Background: In clinical trials of medications to treat attention-deficit/hyperactivity disorder (ADHD) in children, effects on functional impairment have been less well-studied than changes in ADHD symptoms.
Objective: Data regarding functional impairment were analyzed from a multicenter, double-blind, placebo-controlled study of guanfacine extended release (GXR) in children with ADHD, using the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P). The correspondence of changes in WFIRS-P scores with symptomatic and global response to GXR treatment was also examined, with treatment response defined by scores on both the ADHD Rating Scale IV (ADHD-RS-IV) and the Clinical Global Impressions-Improvement Scale (CGI-I).
Methods: In this 8-week, double-blind, placebo-controlled, dose optimization study at 47 sites across the USA and Canada, children aged 6-12 years with a diagnosis of ADHD [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria, and an ADHD-RS-IV score ≥28 and CGI-Severity of Illness Scale score ≥4 at baseline], were randomized 1:1:1 into three groups: GXR AM [GXR (1-4 mg/day) in the morning, placebo in the evening], GXR PM [placebo in the morning, GXR (1-4 mg/day) in the evening], or twice-daily placebo. Parents rated their children on the WFIRS-P at screening, baseline, the end of dose optimization, and at the final on-treatment assessment.
Results: The efficacy population was composed of 333 subjects (GXR AM: n = 107; GXR PM: n = 114; placebo: n = 112). At the final on-treatment assessment, there were significant improvements from baseline in the placebo-adjusted difference in least-squares (LS) mean (95 % confidence interval) WFIRS-P Total scores for both GXR treatment groups combined [GXR all-active: -0.16 (-0.25, -0.07), effect size (ES) = 0.448, P <0.001] and separately [GXR AM: -0.15 (-0.26, -0.05), ES = 0.417, P = 0.004; GXR PM: -0.18 (-0.28, -0.07), ES = 0.478, P = 0.001]. Significant improvements in WFIRS-P domain scores for Family, Learning and School (including Academic Performance and Behavior in School), Social, and Risky Behavior were found for both GXR cohorts compared with placebo. However, the Life Skills and Self-Concept domain scores of the WFIRS-P did not improve with GXR treatment. Post hoc stratification by responder status revealed that significant (P <0.001) improvements in WFIRS-P Total and all domain scores were associated with symptomatic treatment response in the GXR all-active group.
Conclusions: GXR treatment in children with ADHD was associated with reductions in WFIRS-P functional impairment scores compared with placebo, regardless of time of GXR administration. Changes in WFIRS-P scores were congruent with clinical response, as determined by both ADHD symptom reduction and CGI-I scores. CLINICALTRIALS.
Gov identifier: NCT00997984.