An extended-release mixed-amphetamine-salts formulation improved ADHD symptom ratings more than placebo in a four-week pediatric trial. Adverse events were also more common with active treatment, so the efficacy result and tolerability findings need to be considered together.
Brams and colleagues randomized 264 children and adolescents aged 6–17 years to placebo or SHP465 mixed amphetamine salts. Active treatment was optimized within a 12.5–25 mg range. The primary endpoint was change in ADHD Rating Scale IV total score at week four; clinician-rated global improvement was the key secondary endpoint.
This was controlled human treatment research in diagnosed ADHD. Dose optimization within the active group did not independently randomize participants to the final dose that best suited them. Consequently, the study cannot establish a causal dose-response curve by comparing people who finished on different doses.
The primary symptom-score treatment difference favored SHP465 by 9.9 points, with a 95% confidence interval from 6.8 to 13.0 points in the direction of improvement. The primary and key secondary comparisons were significant at p < 0.001. Of the randomized participants, 234 completed the study.
Treatment-emergent adverse events were reported in 67.4% of the active-treatment safety group and 46.6% of the placebo safety group. Events meeting the paper’s frequency criteria included decreased appetite, insomnia, irritability, nausea and decreased weight. Mean pulse and blood-pressure increases were greater with active treatment. No serious treatment-emergent events were reported during this short trial.
The study was industry funded and included a predominantly male, predominantly white sample. Four weeks cannot establish long-term growth, cardiovascular or dependence outcomes, and a lack of serious events in this sample does not establish their impossibility.
Symptom ratings and global clinical improvement do not directly measure classroom attainment, driving or cognition in healthy people. Nor were they used to establish a blood amphetamine threshold. The defensible conclusion is a short-term benefit for the tested formulation and dose-optimization strategy, with a measurable tolerability burden in the same trial.
Read our analysis of a forced-dose SHP465 trial in adults.
SHP465 Mixed Amphetamine Salts in the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: Results of a Randomized, Double-Blind Placebo-Controlled Study. doi:10.1089/cap.2017.0053.