title: Efficacy of a novel biphasic controlled-release methylphenidate formula in adults with attention-deficit/hyperactivity disorder: results of a double-blind, placebo-controlled crossover study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of a new biphasic multilayer-release (MLR) methylphenidate formulation in a double-blind, placebo-controlled crossover study of adults with attention-deficit/hyperactivity disorder (ADHD).
  
  
  METHODS
  Adults 18 to 60 years of age with a DSM-IV diagnosis of ADHD entered a no-medication baseline week and were then randomly assigned to once-daily MLR methylphenidate or matching placebo. Patients were titrated to optimal effect over 1 to 3 weeks followed by 2 weeks of treatment on a stable dose. The same titration protocol was repeated with the alternate treatment. Clinical Global Impressions scale (CGI) and Conners' Adult ADHD Rating Scales (Self-rated, CAARS-S, and Observer-rated, CAARS-O) were collected at weekly clinic visits. The study was conducted between October 2003 and April 2004.
  
  
  RESULTS
  Fifty patients were randomly assigned to treatment, and 39 were analyzed in a per-protocol population (23 men, 16 women; mean age = 37.9 years). CGI-Improvement scores of subjects taking MLR methylphenidate were significantly improved compared with placebo (Global Improvement: 2.6 vs. 3.7; p = .0015). MLR methylphenidate produced improvements over placebo on the ADHD Index T scores of the CAARS-S (12.2 vs. 5.4 [change from baseline score]; p = .0083) and the CAARS-O (10.9 vs. 6.6 [change from baseline score]; p = .1404). The most frequent adverse events for MLR methylphenidate and placebo were headache (26% and 24%, respectively), anorexia (22% and 6%), insomnia (22% and 8%), nervousness (20% and 4%), and nausea (16% and 8%). There were no serious adverse events.
  
  
  CONCLUSIONS
  Once-daily MLR methylphenidate produces significant improvements in ADHD symptoms and situational behavior in adult patients with ADHD, with a prolonged duration of effect and minimal side effects, thus having the potential to improve compliance and, therefore, treatment outcomes in routine clinical use.
authors.affiliation: Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Umesh
authors.initials: U
authors.lastname: Jain
authors.forename: Lily
authors.initials: L
authors.lastname: Hechtman
authors.forename: Margaret
authors.initials: M
authors.lastname: Weiss
authors.forename: Tahira S
authors.initials: TS
authors.lastname: Ahmed
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Reiz
authors.forename: Graeme A E
authors.initials: GA
authors.lastname: Donnelly
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Harsanyi
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Darke
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate