title: A randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy, safety, and tolerability of extended-release metadoxine in adults with attention-deficit/hyperactivity disorder.
abstract: OBJECTIVE
  To evaluate the efficacy, safety, and tolerability of an oral extended-release (ER) formulation of the nonstimulant metadoxine in the treatment of adult attention-deficit/hyperactivity disorder (ADHD).
  
  
  METHODS
  This was a 1:1 randomized, double-blind, placebo-controlled, parallel-design, phase 2 study of metadoxine ER 1,400 mg/d treatment for 6 weeks, following a 2-week baseline/screening period, involving 120 adults with DSM-IV-defined ADHD. A follow-up assessment occurred 2 weeks after the trial was completed. Efficacy measures included changes in Conners' Adult ADHD Rating Scale-Investigator Rated (CAARS-INV) total ADHD symptoms score with adult ADHD prompts (primary measure), response rates (≥ 25% or 40% improvement in CAARS-INV total ADHD symptom score), Test of Variables of Attention (TOVA) performance, and Adult ADHD Quality of Life (AAQoL) total score. The study was conducted from March 15, 2011, to August 21, 2011.
  
  
  RESULTS
  Intent-to-treat analysis revealed that subjects receiving metadoxine ER showed statistically significant improvement in CAARS-INV total ADHD symptoms score (P = .02), higher rate of response (≥ 25% [P = .03] or ≥ 40% [P = .04] improvement) on the CAARS-INV total ADHD symptoms score, and improvement in TOVA score (P = .02) and AAQoL score (P = .01) compared with the placebo group. Improvements in ADHD symptoms (scored by CAARS-INV) were significantly different in subjects treated with metadoxine ER versus placebo as early as 2 weeks following treatment initiation. Metadoxine ER was generally well tolerated, with nausea (17% [10/58] vs 0% [0/59]), fatigue (31% [18/58] vs 27% [16/59]), and headaches (29% [17/58] vs 39% [23/59]) being the most frequently reported adverse effects for the metadoxine ER and placebo groups, respectively.
  
  
  CONCLUSIONS
  Findings suggest that metadoxine ER is a well-tolerated and effective treatment for adults with ADHD.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01243242.
authors.affiliation: Geha Mental Health Center, Petach Tikva, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Manor
authors.forename: Rachel
authors.initials: R
authors.lastname: Ben-Hayun
authors.forename: Judith
authors.initials: J
authors.lastname: Aharon-Peretz
authors.forename: Dana
authors.initials: D
authors.lastname: Salomy
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
authors.forename: Yaron
authors.initials: Y
authors.lastname: Daniely
authors.forename: Dalia
authors.initials: D
authors.lastname: Megiddo
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Newcorn
authors.forename: Joseph
authors.initials: J
authors.lastname: Biederman
authors.forename: Lenard A
authors.initials: LA
authors.lastname: Adler
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011736:Pyridoxine / Q000008:administration & dosage* / Q000009:adverse effects*; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D003692:Delayed-Action Preparations; D004338:Drug Combinations; C037845:metadoxine; D011736:Pyridoxine; D011761:Pyrrolidonecarboxylic Acid