A head-to-head comparison of two commonly prescribed stimulants for Attention Deficit Hyperactivity Disorder found that dexamphetamine and methylphenidate produce comparable improvements in symptoms, but differ in their impact on weight over a 12-month period, according to a study published on Jul. 17.
The randomized, open-label trial was conducted at a pediatric clinic in New South Wales, Australia, between 2016 and 2020. It enrolled 100 stimulant-naïve children and adolescents with ADHD who were assigned to receive either immediate-release dexamphetamine or methylphenidate tablets. After an initial four-week dose adjustment period, further changes to medication were based on clinical indications or family preference. Participants were followed up at three, six, and twelve months after starting treatment.
The study reported that both medications resulted in similar improvements in attention deficit and hyperactivity symptoms as well as oppositional or defiant behavior during the initial four weeks of treatment. There were no statistically significant differences between the groups regarding symptom response.
However, side-effect assessment indicated that dexamphetamine was associated with greater weight loss compared to methylphenidate. Weight loss peaked after three months of dexamphetamine treatment. At the end of twelve months, participants taking methylphenidate had gained an average of 1.26 kilograms, while those on dexamphetamine had lost an average of 0.84 kilograms among those who remained on their allocated medication with complete follow-up data.
The trial also found that most participants did not require a change in medication during the study period, and adverse effects leading to changes—mainly appetite suppression, behavioral change, and sleep difficulty—were similar across both groups.
Researchers noted several limitations including its single-clinician design and open-label methodology, which may have influenced dose adjustments or reporting of adverse effects due to clinician or participant expectations. The study relied on pragmatic clinical assessments rather than formal diagnostic interviews or standardized research tools; conditions such as autism spectrum disorder or anxiety were not systematically recorded as stratification variables; only about half had complete weekly teacher-rated symptom data; no formal intention-to-treat analysis was performed; and it was not specifically powered to detect modest differences in long-term medication persistence.
