Guanfacine Extended-Release In Attention Deficit Hyperactivity Disorder

Guanfacine, an alpha(2A)-adrenoceptor agonist, is available in the US as an extended-release (ER) tablet for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents (aged 6-17 years). In two large, randomized, double-blind, placebo-controlled trials of 8 and 9 weeks' duration, guanfacine ER (1-4 mg once daily) was effective in reducing the symptoms of ADHD (hyperactivity, impulsivity and inattention) in children and adolescents. There were significant reductions (denoting improvements) from baseline in ADHD rating scale IV (ADHD-RS-IV) total scores (the primary end-point), compared with placebo. Oppositional symptoms were also significantly reduced from baseline in children with ADHD with oppositional symptoms who received guanfacine ER in a randomized, double-blind, placebo-controlled trial. Improvements in ADHD symptoms were sustained over 24 months in two noncomparative, open-label extension trials in children and adolescents who received guanfacine ER at an optimized dosage, of 1-4 mg/day. Guanfacine ER was relatively well tolerated in clinical trials in children and adolescents. The most common treatment-emergent adverse events were somnolence-related, and tended to resolve over time. Attention deficit hyperactivity disorder (ADHD) is a highly heritable, neurobiologically based, heterogeneous syndrome([1,2]) that is characterized by inattention, overactivity and impulsivity.([3]) Prevalence rates vary depending on the criteria used for assessment,([4]) but in the US, ADHD occurs in an estimated 4-12% of the school-aged population.([3]) Patients with ADHD frequently have one or more co-morbid conditions including oppositional defiant disorder, conduct disorder, mood and anxiety disorders, and learning disabilities.([3]) Psychostimulants (e.g. methylphenidate, amfetamine, dexamfetamine) are the mainstay of ADHD treatment.([5]) However, around 20% of patients do not respond to stimulants([5]) and their use may be restricted because of the presence of co-morbidities or risk of abuse.([6]) Adverse events, including insomnia and appetite suppression, are also observed with stimulant therapy.([6,7]) Guanfacine is an alpha(2A)-adrenoceptor agonist that, as an immediate-release (IR) tablet formulation, has been used as an antihypertensive agent for over 20 years.([8,9]) The IR formulation of guanfacine has demonstrated preliminary efficacy in reducing ADHD symptoms in small clinical trials but is limited by a short duration of action.([10]) Therefore, for the treatment of ADHD, an extended-release (ER) tablet was developed to allow once-daily administration. The recent approval of this ER formulation (Intuniv (TM)) makes it one of only two nonstimulant treatments approved by the US FDA for the treatment of ADHD (the other is atomoxetine). Guanfacine ER is a nonscheduled medication that shows no abuse potential. Medical literature on the use of guanfacine ER in ADHD in children and adolescents (aged 6-17 years) was identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database). Additional references were identified from the reference list of published articles. Bibliographical information, including contributory unpublished data was also requested from the company developing the drug. Searches were last updated 2 August 2010.