Toward Precision Medicine in ADHD.

Attention-Deficit Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental condition for which curative treatments are lacking. Whilst pharmacological treatments are generally effective and safe, there is considerable inter-individual variability among patients regarding treatment response, required dose, and tolerability. Many of the non-pharmacological treatments, which are preferred to drug-treatment by some patients, either lack efficacy for core symptoms or are associated with small effect sizes. No evidence-based decision tools are currently available to allocate pharmacological or psychosocial treatments based on the patient's clinical, environmental, cognitive, genetic, or biological characteristics. We systematically reviewed potential biomarkers that may help in diagnosing ADHD and/or stratifying ADHD into more homogeneous subgroups and/or predict clinical course, treatment response, and long-term outcome across the lifespan. Most work involved exploratory studies with cognitive, actigraphic and EEG diagnostic markers to predict ADHD, along with relatively few studies exploring markers to subtype ADHD and predict response to treatment. There is a critical need for multisite prospective carefully designed experimentally controlled or observational studies to identify biomarkers that index inter-individual variability and/or predict treatment response.
Competing Interests: JB has been in the past 3 years a consultant to/member of advisory board of / and/or speaker for Shire, Roche, Medice, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. LR has received grant or research support from, served as a consultant to, and served on the speakers' bureau of Eli Lilly and Co., Janssen, Medice, Novartis and Shire. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by LR have received unrestricted educational and research support from the following pharmaceutical companies: Eli Lilly and Co., Janssen, and Novartis. LR has received authorship royalties from Oxford Press and ArtMed and travel grants from Shire to take part in the 2018 APA annual meeting and from Novartis to take part of the 2016 AACAP annual meeting. Barbara Franke has received educational speaking fees from Medice and Shire. SB discloses that he has in the last 5 years acted as an author, consultant or lecturer for Shire, Medice, Roche, Eli Lilly, Prima Psychiatry, GLGroup, System Analytic, Ability Partner, Kompetento, Expo Medica, Clarion Healthcare, and Prophase. He receives royalties for text books and diagnostic tools from Huber/Hogrefe, Kohlhammer and UTB. DB serves as an unpaid scientific advisor for an EU-funded neurofeedback trial unrelated to the present work. TB served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Lundbeck, Medice, Neurim Pharmaceuticals, Novartis, Shire. He received conference support or speaker's fee by Lilly, Medice, Novartis and Shire. He has been involved in clinical trials conducted by Shire & Viforpharma. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships. DC served in an advisory or consultancy role for Medice, Novartis, Shire/Takeda. He received conference support or speaker's fee by Medice, Servier and Shire/Takeda. He has been involved in clinical trials conducted by Shire. He received royalties from Oxford University Press. The present work is unrelated to the above grants and relationships. In the past year, SF received income, potential income, travel expenses continuing education support and/or research support from Tris, Otsuka, Arbor, Ironshore, Shire, Akili, Enzymotec, Sunovion, Supernus and Genomind. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. In previous years, he received support from: Shire, Ironshore, Neurovance, Alcobra, Rhodes, CogCubed, KemPharm, Enzymotec, Akili, Neurolifesciences, Lundbeck/Takeda, Otsuka, McNeil, Janssen, Novartis, Pfizer and Eli Lilly. He also receives royalties from books published by Guilford Press: Straight Talk about Your Child's Mental Health, Oxford University Press: Schizophrenia: The Facts and Elsevier: ADHD: Non-Pharmacologic Interventions. He is principal investigator of www.adhdinadults.com. Guilherme V. Polanczyk has been in the past 3 years a consultant, member of advisory board, and/or speaker for Shire/Takeda and Medice. He received travel expenses for continuing education support from Shire/Takeda and royalties from Editora Manole. In the past three years, Jeffrey Newcorn is/has been an advisor and/or consultant for Adlon Therapeutics, Akili Interactive, Alcobra, Arbor, Cingulate Therapeutics, Enzymotec, KemPharm, Lundbeck/Takeda, Medice, NLS, Rhodes, Shire, and Supernus. He was a DSMB member for Pfizer and Sunovion, and received research funds from Enzymotec, Otsuka, Shire and Supernus. He also has received speaker fees from Shire for disease-state presentations, and served as a consultant for the US National Football League. BV has served as consultant to Medice and Teva Pharm. Markus Gleitz is an employee of Medice Arzneimittel Pütter GmbH & Co. KG. MS received research support from Supernus, Shire, and Akili Interactive labs and in the past year has served in a advisory or consultancy capacity to Genomind, NLS, Shire/Takeda, Supernus, and Sunovian. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer KAJ declared a shared affiliation with the author DC to the handling editor at the time of review.
(Copyright © 2022 Buitelaar, Bölte, Brandeis, Caye, Christmann, Cortese, Coghill, Faraone, Franke, Gleitz, Greven, Kooij, Leffa, Rommelse, Newcorn, Polanczyk, Rohde, Simonoff, Stein, Vitiello, Yazgan, Roesler, Doepfner and Banaschewski.)