medRxiv
Intravenous methylphenidate for acute traumatic disorders of consciousness: A phase 1 dose-finding and target engagement study
By Edlow, B. L., Barra, M. E., Schreier, D. R. and 7 others.
Abstract
Background
There are currently no therapies proven to accelerate recovery of consciousness for patient with acute severe traumatic brain injury (TBI) in the intensive care unit (ICU).
Methods
We performed an open-label, Phase 1 safety and dose-finding study of intravenous methylphenidate (IV MPH) in ICU patients with acute disorders of consciousness (DoC) caused by severe TBI. IV MPH was administered in daily doses of 0.5, 1.0, and 2.0 mg/kg. The primary outcome measure was the number of adverse events (AEs) at each dose. IV MPH pharmacokinetics were measured for 24 hours after each dose. The effect of IV MPH on brain networks was measured using EEG and resting-state functional MRI (rs-fMRI). A pharmacodynamic response was defined by change-point analysis of EEG and rs-fMRI time-series data. Behavioral responses were assessed using the Coma Recovery Scale-Revised (CRS-R).