title: Randomized, double-blind, placebo-controlled, crossover study of the effects of lisdexamfetamine dimesylate and mixed amphetamine salts on cognition throughout the day in adults with attention-deficit/hyperactivity disorder.
abstract: BACKGROUND
  Understanding the nature and time course of the pharmacodynamic effects of attention-deficit/hyperactivity disorder (ADHD) medications is useful. The Cognitive Drug Research Computerized Battery of Tests (CDR-CBT) is a 20-min battery of ten standardized, validated neuropsychometric tasks.
  
  
  OBJECTIVE
  This pilot study examined the sensitivity and responsiveness of the CDR-CBT for assessing cognitive function in adults with ADHD prior to and up to 16 h postdose during treatment with lisdexamfetamine dimesylate (LDX) or mixed amphetamine salts immediate release (MAS-IR; various generics available).
  
  
  METHODS
  This was a double-blind three-period crossover study. Participants received LDX 50 mg/day, MAS-IR 20 mg/day, and placebo (~7 a.m.) for 7 days each in randomized order. CDR-CBT was administered on day 1 of period 1 and day 7 of each period at scheduled times between -0.5 (predose) and 16 h postdose. Composite power of attention (PoA) score (sum of simple reaction time, choice reaction time, and digit vigilance speed) was the primary outcome measure. The Conners' Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S) was administered at baseline and on day 1 of period 1, and days 6 and 7 of each treatment period. Tertiary outcomes included CDR-CBT composite continuity of attention scores, its component task scores, cognitive reaction time, and response variability scores. No inferential statistical comparisons were conducted. Safety assessments included adverse events (AEs) and vital signs.
  
  
  RESULTS
  This analysis included 18 participants (mean age 30.8 years); one withdrew because of AEs. Mean pretreatment PoA scores were 1175.9-1361.2 ms, scores commensurate with a normative age of >40 years. Maximum reductions in PoA scores with LDX and MAS-IR occurred at 5 h postdose at day 7 (least squares mean difference [95% CI] of -150.0 [-235.41 to -64.50] and -79.8 [-165.72 to 6.21] ms vs. placebo, respectively). CAARS-S:S scores were unchanged with LDX and MAS-IR (vs. placebo) at all postdose timepoints. Tertiary attention-related CDR-CBT outcomes were sensitive to LDX and MAS-IR (vs. placebo). Treatment-emergent AEs and vital signs were consistent with previous studies in adult ADHD.
  
  
  CONCLUSIONS
  In adults with ADHD, PoA scores indicated impaired attention at baseline and response to treatment with LDX and MAS-IR (vs. placebo), demonstrating value for measuring the time course of pharmacologic treatment effects.
authors.affiliation: Shire Development LLC, 725 Chesterbrook Blvd, Wayne, PA, 19087-5637, USA, pmartin@shire.com.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Martin
authors.forename: Mary
authors.initials: M
authors.lastname: Corcoran
authors.forename: Pinggao
authors.initials: P
authors.lastname: Zhang
authors.forename: Alain
authors.initials: A
authors.lastname: Katic
mesh_terms: D000328:Adult; D000662:Amphetamines / Q000008:administration & dosage / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D009483:Neuropsychological Tests; D010865:Pilot Projects; D011594:Psychometrics; D011930:Reaction Time / Q000187:drug effects; D012680:Sensitivity and Specificity; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000662:Amphetamines; D000697:Central Nervous System Stimulants; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine