Computerized Cognitive Training in People with Depression: A Systematic Review and Meta-analysis of Randomized Clinical Trials

Importance: Cognitive impairment is a common feature of both symptomatic and remitted states of depression that is associated with poorer psychosocial outcomes and treatment non-response. As such, finding treatments to maintain or enhance cognition in people with depression is imperative. Objective: To investigate the efficacy and moderators of computerized cognitive training (CCT) for cognitive and functional outcomes in people with depression. Data Sources: MEDLINE, EMBASE and PsycINFO databases were screened from inception through to 08 September 2022, with no language or publication type restrictions. Study Selection: Two independent reviewers conducted duplicate study screening and assessed against the following inclusion criteria: (1) adults (mean age 18 years or older) with depression, (2) CCT with minimum three hours practice, (3) active or passive control group, (4) cognitive and/or functional outcomes measured at baseline and post-intervention, (5) randomized controlled trials. Of 4245 identified studies, 34 met selection criteria. Data Extraction and Synthesis: The methods used followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data extraction and risk of bias assessment using the revised Cochrane Risk of Bias Tool (RoB2) was conducted independently by two reviewers. Analyses were conducted using robust variance estimation. Outcomes: The primary outcome was change from baseline to post-intervention in overall cognition. Secondary outcomes were depressive symptoms, psychiatric symptoms, psychosocial functioning, daily functioning, subjective cognition, global cognition and domain-specific cognitive function. Results: Thirty-four studies encompassing 39 comparisons and 2041 unique participants met inclusion criteria. The pooled effect size of CCT was small for both overall cognition (g=0.28; 95% CI 0.17 to 0.38; P<.001; t2=0.078; I2=47%; 95% prediction interval -0.31 to 0.86) and depressive symptoms (g=0.23; 95% CI 0.08 to 0.39; P=.004; t2=0.066; I2=45%; 95% prediction interval -0.32 to 0.78). Benefits of CCT were also found for psychosocial functioning, subjective cognition, fluid reasoning, long-term memory and retrieval, low working memory, shifting, inhibition and processing speed. Greater CCT dose and multidomain programs were associated with greater cognitive response to CCT. There was no evidence for difference across clinical subtypes or between delivery modalities. Conclusions and Relevance: This systematic review and meta-analysis indicates that CCT is an efficacious intervention for overall cognition, depressive symptoms, psychosocial functioning, subjective cognition, and many domain-specific cognitive functions for people with depression. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement This work has been supported by a CR Roper Fellowship from the University of Melbourne provided to AL. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: N/A I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Supplementary tables and figures are available from the link below.