Clinically Meaningful Improvements in Early Morning and Late Afternoon/Evening Functional Impairment in Children with ADHD Treated with Delayed-Release and Extended-Release Methylphenidate

Timothy E Wilens; Stephen V Faraone; Paul G Hammerness; Steven R Pliszka; Cassandra L Uchida; Norberto J DeSousa; Floyd R Sallee; Bev Incledon; Jeffrey H Newcorn

doi:10.1177/10870547211020073

Clinically Meaningful Improvements in Early Morning and Late Afternoon/Evening Functional Impairment in Children with ADHD Treated with Delayed-Release and Extended-Release Methylphenidate

J Atten Disord. 2022 Mar;26(5):696-705. doi: 10.1177/10870547211020073. Epub 2021 Jun 4.

Authors

Timothy E Wilens^{1

2}, Stephen V Faraone³, Paul G Hammerness^{2

4}, Steven R Pliszka⁵, Cassandra L Uchida⁶, Norberto J DeSousa⁷, Floyd R Sallee⁸, Bev Incledon⁷, Jeffrey H Newcorn⁹

Affiliations

¹ Massachusetts General Hospital, Boston, MA, USA.
² Harvard Medical School, Boston, MA, USA.
³ SUNY Upstate Medical University, Syracuse, NY, USA.
⁴ Boston Children's Hospital, MA, USA.
⁵ The University of Texas Health Science Center at San Antonio, TX, USA.
⁶ Highland Therapeutics Inc., Toronto, ON, Canada.
⁷ Ironshore Pharmaceuticals & Development, Inc., Camana Bay, Grand Cayman, Cayman Islands.
⁸ Ironshore Pharmaceuticals Inc., Durham, NC, USA.
⁹ Mount Sinai Medical Center, New York, NY, USA.

Abstract

Objective: The Before School Functioning Questionnaire and Parent Rating of Evening and Morning Behavior-Revised assess early morning (BSFQ, PREMB-R AM subscale) and late afternoon/evening (PREMB-R PM subscale) functional impairment in children with ADHD. Clinically meaningful improvements were identified and applied to a trial of delayed-release and extended-release methylphenidate (DR/ER-MPH) in children with ADHD (NCT02520388) to determine if the statistically-determined improvements in functional impairment were also clinically meaningful.

Method: Clinically meaningful improvements in BSFQ/PREMB-R were established post hoc by receiver operating characteristics curves, using anchors of Clinical Global Impression-Improvement (CGI-I) = 1 and CGI-I ≤ 2. Percentages of participants achieving these thresholds were calculated.

Results: Thresholds for CGI-I = 1/CGI-I ≤ 2, respectively, were 27/20 (BSFQ), 5/3 (PREMB-R AM), and 9/5 (PREMB-R PM)-point decreases. More children achieved clinically meaningful improvements with DR/ER-MPH versus placebo (all p < .05).

Conclusion: DR/ER-MPH increased proportions of children achieving clinically meaningful improvements in BSFQ and PREMB-R.

Keywords: ADHD; BSFQ; PREMB-R; functional impairment; methylphenidate.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Attention Deficit Disorder with Hyperactivity* / drug therapy
Central Nervous System Stimulants* / therapeutic use
Child
Delayed-Action Preparations
Double-Blind Method
Humans
Methylphenidate* / therapeutic use
Treatment Outcome

Substances

Central Nervous System Stimulants
Delayed-Action Preparations
Methylphenidate

Associated data

ClinicalTrials.gov/NCT02520388