Extended Release Guanfacine in Pediatric Anxiety Disorders: A Pilot, Randomized, Placebo-Controlled Trial

Objective: This is a feasibility study evaluating the safety, tolerability, and potential anxiolytic efficacy of the alpha(2) agonist guanfacine extended-release (GXR) in children and adolescents with generalized anxiety disorder (GAD), separation anxiety disorder (SAD), or social phobia/social anxiety disorder. Methods: Youth aged 6-17 years with a primary diagnosis of GAD, SAD, and/or social anxiety disorder were treated with flexibly dosed GXR (1-6 mg daily, n = 62) or placebo (n = 21) for 12 weeks. The primary aim of this study was to determine the safety and tolerability of GXR in youth with anxiety disorders, which involved the analysis of treatment-emergent adverse events (TEAEs), the emergence of suicidal ideation and behaviors, vital signs, and electrocardiographic/laboratory parameters. Exploratory efficacy measures included dimensional anxiety scales (Pediatric Anxiety Rating Scale [PARS] and Screen for Child Anxiety Related Emotional Disorders [ SCARED]), as well as the Clinical Global Impression-Improvement (CGI-I) scale. As this was an exploratory study, no inferential statistical analyses were performed. Results: GXR was safe and well tolerated. Treatment-elated mean-standard deviation changes in heart rate (GXR: 1.8 +/- 12 beats per minute [bpm] decrease; placebo: 0.5 +/- 11 bpm decrease), systolic blood pressure (GXR: 2.3 +/- 11 mm Hg decrease; placebo: 1.7 +/- 11 mm Hg decrease), or diastolic blood pressure (GXR: 1.3 +/- 9 mm Hg decrease; placebo: 0.9 +/- 7 mm Hg increase) were similar between treatment groups. TEAEs, including headache, somnolence/fatigue, abdominal pain, and dizziness, were consistent with the known safety profile of GXR. No differences were observed between treatment groups for PARS and SCARED scores, although at endpoint, a higher proportion of subjects receiving GXR versus placebo demonstrated CGI-I scores <= 2 (54.2% vs. 31.6%), as rated by the clinician investigator. Conclusions: GXR was well tolerated in pediatric subjects with GAD, SAD, and/or social anxiety disorder.