Ketamine Dosing Across Clinical Indications: A Narrative Review Organized by Proposed NMDA-Related Mechanisms.
J Clin Pharmacol June 1, 2026 Paul Glue, Ben Beaglehole
Ketamine, an NMDA glutamate receptor antagonist approved for anesthesia in 1970 and later for esketamine as a nasal spray for depression, has been repurposed by academic researchers for disorders including status epilepticus, acute asthma, hyperactive delirium, and treatment-resistant depression and anxiety. Dosing and treatment length vary by indication. Clinical responses fall into three categories: conditions with normal glutamatergic tone where NMDA antagonism produces desired effects (e.g., anesthesia, sedation, acute pain); disorders with overactive glutamatergic tone where antagonism is therapeutic (e.g., status epilepticus, status asthmaticus); and conditions where NMDA antagonism enhances neuroplasticity (e.g., depression/anxiety). This framework may guide dosing strategies for potential new indications such as eclampsia, anorexia nervosa, or functional neurological disorders.