Ketamine Dosing Across Clinical Indications: A Narrative Review Organized by Proposed NMDA-Related Mechanisms.
The Journal of Clinical Pharmacology June 1, 2026 DOI: 10.1002/jcph.70225 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Esketamine Ketamine |
| Key findings | Ketamine's clinical indications fall into three categories based on glutamatergic tone and therapeutic mechanism, with dosing and treatment length varying accordingly. |
Abstract
Ketamine is a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) glutamate receptor. It was approved by the US Food and Drug Administration for anesthesia in 1970. The only other related US regulatory approval since then has been for esketamine nasal spray for depression in 2019. Over this time ketamine has been repurposed by mainly academic researchers, reporting clinical activity in diverse disorders such as status epilepticus, acute asthma, hyperactive delirium, and treatment resistant depression and anxiety. Importantly, dosing and length of treatment varies considerably by indication. Clinical indications responsive to ketamine fall into three categories: those where glutamatergic tone is normal and NMDA antagonism produces a desired effect (e.g., single bolus dosing for anesthesia, procedural sedation, and acute pain treatment); disorders where there is overactivity in glutamatergic tone and NMDA antagonism is therapeutic (e.g., prolonged infusion dosing for status epilepticus or status asthmaticus); and disorders where NMDA antagonism can enhance neuroplasticity (e.g., intermittent bolus treatment for depression/anxiety). Ketamine doses and duration of dosing differ for each of these three categories. This categorization may help generate hypotheses regarding dosing strategies for other potential novel indications such as eclampsia, anorexia nervosa, or functional neurological disorders.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cites 29
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) CNS Neuroscience & Therapeutics April 10, 2013
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- Taming the Ketamine Tiger Anesthesiology August 6, 2010
- Role of BDNF in the pathophysiology and treatment of depression: Activity‐dependent effects distinguish rapid‐acting antidepressants European Journal of Neuroscience December 6, 2019
and 24 more in the library