Dexamphetamine and methylphenidate work similarly for ADHD but differ in weight effects

By Dr. Sanchari Sinha Dutta, Ph.D.Reviewed by Lauren HardakerJul 17 2026

Head-to-head comparison of two commonly prescribed ADHD stimulants found comparable symptom response but differences in weight outcomes over 12 months.

Study: A Randomised Open-Label Comparison of Dexamphetamine and Methylphenidate in Children With Attention Deficit Hyperactivity Disorder (ADHD): Symptom Response, Adherence and Weight Impact Over 12 Months. Image credit: Jack_the_sparow/Shutterstock.com

Stimulant medications dexamphetamine and methylphenidate have comparable efficacy in improving symptoms in children and adolescents with Attention Deficit Hyperactivity Disorder, reported by a randomized, open-label trial published in the Journal of Pediatrics and Child Health.

Balancing symptom control with treatment side effects

Attention Deficit Hyperactivity Disorder (ADHD) is a childhood neurodevelopmental disorder, characterized by persistent symptoms of inattention, hyperactivity, and impulsivity that cause functional impairment. The condition is generally treated with behavioral, educational, and family-based interventions. However, if symptoms persist even after these interventions, treatment with stimulant medications may be needed.

Methylphenidate and dexamphetamine are the most commonly used stimulant medications for ADHD. However, these medications are associated with clinically relevant side-effects, including appetite suppression, weight loss, and potential effects on growth. Evidence regarding cardiovascular safety also highlights the importance of monitoring blood pressure and heart rate during treatment. Recent evidence also highlights the need for monitoring height, weight, blood pressure, and heart rate during stimulant treatment.

Studies comparing therapeutic efficacy and safety of methylphenidate and dexamphetamine are limited in number. Moreover, these studies were either short-term or did not maintain randomized allocation over the long term, leaving ongoing management to personal preference.

Given the importance of randomized treatment allocation in evaluating adherence, clinical outcomes, and side-effects, a randomized, open-label trial was conducted in a pediatric clinic in New South Wales, Australia, to compare the therapeutic efficacy and safety profiles of dexamphetamine and methylphenidate treatment in children and adolescents with ADHD.

Randomized trial compared first-line ADHD stimulant treatments

The trial, conducted between 2016 and 2020, enrolled a total of 100 stimulant-naïve children and adolescents with ADHD. The participants were randomized at a 1:1 ratio to receive immediate-release tablets of either dexamphetamine or methylphenidate. The initial dose adjustment was continued for four weeks.

After the initial 4-week period, adjustments to medication were done according to clinical indications or family preference. Participants were followed-up at 3, 6, and 12 months after treatment initiation. Under the study protocol, switching to a modified-release formulation of the allocated stimulant, or from dexamphetamine to lisdexamfetamine, was considered remaining on the allocated medication.

Both stimulants achieved similar symptom improvement

Of 100 initially randomized participants, 62 remained within their originally allocated stimulant group, as defined by the study protocol, by 12 months.

The assessment of symptoms revealed that both medications produced comparable improvements in attention deficit and hyperactivity symptoms, as well as oppositional or defiant behavior during the initial four-week dose-titration period, with no statistically significant differences between groups.

The assessment of side-effects indicated that the dexamphetamine treatment is associated with greater weight loss than the methylphenidate treatment. The weight loss was highest after 3 months of dexamphetamine treatment. At 12 months, participants allocated to methylphenidate had gained 1.26 kg, and those allocated to dexamphetamine had lost 0.84 kg. These weight analyses included only participants who remained on their allocated medication and had complete follow-up data.

Findings support either stimulant as an initial option

This randomized, open-label trial reveals that both dexamphetamine and methylphenidate produced comparable short-term improvements in ADHD symptoms during the initial dose-titration period. Over 12 months, there was no statistically significant difference in the proportion of participants remaining on their allocated medication. Compared to methylphenidate, treatment with dexamphetamine was associated with greater weight loss.

The trial also reports that the majority of participants did not require a change in medication, and that clinically relevant adverse effects leading to medication change were similar across groups and were predominantly appetite suppression, behavioral change, and sleep difficulty.

Overall, the trial findings provide a scientific basis for clinical decision-making and suggest that either medication may be considered as an initial stimulant in specialist practice, although methylphenidate may be preferred when weight loss is a particular concern.

Further research should clarify long-term growth effects

The trial also has several important limitations that should be considered when interpreting the findings. Because it was conducted by a single clinician and used an open-label design, decisions about dose adjustments, medication changes and the reporting of adverse effects may have been influenced by clinician or participant expectations.

The study also relied on pragmatic clinical assessment rather than formal diagnostic interviews or standardized research tools, and although autism spectrum disorder, anxiety and eating-related problems were considered during the initial assessment, these conditions were not systematically recorded as stratification variables.

In addition, only around half of participants had complete weekly teacher-rated symptom data, no formal intention-to-treat analysis was performed, and the study was not specifically powered to detect modest differences in long-term medication persistence. 

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