A pilot human study using ketamine to treat disorders of consciousness.
Paolo Cardone, Arthur Bonhomme, Vincent Bonhomme, Nicolas Lejeune, Cécile Staquet, Aline Defresne, Naji Alnagger, Pauline Ezan, Minji Lee, Andrea Piarulli, Sebastien Van Goethem, Javier Montupil, Aurore Thibaut, Charlotte Martial, Olivia Gosseries
iScience January 17, 2025 DOI: 10.1016/j.isci.2024.111639 via PubMed
Summary
AI-generated from the abstractIn a small double-blind, placebo-controlled, cross-over trial with three adults who had prolonged disorders of consciousness after a coma, an intravenous sub-anesthetic dose of the atypical psychedelic ketamine increased brain complexity as measured by Lempel-Ziv complexity, but did not change the explainable consciousness indicator. Patients showed reduced spastic paresis and spent more time with their eyes open, yet their diagnosis of consciousness did not improve. No adverse effects occurred. The findings suggest a potential therapeutic role for ketamine in disorders of consciousness and support a link between brain complexity and conscious states.
Study at a glance
| Characteristics | Double-blind, placebo-controlled, cross-over trial Peer reviewed |
|---|---|
| Sample size | 3 |
| Population | Adult patients with post-comatose prolonged disorders of consciousness |
| Intervention | Intravenous ketamine |
| Dose | sub-anesthetic concentration, incremental concentrations |
| Duration | During infusion, with continuous EEG recording and assessments |
| Keywords | Biological sciences Drugs Neuroscience Pharmacology Psychedelic medicine |
| Citations | 9 |
| Key finding | Ketamine infusion increased Lempel-Ziv complexity and reduced spastic paresis and increased arousal, but did not change the explainable consciousness indicator or improve diagnosis. |
Abstract
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.