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Cited by 317Attention Deficit Hyperactivity DisorderPharmaceutical studies and practicesSchizophrenia research and treatment

A Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine Extended Release in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder

Biederman, Joseph, Melmed, Raun D., Patel, Anil, McBurnett, Keith, Konow, Jennifer, Lyne, Andrew, Scherer, Noreen, for the SPD503 Study Group·2008·Pediatrics
DOI 10.1542/peds.2006-3695
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Abstract

OBJECTIVE. With this study we assessed the efficacy and safety of an extended-release formulation of guanfacine compared with placebo for the treatment of children and adolescents with attention-deficit/hyperactivity disorder. METHODS. In this multicenter, double-blind, placebo-controlled, fixed-dosage escalation study, patients aged 6 to 17 years were randomly assigned to 1 of 3 treatment groups of guanfacine extended release (2, 3, or 4 mg/day) or placebo for 8 weeks. The primary outcome measurement was the Attention-Deficit/Hyperactivity Disorder Rating Scale IV total score. Secondary measurements included Clinical Global Impression of Improvement, Parent's Global Assessment, Conners' Parent Rating Scale–Revised: Short Form, and Conners' Teacher Rating Scale–Revised: Short Form. RESULTS. A total of 345 patients were randomly assigned to placebo (n = 86) or guanfacine extended release 2 mg (n = 87), 3 mg (n = 86), or 4 mg (n = 86) treatment groups. Least-squares mean changes from baseline to the end point in Attention-Deficit/Hyperactivity Disorder Rating Scale IV total scores were significant in all groups of children taking guanfacine extended release: −16.18 in the 2-mg group, −16.43 in the 3-mg group, and −18.87 in the 4-mg group, compared with −8.48 in the placebo group. All groups of children taking guanfacine extended release showed significant improvement on hyperactivity/impulsivity and inattentiveness subscales of the Attention-Deficit/Hyperactivity Disorder Rating Scale IV, Clinical Global Impression of Improvement, Parent's Global Assessment, Conners' Parent Rating Scale–Revised: Short Form, and Conners' Teacher Rating Scale–Revised: Short Form assessments compared with placebo. The most commonly reported treatment-emergent adverse events were headache, somnolence, fatigue, upper abdominal pain, and sedation. Small to modest changes in blood pressure, pulse rate, and electrocardiogram parameters were observed but were not clinically meaningful. CONCLUSIONS. Guanfacine extended release met the primary and secondary efficacy end points. It was well tolerated and effective compared with placebo.

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  • With the exception of one pemoline study and adolescent subgroups in two guanfacine studies, all studies in adolescents with ADHD without SUD reported significant improvements in ADHD symptoms in active medication compared with placebo, with effect sizes of d = 0.53-1.33 for MPH, d = 0.80-1.23 for LDX, d = 0.80 for MAS-XR, d = 2.05 for pemoline, d = 0.99 for atomoxetine, and d = 0.52 for guanfacne

    “With the exception of one pemoline study [33] and the adolescent subgroups in two guanfacine studies [45,46], all studies reported significant improvements in ADHD symptoms in the active medication compared with the placebo groups, with moderate to large effect sizes of Cohen’s d = 0.53–1.33 for MPH, d = 0.80–1.23 for LDX, d = 0.80 for MAS-XR, d = 2.05 for pemoline, d = 0.99 for atomoxetine, and d”

    From Treatment of Adolescents with Concurrent Substance Use Disorder and Attention-Deficit/Hyperactivity Disorder: A Systematic Review (2021) · cites this paper as [45]

  • Atomoxetine, extended-release guanfacine, and extended-release clonidine have demonstrated efficacy in reducing core symptoms among school-aged children and adolescents.

    “Among nonstimulant medications, 1 selective norepinephrine reuptake inhibitor, atomoxetine,99,100 and 2 selective α-2 adrenergic agonists, extended-release guanfacine101,102 and extended-release clonidine,103 have also demonstrated efficacy in reducing core symptoms among school-aged children and adolescents”

    From Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents (2019) · cites this paper as [101]

  • Double-blind placebo-controlled studies have demonstrated that guanfacine is effective in treating ADHD symptoms.

    “double-blind placebo-controlled studies have demonstrated that guanfacine is effective in treating ADHD symptoms”

    From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Biederman et al., 2008

  • Guanfacine mimics noradrenergic actions at α2A-receptors, and its activity at postsynaptic α2-receptors may restore PFC function in patients with ADHD.

    “Not only does guanfacine mimic noradrenergic actions at α2A-receptors, its activity at postsynaptic α2-receptors may restore PFC function in patients with ADHD (Biederman et al., 2008; Scahill et al., 2001).”

    From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Biederman et al., 2008

  • In two short-term, placebo-controlled, double-blind pivotal trials, extended-release guanfacine (Intuniv) as monotherapy reduced symptoms of ADHD, as measured by clinician-rated ADHD-RS-IV total score and the hyperactivity/impulsivity and inattentiveness subscale scores.

    “In 2 short-term, placebo-controlled, double-blind pivotal trials, an extended-release formulation of guanfacine (Intuniv™, Shire US Inc.) has shown efficacy as monotherapy for reducing symptoms of ADHD based on clinician-rated ADHD Rating Scale IV (ADHD-RS-IV) total score as well as the hyperactivity/impulsivity and inattentiveness subscale scores (Biederman et al., 2008; Sallee et al., 2009).”

    From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Biederman et al., 2008

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Authors
Biederman, J., Melmed, R. D., Patel, A., McBurnett, K., Konow, J., Lyne, A., Scherer, N., & for the SPD503 Study Group
Affiliations
  • Massachusetts General Hospital (US)
  • General Pediatrics, Melmed Center, Scottsdale, Arizona
  • Psychiatric Centers at San Diego, San Marcos, California
  • University of California, San Francisco (US)
  • Late Phase Research, Kendle International Inc, Cincinnati, Ohio
  • Shire (United Kingdom) (GB)
  • Takeda (United States) (US)
ORCID
Venue
Pediatrics
Publisher
American Academy of Pediatrics (AAP)
Published
2008-01-01
Volume
121
Issue
1
Pages
e73-e84
ISSN
  • 0031-4005 (ISSN-L)
  • 1098-4275
DOI
10.1542/peds.2006-3695
OpenAlex
W2002134787
Cited by
317
References
38
Citations by year
2026: 6 · 2025: 7 · 2024: 14 · 2023: 12 · 2022: 7 · 2021: 11 · 2020: 15 · 2019: 5 · 2018: 13 · 2017: 14 · 2016: 15 · 2015: 14 · 2014: 39 · 2013: 28 · 2012: 28
FWCI
12.18
Type
journal article
Language
en
Open access
closed
Locations
  • PEDIATRICS (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
guanfacine extended release, attention deficit hyperactivity disorder, children and adolescents, ADHD treatment efficacy, ADHD Rating Scale, hyperactivity/impulsivity, inattention, adverse events, blood pressure changes, alpha-2 adrenergic agonists
MeSH terms
Adolescent, Attention Deficit Disorder with Hyperactivity, Child, Delayed-Action Preparations, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Male, Probability, Reference Values, Severity of Illness Index, Multivariate Analysis, Guanfacine, Treatment Outcome, Risk Assessment

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