title: Clinical utility of ADHD symptom thresholds to assess normalization of executive function with lisdexamfetamine dimesylate treatment in adults.
abstract: OBJECTIVE
  This analysis assessed the relationship of various cutoff scores of the ADHD Rating Scale IV (ADHD-RS-IV) to levels of improvement in ADHD-related executive function (EF), measured by the Brown ADD Scale for Adults (BADDS), which may provide a measure of clinically meaningful EF improvement after ADHD treatment.
  
  
  METHODS
  Post hoc analysis of a 4-week, open-label, dose-optimization phase in a double-blind, placebo-controlled study of lisdexamfetamine dimesylate (LDX) in adults with ADHD. The BADDS for Adults, a validated, normed, self-report measure of EF in ADHD, provides a qualitative measure to rate treatment progress. The ADHD-RS-IV assesses current symptom status based on DSM-IV criteria. Postbaseline ADHD-RS-IV scores were categorized according to four cutoff criteria of symptom remission: (1) ADHD-RS-IV total score ≤ 18; (2) ADHD-RS-IV total score ≤ 10; (3) no ADHD-RS-IV item scored >1; and (4) ADHD-RS-IV total score ≤ 18 and ≤ 2 items per subscale with a score of 2. Sensitivity and specificity of criteria for identifying participants with optimal BADDS scores were assessed using receiver operating characteristics (ROC). Safety evaluation included treatment-emergent adverse events (TEAEs).
  
  
  RESULTS
  At endpoint, 85/127 participants had optimal BADDS scores. Linear ANOVA indicated limited overlap between BADDS and ADHD-RS-IV scores (r (2) = 0.20; P < 0.0001). Specificity was similar for criteria 1-4 (0.46, 0.39, 0.39, and 0.42), as were ROC (0.699, 0.776, 0.732, and 0.668). Sensitivity was high for criteria 2 and 3 (0.96, 0.92), lower for criteria 1 and 4 (0.72, 0.75). TEAEs were consistent with those of stimulants.
  
  
  CONCLUSIONS
  Criteria 2 and 3 had satisfactorily high sensitivity, but no criteria had adequate specificity. AUC comparison indicated that criteria 2 and 3 ADHD-RS-IV thresholds may be more accurate assessments of EF normalization as measured by the BADDS. The open-label design, small sample size, and selection criteria limit the applicability of these results to a larger treatment population.
authors.affiliation: Yale University School of Medicine, New Haven, CT 06517, USA. tebrownyu@aol.com
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Brown
authors.forename: Matthew
authors.initials: M
authors.lastname: Brams
authors.forename: Maria
authors.initials: M
authors.lastname: Gasior
authors.forename: Ben
authors.initials: B
authors.lastname: Adeyi
authors.forename: Thomas
authors.initials: T
authors.lastname: Babcock
authors.forename: Bryan
authors.initials: B
authors.lastname: Dirks
authors.forename: Brian
authors.initials: B
authors.lastname: Scheckner
authors.forename: Timothy
authors.initials: T
authors.lastname: Wigal
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*; D003913:Dextroamphetamine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D056344:Executive Function; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012372:ROC Curve; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine