Extended Release Guanfacine in Pediatric Anxiety Disorders: A Pilot, Randomized, Placebo-Controlled Trial.
This is a feasibility study evaluating the safety, tolerability, and potential anxiolytic efficacy of the α2agonist guanfacine extended-release (GXR) in children and adolescents with generalized anxiety disorder (GAD), separation anxiety disorder (SAD), or social phobia/social anxiety disorder.



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.



GXR was safe and well tolerated. Treatment-related 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.



GXR was well tolerated in pediatric subjects with GAD, SAD, and/or social anxiety disorder. ClinicalTrials.gov Identifier: NCT01470469.
1 Anxiety Disorders Research Program, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine , Cincinnati, Ohio.
Jeffrey R
JR
Strawn
2 Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine , Durham, North Carolina.
Scott N
SN
Compton
3 Shire , Lexington, Massachusetts.
Brigitte
B
Robertson
4 New York State Psychiatric Institute, Columbia University , New York, New York.
Anne Marie
AM
Albano
3 Shire , Lexington, Massachusetts.
Mohamed
M
Hamdani
5 New York Presbyterian Morgan Stanley Children's Hospital, Columbia University/New York State Psychiatric Institute, New York, New York.
Moira A
MA
Rynn
D000293:Adolescent; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000503:physiopathology; D001010:Anxiety, Separation / Q000188:drug therapy*; D002648:Child; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D016316:Guanfacine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D000072861:Phobia, Social / Q000188:drug therapy*; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D059020:Suicidal Ideation; D016896:Treatment Outcome
D058647:Adrenergic alpha-2 Receptor Agonists; D003692:Delayed-Action Preparations; D016316:Guanfacine
adolescent; generalized anxiety disorder; separation anxiety disorder; social anxiety disorder; social phobia; α2 agonist