Atomoxetine-associated Raynaud’s phenomenon in children: an under-recognized risk of non-stimulant ADHD therapy

Raynaud’s phenomenon (RP) is an increasingly recognized yet still underreported adverse effect of ADHD pharmacotherapy. Whereas stimulant-associated RP is well documented, atomoxetine-related RP has surfaced only in isolated pediatric cases, leaving a gap in our understanding of non-stimulant toxicity. This narrative review reports the first Asian pediatric case identified in English- and regional-language literature and synthesizes the global evidence base, integrating five pediatric cases, targeted literature retrieval, and disproportionality analyses of FAERS and WHO VigiBase. Atomoxetine carries a consistent pharmacovigilance signal for RP. Beyond the elevation of synaptic cleft norepinephrine, the five cases point to suspected contributors: plasma drug concentration, CYP2D6-mediated metabolic variability—particularly relevant in East Asian populations—and individual susceptibility with superimposed triggers. Onset latency is highly variable (hours to years), and the course in reported cases is milder and fully reversible, without digital ulceration, features consistent with, though not determined by, the sustained, gradual peripheral noradrenergic elevation produced by selective norepinephrine transporter inhibition, in contrast to the rapid catecholamine surges typical of stimulants. These findings call for longitudinal vigilance beyond the titration phase, prompt exclusion of secondary causes, and systematic pharmacovigilance reporting.