Methylphenidate and Memory and Attention Adaptation Training for Persistent Cognitive Symptoms after Traumatic Brain Injury: A Randomized, Placebo-Controlled Trial

Neuropsychopharmacology. 2017 Aug;42(9):1766-1775. doi: 10.1038/npp.2016.261. Epub 2016 Nov 22.


The purpose of this multicenter, prospective, randomized, placebo-controlled study was to evaluate and compare the efficacy of two cognitive rehabilitation interventions (Memory and Attention Adaptation Training (MAAT) and Attention Builders Training (ABT)), with and without pharmacological enhancement (ie, with methylphenidate (MPH) or placebo), for treating persistent cognitive problems after traumatic brain injury (TBI). Adults with a history of TBI at least 4 months before study enrollment with either objective cognitive deficits or subjective cognitive complaints were randomized to receive MPH or placebo and MAAT or ABT, yielding four treatment combinations: MAAT/MPH (N=17), ABT/MPH (N=19), MAAT/placebo (N=17), and ABT/placebo (N=18). Assessments were conducted pre-treatment (baseline) and after 6 weeks of treatment (post treatment). Outcome measures included scores on neuropsychological measures and subjective rating scales. Statistical analyses used linear regression models to predict post-treatment scores for each outcome variable by treatment type, adjusting for relevant covariates. Statistically significant (P<0.05) treatment-related improvements in cognitive functioning were found for word-list learning (MAAT/placebo>ABT/placebo), nonverbal learning (MAAT/MPH>MAAT/placebo and MAAT/MPH>ABT/MPH), and auditory working memory and divided attention (MAAT/MPH>ABT/MPH). These results suggest that combined treatment with metacognitive rehabilitation (MAAT) and pharmacotherapy (MPH) can improve aspects of attention, episodic and working memory, and executive functioning after TBI.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Attention / drug effects
  • Brain Injuries, Traumatic / complications
  • Brain Injuries, Traumatic / psychology
  • Brain Injuries, Traumatic / therapy*
  • Central Nervous System Stimulants / therapeutic use*
  • Cognition Disorders / etiology
  • Cognition Disorders / therapy*
  • Cognitive Behavioral Therapy*
  • Combined Modality Therapy
  • Double-Blind Method
  • Executive Function / drug effects
  • Female
  • Humans
  • Linear Models
  • Male
  • Memory / drug effects
  • Methylphenidate / therapeutic use*
  • Neuropsychological Tests
  • Treatment Outcome


  • Central Nervous System Stimulants
  • Methylphenidate