title: Efficacy of lisdexamfetamine dimesylate throughout the day in children and adolescents with attention-deficit/hyperactivity disorder: results from a randomized, controlled trial.
abstract: Lisdexamfetamine dimesylate (LDX) is a long-acting, prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder (ADHD). This randomized placebo-controlled trial of an optimized daily dose of LDX (30, 50 or 70 mg) was conducted in children and adolescents (aged 6-17 years) with ADHD. To evaluate the efficacy of LDX throughout the day, symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners' Parent Rating Scale-Revised (CPRS-R) at 1000, 1400 and 1800 hours following early morning dosing (0700 hours). Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference treatment, but the study was not designed to support a statistical comparison between LDX and OROS-MPH. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107). At baseline, CPRS-R total scores were similar across treatment groups. At endpoint, differences (active treatment - placebo) in least squares (LS) mean change from baseline CPRS-R total scores were statistically significant (P < 0.001) throughout the day for LDX (effect sizes: 1000 hours, 1.42; 1400 hours, 1.41; 1800 hours, 1.30) and OROS-MPH (effect sizes: 1000 hours, 1.04; 1400 hours, 0.98; 1800 hours, 0.92). Differences in LS mean change from baseline to endpoint were statistically significant (P < 0.001) for both active treatments in all four subscales of the CPRS-R (ADHD index, oppositional, hyperactivity and cognitive). In conclusion, improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening (1800 hours).
authors.affiliation: Division of Neuroscience, Ninewells Hospital, University of Dundee, Dundee, UK, d.r.coghill@dundee.ac.uk.
authors.forename: David R
authors.initials: DR
authors.lastname: Coghill
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.forename: Michel
authors.initials: M
authors.lastname: Lecendreux
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zuddas
authors.forename: Ralf W
authors.initials: RW
authors.lastname: Dittmann
authors.forename: Isabel Hernández
authors.initials: IH
authors.lastname: Otero
authors.forename: Richard
authors.initials: R
authors.lastname: Civil
authors.forename: Ralph
authors.initials: R
authors.lastname: Bloomfield
authors.forename: Liza A
authors.initials: LA
authors.lastname: Squires
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010290:Parents; D011355:Prodrugs; D016896:Treatment Outcome
chemical_list: D000697:Central Nervous System Stimulants; D011355:Prodrugs; D008774:Methylphenidate; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine