Interpreting Improvements in Emotional Lability with Delayed-Release and Extended-Release Methylphenidate Treatment in Children with Attention-Deficit/Hyperactivity Disorder

Abstract: Purpose: Emotional lability (EL) is commonly seen in individuals with attention-deficit/hyperactivity disorder (ADHD). A post hoc analysis found that DR/ER-MPH (formerly HLD200), an evening-dosed delayed-release and extended-release methylphenidate that is released in the colon and does not include an immediate-release component, improved scores on the Connors’ Global Index–Parent (CGI-P) EL subscale in two phase 3 trials of DR/ER-MPH in children. Herein, CGI-P EL scores were converted to age- and gender-adjusted standardized T-scores to help interpret EL improvements. Methods: T-scores were determined at baseline and Week 3 in the forced-dose HLD200-108 trial and at baseline and Week 6 of the HLD200-107 open-label phase. Proportions of participants meeting each threshold for EL severity for their gender and age (Average, High Average, Elevated, Very Elevated) were calculated, with Average generally indicating typical or absent concerns for the child’s age and gender. Results: At baseline in HLD200-108, 89% and 82% reported EL concerns (≥High Average) in DR/ER-MPH and placebo groups, respectively; of those that reported EL at baseline, 44% and 27% reported Average severity after 3 weeks. At baseline in HLD200-107, 81% of participants reported EL; of those that reported EL at baseline, 73% reported Average severity after 6 weeks. Conclusions: In this post hoc analysis, DR/ER-MPH treatment resulted in participants with baseline EL achieving scores indicating typical/absent concerns, possibly due to its smooth pharmacokinetic profile and/or dose-dependent duration of effect that can provide treatment effects from early morning to late afternoon/evening. Improvements in EL severity were more pronounced with continued DR/ER-MPH treatment.Short Description: DR/ER-MPH is an evening-dosed delayed-release and extended-release methylphenidate that is released in the colon; it has no immediate-release component and provides a dose-dependent duration of effect for individuals with attention-deficit/hyperactivity disorder (ADHD). This study evaluated gender-and age-adjusted emotional lability T-scores to help interpret emotional lability score improvements. DR/ER-MPH treatment resulted in participants with baseline emotional lability achieving scores indicating typical/absent emotional lability concerns, with more pronounced improvements observed with continued DR/ER-MPH treatment.Name of Sponsoring Organization(s): Ironshore Pharmaceuticals & Development, Inc., manufacturer of DR/ER-MPH (formerly HLD200)