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Management of cognitive impairment in bipolar disorder: a systematic review of randomized controlled trials

Published online by Cambridge University Press:  28 January 2021

Jocelyn K. Tamura
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
Isabelle P. Carvalho
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
Lui M. W. Leanna
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
Jia Nuo Feng
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
Joshua D. Rosenblat
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
Rodrigo Mansur
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
Yena Lee
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
Danielle S. Cha
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
Kayla Teopiz
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
Zara Ahmad
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
Flora Nasri
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
Jiin Kim
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
Roger S. McIntyre*
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada
*Author for correspondence: Roger S. McIntyre Email:


Cognitive impairment is common in bipolar disorder and is emerging as a therapeutic target to enhance quality of life and function. A systematic search was conducted on PubMed, PsycInfo, Cochrane,, and Embase databases for blinded or open-label randomized controlled trials evaluating the pro-cognitive effects of pharmacological, neurostimulation, or psychological interventions for bipolar disorder. Twenty-two trials were identified, evaluating a total of 16 different pro-cognitive interventions. The methodological quality of the identified trials were assessed using the Cochrane Risk of Bias tool. Currently, no intervention (i.e., pharmacologic, neurostimulation, cognitive remediation) has demonstrated robust and independent pro-cognitive effects in adults with bipolar disorder. Findings are preliminary and methodological limitations limit the interpretation of results. Methodological considerations including, but not limited to, the enrichment with populations with pre-treatment cognitive impairment, as well as the inclusion of individuals who are in remission are encouraged. Future trials may also consider targeting interventions to specific cognitive subgroups and the use of biomarkers of cognitive function.

© The Author(s), 2021. Published by Cambridge University Press

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Jocelyn K. Tamura, Isabelle P. Carvalho, Lui M. W. Leanna, and Jia Nuo Feng are co-first authors.


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