A rare randomized trial pits the two classic stimulants against each other for a full year
STUDY: Poulton A et al, Journal of Paediatrics and Child Health 2026
STUDY TYPE: Randomized, open-label trial
FUNDING: Independent
Background
There are two stimulants for ADHD: Amphetamines and methylphenidates, and over 30 branded variations on them. An earlier analysis suggested methylphenidates were safer for children, but few studies have compared them head-to-head.
The Study
- 100 stimulant-naive children with ADHD (mean age 9, 73% male) in New South Wales, Australia.
- Randomized to instant-release dextroamphetamine or methylphenidate, titrated over 4 weeks using a weight-based protocol, then the dose adjusted flexibly based on response.
- Followed for 12 months, with teacher-rated symptom scores (IOWA Conners scale) tracked throughout and weight and height measured at every visit.
Results
Benefits were similar at every time point for inattention and oppositional symptoms.
By 12 months, 62% of children were still on their original medication, with a similar rate on each drug (68% methylphenidate vs. 56% dexamphetamine).
Side Effects
Dextroamphetamine caused more weight loss (loss of 0.84 kg after 1 year, while methylphenidate lead to 1.26 kg weight gain). Sleep disruption, behavior change, and height changes were similar for both groups.
Discontinuations were worse for dextroamphetamine. Five children stopped stimulants altogether, four of them from the dextroamphetamine group.
Similar Past Trials
Surprisingly, there are only two prior head-to-head comparisons like this, and both used a cross-over design. One found similar efficacy in 48 children, using a flexible-dose design similar to the current trial. The other found greater efficacy with methylphenidate in 125 children, using a fixed dose design which assumed dextroamphetamine is twice as potent as methylphenidate (eg, 10 mg dextroamphetamine = 20 mg methylphenidate); possibly a false assumption.
Limitations
Open label, run by a single clinician, so bias in dose adjustments and switching decisions is possible. Weekly symptom data were only complete for about half the group, and the number of kids with full 12-month weight data was well below the original 100 enrolled. ADHD subtype and comorbidities weren’t tracked as formal variables.
Practice Implications
- This head-to-head comparison supports the general recommendation of starting with methylphenidate in children for its greater safety profile.
- Other studies find amphetamines have higher rates of psychosis, mania, insomnia, and misuse. For driving, only methylphenidate has robust data supporting improved performance.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
