title: Methylphenidate hydrochloride modified-release in adults with attention deficit hyperactivity disorder: a randomized double-blind placebo-controlled trial.
abstract: BACKGROUND
  Treatment options for adults with attention deficit hyperactivity disorder (ADHD) are limited. The study was conducted to confirm the clinically effective and safe dose of methylphenidate hydrochloride modified-release (MPH-LA) in adults with ADHD and evaluate the maintenance of effect of MPH-LA.
  
  
  METHODS
  The study consisted of three treatment phases. The double-blind dose-confirmation phase: 9-week double-blind period (3-week titration period, 6-week fixed dose) with randomization to MPH-LA 40, 60, or 80 mg/day or placebo. The real-life dose-optimization phase: a 5-week re-titration period to optimal dose; and the double-blind maintenance of effect phase, a 6-month double-blind randomized placebo-controlled maintenance of effect phase. The three co-primary endpoints were change in Diagnostic and Statistical Manual of Mental Disorders-IV ADHD Rating Scale (DSM-IV ADHD RS) and Sheehan Disability Scale (SDS) total scores from baseline to end of 9-week confirmation phase and the percentage of treatment failures during the 6-month maintenance of effect phase.
  
  
  RESULTS
  725 of 863 screened patients were randomized to 40 (N = 181), 60 (N = 182), or 80 mg (N = 181) MPH-LA or placebo (N = 181), and 584 (80.6%) completed. 489 (83.7%) of completers were re-randomized to the double-blinded maintenance of effect phase and 235 (48.1%) of them completed. Improvement from baseline in DSM-IV ADHD RS (P < 0.0001 for all comparisons) and SDS (40 mg, P = 0.0003; 60 mg, P = 0.0176; 80 mg, P < 0.0001) total scores was significantly greater vs. placebo for all MPH-LA doses. Treatment failure rate was significantly lower with MPH-LA (21.3%) versus placebo (49.6%) during the 6-month maintenance of effect phase. Safety profile was consistent with the profile for MPH-LA in children; percentage of serious adverse events was comparable between all MPH-LA arms (1.3%) and placebo (1.5%), while percentage of adverse events was higher in MPH-LA arms.
  
  
  CONCLUSIONS
  MPH-LA provided and maintained significant symptomatic and functional improvement in adult ADHD patients.
authors.affiliation: Child and Adolescent Psychiatry, University of Medicine, Mainz, Germany, michael.huss@unimedizin-mainz.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Huss
authors.forename: Ylva
authors.initials: Y
authors.lastname: Ginsberg
authors.forename: Torbjorn
authors.initials: T
authors.lastname: Tvedten
authors.forename: Torben
authors.initials: T
authors.lastname: Arngrim
authors.forename: Alexandra
authors.initials: A
authors.lastname: Philipsen
authors.forename: Katherine
authors.initials: K
authors.lastname: Carter
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Chen
authors.forename: Vinod
authors.initials: V
authors.lastname: Kumar
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate