The effect of atomoxetine and methylphenidate on emotional dysregulation in children with attention deficit/hyperactivity disorder: a multicenter randomized clinical trial
In brief
Atomoxetine and methylphenidate similarly reduce emotional lability in children with ADHD
In a multicenter trial of 152 kids, both atomoxetine and methylphenidate lowered emotional lability scores significantly over four weeks, with no meaningful difference between the two drugs. The improvement persisted after accounting for overall ADHD symptom change, and was linked to increased amygdala-frontal connectivity, suggesting a distinct neural effect.
- Journal
- Journal of child psychology and psychiatry, and allied disciplines (Q1)
- Published
- 10 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Yuan Gao, Zhaomin Wu, Binrang Yang, Wai Chen, Chen Dang, Yu Zhu, et al.
- PMID
- 42576119
- DOI
- 10.1111/jcpp.70217
Why clinicians should know about it
- Picked for Pediatrics and Child Health (top studies of the week, 16 August 2026): High-quality evidence in a top journal
Abstract
BACKGROUND: This study aimed to compare the effects of atomoxetine (ATX) and methylphenidate (MPH) on emotional dysregulation (ED) in children with attention deficit/hyperactivity disorder (ADHD), and to explore potential neural correlates underlying treatment-related changes. METHODS: A total of 152 children with ADHD were randomly assigned to receive ATX (n = 76) or MPH (n = 76). After individualized dose titration, participants received a stable dose for 4 weeks. Emotional lability (EL) was the primary outcome, while emotion regulation strategies, ADHD symptoms, and overall illness severity were secondary outcomes. Mixed-effects linear models were applied to examine group differences across three time points (baseline, post-titration, and endpoint). Resting-state functional MRI data were acquired at baseline and endpoint and analyzed using whole-brain functional connectivity (FC) analysis with six amygdala subregions as seeds. TRIAL REGISTRATION: ChiCTR2200062905; approved on August 23, 2022. RESULTS: In both ATX and MPH groups, EL scores decreased significantly over time (β = -1.54, p < .001), with treatment effects in a similar range and no statistically significant between-group difference (MPH: d = -1.46; ATX: d = -0.93). After controlling for ADHD symptom improvement, treatment effects remained significant (β = -0.75, p < .001), suggesting that EL improvement was not solely accounted for by ADHD symptom reduction. Increased FC between the right basolateral amygdala and left orbital middle frontal gyrus (r = -0.46, p = .043), and between the left superficial amygdala and left middle cingulate cortex (r = -0.48, p = .031), was associated with EL changes and remained significant after controlling for ADHD symptom changes. No significant changes were found in self-reported emotion regulation strategies. CONCLUSIONS: ATX and MPH both alleviate ED in children with ADHD, and these effects are not solely accounted for by improvements in ADHD symptoms. Increased amygdala-centered FC may be associated with medication-related ED improvements.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.