title: Comparative efficacy and safety of attention-deficit/hyperactivity disorder pharmacotherapies, including guanfacine extended release: a mixed treatment comparison.
abstract: This study compared the clinical efficacy and safety of attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in children and adolescents 6-17 years of age. A systematic literature review was conducted to identify randomized controlled trials (RCTs) of pharmacologic monotherapies among children and adolescents with ADHD. A Bayesian network meta-analysis was conducted to compare change in symptoms using the ADHD Rating Scale Version IV (ADHD-RS-IV), Clinical Global Impression-Improvement (CGI-I) response, all-cause discontinuation, and adverse event-related discontinuation. Thirty-six RCTs were included in the analysis. The mean (95% credible interval [CrI]) ADHD-RS-IV total score change from baseline (active minus placebo) was -14.98 (-17.14, -12.80) for lisdexamfetamine dimesylate (LDX), -9.33 (-11.63, -7.04) for methylphenidate (MPH) extended release, -8.68 (-10.63, -6.72) for guanfacine extended release (GXR), and -6.88 (-8.22, -5.49) for atomoxetine (ATX); data were unavailable for MPH immediate release. The relative risk (95% CrI) for CGI-I response (active versus placebo) was 2.56 (2.21, 2.91) for LDX, 2.13 (1.70, 2.54) for MPH extended release, 1.94 (1.59, 2.29) for GXR, 1.77 (1.31, 2.26) for ATX, and 1.62 (1.05, 2.17) for MPH immediate release. Among non-stimulant pharmacotherapies, GXR was more effective than ATX when comparing ADHD-RS-IV total score change (with a posterior probability of 93.91%) and CGI-I response (posterior probability 76.13%). This study found that LDX had greater efficacy than GXR, ATX, and MPH in the treatment of children and adolescents with ADHD. GXR had a high posterior probability of being more efficacious than ATX, although their CrIs overlapped.
authors.affiliation: Shire, Zug, Switzerland.
authors.forename: Alain
authors.initials: A
authors.lastname: Joseph
authors.affiliation: Analysis Group, Inc., Economic, Financial, and Strategy Consulting, 111 Huntington Avenue, 14th Floor, Boston, MA, 02199, USA. Rajeev.Ayyagari@analysisgroup.com.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Ayyagari
authors.affiliation: Analysis Group, Inc., Economic, Financial, and Strategy Consulting, 111 Huntington Avenue, 14th Floor, Boston, MA, 02199, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Xie
authors.affiliation: Analysis Group, Inc., New York, NY, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Cai
authors.affiliation: Analysis Group, Inc., New York, NY, USA.
authors.forename: Jipan
authors.initials: J
authors.lastname: Xie
authors.affiliation: University Medicine, Department of Child and Adolescent Psychiatry, Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Huss
authors.affiliation: Shire, Wayne, PA, USA.
authors.forename: Vanja
authors.initials: V
authors.lastname: Sikirica
mesh_terms: D000293:Adolescent; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D016316:Guanfacine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D016316:Guanfacine
keywords: Adolescents; Attention-deficit/hyperactivity disorder; Children; Efficacy; Meta-analysis; Mixed treatment comparison