Discussion
ADHD
SECONDARY
The reported data indicate that d-ATS was effective in the treatment of ADHD in children and adolescents, meeting all secondary endpoints. Throughout the DOP, treatment with d-ATS resulted in consistent improvement as measured by ADHD-RS-IV score, with a significant improvement versus placebo observed during the DBP. A significant difference between placebo and d-ATS treatment was also observed on the CPRS-R:S scale during the DBP, and significantly more patients treated with d-ATS versus placebo were considered responders according to the CGI-I scale. As reported previously, d-ATS met its primary endpoint in a pivotal phase 2 study, resulting in significant improvement versus placebo in ADHD symptoms from 2 through 12 hours postdose, as measured by SKAMP total score (Cutler et al., d-ATS has been observed to be safe and well tolerated. A systemic safety profile consistent with oral amphetamines was observed, according to this and previous reports (Cutler et al., These efficacy results are also supported by a The NNT values calculated for the selected endpoints indicate the clinical relevance of d-ATS treatment. Only three patients needed to be treated with d-ATS instead of placebo to observe one additional patient achieving a clinically meaningful change, that is, a 50% or greater reduction from baseline in ADHD-RS-IV score. Only two patients needed to be treated with d-ATS instead of placebo to observe one additional patient experiencing “much improved” or “very much improved” ADHD symptoms, as measured by CGI-I scores.The observed d-ATS efficacy is comparable to oral preparations of amphetamine and methylphenidate, with an observed effect size and NNT similar to those reported elsewhere. In a study investigating the efficacy of oral lisdexamfetamine and osmotic-release oral system methylphenidate in children and adolescents with ADHD, effect sizes for LS mean change in ADHD-RS-IV total score versus placebo were 1.80 and 1.26, respectively (Soutullo et al., One limitation of this study is its relatively short duration. Furthermore, the classroom setting does not perfectly replicate a typical elementary or secondary classroom, which limits the generalizability of the results. Although a carryover effect was investigated for the primary endpoint (Cutler et al., This analysis defined ≥30% as the lower threshold for ADHD-RS-IV response; however, some patients achieving a 30% change in ADHD-RS-IV score, particularly those with severe symptoms at baseline, may not experience clinical improvement (i.e., a CGI-I response) (Weiss et al., Transdermal delivery has the potential to provide several advantages over oral medications, including avoiding gastrointestinal side effects, allowing flexibility in treatment duration, providing an additional treatment option for patients who may not be able or willing to swallow medications, and enabling a simple visual check for treatment compliance (Findling and Dinh, 