A small Japanese trial found that each of three lisdexamfetamine dose regimens improved ADHD symptom ratings more than placebo. Its results do not identify one dose as best for every child, or establish that a higher assigned dose necessarily produced a larger benefit.
Ichikawa and colleagues randomized 76 children and adolescents aged 6–17 years to placebo or target lisdexamfetamine doses of 30, 50 or 70 mg daily. The double-blind study used a fixed-dose design and assessed change in ADHD Rating Scale IV total score as its primary endpoint.
This was human therapeutic research in a selected Japanese ADHD population. With approximately 18–20 participants per arm and four weeks of follow-up, the study was designed to assess short-term efficacy and tolerability rather than rare or delayed outcomes.
Mean symptom-score changes reported for the 30, 50 and 70 mg groups were approximately −16.4, −18.1 and −16.5 points, respectively, compared with −2.8 for placebo. All three active-versus-placebo primary comparisons were significant at p < 0.0001.
The numerical ordering does not establish that 50 mg is superior to 70 mg, or that the dose-response curve is flat. Those conclusions require appropriate direct comparisons and adequate precision. A significant comparison of each dose against placebo is a different statistical question from determining differences between active doses.
Common active-treatment adverse events included decreased appetite, headache and initial insomnia. No serious or severe treatment-emergent events were reported during the trial, but the small, short study cannot exclude such events in larger or longer-term use. It was industry funded.
The authors also noted that no active-treatment participants had the predominantly hyperactive/impulsive ADHD subtype. The findings therefore do not establish equal benefit across all presentations. Symptom-rating improvement is not a direct measure of school achievement, drug concentration or driving performance. The study supports efficacy of the tested regimens against placebo within its sample, while individual dose selection and long-term outcomes require separate evidence.
Read our analysis of longer-term Japanese lisdexamfetamine surveillance.
Phase II/III Study of Lisdexamfetamine Dimesylate in Japanese Pediatric Patients with Attention-Deficit/Hyperactivity Disorder. doi:10.1089/cap.2019.0076.