Alpha-2 Adrenergic Agonists in Attention Deficit Hyperactivity Disorder

Stimulants are the first-line of treatment for attention deficit hyperactivity disorder (ADHD) in children. Alpha-2 agonists; have been used to treat neuropsychiatric disorders in children for nearly 3 decades and are often used in patients when stimulants are not successful. This paper reviews the mode of action and findings of clonidine and guanfacine in the treatment of children with ADHD. Both clonidine and guanfacine demonstrate affinity for alpha-2A subtype receptors; however, clonidine also has affinity for alpha-2B and -2C subtypes. These differences in receptor affinity may underlie the differences in clinical effect, especially for cardiovascular effects and sedation. In addition, increased specificity for alpha-2A receptors for guanfacine appears to enhance prefrontal function compared with clonidine. Until recently, most neuropsychiatric studies with clonidine and guanfacine have focused on treating Tourette's syndrome and tic disorders. Beneficial effects on hyperactivity and impulsiveness in these studies suggest these drugs may be useful in patients with ADHD. Recent trials demonstrate that these 2 drugs are effective and well tolerated. Although both guanfacine and clonidine are associated with sedation, clonidine appears more likely to cause cardiovascular adverse effects. The alpha-2 agonists may be a viable option for treating children with ADHD, especially those who do not show a positive response to stimulants. (J Pediatr 2009;154:S32-S37)