title: Attention benefits after a single dose of metadoxine extended release in adults with predominantly inattentive ADHD.
abstract: OBJECTIVE
  To assess the first-dose effectiveness and tolerability of metadoxine extended release (MDX) in adults with predominantly inattentive attention-deficit/hyperactivity disorder (ADHD-PI).
  
  
  METHODS
  In this double-blind, placebo-controlled, crossover study, adults with ADHD-PI were randomized 1:1:1 to receive a single dose of MDX 1400 mg, MDX 700 mg, and placebo (ClinicalTrials.gov identifier: NCT01685281). The primary efficacy end point was the mean change in the Test of Variables of Attention (TOVA) ADHD score from baseline to 3 to 5 hours after drug administration. Secondary assessments included TOVA subscores, TOVA response rates (defined as an increase of 0.8 points in the TOVA ADHD score), and the Cambridge Neuropsychological Automated Test Battery. Safety assessments included adverse events and vital signs.
  
  
  RESULTS
  The intention-to-treat population included 36 patients (52.8% men; mean age, 32 years). The efficacy of MDX 1400 mg was demonstrated by a statistically significant difference in the mean (± SD) change in the TOVA ADHD score at baseline to 3 to 5 hours after drug administration compared with placebo (2.0 [4.2]; P = 0.009). The TOVA response time variability subscore was significantly different between MDX 1400 mg and placebo (mean difference, 7.9 [19.2] points; P = 0.022). Significantly more adults responded to single-dose MDX 1400 mg versus placebo (97.1% vs 71.4%, P = 0.006). There were no statistically significant differences between MDX 700 mg and placebo on any measures. Exploratory analyses of the Cambridge Neuropsychological Automated Test Battery did not yield significant findings. Fatigue and headache were the 2 most frequently reported adverse events. There were no clinically significant abnormalities in laboratory values, vital signs measurements, Columbia-Suicide Severity Rating Scale scores, or electrocardiographic parameters.
  
  
  CONCLUSIONS
  Single-dose MDX 1400 mg significantly improved sustained and selective attention in adults with ADHD-PI as measured by the TOVA ADHD score 3 to 5 hours after drug administration. Single doses of MDX 700 and 1400 mg were well tolerated.
authors.affiliation: Associate Professor of Psychiatry, Geha Mental Health Center, Petah Tikva, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Manor
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rubin
authors.forename: Yaron
authors.initials: Y
authors.lastname: Daniely
authors.forename: Lenard A
authors.initials: LA
authors.lastname: Adler
mesh_terms: D000293:Adolescent; D000328:Adult; D001288:Attention / Q000187:drug effects*; 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; D004311:Double-Blind Method; D004338:Drug Combinations; D056344:Executive Function; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011736:Pyridoxine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D004338:Drug Combinations; C037845:metadoxine; D011736:Pyridoxine; D011761:Pyrrolidonecarboxylic Acid