An Open-Label Study of Guanfacine Extended Release for Traumatic Stress Related Symptoms in Children and Adolescents

Abstract

The purpose of this open-label pilot study was to investigate the effectiveness and tolerability of guanfacine extended release (GXR) 1-4 mg given in the evening, on the symptoms of traumatic stress (reexperiencing, avoidance, overarousal), generalized anxiety, and functional impairment in children and adolescents with a history of traumatic stress with or without posttraumatic stress disorder (PTSD). As many of our sample had associated attention-deficit/hyperactivity disorder (ADHD) symptoms, we also assessed whether the presence of traumatic stress symptoms impaired the effectiveness of GXR in the treatment of comorbid ADHD symptoms. Participants were 19 children and adolescents 6-18 years of age, with current traumatic stress symptoms. In an 8 week open-label design, each patient's scores on parent-, child-, and clinician-reported symptom rating scales assessing traumatic stress symptoms, generalized anxiety, ADHD symptoms, functional impairment, and global symptom severity and improvement (n=17) were evaluated off and on GXR using χ(2) goodness-of-fit tests, paired t tests, and repeated measures analyses of variance (ANOVAs). To examine patterns of change in outcome measures across treatment, MPlus software was used to conduct linear growth curves modeled with individual-varying times of observation (i.e., random slopes). Using an average GXR daily dose of 1.19 mg±0.35 mg and an average weight-adjusted daily dose of 0.03 mg/kg±0.01 mg/kg, significant differences were found on all symptom severity measures. Parent reported UCLA Reaction Index scores assessing cluster B (reexperiencing), C (avoidant), and D (overarousal) symptoms significantly improved. In the presence of PTSD symptoms, children with ADHD experienced significantly improved ADHD symptom scores, suggesting that comorbidity does not attenuate an ADHD symptom response to GXR therapy. Medication was generally well tolerated. Within the limits of an open-label, hypothesis-generating pilot study, our results suggest that the α2A-adrenoceptor agonist GXR may have therapeutic effects in the treatment of PTSD symptoms in traumatically stressed children and adolescents. The effective dose may be lower than that found for ADHD. Our pilot study supports the need for further controlled research on the effects of GXR and other α2A-adrenoceptor agonists in pediatric disorders of traumatic stress.