Investigators conducted the study between 2016 and 2020 in a pediatric clinic in New South Wales, Australia, where care was provided by a single academic pediatrician specializing in attention-deficit/hyperactivity disorder. The study enrolled 100 pediatric patients who had not previously received psychotropic medication. Attention-deficit/hyperactivity disorder diagnosis was based on clinical assessment supported by DSM-5-based parent and teacher ratings. All participants had ongoing impairment in more than one setting despite behavioral interventions. Participants ranged in age from 4.5 to 16.4 years, had a mean age of 9 years, and were predominantly male. Patients were excluded if attention-deficit/hyperactivity disorder was not the primary condition requiring treatment or if they had intellectual disability, previous psychotropic treatment, a contraindication to stimulant medication, or other clinical complexity requiring a different treatment priority.
Participants were randomly assigned 1:1 to immediate-release dexamphetamine or methylphenidate using concealed allocation. Investigators adjusted doses during a 4-week weight-based titration protocol according to tolerability. Teachers completed the IOWA Conners rating scale at baseline and weekly, assessing morning and afternoon inattention or overactivity and oppositional or defiant behavior. After titration, medication could be adjusted or changed when clinically indicated or according to family preference.
Symptom scores declined from baseline with both medications throughout titration. Repeated-measures analyses detected no statistically significant between-group differences on individual IOWA Conners items. However, incomplete weekly ratings reduced the analyzed sample to approximately 25 participants per group, and no formal intention-to-treat analysis was performed.
At 12 months, 34 of 50 participants assigned to methylphenidate and 28 of 50 assigned to dexamphetamine remained on their allocated medication. Switching to a modified-release formulation of the assigned stimulant counted as continued allocated treatment, as did switching from dexamphetamine to lisdexamfetamine. Follow-up data were unavailable for 18 participants.
The completer-only weight analysis excluded participants who changed stimulant medication, stopped treatment, had missing measurements, or were unavailable for follow-up. Among participants included in the weight analysis, weight decreased at 3 months by 1.44 kg with dexamphetamine and 0.31 kg with methylphenidate. At 12 months, weight had increased by 1.26 kg from baseline in the methylphenidate group and decreased by 0.84 kg in the dexamphetamine group. No statistically significant between-group difference in height gain was detected.
“[O]ur data should be interpreted as a clinically important signal rather than a definitive dose-adjusted causal estimate, because anthropometric analyses were not framed as multiplicity-corrected confirmatory analyses,” wrote lead author Alison Poulton of the Nepean Clinical School, Faculty of Medicine and Health, The University of Sydney, Kingswood, New South Wales, Australia, and the Department of Paediatrics, Nepean Hospital, Nepean Blue Mountains Local Health District, Kingswood, New South Wales, Australia, and colleagues.
Limitations included the open-label, single-clinician design, incomplete weekly symptom ratings, the absence of an intention-to-treat analysis, and anthropometric analyses that excluded participants who changed or stopped treatment, had missing measurements, or were unavailable for follow-up.
Disclosures: The study reported no funding. Alison Poulton reported personal fees from Medcast and Novartis, nonfinancial support from Shire/Takeda outside the submitted work, as well as book royalties from Disruptive Publishing. The other authors reported no conflicts of interest.