Objective: The purpose of this study was to assess the effect of guanfacine extended release (GXR) adjunctive to a psychostimulant on oppositional symptoms in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: A multicenter, double-blind, placebo-controlled dose-optimization study of GXR (1-4mg/d) or placebo administered morning (a.m.) or evening (p.m.) adjunctive to psychostimulant was conducted in subjects ages 6-17 with suboptimal response to psychostimulant alone. Suboptimal response was defined as treatment with a stable dose of psychostimulant for 4 weeks with ADHD Rating Scale IV total score 24 and Clinical Global Impressions-Severity of Illness score 3, as well as investigator opinion. Primary efficacy and safety results have been reported previously. Secondary efficacy measures included the oppositional subscale of the Conners' Parent Rating Scale-Revised: Long Form (CPRS-R:L); these are reported herein. Results: Significant reductions from baseline to the final on-treatment assessment on the oppositional subscale of the CPRS-R:L were seen with GXR plus psychostimulant compared with placebo plus psychostimulant, both in the overall study population (placebo-adjusted least squares [LS] mean change from baseline to the final on-treatment assessment: GXR a.m.+psychostimulant, -2.4, p=0.001; GXR p.m.+psychostimulant, -2.2, p=0.003) as well as in the subgroup of subjects with significant baseline oppositional symptoms (GXR a.m.+psychostimulant, -3.6, p=0.001; GXR p.m.+psychostimulant, -2.7, p=0.013). Treatment-emergent adverse events were reported by 77.3%, 76.3%, and 63.4% of subjects in the GXR a.m., GXR p.m., and placebo groups, respectively, in the overall study population. Conclusions: GXR adjunctive to a psychostimulant significantly reduced oppositional symptoms compared with placebo plus a psychostimulant in subjects with ADHD and a suboptimal response to psychostimulant alone.
