title: Guanfacine Extended Release: A New Pharmacological Treatment Option in Europe.
abstract: Children/adolescents with attention-deficit/hyperactivity disorder (ADHD) may have a poor or inadequate response to psychostimulants or be unable to tolerate their side-effects; furthermore, stimulants may be inappropriate because of co-existing conditions. Only one non-stimulant ADHD pharmacotherapy, the noradrenaline transporter inhibitor atomoxetine, is currently approved for use in Europe. We review recent advances in understanding of the pathophysiology of ADHD with a focus on the roles of catecholamine receptors in context of the α2A-adrenergic receptor agonist guanfacine extended release (GXR), a new non-stimulant treatment option in Europe. Neuroimaging studies of children/adolescents with ADHD show impaired brain maturation, and structural and functional anomalies in brain regions and networks. Neurobiological studies in ADHD and medication response patterns support involvement of monoaminergic neurotransmitters (primarily dopamine and noradrenaline). Guanfacine is a selective α2A-adrenergic receptor agonist that has been shown to improve prefrontal cortical cognitive function, including working memory. The hypothesized mode of action of guanfacine centres on direct stimulation of post-synaptic α2A-adrenergic receptors to enhance noradrenaline neurotransmission. Preclinical data suggest that guanfacine also influences dendritic spine growth and maturation. Clinical trials have demonstrated the efficacy of GXR in ADHD, and it is approved as monotherapy or adjunctive therapy to stimulants in Canada and the USA (for children and adolescents). GXR was approved recently in Europe for the treatment of ADHD in children and adolescents for whom stimulants are not suitable, not tolerated or have been shown to be ineffective. GXR may provide particular benefit for children/adolescents who have specific co-morbidities such as chronic tic disorders or oppositional defiant disorder (or oppositional symptoms) that have failed to respond to first-line treatment options.
authors.affiliation: Child and Adolescent Psychiatry of the University Medicine Johannes Gutenberg University, Langenbeckstr. 1, 55131, Mainz, Germany. M.HUSS@rfk.landeskrankenhaus.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Huss
authors.affiliation: Department of Child and Adolescent Psychiatry, School of Paediatrics and Child Health and School of Psychiatry and Clinical Neurosciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Perth, WA, Australia.|Department of Health, Complex Attention and Hyperactivity Disorder Service, Perth, WA, Australia.
authors.forename: Wai
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Child and Adolescent Psychiatry/Psychotherapy, University of Ulm, Steinhoevelstrasse 5, 89075, Ulm, Germany.
authors.forename: Andrea G
authors.identifier: http://orcid.org/0000-0003-0765-8481
authors.initials: AG
authors.lastname: Ludolph
mesh_terms: D000293:Adolescent; D000069445:Atomoxetine Hydrochloride / Q000008:administration & dosage; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D002648:Child; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D005060:Europe; D016316:Guanfacine / Q000008:administration & dosage*; D006801:Humans; D016896:Treatment Outcome
chemical_list: D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D016316:Guanfacine; D000069445:Atomoxetine Hydrochloride