@article{ea625536f7b14a6f9e9bcca8ec889e2d,
title = "Long-Term Treatment With Extended-Release Methylphenidate Treatment in Children Aged 4 to <6 Years",
abstract = "Objective: To investigate long-term (12-month) safety and symptom control of extended-release methylphenidate (MPH-MLR) in children aged 4 to <6 years after treatment optimization. Method: A total of 90 children aged 4 to <6 years with attention-deficit/hyperactivity disorder (ADHD) were enrolled from 2 MPH-MLR studies. Treatment-emergent adverse events (TEAEs) and ADHD symptom control were assessed in the safety population (n = 89) and modeled with mixed model analyses. Results: Most TEAEs (89.9%) were rated by investigators as of mild or moderate severity. One serious AE was reported (unrelated to study drug). Ten children discontinued because of TEAEs. Two discontinued because of weight loss; no significant increase in the rate of underweight children from baseline to endpoint was observed. Overall, 18% lost weight and 18% reported decreased appetite. Weight and height z scores and obesity rates decreased significantly from baseline to endpoint. Insomnia was reported (9%); none of these children discontinued. Sleep quality did not change significantly. Hypertension was reported (6.7%); none of these children dropped out. Diastolic, but not systolic, blood pressure increased significantly during the follow-up. Control of ADHD symptoms was maintained throughout follow-up. Conclusion: These data contribute to the understanding of the long-term safety of an extended-release stimulant in children 4 to <6 years of age. The observed risk of a TEAE-related discontinuation was ∼11%. TEAEs were not dose related, and most were of mild to moderate severity. Symptom control was maintained through the year-long study. Clinical trial registration information: A 12-Month Open Label Safety Study of Aptensio XR{\textregistered} in Children Ages 4-5 Years Diagnosed With ADHD (EF004); https://clinicaltrials.gov; NCT02677519.",
keywords = "ADHD, methylphenidate, preschool children, safety",
author = "Childress, {Ann C.} and Foehl, {Henry C.} and Newcorn, {Jeffrey H.} and Faraone, {Stephen V.} and Benjamin Levinson and Adjei, {Akwete L.}",
note = "Funding Information: The authors would like to acknowledge the contributions of all study participants, their parents/guardians, and the investigators. The authors wish to thank Linda Wagner, PharmD, Excel Medical Affairs / Scientific Solutions at Envision Pharma Group, Fairfield, Connecticut, for assistance with manuscript preparation; assistance was funded by Rhodes Pharmaceuticals L.P. Funding Information: This study was funded by Rhodes Pharmaceuticals, L.P., Coventry, Rhode Island. Rhodes reviewed and provided feedback on the paper to the authors. Formal analyses were conducted by Accenture Life Sciences (primary) and Dr. Foehl (post hoc) with funding provided by Rhodes Pharmaceuticals L.P. The authors had full editorial control of the paper and provided their final approval of all content. Author Contributions Investigation: Childress, Foehl, Newcorn, Faraone, Levinson, Adjei Visualization: Childress, Foehl, Newcorn, Faraone, Levinson, Adjei Writing ? original draft: Childress, Foehl, Newcorn, Faraone, Levinson, Adjei Writing ? review and editing: Childress, Foehl, Newcorn, Faraone, Levinson, Adjei Formal analyses were conducted by Accenture Life Sciences (primary) and Dr. Foehl (post hoc) with funding provided by Rhodes Pharmaceuticals L.P. The authors would like to acknowledge the contributions of all study participants, their parents/guardians, and the investigators. The authors wish to thank Linda Wagner, PharmD, Excel Medical Affairs / Scientific Solutions at Envision Pharma Group, Fairfield, Connecticut, for assistance with manuscript preparation; assistance was funded by Rhodes Pharmaceuticals L.P. Disclosure: Dr. Childress has received research support from AEVI, Akili, Arbor, Emalex, Ironshore, KemPharm, Lundbeck, Neos, Otsuka, Purdue, Rhodes Pharmaceuticals L.P., Servier, Shire (a Takeda company), Sunovion, Supernus, and Tris; has served as a consultant to and/or advisory board member for and honoraria from AEVI, Akili, Arbor, Ironshore, KemPharm, Neos, Purdue, Rhodes Pharmaceuticals L.P., Shire, Sunovion, Supernus, and Tris; has received payment for lectures from Ironshore, Neos, Pfizer, Shire, Supernus, Takeda, and Tris; and has provided writing assistance on projects from Arbor, Ironshore, Neos, Purdue, Rhodes Pharmaceuticals L.P., Shire, Sunovion, Takeda, and Tris. Dr. Foehl has served as a consultant to Rhodes Pharmaceuticals L.P. Dr. Newcorn has served as a consultant to and/or advisory board member for Adlon Therapeutics, Arbor, Cingulate Therapeutics, Corium, Esai. Ironshore, Lundbeck, Medice, Mind Medicine, MyriadNLS, OnDosis, Rhodes, Shire/Takeda, and Supernus; has received research support from Otsuka, Shire, Supernus; has received honoraria for disease state lectures from Shire; and has served as a consultant for the US National Football League. Dr. Faraone has received support from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602805, the European Union's Horizon 2020 research and innovation programme under grant agreements no 667302 and 728018, and the National Institute of Mental Health grants 5R01MH101519 and U01 MH109536-01. He has received income, potential income, and travel expenses, continuing education support, and/or research support from Akili Interactive Labs, Arbor, Genomind, Ironshore, Ondosis, Otsuka, Rhodes, Shire/Takeda, Sunovion, Supernus, Tris, and Vallon. 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 has received support from Alcobra, CogCubed, Eli Lilly and Co., Enzymotec, Janssen, KemPharm, Lundbeck/Takeda, McNeil, NeuroLifeSciences, Neurovance, Novartis, Pfizer, and Vaya. He has received 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 Program Director of www.adhdinadults.com. Dr. Levinson has served as a consultant to Rhodes Pharmaceuticals L.P. Dr. Adjei has reported being an employee of Rhodes Pharmaceuticals L.P. Funding Information: This study was funded by Rhodes Pharmaceuticals, L.P., Coventry, RI, USA . Rhodes reviewed and provided feedback on the paper to the authors. Formal analyses were conducted by Accenture Life Sciences (primary) and Dr. Foehl (post hoc) with funding provided by Rhodes Pharmaceuticals L.P. The authors had full editorial control of the paper and provided their final approval of all content. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2022",
month = jan,
doi = "10.1016/j.jaac.2021.03.019",
language = "English",
volume = "61",
pages = "80--92",
journal = "Journal of the American Academy of Child and Adolescent Psychiatry",
issn = "0890-8567",
publisher = "Elsevier Ltd.",
number = "1",
}