A controlled trial of extended-release guanfacine and psychostimulants for attention-deficit/hyperactivity disorder

Timothy E Wilens; Oscar Bukstein; Matthew Brams; Andrew J Cutler; Ann Childress; Thomas Rugino; Andrew Lyne; Kara Grannis; Sharon Youcha

doi:10.1016/j.jaac.2011.10.012

A controlled trial of extended-release guanfacine and psychostimulants for attention-deficit/hyperactivity disorder

J Am Acad Child Adolesc Psychiatry. 2012 Jan;51(1):74-85.e2. doi: 10.1016/j.jaac.2011.10.012. Epub 2011 Nov 25.

Authors

Timothy E Wilens¹, Oscar Bukstein, Matthew Brams, Andrew J Cutler, Ann Childress, Thomas Rugino, Andrew Lyne, Kara Grannis, Sharon Youcha

Affiliation

¹ Massachusetts General Hospital, Boston, MA, USA. twilens@partners.org

PMID: 22176941
DOI: 10.1016/j.jaac.2011.10.012

Abstract

Objective: To examine efficacy, tolerability, and safety of guanfacine extended release (GXR; ≤4 mg/d) adjunctive to a long-acting psychostimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents 6 to 17 years of age with suboptimal, but partial, response to psychostimulant alone.

Method: In this multicenter, 9-week, double-blind, placebo-controlled, dose-optimization study, subjects (N = 461) continued their stable dose of psychostimulant given in the morning and were randomized to receive GXR in the morning (GXR AM), GXR in the evening (GXR PM), or placebo. Efficacy measures included ADHD Rating Scale IV (ADHD-RS-IV) and Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) scales. Safety measures included adverse events (AEs), vital signs, electrocardiograms, and laboratory evaluations.

Results: At endpoint, GXR treatment groups showed significantly greater improvement from baseline ADHD-RS-IV total scores compared with placebo plus psychostimulant (GXR AM, p = .002; GXR PM, p < .001). Significant benefits of GXR treatment versus placebo plus psychostimulant were observed on the CGI-S (GXR AM, p = .013; GXR PM, p < .001) and CGI-I (GXR AM, p = .024; GXR PM, p = .003). At endpoint, small mean decreases in pulse, systolic, and diastolic blood pressure were observed in GXR treatment groups versus placebo plus psychostimulant. No new safety signals emerged following administration of GXR with psychostimulants versus psychostimulants alone. Most AEs were mild to moderate in severity.

Conclusions: Morning or evening GXR administered adjunctively to a psychostimulant showed significantly greater improvement over placebo plus psychostimulant in ADHD symptoms and generated no new safety signals. Clinical trial registration information-Efficacy and Safety of SPD503 in Combination With Psychostimulants; http://www.clinicaltrials.gov; NCT00734578.

Publication types

Comparative Study
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adrenergic alpha-Agonists / administration & dosage*
Adrenergic alpha-Agonists / adverse effects*
Attention Deficit Disorder with Hyperactivity / drug therapy*
Central Nervous System Stimulants / therapeutic use
Child
Delayed-Action Preparations
Dose-Response Relationship, Drug
Double-Blind Method
Drug Administration Schedule
Drug Therapy, Combination
Female
Guanfacine / administration & dosage*
Guanfacine / adverse effects*
Humans
Male
Placebos
Psychiatric Status Rating Scales
Severity of Illness Index
Treatment Outcome

Substances

Adrenergic alpha-Agonists
Central Nervous System Stimulants
Delayed-Action Preparations
Placebos
Guanfacine

Associated data

ClinicalTrials.gov/NCT00734578