A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder

J Am Acad Child Adolesc Psychiatry. 2015 Nov;54(11):916-25.e2. doi: 10.1016/j.jaac.2015.08.016. Epub 2015 Sep 15.


Objective: Despite the continuity of attention-deficit/hyperactivity disorder (ADHD) into adolescence, little is known regarding use of nonstimulants to treat ADHD in adolescents. This phase 3 trial evaluated the safety and efficacy of guanfacine extended release (GXR) in adolescents with ADHD.

Method: This 13-week, multicenter, randomized, double-blind, placebo-controlled trial evaluated once-daily GXR (1-7 mg per day) in adolescents with ADHD aged 13 to 17 years. The primary endpoint was the change from baseline in the ADHD Rating Scale-IV (ADHD-RS-IV) total score; key secondary endpoints included scores from the Clinical Global Impressions-Severity of Illness (CGI-S), and Learning and School domain and Family domain scores from the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at week 13.

Results: A total of 314 participants were randomized (GXR, n = 157; placebo, n = 157). The majority of participants received optimal doses of 3, 4, 5, or 6 mg (30 [22.9%], 26 [19.8%], 27 [20.6%], or 24 [18.3%] participants, respectively), with 46.5% of participants receiving an optimal dose above the currently approved maximum dose limit of 4 mg. Participants receiving GXR showed improvement in ADHD-RS-IV total score compared with placebo (least-squares mean score change, -24.55 [GXR] versus -18.53 [placebo]; effect size, 0.52; p <.001). More participants on GXR also showed significant improvement in CGI-S scores compared with placebo (50.6% versus 36.1%; p = .010). There was no statistically significant difference between treatments at week 13 in the 2 WFIRS-P domains. Most treatment-emergent adverse events were mild to moderate, with sedation-related events reported most commonly.

Conclusion: GXR was associated with statistically significant improvements in ADHD symptoms in adolescents. GXR was well tolerated, with no new safety signals reported.

Clinical trial registration information: Dose-Optimization in Adolescents Aged 13-17 Diagnosed With Attention-Deficit/Hyperactivity Disorder (ADHD) Using Extended-Release Guanfacine HCl; http://ClinicalTrials.gov/; NCT01081132.

Keywords: GXR; attention-deficit/hyperactivity disorder; guanfacine; nonstimulants.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic alpha-2 Receptor Agonists / administration & dosage*
  • Adrenergic alpha-2 Receptor Agonists / adverse effects
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Behavior Rating Scale
  • Delayed-Action Preparations / administration & dosage
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Guanfacine / administration & dosage*
  • Guanfacine / adverse effects
  • Humans
  • Male
  • Psychiatric Status Rating Scales
  • Schools
  • Severity of Illness Index
  • Treatment Outcome
  • United States


  • Adrenergic alpha-2 Receptor Agonists
  • Delayed-Action Preparations
  • Guanfacine

Associated data

  • ClinicalTrials.gov/NCT01081132