REVIEW OF: Chen L and Du W, Psychiatry Investig 2025;22(2):140–147

STUDY TYPE: Open-label RCT

When choosing between stimulant and non-stimulant treatment for ADHD, clinicians often balance symptom control against tolerability and comorbidity. Nobody expects atomoxetine to beat methylphenidate for core ADHD symptoms; that battle was settled years ago. But this head-to-head trial adds detail on how the two stack up regarding executive function and emotional symptoms.

Sixty medication-naive children ages 6–14 with ADHD were randomized to sustained-release methylphenidate or atomoxetine and followed for 12 weeks. Doses were flexibly titrated from 18 mg to 54 mg (for methylphenidate) and from 12.5 mg to 1.2 mg/kg over 4 weeks (for atomoxetine). Outcomes included parent-rated ADHD symptoms, objective attention testing, emotional and behavioral symptoms, and executive function measures.

Both medications improved ADHD symptoms, but methylphenidate consistently produced larger gains. Methylphenidate also led to stronger reductions in hyperactivity and impulsivity, and greater improvements on executive function tasks related to cognitive flexibility (eg, on the Wisconsin Card Sorting Task). Atomoxetine, however, showed relative advantages for anxiety-related and psychosomatic symptoms.

CARLAT TAKE

Methylphenidate remains the strongest first-line option for core ADHD symptoms and executive dysfunction. If anxiety is prominent, stimulants are poorly tolerated, or families want a non-stimulant option, atomoxetine is a reasonable choice. Start with methylphenidate for most kids. If that’s ineffective, try dextroamphetamine as a second-line choice. When anxiety or tolerability changes the equation, try therapy and either supplement with an SSRI (if needed) or consider adding or pivoting to atomoxetine.