Ketamine in neuropsychiatric disorders: an update.
Jenessa N Johnston, Bashkim Kadriu, Christoph Kraus, Ioline D. Henter, Carlos A. Zarate
Neuropsychopharmacology January 2024 DOI: 10.1038/s41386-023-01632-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Subanesthetic-dose ketamine Esketamine |
| Topics | Esketamine Ketamine |
| Key findings | Considerable clinical research supports subanesthetic-dose ketamine and esketamine for multiple neuropsychiatric disorders and chronic pain, with rapid antidepressant responses within hours or days. The authors review pharmacology and proposed mechanisms, compare racemic ketamine, its (S) and (R) enantiomers, and the hydroxynorketamine (HNK) metabolite, and discuss clinical use, other psychiatric applications, and insights from novel therapeutics and neuroimaging. |
Abstract
The discovery of ketamine as a rapid-acting antidepressant led to a new era in the development of neuropsychiatric therapeutics, one characterized by an antidepressant response that occurred within hours or days rather than weeks or months. Considerable clinical research supports the use of-or further research with-subanesthetic-dose ketamine and its (S)-enantiomer esketamine in multiple neuropsychiatric disorders including depression, bipolar disorder, anxiety spectrum disorders, substance use disorders, and eating disorders, as well as for the management of chronic pain. In addition, ketamine often effectively targets symptom domains associated with multiple disorders, such as anxiety, anhedonia, and suicidal ideation. This manuscript: 1) reviews the literature on the pharmacology and hypothesized mechanisms of subanesthetic-dose ketamine in clinical research; 2) describes similarities and differences in the mechanism of action and antidepressant efficacy between racemic ketamine, its (S) and (R) enantiomers, and its hydroxynorketamine (HNK) metabolite; 3) discusses the day-to-day use of ketamine in the clinical setting; 4) provides an overview of ketamine use in other psychiatric disorders and depression-related comorbidities (e.g., suicidal ideation); and 5) provides insights into the mechanisms of ketamine and therapeutic response gleaned from the study of other novel therapeutics and neuroimaging modalities.
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
Cited by 56
- Mechanisms of SSRI Therapy and Discontinuation. Current Topics in Behavioral Neurosciences 2024
- Ketamine and its two enantiomers in anesthesiology and psychiatry: A historical review and future directions Journal of Anesthesia and Translational Medicine July 11, 2024
- Ketamine ameliorates post-traumatic social avoidance by erasing the traumatic memory encoded in VTA-innervated BLA engram cells. Neuron September 25, 2024
- Efficacy and safety of ketamine and esketamine for unipolar and bipolar depression: an overview of systematic reviews with meta-analysis Frontiers in Psychiatry February 1, 2024
- Novel rapid treatment options for adolescent depression. Pharmacological Research March 1, 2024
and 51 more in the library
Cites 95
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
and 90 more in the library