Guanfacine in the Treatment of Attention – Deficit/Hyperactivity Disorder: Mechanisms, Clinical Evidence and Therapeutic Implications

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition associated with persistent impairments in attention and executive functioning. Although psychostimulants remain the most effective pharmacological treatment, not all patients tolerate them well, and a considerable proportion shows only partial response. For this reason, interest in non-stimulant medications, including guanfacine, has grown in recent years. Guanfacine, a selective α2A-adrenergic receptor agonist, primarily acts on prefrontal cortical networks involved in cognitive control. This review summarizes current evidence on its mechanism of action, clinical efficacy, and safety profile. Overall, available data indicate that guanfacine provides clinically meaningful benefits—particularly in pediatric populations and as adjunctive therapy—although its effect size is generally smaller than that of psychostimulants. Nevertheless, due to its favorable tolerability and distinct pharmacological profile, it represents a useful option within individualized treatment strategies.