Response/remission with guanfacine extended-release and psychostimulants in children and adolescents with attention-deficit/hyperactivity disorder

J Am Acad Child Adolesc Psychiatry. 2014 Oct;53(10):1092-101. doi: 10.1016/j.jaac.2014.08.001. Epub 2014 Aug 15.

Abstract

Objective: In this post hoc analysis, we assessed whether guanfacine extended-release (GXR) adjunctive to a psychostimulant resulted in greater response and remission rates than placebo + psychostimulant in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).

Method: In this 9-week, double-blind, placebo-controlled dose-optimization study, participants (N = 461) aged 6 to 17 years with suboptimal response to psychostimulants were randomized to GXR on awakening (AM) + psychostimulant, GXR at bedtime (PM) + psychostimulant, or placebo + psychostimulant.

Results: At the final on-treatment assessment, more participants in both GXR + psychostimulant groups versus the placebo + psychostimulant group achieved response as assessed by 2 criteria: reduction from baseline in ADHD Rating Scale IV (ADHD-RS-IV) total score (1) ≥40% (GXR AM + psychostimulant = 69.8%, GXR PM + psychostimulant = 70.3%, versus placebo + psychostimulant = 57.9%; p = .032 and p = .026, respectively), or (2) ≥50% (63.1%, 64.9%, versus 43.4%; p <.001 for both). Results were similar for symptomatic remission (ADHD-RS-IV total score ≤18; 61.1%, 62.2%, versus 46.1%; p = .010 and p = .005, respectively) and syndromal remission (symptomatic remission plus Clinical Global Impressions of Severity of Illness score ≤2). The most common treatment-emergent adverse events in participants receiving GXR + psychostimulant were headache (21.2%) and somnolence (13.6%).

Conclusion: GXR + psychostimulant treatment resulted in a greater percentage of participants meeting stringent criteria for response and remission compared with placebo + psychostimulant. The adverse event profile of adjunctive therapy was consistent with known effects of either treatment alone. Clinical trial registration information-Efficacy and Safety of SPD503 in Combination With Psychostimulants; http://clinicaltrials.gov/; NCT00734578.

Keywords: ADHD; guanfacine XR; remission; response; α(2A)-agonist.

Publication types

  • 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
  • Adrenergic alpha-2 Receptor Agonists / pharmacology*
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Central Nervous System Stimulants / therapeutic use*
  • Child
  • Drug Therapy, Combination
  • Female
  • Guanfacine / administration & dosage
  • Guanfacine / adverse effects
  • Guanfacine / pharmacology*
  • Humans
  • Male
  • Treatment Outcome

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Central Nervous System Stimulants
  • Guanfacine

Associated data

  • ClinicalTrials.gov/NCT00734578