Guanfacine extended-release (GXR), a selective α2A-adrenergic agonist, is a non-stimulant treatment for attention-deficit/hyperactivity disorder (ADHD). This study assessed the efficacy (symptoms and function) and safety of dose-optimized GXR compared with placebo in children and adolescents with ADHD. An atomoxetine (ATX) arm was included to provide reference data against placebo. Patients (6-17 years) were randomized at baseline to dose-optimized GXR (0.05-0.12mg/kg/day - 6-12 years: 1-4mg/day; 13-17 years: 1-7mg/day), ATX (10-100mg/day) or placebo for 4 or 7 weeks. The primary efficacy measure was change from baseline in ADHD Rating Scale version IV (ADHD-RS-IV). Key secondary measures were Clinical Global Impression-Improvement (CGI-I) and the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P; learning and school, and family domains). Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms and vital signs. A total of 272 (80.5%) patients from Europe, the USA and Canada completed the study. Significant differences were observed in least squares mean change from baseline in ADHD-RS-IV total score (placebo-adjusted differences) (GXR: [-8.9, p<0.001]; ATX: [-3.8, p<0.05]), the difference from placebo in the percentage of patients showing improvement (1 ['very much improved'] or 2 ['much improved']) for CGI-I (GXR: [23.7, p<0.001]; ATX: [12.1, p<0.05]), WFIRS-P learning and school domain (GXR: [-0.22, p<0.01]; ATX: [-0.16, p<0.05]) and WFIRS-P family domain (GXR: [-0.21, p<0.01]; ATX: [-0.09, p=0.242]). Most common TEAEs for GXR were somnolence, headache and fatigue; 70.1% of GXR subjects reported mild-to-moderate TEAEs. GXR was effective and well tolerated in children and adolescents with ADHD.

BackgroundChamplain BASE™ (Building Access to Specialists through eConsultation) is a web-based asynchronous electronic communication service that allows primary-care- practitioners (PCPs) to submit “elective” clinical questions to a specialist. For adults, PCPs have reported improved access and timeliness to specialist advice, averted face-to-face specialist referrals in up to 40% of cases and high provider satisfaction.ObjectiveTo determine whether the expansion of eConsult to a pediatric setting would result in similar measures of improved healthcare system process and high provider acceptance reported in adults.DesignProspective observational cohort study.SettingSingle Canadian tertiary-care academic pediatric hospital (June 2014–16) servicing 1.2 million people.Participants1. PCPs already using eConsult. 2.Volunteer pediatric specialists provided services in addition to their regular workload. 3.Pediatric patients (< 18 years-old) referred for none-acute care conditions.Main outcomes and measuresSpecialty service utilization and access, impact on PCP course-of-action and referral-patterns and survey-based provider satisfaction data were collected.Results1064 eConsult requests from 367 PCPs were answered by 23 pediatric specialists representing 14 specialty-services. The top three specialties represented were: General Pediatrics 393 cases (36.9%), Orthopedics 162 (15.2%) and Psychiatry 123 (11.6%). Median specialist response time was 0.9 days (range <1 hour-27 days), most consults (63.2%) required <10minutes to complete and 21/21(100%) specialist survey-respondents reported minimal workload burden. For 515/1064(48.4%) referrals, PCPs received advice for a new or additional course of action; 391/1064(36.7%) referrals resulted in an averted face-to-face specialist visit. In 9 specialties with complete data, the median wait-time was significantly less (p<0.001) for an eConsult (1 day, 95%CI:0.9–1.2) compared with a face-to-face referral (132 days; 95%CI:127–136). The majority (>93.3%) of PCPs rated eConsult as very good/excellent value for both patients and themselves. All specialist survey-respondents indicated eConsult should be a continued service.Conclusions and relevanceSimilar to adults, eConsult improves PCP access and timeliness to elective pediatric specialist advice and influences their care decisions, while reporting high end-user satisfaction. Further study is warranted to assess impact on resource utilization and clinical outcomes.

Emotional dysregulation is increasingly recognized as a core feature of attention-deficit/hyperactivity disorder (ADHD). The purpose of the present systematic literature review was to identify published data related to the neuropsychology of emotional dysregulation in children with ADHD. The literature obtained is discussed in the contexts of deficits in emotional control, impairments in executive function, the emotional components of comorbidities, neurophysiological and autonomic correlates of emotional dysregulation, and the significance of multiple neuropsychological pathways of ADHD on emotional dysregulation. These various lines of evidence are used to create a patient-oriented conceptual model framework of the pathway from stimulus to inappropriate internalized (sadness, moodiness) or externalized (anger, aggressiveness) emotional responses. The article concludes by calling for continued research into the development of reliable and universally accepted measures of emotional dysregulation in order to provide children affected with ADHD, and their caregivers, some explanation for their emotional lability and, ultimately, to be used as tools to evaluate potential treatments.

Background: Extended-release guanfacine hydrochloride (GXR), a selective a2A-adrenergic agonist, is a nonstimulant medication for attention-deficit/hyperactivity disorder (ADHD). This phase 3, double-blind, placebo-controlled, randomised-withdrawal study evaluated the long-term maintenance of GXR efficacy in children/adolescents with ADHD. Methods: Children/adolescents (6-17 years) with ADHD received open-label GXR (1-7 mg/day). After 13 weeks, responders were randomised to GXR or placebo in the 26-week, double-blind, randomised-withdrawal phase (RWP). The primary endpoint was the percentage of treatment failure (≥50% increase in ADHD Rating Scale version IV total score and ≥2-point increase in Clinical Global Impression-Severity compared with RWP baseline, at two consecutive visits). The key secondary endpoint was time to treatment failure (TTF). Trial registration: ClinicalTrials.gov identifier NCT01081145; EudraCT 2009-018161-12. Results: A total of 528 participants enrolled; 316 (59.8%) entered the RWP. Treatment failure occurred in 49.3% of the GXR and 64.9% of the placebo group (p = 0.006). TTF was significantly longer in GXR versus placebo (p = 0.003). GXR was well tolerated. Conclusions: Guanfacine hydrochloride demonstrated long-term maintenance of efficacy compared with placebo in children/ adolescents with ADHD. Implications of the placebo substitution design and findings with different ADHD medications are discussed.

Use of an AAP among stimulant-treated children and adolescents with ADHD in Quebec was associated with high rates of therapy changes and increased HRU and costs.