Efficacy of methylphenidate in the rehabilitation of attention following traumatic brain injury: a randomised, crossover, double blind, placebo controlled inpatient trial.
OBJECTIVE
Most previous studies evaluating the use of methylphenidate following traumatic brain injury (TBI) have been conducted many years post-injury. This study evaluated the efficacy of methylphenidate in facilitating cognitive function in the inpatient rehabilitation phase.


METHODS
40 participants with moderate-severe TBI (mean 68 days post-injury) were recruited into a randomised, crossover, double blind, placebo controlled trial. Methylphenidate was administered at a dose of 0.3 mg/kg twice daily and lactose in identical capsules served as placebo. Methylphenidate and placebo administration was randomised in a crossover design across six sessions over a 2 week period. Primary efficacy outcomes were neuropsychological tests of attention.


RESULTS
No participants were withdrawn because of side effects or adverse events. Methylphenidate significantly increased speed of information processing on the Symbol Digit Modalities Test (95% CI 0.30 to 2.95, Cohen's d = 0.39, p = 0.02), Ruff 2 and 7 Test-Automatic Condition (95% CI 1.38 to 6.12, Cohen's d = 0.51, p = 0.003), Simple Selective Attention Task (95% CI -58.35 to -17.43, Cohen's d = 0.59, p = 0.001) and Dissimilar Compatible (95% CI -70.13 to -15.38, Cohen's d = 0.51, p = 0.003) and Similar Compatible (95% CI -74.82 to -19.06, Cohen's d = 0.55, p = 0.002) conditions of the Four Choice Reaction Time Task. Those with more severe injuries and slower baseline information processing speed demonstrated a greater drug response.


CONCLUSIONS
Methylphenidate enhances information processing speed in the inpatient rehabilitation phase following TBI. This trial is registered with the Australian New Zealand Clinical Trials Registry (12607000503426).
Willmott
C
C
Psychology Department, School of Psychology, Psychiatry and Psychological Medicine, Monash University, Clayton, Victoria, Australia. catherine.willmott@med.monash.edu.au
Ponsford
J
J
D000293:Adolescent; D000328:Adult; D001288:Attention / Q000187:drug effects*; D001930:Brain Injuries / Q000523:psychology / Q000534:rehabilitation*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008570:Memory, Short-Term; D008774:Methylphenidate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D016896:Treatment Outcome; D014888:Wechsler Scales; D055815:Young Adult
D000697:Central Nervous System Stimulants; D008774:Methylphenidate