Alpha 2 Agonists: Clonidine and Guanfacine

This chapter examines α2-adrenergic agonists—clonidine and guanfacine—as antihypertensives repurposed for ADHD (Attention deficit hyperactivity disoder) and related neurodevelopmental presentations. Although both have been used clinically for decades, their ADHD approvals are relatively recent, and their shared receptor class masks meaningful differences. Clonidine is a broader, less selective α2 agonist with stronger systemic sympatholytic action, making it particularly useful for hyperarousal, sleep-onset problems, stimulant rebound, and aggression/irritability driven by heightened fight-or-flight activation in neurodivergent children. Guanfacine is more α2A-selective and centrally active; its acute effects reduce arousal, while its longer-term actions enhance executive functioning, working memory, and impulse control through modulation of noradrenergic–dopaminergic networks. The chapter summarises prescribing practice points: frequent adjunctive use with stimulants to improve efficacy and offset side-effects; slow titration from low doses; and mandatory cardiovascular screening and monitoring due to predictable effects on heart rate and blood pressure. Key adverse effects include sedation, hypotension, bradycardia, lethargy, nightmares, and occasional paradoxical agitation, especially in younger children. Clinical cautions address use in autonomic vulnerability, the high-risk nature of clonidine–guanfacine co-prescribing or combination with sedating agents, and the need for gradual tapering to avoid rebound hypertension.