Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: A systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force
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Background: Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations. Methods: The review included RCTs of candidate pro-cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials. Results: We identified 16 RCTs (N = 859) investigating cognitive remediation (CR; k = 6; N = 311), direct current or repetitive magnetic stimulation (k = 3; N = 127), or pharmacological interventions (k = 7; N = 421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre-screening for objective cognitive impairment, no primary outcome and no information on allocation sequence masking. Conclusions: Evidence for pro-cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre-screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real-world functioning, investigate multimodal interventions and include neuroimaging.
Original language | English |
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Journal | Bipolar Disorders |
Volume | 24 |
Issue number | 4 |
Pages (from-to) | 354-374 |
ISSN | 1398-5647 |
DOIs | |
Publication status | Published - 2022 |
Bibliographical note
Funding Information:
The authors thank the International Society for Bipolar Disorders executives and staff for their support of the ISBD Targeting Cognition Task Force. This work is non‐funded. KWM holds a 5‐year Lundbeck Foundation Fellowship (grant no. R215‐2015‐4121). TVR was supported by an NHMRC Early Career Fellowship (GNT1088785) and a Dame Kate Campbell Fellowship from the University of Melbourne. KD holds a Sir Charles Hercus Health Research Fellowship from the Health Research Council of New Zealand (grant no. 19/082). EV thanks the support of the Spanish Ministry of Science and Innovation (PI15/00283, PI18/00805) integrated into the Plan Nacional de I+D+I and co‐financed by the ISCIII‐Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357.
Funding Information:
The authors thank the International Society for Bipolar Disorders executives and staff for their support of the ISBD Targeting Cognition Task Force. This work is non-funded. KWM holds a 5-year Lundbeck Foundation Fellowship (grant no. R215-2015-4121). TVR was supported by an NHMRC Early Career Fellowship (GNT1088785) and a Dame Kate Campbell Fellowship from the University of Melbourne. KD holds a Sir Charles Hercus Health Research Fellowship from the Health Research Council of New Zealand (grant no. 19/082). EV thanks the support of the Spanish Ministry of Science and Innovation (PI15/00283, PI18/00805) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357.
Funding Information:
KWM has received consultancy fees from Janssen and Lundbeck in the past 3 years. RP uses computer software at no cost for research – provided by SBT‐pro and has received support for travel to educational meetings from Servier and Lundbeck. AS has received advisory or speaking fees from AbbVie, Janssen, Lundbeck, Otsuka and Sunovion in the past 3 years. KD uses computer software at no cost for research provided by SBT‐pro. LVK has received consultancy fees from Lundbeck and Teva in the past 3 years. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB‐Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka, Sage, Sanofi‐Aventis, Sunovion, Takeda, all them unrelated to the present work. VBM has been a consultant, advisor or Continuing Medical Education (CME) speaker over the last 3 years for the following companies: Angelini, Lundbeck, Nutrición Médica and Otsuka. AY has conducted paid lectures and advisory boards for Allergan, AstraZeneca, Bionomics, BrainCells Inc., Bristol‐Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Lundbeck, Novartis, Otsuka Pharmaceutical Co., Pharmaceutica, Pfizer, Roche, Sanofi‐Aventis, Servier Laboratories, Sunovion and Wyeth. He was lead Investigator for the EMBOLDEN Study (AstraZeneca), BCI Neuroplasticity Study and Aripiprazole Mania Study, and has been involved in investigator‐initiated studies for AstraZeneca, Eli Lilly and Wyeth. PS reports grants and non‐financial support from Corcept Therapeutics, non‐financial support from Janssen Research and Development LLC, grant funding from Lundbeck and personal fees from Frontiers in Psychiatry and Allergan outside the submitted work. IJT has received has served as consultant for Lundbeck Canada, Sumitomo Dainippon and Community Living British Columbia. LNY has been on speaker/advisory boards for, or has received research grants from Alkermes, Allergan, AstraZeneca, Bristol Myers Squibb, CANMAT, CIHR, Dainippon Sumitomo Pharma, GSK, Janssen, Lilly, Lundbeck, Merck, Otsuka, Pfizer, Sanofi, Sunovion and Teva. RM has received personal fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Minerva, Intra‐Cellular, Abbvie and Eisai and is a shareholder in the 420 Company and CEO of Champignon. AD, AC, BL, IS, MBJ, CRB, CMB, KEL, PG, CLJ, AMA, SEP, TS and TVR report no conflict of interest.
- bipolar disorder, cognitive impairment, intervention, ISBD Task Force, major depressive disorder, randomised controlled trials, recommendations, systematic review
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