A direct comparison of two commonly prescribed ADHD stimulants showed similar symptom responses but differences in 12-month weight outcomes.
Study: A randomized, open-label comparison of desamphetamine and methylphenidate in children with attention-deficit hyperactivity disorder (ADHD): Effects on symptom response, adherence, and weight over 12 months. Image credit: Jack_the_sparrow/Shutterstock.com
The stimulants desamphetamine and methylphenidate have been found to be equally effective in improving symptoms in children and adolescents with attention-deficit hyperactivity disorder. Journal of Pediatrics and Child Health.
Balancing symptom control and treatment side effects
Attention-deficit/hyperactivity disorder (ADHD) is a childhood neurodevelopmental disorder characterized by persistent symptoms of inattention, hyperactivity, and impulsivity that lead to functional impairment. This condition is usually treated with behavioral, educational, and family-based interventions. However, if symptoms persist after these interventions, treatment with stimulants may be necessary.
Methylphenidate and desamphetamine are the most commonly used stimulants for ADHD. However, these drugs are associated with clinically relevant side effects, including appetite suppression, weight loss, and potential effects on growth. Evidence regarding cardiovascular safety also emphasizes the importance of monitoring blood pressure and heart rate during treatment. Recent evidence also highlights the need to monitor height, weight, blood pressure, and heart rate during stimulant treatment.
There are a limited number of studies comparing the therapeutic efficacy and safety of methylphenidate and dexamphetamine. Furthermore, these studies were short-term or did not maintain randomized assignment over time, leaving ongoing management to individual preference.
Given the importance of randomized treatment allocation in assessing adherence, clinical outcomes, and side effects, a randomized, open-label trial was conducted to compare the treatment efficacy and safety profile of desamphetamine and methylphenidate treatment for children and adolescents with ADHD at a pediatric clinic in New South Wales, Australia.
Randomized trials comparing first-line treatment with ADHD stimulants
The study was conducted from 2016 to 2020 and enrolled 100 children and adolescents with ADHD who had never used stimulants. Participants were randomized in a 1:1 ratio to receive immediate-release tablets of desamphetamine or methylphenidate. Initial dose titration continued for 4 weeks.
After an initial 4-week period, medication adjustments were made according to clinical indications or family wishes. Participants were followed up 3, 6, and 12 months after starting treatment. In the study protocol, switching to a modified-release formulation of the assigned stimulant or switching from dexamphetamine to lisdexamfetamine was considered continuation of the assigned drug therapy.
Both stimulants achieved similar symptom improvement
Of the first 100 participants randomized; Sixty-two remained within their originally assigned stimulant group as defined by the study protocol for up to 12 months.
Symptom evaluation revealed that during the initial 4-week dose escalation period, both drugs produced comparable improvements in attention-deficit and hyperactivity symptoms and defiant or defiant behavior, with no statistically significant differences between groups.
Evaluation of side effects showed that dexamphetamine treatment was associated with greater weight loss than methylphenidate treatment. The highest weight loss occurred after 3 months of dexamphetamine treatment. At 12 months, participants assigned methylphenidate gained 1.26 kg and participants assigned dexamphetamine lost 0.84 kg. These weight analyzes included only participants who continued on their assigned medication and had complete follow-up data.
Research supporting either stimulant as an initial option
In this randomized, open-label trial, both dexamphetamine and methylphenidate produced comparable short-term improvements in ADHD symptoms during the initial dose escalation period. There was no statistically significant difference in the proportion of participants remaining on their assigned medication over 12 months. Compared with methylphenidate, treatment with dexamphetamine was associated with greater weight loss.
The trial also reported that the majority of participants did not require medication changes and that clinically relevant side effects leading to medication changes were similar between groups, primarily appetite suppression, behavioral changes, and difficulty sleeping.
Overall, the study results provide a scientific basis for clinical decision-making and suggest that either drug may be considered as an initial stimulant in specialist practice, although methylphenidate may be preferred when weight loss is of particular concern.
Further research should reveal long-term growth effects
This study also has some important limitations that should be considered when interpreting the results. Because this study was conducted by a single clinician and used an open-label design, decisions regarding dose adjustments, drug changes, and reporting of side effects may have been influenced by clinician or participant expectations.
The study also relied on pragmatic clinical assessments rather than formal diagnostic interviews or standardized research tools, and although autism spectrum disorders, anxiety, and eating-related issues were considered during initial assessment, these conditions were not systematically recorded as stratifying variables.
Furthermore, only about half of the participants had complete weekly teacher-rated symptom data, no formal intention-to-treat analysis was conducted, and the study was not specifically equipped to detect small differences in long-term medication adherence.
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Reference magazines:
- Poulton, A. (2026). A randomized, open-label comparison of desamphetamine and methylphenidate in children with attention-deficit hyperactivity disorder (ADHD): Effects on symptom response, adherence, and weight over 12 months. Journal of Pediatrics and Child Health.Doi: https://doi.org/10.1111/jpc.70487 Digital. https://onlinelibrary.wiley.com/doi/10.1111/jpc.70487.
