AIM: Stimulant medications dexamphetamine and methylphenidate are well-established for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), but few studies directly compare their efficacy. We aimed to compare the therapeutic and adverse effects of immediate-release formulations of dexamphetamine and methylphenidate during the initial treatment of children with ADHD. METHODS: This open-label study was conducted in public and private specialist paediatric clinics in New South Wales, Australia, between 2016 and 2020. One hundred stimulant-naïve children and adolescents with DSM-5-confirmed ADHD were randomised 1:1 to dexamphetamine or methylphenidate. ADHD diagnosis was based on detailed clinical assessment supported by parent and teacher DSM-5-based ratings. Dose titration followed a standardised 4-week weight-based protocol monitored with weekly school-based IOWA Conners ratings, after which dose adjustment or switching was made as clinically indicated. Participants were followed for 12 months. RESULTS: Study participants (mean age 9.08 SD 2.87 years; range 4.5-16.4 years; 73% male) showed significant ADHD symptom improvement on either medication at all time periods (p = 0.001), with no significant between-group difference on repeated-measures ANOVA. At 12 months, 62 participants remained on their allocated medication, with no apparent preference between methylphenidate and dexamphetamine (34/50 68% vs. 28/50 56%, p = 0.15). Both medications were associated with weight loss which was greater on dexamphetamine at 3 months (-1.44 SD 2.42 kg vs. -0.31 SD 0.97 kg; p = 0.005). CONCLUSIONS: Stimulant medications dexamphetamine and methylphenidate appear comparable in short-term symptom response and 12-month persistence after initial randomised allocation, but dexamphetamine may be associated with greater weight loss. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry number: ACTRN12616000569404.
Poulton et al. (Tue,) studied this question.