title: Effect size of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder.
abstract: OBJECTIVE
  To examine duration of efficacy of lisdexamfetamine dimesylate (LDX) in adults with attention-deficit/hyperactivity disorder (ADHD) by effect size in performance and symptom improvement in a simulated adult workplace environment (AWE).
  
  
  METHODS
  Adults (aged 18-55 years) with ADHD enrolled in the AWE study of LDX with open-label dose-optimization and randomized, placebo-controlled, double-blind, 2-way crossover phases. Efficacy measures included the Permanent Product Measure of Performance (PERMP)-Attempted (-A) and PERMP-Correct (-C) scores assessed throughout the day and the ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts. Model-based least-squares (LS) mean effect size was assessed for PERMP and post-hoc ADHD-RS-IV with adult prompts. Remission was defined as an ADHD-RS-IV total scores ≤ 18. Safety assessments included treatment-emergent adverse events (TEAEs) and vital signs.
  
  
  RESULTS
  Least-squares mean (standard error [SE]) effect sizes were 0.9 (0.17) for PERMP-A and 0.8 (0.16) for PERMP-C for all postdose sessions. For PERMP-A, postdose LS mean (SE) effect sizes were 0.5 (0.15), 0.8 (0.16), 0.7 (0.16), 0.7 (0.16), 0.7 (0.16), and 0.6 (0.16) at 2, 4, 8, 10, 12, and 14 hours, respectively. Medium-to-large effect sizes (0.5-0.8) were generally maintained from 2 to 14 hours for all PERMP assessments. Overall LS mean (SE) ADHD-RS-IV total and subscale effect sizes were -1.2 (0.19), -1.2 (0.19), and -1.0 (0.17), respectively. Remission was achieved in 67.6% of participants receiving LDX. Treatment-emergent adverse events (≥ 5% with LDX) during the 4-week dose-optimization phase were decreased appetite, dry mouth, headache, insomnia, upper respiratory tract infection, irritability, nausea, anxiety, and feeling jittery. During the crossover week on LDX, there were no TEAEs ≥ 5%.
  
  
  CONCLUSIONS
  In adults studied in the AWE, medium-to-large model-based effect sizes were maintained from 2 to 14 hours postdose, on a performance-based measure of productivity, suggesting participants experienced improvement in sustained attention throughout the day and into the evening hours. Lisdexamfetamine dimesylate demonstrated a safety profile consistent with long-acting stimulants.
authors.affiliation: University of California, Irvine, Child Development Center, Irvine, CA 92612, USA. tlwigal@uci.edu
authors.forename: Timothy
authors.initials: T
authors.lastname: Wigal
authors.forename: Matthew
authors.initials: M
authors.lastname: Brams
authors.forename: Maria
authors.initials: M
authors.lastname: Gasior
authors.forename: Joseph
authors.initials: J
authors.lastname: Gao
authors.forename: John
authors.initials: J
authors.lastname: Giblin
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003913:Dextroamphetamine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine