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

This publication is available from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu.

Copyright 2024 by the National Academy of Sciences. National Academies of Sciences, Engineering, and Medicine and National Academies Press and the graphical logos for each are all trademarks of the National Academy of Sciences. All rights reserved.

Printed in the United States of America.

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.

The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president.

The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. John L. Anderson is president.

The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president.

The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The National Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine.

Learn more about the National Academies of Sciences, Engineering, and Medicine at www.nationalacademies.org.

Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process and it represents the position of the National Academies on the statement of task.

Proceedings published by the National Academies of Sciences, Engineering, and Medicine chronicle the presentations and discussions at a workshop, symposium, or other event convened by the National Academies. The statements and opinions contained in proceedings are those of the participants and are not endorsed by other participants, the planning committee, or the National Academies.

Rapid Expert Consultations published by the National Academies of Sciences, Engineering, and Medicine are authored by subject-matter experts on narrowly focused topics that can be supported by a body of evidence. The discussions contained in rapid expert consultations are considered those of the authors and do not contain policy recommendations. Rapid expert consultations are reviewed by the institution before release.

For information about other products and activities of the National Academies, please visit www.nationalacademies.org/about/whatwedo.

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:

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.

This page intentionally left blank.

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.

This page intentionally left blank.

Contents

ACRONYMS AND ABBREVIATIONS

1 INTRODUCTION

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

Misdiagnosis

Stigma, Disbelief, and Inequity Surrounding Adult ADHD

Assessing Adult ADHD: Precision vs. Pragmatism

4 SHARED DECISION-MAKING

Adopting Measurement-Based Care

Using Shared Decision Making

Accessing Resources

Leveraging Social Media to Educate Patients

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

Stimulant Drugs for ADHD

Nonstimulant Drugs for ADHD

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

Looking Toward the Future

REFERENCES

APPENDIXES

A WORKSHOP AGENDA

B BIOGRAPHICAL SKETCHES OF THE WORKSHOP PLANNING COMMITTEE, SPEAKERS, PANELISTS, AND STAFF

Box and Figures

BOX

1-1 Workshop Statement of Task

FIGURES

4-1 Tracking data from a patient undergoing ADHD treatment, comparing the HII-5 score to the PHQ-9 and GAD-7 scores

5-1 Comparison of methylphenidate-based stimulants or viloxazine nonstimulant to placebo on ADHD score in adults from two randomized double-blind studies

5-2 Number of stimulant prescriptions in the United States, 2012–2021

5-3 Pattern of nonmedical stimulant use among U.S. individuals ages 18–50

5-4 Association between stimulant treatment and substance use through adolescence into early adulthood

6-1 Attention and working memory dose-response curves

This page intentionally left blank.

Acronyms and Abbreviations