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Review, Early Access, 2024

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

BIPOLAR DISORDERS, ISSN 1398-5647, 1398-5647, 10.1111/bdi.13414

Contributors

Miskowiak, Kamilla W. (Corresponding author) [1] [2] Obel, Zacharias K. [2] Gugliemo, Riccardo [3] [4] Bonnin, Caterina del Mar [5] [6] [7] [8] [9] Bowie, Christopher R. [10] Balanza-Martinez, Vicente [11] Burdick, Katherine E. [12] [13] [14] Carvalho, Andre F. [15] Dols, Annemieke [16] [17] Douglas, Katie [18] Gallagher, Peter [19] Kessing, Lars V. [2] Lafer, Beny [20] Lewandowski, Kathryn E. [13] [14] [21] Lopez-Jaramillo, Carlos [22] Martinez-Aran, Anabel [5] [6] [7] [8] [9] McIntyre, Roger S. [23] Porter, Richard J. [18] Purdon, Scot E. [24] Schaffer, Ayal [23] Stokes, Paul R. A. [25] [26] Sumiyoshi, Tomiki [27] Torres, Ivan J. [28] Van Rheenen, Tamsyn E. [29] [30] Yatham, Lakshmi N. [28] Young, Allan H. [25] [26] Vieta, Eduard [5] [6] [7] [8] [9] Hasler, Gregor [4]

Affiliations

[1] Frederiksberg Univ Hosp, NEAD Ctr, Psychiat Ctr Copenhagen, Mental Hlth Serv, Hovedvejen 17, DK-2000 Frederiksberg, Denmark

[NORA names:

Capital Region of Denmark

[2] Copenhagen Univ Hosp, Copenhagen Affect Disorder Res Ctr CADIC, Psychiat Ctr Copenhagen, Copenhagen, Denmark

[NORA names:

KU University of Copenhagen

[3] Univ Genoa, Sect Psychiat, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy

[NORA names:

[4] Univ Fribourg, Psychiat Res Unit, Fribourg, Switzerland

[NORA names:

[5] Univ Barcelona, Hosp Clin, Clin Inst Neurosci, IDIBAPS,CIBERSAM, Barcelona, Spain

[NORA names:

(... more)

[6] Univ Barcelona, Hosp Clin, Clin Inst Neurosci, IDIBAPS,CIBERSAM, Barcelona, Spain

[NORA names: Spain; Europe, EU; OECD];

[7] Univ Barcelona, Hosp Clin, Clin Inst Neurosci, IDIBAPS,CIBERSAM, Barcelona, Spain

[NORA names: Spain; Europe, EU; OECD];

[8] Univ Barcelona, Hosp Clin, Clin Inst Neurosci, IDIBAPS,CIBERSAM, Barcelona, Spain

[NORA names: Spain; Europe, EU; OECD];

[9] Univ Barcelona, Hosp Clin, Clin Inst Neurosci, IDIBAPS,CIBERSAM, Barcelona, Spain

[NORA names: Spain; Europe, EU; OECD];

[10] Queens Univ, Dept Psychol, Kingston, ON, Canada

[NORA names: Canada; America, North; OECD];

[11] Univ Valencia, Dept Med, Valencia, Spain

[NORA names: Spain; Europe, EU; OECD];

[12] Brigham & Womens Hosp, Dept Psychiat, Boston, MA USA

[NORA names: United States; America, North; OECD];

[13] Harvard Med Sch, Dept Psychiat, Boston, MA USA

[NORA names: United States; America, North; OECD];

[14] Brigham & Womens Hosp, Dept Psychiat, Boston, MA USA

[NORA names: United States; America, North; OECD];

[15] Deakin Univ, IMPACT Strateg Res Ctr Innovat Mental & Phys Hlth, Geelong, Vic, Australia

[NORA names: Australia; Oceania; OECD];

[16] Univ Med Ctr Utrecht, UMC Utrecht Brain Ctr, Dept Psychiat, Utrecht, Netherlands

[NORA names: Netherlands; Europe, EU; OECD];

[17] Univ Med Ctr Utrecht, UMC Utrecht Brain Ctr, Dept Psychiat, Utrecht, Netherlands

[NORA names: Netherlands; Europe, EU; OECD];

[18] Univ Otago, Dept Psychol Med, Christchurch, New Zealand

[NORA names: New Zealand; Oceania; OECD];

[19] Newcastle Univ, Translat & Clin Res Inst, Fac Med Sci, Newcastle Upon Tyne, England

[NORA names: United Kingdom; Europe, Non-EU; OECD];

[20] Univ Sao Paulo, Hosp Clin, Inst Psychiat, Fac Med,Bipolar Disorder Res Program, Sao Paulo, Brazil

[NORA names: Brazil; America, South];

[21] McLean Hosp, Schizophrenia & Bipolar Disorder Program, Belmont, MA USA

[NORA names: United States; America, North; OECD];

[22] Univ Antioquia, Res Grp Psychiat, Dept Psychiat, Medellin, Colombia

[NORA names: Colombia; America, South; OECD];

[23] Univ Toronto, Brain & Cognit Discovery Fdn, Mood Disorders Psychopharmacol Unit, Toronto, ON, Canada

[NORA names: Canada; America, North; OECD];

[24] Univ Alberta, Dept Psychiat, Edmonton, AB, Canada

[NORA names: Canada; America, North; OECD];

[25] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, London, England

[NORA names: United Kingdom; Europe, Non-EU; OECD];

[26] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, London, England

[NORA names: United Kingdom; Europe, Non-EU; OECD];

[27] Natl Inst Mental Hlth, Natl Ctr Neurol & Psychiat, Dept Prevent Intervent Psychiat Disorders, Tokyo, Japan

[NORA names: Japan; Asia, East; OECD];

[28] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada

[NORA names: Canada; America, North; OECD];

[29] Swinburne Univ, Fac Hlth Arts & Design, Ctr Mental Hlth, Melbourne, Vic, Australia

[NORA names: Australia; Oceania; OECD];

[30] Univ Melbourne, Melbourne Neuropsychiat Ctr, Dept Psychiat, Carlton, Vic, Australia

[NORA names: Australia; Oceania; OECD]

Abstract

BackgroundAbnormalities 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.MethodsWe 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.ResultsSeventeen 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.ConclusionsMethylphenidate 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.

Keywords

ISBD task force, attention-deficit hyperactivity disorder, cognitive impairment, bipolar disorder, medication, recommendations, systematic review

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