A prospective open-label trial of long-acting liquid methylphenidate for the treatment of attention deficit/hyperactivity disorder in intellectually capable adults with autism spectrum disorder

Abstract

Objectives: This treatment trial is aimed at assessing the short-term tolerability and efficacy of liquid-formulation extended-release methylphenidate (MPH-ER) for the treatment of attention deficit/hyperactivity disorder (ADHD) in adults with high-functioning autism spectrum disorder (HF-ASD).

Methods: A 6-week open-label trial (ClinicalTrials.gov: NCT02096952) was conducted in 15 HF-ASD adults (mean age 24.9 ± 4.6; male, 12 (80%)) suffering from moderate-severe ADHD. MPH-ER was administered based on a flexible titration schedule. Efficacy was assessed on clinician- and self-rated measures. Tolerability was assessed by documenting treatment-emergent adverse events (AEs) and other safety measures.

Results: Short-term MPH-ER treatment was associated with significant improvement in ADHD severity (Adult ADHD Investigator Symptom Report Scale (AISRS) mean change (MC), −22.8 ± 8.8, P < 0.001; Adult ADHD Self-Report Scale (ASRS) MC, −8.2 ± 15.3, P < 0.001). Twelve (80%) participants were deemed responders, based on ≥30% reduction in AISRS score and an ADHD Clinical Global Impression-Improvement score ≤2. MPH-ER was well-tolerated (treatment-limiting AEs, 1/15; severe AEs, 1/15) at mean dose of 48.7 ± 15 mg/day. AEs were transient and experienced by 13/15 (87%) participants at mild to moderate severity. Frequently reported AEs were as typically expected (headache (53%), insomnia (33%), anxiety (33%), decreased appetite (27%)).

Conclusions: Our findings suggest that MPH-ER is effective and well-tolerated in the treatment of ADHD in HF-ASD adults.

Keywords:

• ASD
• ADHD
• psychopharmacology
• methylphenidate
• open-label

Acknowledgements

The data acquisition for this analysis was funded by the Pfizer Corporation and conducted within the Alan and Lorraine Bressler Clinical and Research Programme for Autism Spectrum Disorder at Massachusetts General Hospital, Boston, Massachusetts. The manuscript and analysis of the data were further indirectly supported by the Alan and Lorraine Bressler Clinical and Research Programme for Autism Spectrum Disorder and the MGH Paediatric Psychopharmacology Council Fund.

Disclosure statement

None to declare.

Data availability

The data that support the findings of this study are available from the corresponding author, Dr. Gagan Joshi, upon reasonable request.

Additional information

Funding

Dr. Gagan Joshi has received research support from the Demarest Lloyd, Jr. Foundation, F. Hoffman-La Roche, the National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH) under Award Number K23MH100450, Pfizer and the Simons Centre for the Social Brain as a principal investigator (PI) for investigator-initiated studies. In addition, he has received research support from Duke University and Sunovion Pharmaceuticals as a site PI for multi-site trials. He has been a co-investigator for a clinical trial sponsored by the U.S. Department of Defence. He received an honorarium from the Governor's Council for Medical Research and Treatment of Autism in New Jersey for grant review activities and speaker’s honorariums from the American Academy of Child and Adolescent Psychiatry, Massachusetts General Hospital Psychiatry Academy, and the Medical Society of Delaware. Dr. Janet Wozniak has received research support from PCORI. She is the author of the book, ‘Is Your Child Bipolar’ published May 2008, Bantam Books. In 2015–2017, her spouse, Dr. John Winkelman, received an honorarium from Otsuka; royalties from Cambridge University Press and UptoDate; consultation fees from Advance Medical, FlexPharma and Merck; and research support from UCB Pharma, NeuroMetrix, and Luitpold. Dr. T. Atilla Ceranoglu has received research support from the Department of Defence, the Massachusetts Department of Mental Health, the National Institutes of Health, Lundbeck, Magceutics, Alfasigma USA, Inc., Pfizer Inc., Sunovion Pharmaceuticals Inc., and F. Hoffmann-LaRoche Ltd. Dr. Ceranoglu has also served as a member of an advisory board for the Jack Kent Cooke Foundation and as a consultant for L.E.K. Consulting LLC. Dr. Amy Yule has received grant support from the Massachusetts General Hospital Louis V. Gerstner III Research Scholar Award from 2014 to 2016. Dr. Yule is currently receiving funding through the American Academy of Child and Adolescent Psychiatry Physician Scientist Programme in Substance Abuse [K12DA000357-17). She was a consultant to the Phoenix House from 2015 to 2017 and is currently a consultant to the Gavin House (clinical services). Dr. Craig Surman has received, in his lifetime, consulting fees or honorarium from McNeil, Nutricia, Pfizer, Rhodes, Shire, Somaxon, Takeda, Sunovion, and NLS. He has also received payments for lectures for Alcobra, McNeil, Janssen, Janssen-Ortho, Novartis, Shire, GME Psychiatry and Reed/MGH Academy (funded by multiple companies). Royalties have been given to Dr. Surman from Berkeley/Penguin for ‘Fastminds’ How to Thrive if You have ADHD (or think you might)’ and from Humana/Springer for ‘ADHD in Adults: A Practical Guide to Evaluation and Management’. In addition, Dr. Surman has conducted clinical research at Massachusetts General Hospital supported by Abbot, Cephalon, Hilda and Preston Davis Foundation, Eli Lilly, Magceutics, Johnson & Johnson/McNeil, Lundbeck, Merck, Nordic Naturals. Dr. Ronna Fried has received research support from the Demarest Lloyd, Jr. Foundation, F. Hoffman-La Roche, and the FDA, as well as honoraria from the MGH Psychiatry Academy for tuition-funded CME courses. She has also been on an advisory board for Lundbeck. During previous years, Dr. Fried received research support from the National Institutes of Health and Shire. Dr. Joseph Biederman has received research support from the following sources: the Demarest Lloyd, Jr. Foundation, AACAP, The Department of Defence, Food & Drug Administration, Headspace, Lundbeck, Neurocentria Inc., NIDA, PamLab, Pfizer, Shire Pharmaceuticals Inc., Sunovion, and NIH. Dr. Biederman has a financial interest in Avekshan LLC, a company that develops treatments for attention deficit hyperactivity disorder (ADHD). His interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. Dr. Biederman’s programme has received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Ingenix, Prophase, Shire, Bracket Global, Sunovion, and Theravance; these royalties were paid to the Department of Psychiatry at MGH. In 2017, Dr. Biederman is a consultant for Aevi Genomics, Akili, Guidepoint, Ironshore, Medgenics, and Piper Jaffray. He is on the scientific advisory board for Alcobra and Shire. He received honoraria from the MGH Psychiatry Academy for tuition-funded CME courses. Through MGH corporate licencing, he has a US Patent (#14/027,676) for a non-stimulant treatment for ADHD, and a patent pending (#61/233,686) on a method to prevent stimulant abuse. In 2016, Dr. Biederman received honoraria from the MGH Psychiatry Academy for tuition-funded CME courses, and from Alcobra and APSARD. He was on the scientific advisory board for Arbour Pharmaceuticals. He was a consultant for Akili and Medgenics. He received research support from Merck and SPRITES. In 2015, Dr. Biederman received honoraria from the MGH Psychiatry Academy for tuition-funded CME courses, and from Avekshan. He received research support from Ironshore, Magceutics Inc., and Vaya Pharma/Enzymotec. In 2014, Dr. Biederman received honoraria from the MGH Psychiatry Academy for tuition-funded CME courses. He received research support from AACAP, Alcobra, Forest Research Institute, and Shire Pharmaceuticals Inc. In previous years, Dr. Biederman received research support, consultation fees, or speaker’s fees for/from the following additional sources: Abbott, Alza, APSARD, AstraZeneca, Boston University, Bristol Myers Squibb, Cambridge University Press, Celltech, Cephalon, The Children’s Hospital of Southwest Florida/Lee Memorial Health System, Cipher Pharmaceuticals Inc., Eli Lilly and Co., Esai, ElMindA, Fundacion Areces (Spain), Forest, Fundación Dr.Manuel Camelo A.C., Glaxo, Gliatech, Hastings Centre, Janssen, Juste Pharmaceutical Spain, McNeil, Medice Pharmaceuticals (Germany), Merck, MGH Psychiatry Academy, MMC Paediatric, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Phase V Communications, Physicians Academy, The Prechter Foundation, Quantia Communications, Reed Exhibitions, Shionogi Pharma Inc, Shire, the Spanish Child Psychiatry Association, The Stanley Foundation, UCB Pharma Inc., Veritas, and Wyeth. All other authors report no conflict of interest.