Adult Attention-Deficit/
Hyperactivity Disorder
Diagnosis, Treatment, and Implications
for Drug Development
__________
Kelsey R. Babik, Noah Ontjes,
Carol Berkower,
Sheena M. Posey Norris, and
Carolyn Shore, Rapporteurs
Forum on Drug Discovery,
Development, and Translation
Forum on Neuroscience and Nervous
System Disorders
Board on Health Sciences Policy
Health and Medicine Division
Proceedings of a Workshop
NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
This activity was supported by contracts between the National Academy of Sciences and Acadia Pharmaceuticals; Alzheimer’s Association; American Brain Coalition; American Neurological Association; Amgen Inc.; Association of American Medical Colleges; AstraZeneca; Biogen; Boehringer Ingelheim (Contract No. 755326); BrightFocus Foundation; Burroughs Wellcome Fund (Contract No. 1023129); California Institute for Regenerative Medicine; Cerevel Therapeutics; Cohen Veterans Bioscience; Department of Veteran Affairs (Contract No. 36C24E20C009); Eisai; Eli Lilly and Company; FasterCures, Milken Institute; Foundation for the National Institutes of Health; Friends of Cancer Research; Gatsby Charitable Foundation; Harmony Biosciences; Janssen Research & Development, LLC; Johnson & Johnson; Karuna Therapeutics; Lundbeck Research USA, Inc.; Medable Inc.; Merck & Co., Inc. (Contract No. MRLCPO-23-166623); Michael J. Fox Foundation for Parkinson’s Research; National Institutes of Health (Contract No. HHSN263201800029I; Task Order Nos. HHSN26300007 and 75N98024F00001): BRAIN Initiative, National Cancer Institute, National Center for Advancing Translational Sciences, National Center for Complementary and Integrative Health, National Eye Institute, National Institute of Allergy and Infectious Diseases, National Institute of Environmental Health Sciences, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, and National Institute on Drug Abuse, Office of the Director; National Multiple Sclerosis Society; National Science Foundation; New England Journal of Medicine; One Mind; Paul G. Allen Frontiers Group; Sanofi (Contract No. 77646387); Simons Foundation (Contract No. 995152); Takeda (Contract No. A62909); The George & Anne Ryan Institute for Neuroscience at the University of Rhode Island; U.S. Food and Drug Administration (Contract No. 1R13FD007302-01, Contract No. 1R13FD005362-01, and Contract No. 1R13FD008016); Wellcome Trust. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-71916-2
International Standard Book Number-10: 0-309-71916-X
Digital Object Identifier: https://doi.org/10.17226/27770
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2024. Adult attention-deficit/hyperactivity disorder: Diagnosis, treatment, and implications for drug development: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/27770.
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PLANNING COMMITTEE FOR A WORKSHOP ON ADULT ATTENTION-DEFICIT/HYPERACTIVITY DISORDER (ADHD): DIAGNOSIS, TREATMENT, AND IMPLICATIONS FOR DRUG DEVELOPMENT1
CARLOS BLANCO (Co-Chair), Director, Division of Epidemiology, Services, and Prevention Research, National Institute on Drug Abuse
CRAIG B. H. SURMAN (Co-Chair), Director, Clinical and Research Program in Adult ADHD, Massachusetts General Hospital; Associate Professor of Psychiatry, Harvard Medical School
AMY F. T. ARNSTEN, Albert E. Kent Professor of Neuroscience and Professor of Psychology, Yale University School of Medicine
ANDREA M. CHRONIS-TUSCANO, Joel and Kim Feller Professor of Psychology and Director of the SUCCEEDS: Students Understanding College Choices, Encouraging and Executing Decisions for Success program, University of Maryland, College Park
TALEED EL-SABAWI, Assistant Professor of Law, Florida International University; Visiting Assistant Professor of Law, St. Louis University School of Law; Research Scholar, O’Neill Institute for National and Global Health Law, Georgetown Law Center
EVELYN POLK GREEN, Immediate Past President, Attention Deficit Disorder Association; Past President, Children and Adults with ADHD
STEVE S. LEE, Professor of Psychology, Director of Clinical Psychology Training, University of California, Los Angeles
JAMES (JIMMY) LEONARD, Director Clinical Services, Maryland Poison Center; Associate Professor, University of Maryland School of Pharmacy
TAMARA ROSIER, Founder, ADHD Center of West Michigan; President, ADHD Coaches Organization
MATTHEW RUDORFER, Chief, Psychopharmacology, Somatic, and Integrated Treatment Research Program, National Institute of Mental Health
ALMUT G. WINTERSTEIN, Distinguished Professor of Pharmaceutical Outcomes and Policy, Director of the Center for Drug Evaluation and Safety, University of Florida
STEVIN H. ZORN, President and Chief Executive Officer, MindImmune Therapeutics, Inc.
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
Health and Medicine Division Staff
CAROLYN SHORE, Director, Forum on Drug Discovery, Development, and Translation
SHEENA M. POSEY NORRIS, Director, Forum on Neuroscience and Nervous System Disorders
KELSEY R. BABIK, Associate Program Officer
NOAH ONTJES, Associate Program Officer (starting February 2024)
MELVIN JOPPY, Senior Program Assistant
CLARE STROUD, Senior Director, Board on Health Sciences Policy
Consultants
CAROL BERKOWER, Science Writer
JONATHAN PAIK, Webcast Producer
MARK ROWLAND, Webcast Producer
KAT SMITH, Webcast Producer
FORUM ON DRUG DISCOVERY, DEVELOPMENT, AND TRANSLATION1
GREGORY SIMON (Co-Chair), Kaiser Permanente Washington Health Research Institute; University of Washington
ANN TAYLOR (Co-Chair), Retired
BARBARA E. BIERER, Harvard Medical School; Brigham and Women’s Hospital
LINDA BRADY, National Institute of Mental Health, NIH
JOHN BUSE, University of North Carolina, Chapel Hill School of Medicine
LUTHER T. CLARK, Merck & Co., Inc.
BARRY S. COLLER, The Rockefeller University
TAMMY R. L. COLLINS, Burroughs Wellcome Fund
THOMAS CURRAN, Children’s Mercy, Kansas City
RICHARD DAVEY, National Institute of Allergy and Infectious Diseases, NIH
KATHERINE DAWSON, Biogen
JAMES H. DOROSHOW, National Cancer Institute, NIH
JEFFREY M. DRAZEN, New England Journal of Medicine
STEVEN K. GALSON, Retired
CARLOS O. GARNER, Eli Lilly and Company
SALLY L. HODDER, West Virginia University
TESHEIA JOHNSON, Yale School of Medicine
LYRIC JORGENSON, Office of the Director, NIH
ESTHER KROFAH, FasterCures, Milken Institute
LISA M. LAVANGE, University of North Carolina
ARAN MAREE, Johnson & Johnson
CRISTIAN MASSACESI, AstraZeneca
ROSS MCKINNEY JR., Association of American Medical Colleges
JOSEPH P. MENETSKI, Foundation for the National Institutes of Health
ANAEZE C. OFFODILE II, Memorial Sloan Kettering Center
SALLY OKUN, Clinical Trials Transformation Initiative
ARTI RAI, Duke University School of Law
KLAUS ROMERO, Critical Path Institute
JONI RUTTER, National Center for Advancing Translational Sciences, NIH
SUSAN SCHAEFFER, The Patients’ Academy for Research Advocacy
ANANTHA SHEKHAR, University of Pittsburgh School of Medicine
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
ELLEN V. SIGAL, Friends of Cancer Research
MARK TAISEY, Amgen Inc.
AMIR TAMIZ, National Institute of Neurological Disorders and Stroke, NIH
PAMELA TENAERTS, Medable Inc.
JONATHAN WATANABE, University of California, Irvine School of Pharmacy and Pharmaceutical Sciences
ALASTAIR WOOD, Vanderbilt University
CRIS WOOLSTON, Sanofi
JOSEPH C. WU, Stanford University School of Medicine
Forum Staff
CAROLYN SHORE, Director, Forum on Drug Discovery, Development, and Translation
KYLE CAVAGNINI, Associate Program Officer
BRITTANY HSIAO, Associate Program Officer (until March 2024)
NOAH ONTJES, Associate Program Officer (starting February 2024)
MELVIN JOPPY, Senior Program Assistant
CLARE STROUD, Senior Director, Board on Health Sciences Policy
FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS1
FRANCES JENSEN (Co-Chair), University of Pennsylvania
JOHN KRYSTAL (Co-Chair), Yale University
RITA BALICE-GORDON, Muna Therapeutics
DEANNA BARCH, Washington University in St. Louis
DIANE BOVENKAMP, BrightFocus Foundation (as of August 2023)
KATJA BROSE, Chan Zuckerberg Initiative
TERESA BURACCHIO, Food and Drug Administration
SARAH CADDICK, The Gatsby Charitable Foundation
ROSA CANET-AVILÉS, California Institute for Regenerative Medicine (CIRM)
MARIA CARRILLO, Alzheimer’s Association
MICHAEL CHIANG, National Eye Institute
TIM COETZEE, National Multiple Sclerosis Society
BEVERLY DAVIDSON, University of Pennsylvania
NITA FARAHANY, Duke University
EVA FELDMAN, University of Michigan
BRIAN FISKE, The Michael J. Fox Foundation for Parkinson’s Research
JOSHUA GORDON, National Institute of Mental Health
MORTEN GRUNNET, Lundbeck
MAGALI HAAS, Cohen Veterans Bioscience
RICHARD HODES, National Institute on Aging
STUART HOFFMAN, Department of Veterans Affairs
YASMIN HURD, Icahn School of Medicine at Mount Sinai
STEVEN HYMAN, The Broad Institute of MIT and Harvard
MICHAEL IRIZARRY, Eisai Inc.
GEORGE KOOB, National Institute on Alcohol Abuse and Alcoholism
WALTER KOROSHETZ, National Institute of Neurological Disorders and Stroke
ROBERT MALENKA, Stanford University
HUSSEINI MANJI, Oxford University; Duke University; UK Government Mental Health Mission
HUGH MARSTON, Boehringer Ingelheim
BILL MARTIN, Janssen Research & Development
CAROLINE MONTOJO, Dana Foundation (as of March 2024)
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
JOHN NGAI, National Institute of Health’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN®) Initiative
GENTRY PATRICK, University of California San Diego
STEVE PAUL, Karuna Therapeutics
KATHRYN RICHMOND, Allen Institute
M. ELIZABETH ROSS, American Neurological Association
MARSIE ROSS, Harmony Biosciences
KATIE SALE, American Brain Coalition
RAYMOND SANCHEZ, Cerevel Therapeutics
TERRENCE SEJNOWSKI, Salk Institute for Biological Studies (as of August 2023)
SARAH SHEIKH, Takeda
SARAH SHNIDER, One Mind
DAVID SHURTLEFF, National Center for Complementary and Integrative Health
JOHN SPIRO, Simons Foundation
ALESSIO TRAVAGLIA, Foundation for the National Institutes of Health
NORA VOLKOW, National Institute on Drug Abuse
DOUG WILLIAMSON, Acadia Pharmaceuticals, Inc.
RICHARD WOYCHIK, National Institute of Environmental Health Sciences
STEVIN H. ZORN, MindImmune Therapeutics, Inc.
Forum Staff
SHEENA M. POSEY NORRIS, Director, Forum on Neuroscience and Nervous System Disorders
EVA CHILDERS, Program Officer
MAYA THIRKILL, Associate Program Officer (as of May 2023)
KIMBERLY OGUN, Senior Program Assistant (as of October 2023)
CHRISTIE BELL, Senior Finance Business Partner
CLARE STROUD, Senior Director, Board on Health Sciences Policy
Reviewers
This Proceedings of a Workshop was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.
We thank the following individuals for their review of this proceedings:
EVELYN POLK GREEN, Attention Deficit Disorder Association
AMELIA M. ARRIA, University of Maryland School of Public Health
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by BRADFORD H. GRAY, The Urban Institute (ret.). He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies.
We also thank staff member Alexandra Beatty for reading and providing helpful comments on this manuscript.
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Acknowledgments
Support from the sponsors of the Forum on Drug Discovery, Development, and Translation and the Forum on Neuroscience and Nervous System Disorders is crucial to support this and other work of the National Academies.
The National Academies staff wish to express gratitude to the Food and Drug Administration’s Center for Drug Evaluation and Research for supporting this workshop in part; to the speakers whose presentations and discussions helped inform workshop discussions on the diagnosis, treatment, and drug development for adult attention-deficit/hyperactivity disorder (ADHD); to the members of the planning committee for their work in developing the workshop agenda and shaping the discussions; and to additional National Academies staff, without whom this workshop and the accounting thereof would not have been possible: Christie Bell, Lori Brenig, Samantha Chao, Robert Day, Alexandra Molina, Marguerite Romatelli, and Taryn Young.
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Contents
History of ADHD Diagnosis and Treatment
The Regulatory Landscape of Adult ADHD
Organization of the Proceedings
2 ADHD DIAGNOSIS AND TREATMENT IN THE UNITED STATES
Exploring Current ADHD Diagnosis and Treatment
Reflections on Thirty Years as an ADHD Advocate
3 IMPACT OF MISDIAGNOSIS, BIAS, AND STIGMA
Stigma, Disbelief, and Inequity Surrounding Adult ADHD
Assessing Adult ADHD: Precision vs. Pragmatism
5 BALANCING RISKS AND BENEFITS OF ADHD TREATMENT FOR ADULTS
Current Pharmacologic and Nonpharmacologic Treatments
Balancing Risks and Benefits of Using ADHD Medications
Diversion and Misuse of ADHD Medication
6 POTENTIAL STRATEGIES AND IMPLICATIONS FOR DRUG DEVELOPMENT
Barriers to New Drug Development
Filling Gaps And Meeting Patients’ Needs
7 PUBLIC HEALTH CONSIDERATIONS AND HARM REDUCTION STRATEGIES
A Public Health Approach to ADHD
An Integrated Treatment Model for Adult ADHD
Harm Reduction Strategies to Curb Misuse
B BIOGRAPHICAL SKETCHES OF THE WORKSHOP PLANNING COMMITTEE, SPEAKERS, PANELISTS, AND STAFF
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Acronyms and Abbreviations
ADDA | Attention Deficit Disorder Association |
ADHD | attention-deficit/hyperactivity disorder |
APSARD | American Professional Society of ADHD and Related Disorders |
ASRS | Adult ADHD Self-Report Scale |
CBT | cognitive behavioral therapy |
CDC | Centers for Disease Control and Prevention |
CDER | Center for Drug Evaluation and Research |
CHADD | Children and Adults with ADHD |
CRF | corticotropin-releasing factor |
DEA | Drug Enforcement Administration |
DSM-5 | Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition |
ER | extended release |
FDA | Food and Drug Administration |
GAD-7 | Generalized Anxiety Disorder 7-item |
HII-5 | Hyperactivity, Impulsivity, Inattention Symptom Rating Scale |
IQ | intelligence quotient |
MPH | methylphenidate |
MTA | Multimodal Treatment of ADHD study |
NIH | National Institutes of Health |
PFC | prefrontal cortex |
PHQ-9 | Patient Health Questionnaire-9 |
SAMHSA | Substance Abuse and Mental Health Services Administration |
SNRI | selective norepinephrine reuptake inhibitor |
SDP | stimulant diversion prevention |
SUD | substance use disorder |