Ketamine as a therapeutic agent for depression and pain: mechanisms and evidence.
Subha Subramanian, S. Haroutounian, Ben J Palanca, Eric J Lenze
Journal of Neurological Sciences 2022 DOI: 10.1016/j.jns.2022.120152 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Randomized Peer reviewed |
|---|---|
| Topics | Depression Esketamine Ketamine |
| Citations | 58 |
| Key findings | Intravenous and intranasal ketamine are both effective for acute depressive episodes, and intravenous ketamine is advantageous for post-operative analgesia with reduced opioid requirements, but more research is needed on treating concurrent depression and pain. |
Abstract
Ketamine is an anesthetic drug which is now used to treat chronic pain conditions and psychiatric disorders, especially depression. It is an N-methyl-D-aspartate (NMDA) receptor antagonist with additional effects on α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, opioid receptors, and monoaminergic receptors. This article focuses on ketamine's role in treating depression and pain, two commonly comorbid challenging conditions with potentially shared neurobiologic circuitry. Many clinical trials have utilized intravenous or intranasal ketamine for treating depression and pain. Intravenous ketamine is more bioavailable than intranasal ketamine and both are effective for acute depressive episodes. Intravenous ketamine is advantageous for post-operative analgesia and is associated with a reduction in total opioid requirements. Few studies have treated chronic pain or concurrent depression and pain with ketamine. Larger, randomized control trials are needed to examine the safety and efficacy of intravenous vs. intranasal ketamine, ideal target populations, and optimal dosing to treat both depression and pain.
Comparable studies
Other narrative reviews on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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: a paradigm shift for depression research and treatment | 2019 | Review | |
| Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective | 2019 | Review | |
| Ketamine: A tale of two enantiomers | 2020 | Review | |
| Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor | 2021 | Review |
Citations in the library
Cited by 17
- Perioperative Adjunctive Esketamine for Postpartum Depression Among Women Undergoing Elective Cesarean Delivery JAMA Network Open March 6, 2024
- Ketamine, an Old–New Drug: Uses and Abuses Pharmaceuticals December 21, 2023
- Effects of esketamine on postoperative fatigue syndrome in patients after laparoscopic resection of gastric carcinoma: a randomized controlled trial. BMC Anesthesiology May 24, 2024
- Low-dose ketamine for acute pain: A narrative review. The American Journal of Emergency Medicine December 1, 2024
- Optimizing esketamine administration for postoperative depression: a comprehensive study on laparoscopic bariatric surgery patients. Psychopharmacology February 1, 2025
and 12 more in the library
Cites 59
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
and 54 more in the library