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Lookup NU author(s): Dr Peter GallagherORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Introduction Major depressive disorder (MDD) and bipolar disorder (BD) are often associated with persistent cognitive deficits that impair psychosocial functioning. While pro-cognitive interventions show promise, trial findings are inconsistent, potentially due to baseline factors influencing treatment response. This systematic review summarizes evidence on pre-treatment characteristics associated with cognitive improvement and offers methodological recommendations. Methods A systematic search was conducted in PubMed/MEDLINE, EMBASE, PsycINFO, and Cochrane Library from inception to February 28, 2025. Eligible studies included primary or secondary analyses of randomized controlled trials (RCTs) investigating predictors of cognitive response to pro-cognitive interventions in MDD and/or BD. Two researchers independently conducted study selection and risk of bias assessments. Findings were synthesized qualitatively. Results Forty studies (N = 3864) were identified, covering pharmacological treatments (k = 20; N = 2299), psychological therapies (k = 16; N = 1165), brain stimulation (k = 2; N = 168), and physical activity (k = 2; N = 232). Poorer baseline cognitive performance was the most consistent predictor of greater cognitive improvement, though the direction of the effect was not entirely uniform across all studies. Baseline depression severity showed no significant association with cognitive outcomes. Age, education, sex, IQ, diagnosis, and medication status were similarly non-predictive. Risk of bias was high in 77% of studies, mainly due to deviations from specified outcomes, poor randomization processes, and inconsistent handling of missing data. Considerable heterogeneity in interventions, outcome measures, and sample characteristics limited replicability and precluded meta-analysis. Conclusion Poorer baseline cognition emerged as the most reliable predictor of greater cognitive improvement across interventions. More rigorous, well-powered studies are needed to replicate these findings and identify robust predictors to guide personalized pro-cognitive treatment approaches in mood disorders.
Author(s): Tsapekos D, Kalfas M, Schandorff JM, del Mar Bonnin C, Bowie CR, Balanzá-Martínez V, Burdick KE, Carvalho AF, Dols A, Douglas K, Gallagher P, Hasler G, Kessing LV, Kjærstad HL, Lafer B, Lewandowski KE, López-Jaramillo C, Martinez-Aran A, McIntyre RS, Porter RJ, Purdon SE, Schaffer A, Stokes PRA, Sumiyoshi T, Torres IJ, Van Rheenen TE, Yatham LN, Zarp J, Young AH, Vieta E, Miskowiak KW
Publication type: Review
Publication status: Published
Journal: Acta Psychiatrica Scandinavica
Year: 2025
Pages: epub ahead of print
Online publication date: 13/10/2025
Acceptance date: 14/09/2025
ISSN (print): 0001-690X
ISSN (electronic): 1600-0447
URL: https://doi.org/10.1111/acps.70038
DOI: 10.1111/acps.70038
Data Access Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
