A pilot human study using ketamine to treat disorders of consciousness.

Post-comatose disorders of consciousness (DoC) represent persistent neurological conditions with limited therapeutic options and a poor prognosis. Recent works advocate for exploring the effects of psychedelics to enhance brain complexity in DoC and ameliorate their consciousness. We investigated sub-anesthetic concentration of the atypical psychedelic ketamine for treating post-comatose prolonged DoC through a double-blind, placebo-controlled, cross-over trial involving three adult patients. Incremental concentrations of intravenous ketamine and saline were administered, alongside continuous electroencephalogram (EEG) recording and assessments of conscious behaviors and spastic paresis. Brain complexity, measured by Lempel-Ziv complexity (LZC) and explainable consciousness indicator (ECI), revealed increased LZC during ketamine infusion but no change in ECI. Patients exhibited reduced spastic paresis and increased arousal as time spent with eyes open but no positive change in diagnosis. No adverse effects were noted. This study contributes to understanding the relationship between consciousness and brain complexity and suggests a potential therapeutic role for ketamine in DoC.