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

Research output: Contribution to journalReviewResearchpeer-review

  • Zacharias K. Obel
  • Riccardo Gugliemo
  • Caterina del Mar Bonnin
  • Christopher R. Bowie
  • Vicente Balanzá-Martínez
  • Katherine E. Burdick
  • Andre F. Carvalho
  • Annemieke Dols
  • Katie Douglas
  • Peter Gallagher
  • Beny Lafer
  • Kathryn E. Lewandowski
  • Carlos López-Jaramillo
  • Anabel Martinez-Aran
  • Roger S. McIntyre
  • Richard J. Porter
  • Scot E. Purdon
  • Ayal Schaffer
  • Paul R.A. Stokes
  • Tomiki Sumiyoshi
  • Ivan J. Torres
  • Tamsyn E. Van Rheenen
  • Lakshmi N. Yatham
  • Allan H. Young
  • Eduard Vieta
  • Gregor Hasler

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.

Original languageEnglish
JournalBipolar Disorders
ISSN1398-5647
DOIs
Publication statusE-pub ahead of print - 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.

    Research areas

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

ID: 385267579