Efficacy of methylphenidate in the rehabilitation of attention following traumatic brain injury: a randomised, crossover, double blind, placebo controlled inpatient trial

Abstract

Objectives: 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Results: No participants were withdrawn because of side effects or adverse events.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).