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A Practical, Evidence-informed Approach to Managing Stimulant-Refractory Attention Deficit Hyperactivity Disorder (ADHD)

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Abstract

Stimulants (methylphenidate or amphetamines) are the recommended first-line option for the pharmacological treatment of individuals with attention deficit hyperactivity disorder (ADHD). However, some patients with ADHD will not respond optimally to stimulants. Here, we discuss strategies to manage stimulant-refractory ADHD, based on the recommendations advanced in clinical guidelines, knowledge of expert practice in the field, and our own clinical recommendations, informed by a comprehensive literature search in PubMed, PsycInfo, EMBASE + EMBASE classic, OVID Medline, and Web of Science (up to 30 March 2021). We first highlight the importance of stimulant optimization as an effective strategy to increase response. We then discuss a series of factors that should be considered before using alternative pharmacological strategies for ADHD, including poor adherence, time action properties of stimulants (and wearing-off of effects), poor tolerability (that prevents the use of higher, more effective doses), excessive focus on or confounding from presence of comorbid non-ADHD symptoms, and tolerance. Finally, we consider the role of non-stimulants and combined pharmacological approaches. While the choice of medication for ADHD is still to a large extent based on a trial-and-error process, there are reasonably accepted data and guidelines to aid in clinical decision-making. It is hoped that advances in precision psychiatry in the years ahead will further guide prescribers to tailor medication choice to the specific characteristics of the patient.

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Authors and Affiliations

  1. School of Psychology, Centre for Innovation in Mental Health (CIMH), Faculty of Environmental and Life Sciences, University of Southampton, Highfield Campus, Building 44, Southampton, SO17 1BJ, UK

    Samuele Cortese

  2. Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK

    Samuele Cortese

  3. Solent NHS Trust, Southampton, UK

    Samuele Cortese

  4. Hassenfeld Children’s Hospital at NYU Langone, New York University Child Study Center, New York, NY, USA

    Samuele Cortese

  5. Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK

    Samuele Cortese

  6. Division of ADHD and Learning Disorders, Departments of Psychiatry and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Jeffrey H. Newcorn

  7. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia

    David Coghill

  8. Murdoch Children’s Research Institute, Melbourne, VIC, Australia

    David Coghill

  9. The Royal Children’s Hospital, Melbourne, VIC, Australia

    David Coghill

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  1. Samuele Cortese
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Correspondence to Samuele Cortese.

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SC declares honoraria and reimbursement for travel and accommodation expenses for lectures from the following non-profit associations: Association for Child and Adolescent Central Health (ACAMH), Canadian ADHD Alliance Resource (CADDRA), British Association of Pharmacology (BAP), and the Healthcare Convention for educational activity on ADHD. In the past year, JN has been an advisor and/or consultant for Adlon Therapeutics, Arbor, Cingulate Therapeutics, Corium, Eisai, Lundbeck, Medice, Myriad Neuroscience, NLS, OnDosis, Rhodes, Shire/Takeda, and Supernus. He has received research support from the National Institute on Drug Abuse (NIDA), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Adlon, Shire and Supernus. He also has received speaker fees from Shire/Takeda for disease-state presentations and has served as a consultant for the US National Football League. DC has received research support from the National Health and Medical Research Council (NHMRC) Australia, research support and/or honoraria from Shire/Takeda, Medice, and Servier, and royalties from Oxford University Press and Cambridge University Press.

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Cortese, S., Newcorn, J.H. & Coghill, D. A Practical, Evidence-informed Approach to Managing Stimulant-Refractory Attention Deficit Hyperactivity Disorder (ADHD). CNS Drugs 35, 1035–1051 (2021). https://doi.org/10.1007/s40263-021-00848-3

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