The effect of atomoxetine and methylphenidate on emotional dysregulation in children with attention deficit/hyperactivity disorder: a multicenter randomized clinical trial
Yuan Gao, Zhaomin Wu, Binrang Yang, Wai Chen, Chen Dang, Yu Zhu, Meirong Pan, Min Dong, Haimei Li, Mengjie Zhao, Xinxin Yue, Haifei Guo, Shan Fu, Yi Su, Yufeng Wang, Qiujin Qian, Li Sun, Lu LiuBackground
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.