Delayed/extended-release methylphenidate improves children's control of ADHD symptoms

Optimized dosing of delayed-release and extended-release methylphenidate increased children’s control of ADHD symptoms throughout the day, according to study results published in Journal of Clinical Psychiatry.

“HLD200, a delayed-release and extended-release formulation of methylphenidate [DR/ER- MPH; Jornay PM; Ironshore Pharmaceuticals & Development Inc.) approved by the [FDA] for the treatment of ADHD in individuals aged 6 years and older, is the first stimulant that is predicted to be absorbed primarily in the colon following evening administration without an immediate-release component,” Ann C. Childress, MD, of the Center for Psychiatry and Behavioral Medicine in Nevada, and colleagues wrote. “Because the colon is a less efficient site of absorption compared to the upper gastrointestinal tract, colonic absorption is predicted to underlie several of the pharmacokinetic properties of DR/ER- MPH, including a gradual ascending curve in the early morning, attenuated peak plasma concentration, protracted elimination phase into the evening and a dose-dependent duration of effect.”

Results of two prior phase 3 studies conducted among children with ADHD showed DR/ER- MPH treatment improved symptoms and functional impairment in the early morning, over a laboratory classroom test day and in the late afternoon/evening compared with placebo. In the current study, Childress and colleagues assessed the clinical significance of these improvements post hoc by evaluating response and remission thresholds and safety as they related to dose optimization. They analyzed data of children aged 6 to 12 years diagnosed with ADHD according to DSM-5 criteria who were included in an open-label, treatment-optimization phase of a phase 3 study of DR/ER-MPH, with enrollment between July 2015 and March 2016. Further, the researchers applied thresholds for response, anchored to the Clinical Global Impressions-Improvement scale, and remission to ADHD Rating Scale-IV, Before School Functioning Questionnaire and Parent Rating of Evening and Morning Behavior, Revised, Morning Subscale and Evening Subscale scores. They also assessed rate of response, remission and treatment-emergent adverse events by starting dose.

Results showed an increase of mean DR/ER-MPH dose from baseline to week 6 of 29.7 mg per day to 66.2 mg per day, respectively. Most participants reached response/remission thresholds at week 6. More participants who started on a 40-mg compared with a 20-mg dose reached thresholds at week 1 (P < .02). The researchers noted similar weekly treatment-emergent adverse event rates over the open-label period between starting doses.

“The results presented here are consistent with symptom and functional response and remission being realistic and achievable outcome goals with DR/ER-MPH when doses are optimized for control of ADHD symptoms and functional impairment throughout the day,” Childress and colleagues wrote.