title: Placebo-controlled trial of amantadine for severe traumatic brain injury.
abstract: BACKGROUND
  Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery.
  
  
  METHODS
  We enrolled 184 patients who were in a vegetative or minimally conscious state 4 to 16 weeks after traumatic brain injury and who were receiving inpatient rehabilitation. Patients were randomly assigned to receive amantadine or placebo for 4 weeks and were followed for 2 weeks after the treatment was discontinued. The rate of functional recovery on the Disability Rating Scale (DRS; range, 0 to 29, with higher scores indicating greater disability) was compared over the 4 weeks of treatment (primary outcome) and during the 2-week washout period with the use of mixed-effects regression models.
  
  
  RESULTS
  During the 4-week treatment period, recovery was significantly faster in the amantadine group than in the placebo group, as measured by the DRS score (difference in slope, 0.24 points per week; P=0.007), indicating a benefit with respect to the primary outcome measure. In a prespecified subgroup analysis, the treatment effect was similar for patients in a vegetative state and those in a minimally conscious state. The rate of improvement in the amantadine group slowed during the 2 weeks after treatment (weeks 5 and 6) and was significantly slower than the rate in the placebo group (difference in slope, 0.30 points per week; P=0.02). The overall improvement in DRS scores between baseline and week 6 (2 weeks after treatment was discontinued) was similar in the two groups. There were no significant differences in the incidence of serious adverse events.
  
  
  CONCLUSIONS
  Amantadine accelerated the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness. (Funded by the National Institute on Disability and Rehabilitation Research; ClinicalTrials.gov number, NCT00970944.).
authors.affiliation: JFK Johnson Rehabilitation Institute, Edison, NJ, USA. jgiacino@partners.org
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Giacino
authors.forename: John
authors.initials: J
authors.lastname: Whyte
authors.forename: Emilia
authors.initials: E
authors.lastname: Bagiella
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kalmar
authors.forename: Nancy
authors.initials: N
authors.lastname: Childs
authors.forename: Allen
authors.initials: A
authors.lastname: Khademi
authors.forename: Bernd
authors.initials: B
authors.lastname: Eifert
authors.forename: David
authors.initials: D
authors.lastname: Long
authors.forename: Douglas I
authors.initials: DI
authors.lastname: Katz
authors.forename: Sooja
authors.initials: S
authors.lastname: Cho
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Yablon
authors.forename: Marianne
authors.initials: M
authors.lastname: Luther
authors.forename: Flora M
authors.initials: FM
authors.lastname: Hammond
authors.forename: Annette
authors.initials: A
authors.lastname: Nordenbo
authors.forename: Paul
authors.initials: P
authors.lastname: Novak
authors.forename: Walt
authors.initials: W
authors.lastname: Mercer
authors.forename: Petra
authors.initials: P
authors.lastname: Maurer-Karattup
authors.forename: Mark
authors.initials: M
authors.lastname: Sherer
mesh_terms: D000328:Adult; D000547:Amantadine / Q000009:adverse effects / Q000627:therapeutic use*; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D020207:Coma, Post-Head Injury / Q000188:drug therapy*; D004185:Disability Evaluation; D015259:Dopamine Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D008297:Male; D018458:Persistent Vegetative State / Q000188:drug therapy / Q000209:etiology; D020127:Recovery of Function
chemical_list: D015259:Dopamine Agents; D000547:Amantadine