Objective: This study compared the efficacy of guanfacine extended release (GXR), a selective alpha(2A)-adrenoceptor agonist, with placebo in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).
Method: This double-blind, 9-week, dose-ranging, parallel-design, multicenter trial randomized 6- to 17-year-olds with ADHD to once-daily oral GXR in 1-, 2-, 3-, and 4-mg doses or placebo. Primary outcome was change in total ADHD Rating Scale-IV score from baseline to endpoint. Secondary outcomes included changes in scores of hyperactive/impulsive and inattentive subscales; clinician and parent ratings; duration of clinical effect; and safety measures.
Results: Statistically significant reductions in ADHD Rating Scale-IV scores were observed from baseline to endpoint at all doses of GXR, with effect sizes ranging from 0.43 to 0.62. In subjects receiving GXR, mean heart rate and systolic and diastolic blood pressure decreased as the dose of GXR increased and then returned toward baseline during the dose-maintenance and dose-tapering phases of the trial. Most frequent treatment-emergent adverse events (> or = 5%) were somnolence, headache, fatigue, sedation, dizziness, irritability, upper abdominal pain, and nausea. Somnolence, sedation, and fatigue adverse events emerged within the first 2 weeks of dosing and generally resolved by study end.
Conclusions: : Guanfacine extended-release was effective in reducing symptoms of ADHD. Adverse events were mild to moderate, did not interfere with improvements in attention, and rarely led to discontinuation.