Geriatrics Society for book authorship and editorial services; and he holds provisional patents in the United States (16/490,680 and 17/396,030) and Canada (3,054,093) for a cell-based assay and kits for assessing serum anticholinergic activity. Dr. Rajji has received research support from the Brain and Behavior Research Foundation, Brain Canada, BrightFocus Foundation, the Canada Foundation for Innovation, Canada Research Chair, the Centre for Aging and Brain Health Innovation, CIHR, NIH, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, and the Weston Brain Institute; he has received in-kind equipment support for an investigator-initiated study from Newronika and in-kind research online accounts from Scientific Brain Training Pro; he has participated in advisory activities for Biogen Canada; and he is listed as an inventor on a U.S. provisional patent (17/396,030) for cell-based assays and kits to assess serum cholinergic receptor activity. Dr. Mulsant has received support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto; he has received research support from Brain Canada, the CAMH Foundation, Capital Solution Design, CIHR, HAPPYneuron, NIH, and the Patient-Centered Outcomes Research Institute; and he has served as a consultant for Myriad Neuroscience. The other authors report no financial relationships with commercial interests.