Abstract Objective To characterize clinical presentations, management strategies and outcomes associated with extended-release guanfacine (ER guanfacine) overdose in pediatric patients presenting to a tertiary care pediatric emergency department (ED) supplemented with a systematic review of published pediatric cases. Methods A retrospective chart review included patients aged 0 to 18 years presenting with guanfacine overdose to a tertiary pediatric ED between August 2013 and July 2023. Data were extracted on demographics, cause of overdose, clinical features, management and outcomes. Concurrently, a systematic review using the population, exposure, and outcome approach searched MEDLINE and Embase (1974–November 2025) to consolidate existing case-report evidence on emergent management of guanfacine overdose in pediatric patients. Results Ten studies met inclusion criteria, describing eleven pediatric cases, mostly accidental with ingestions in younger children, with bradycardia and hypotension reported frequently. Management was supportive; naloxone produced variable benefit, and when used no deaths occurred. For the retrospective cohort, (n = 15; median age 14), 73% involved intentional ingestions and were frequently associated with psychiatric comorbidities. Bradycardia and hypotension were nearly universal; with some patients demonstrating transient hypertension. Treatment included intravenous fluids (87%) and atropine for symptomatic bradycardia (20%). Three patients required pediatric intensive care unit admission; none received naloxone. All patients recovered fully without mortality. Conclusion ER guanfacine overdose most commonly affects adolescents with underlying mental health conditions and presents with clinically significant cardiovascular depression. Management is supportive, emphasizing fluid resuscitation and cardiac monitoring. Findings support the need for standardized ED care pathways and integrated mental-health interventions.
