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Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force

Lookup NU author(s): Dr Peter GallagherORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2024 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.Background: Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD. Methods: We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials. Results: Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias. Conclusions: Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.

Publication metadata

Author(s): Miskowiak KW, Obel ZK, Gugliemo R, Bonnin CDM, Bowie CR, Balanza-Martinez V, Burdick KE, Carvalho AF, Dols A, Douglas K, Gallagher P, Kessing LV, Lafer B, Lewandowski KE, Lopez-Jaramillo C, Martinez-Aran A, McIntyre RS, Porter RJ, Purdon SE, Schaffer A, Stokes PRA, Sumiyoshi T, Torres IJ, VanRheenen TE, Yatham LN, Young AH, Vieta E, Hasler G

Publication type: Review

Publication status: Published

Journal: Bipolar Disorders

Year: 2024

Volume: 26

Issue: 3

Pages: 216-239

Print publication date: 01/05/2024

Online publication date: 03/03/2024

Acceptance date: 02/04/2018

ISSN (print): 1398-5647

ISSN (electronic): 1399-5618

Publisher: John Wiley and Sons Inc


DOI: 10.1111/bdi.13414

PubMed id: 38433530