Response/Remission With Guanfacine Extended-Release and Psychostimulants in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder

Abstract

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). 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. 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 frombaseline 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 syndromalremission (symptomatic remission plus Clinical Global Impressions of Severity ofIllness score≤2). The most common treatment-emergent adverse events in participantsreceiving GXR+ psychostimulant were headache (21.2%) and somnolence (13.6%). 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 ofSPD503 in Combination With Psychostimulants; http://clinicaltrials.gov/; NCT00734578.