Guanfacine and Clonidine: What Are Their Roles in ADHD Treatment in Children?

The α-2 agonists, guanfacine and clonidine, are used off-label by some clinicians for treating ADHD in children and adolescents, typically in patients who continue to have substantial disruptive behaviors, frequent tics, or sleep disturbances when they are treated with a stimulant or atomoxetine. In two recent studies, researchers evaluated the efficacy of α-2 agonists for treating children with core symptoms of ADHD.

In a manufacturer-supported, multicenter trial, investigators randomized 345 patients (age range, 6–17 years) with ADHD to receive placebo or one of three doses of an extended-release form of guanfacine (2, 3, or 4 mg daily, starting at 1 mg daily and increasing by 1 mg weekly to the assigned dose). After 5 weeks, dosages were tapered during 3 weeks. At baseline, mean scores on a standard ADHD rating scale were similar in treatment and placebo groups. By week 3, mean changes in ADHD scores were significantly greater in the guanfacine groups, combined and individually, than in the placebo group, with the greatest benefit in the 4-mg–guanfacine group. Similar improvements were noted on teacher, parent, and clinician global assessments. Specifically, guanfacine was associated with significant improvements in symptoms of hyperactivity, impulsivity, and inattentiveness, although the change from baseline in patients with the inattentive ADHD subtype was not statistically significant. Younger children (age range, 6–12 years) had greater responses to guanfacine than did adolescents (age range, 13–17 years). Only 62% of all enrolled patients completed the study; the most common side effects among guanfacine recipients were fatigue, somnolence, and sedation; predictably, blood pressure and pulse rate decreased with guanfacine, but the changes were not clinically significant.

In a government-sponsored, double-blind, placebo-controlled study, investigators randomized 122 children (age range, 7–12 years) with ADHD to one of four treatment groups: clonidine, methylphenidate, clonidine plus methylphenidate, or placebo. At 16 weeks, compared with placebo, teacher assessments on a standardized ADHD symptom scale (the primary efficacy measure) did not show improvement in the clonidine-only group but did indicate statistically significant improvement in both methylphenidate groups. However, parents of children in the clonidine-only group, but not the methylphenidate-only group, reported significant symptom improvement. Sedating effects were reported more often with clonidine.