Ready for a "breakthrough" with ketamine? A look at recent pharmacological insights!
Sabine Himmelseher, Eberhard F Kochs
Current Opinion in Anaesthesiology August 1, 2021 DOI: 10.1097/aco.0000000000001017 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Esketamine Ketamine |
| Key findings | The authors argue that ketamine's antidepressant effects are explained by "disinhibition" of GABAergic interneurons and synaptogenic mechanisms, while its psychic adverse effects relate to a "disconnected consciousness" marked by disrupted resting-state and frontoparietal connectivity. They contend that more precise pharmacokinetic/pharmacodynamic models may improve ketamine regimens, but that volunteer data may not transfer to clinical conditions and the "breakthrough" has yet to come. |
Abstract
To update pharmacological insights on ketamine integrating information from different disciplines for developing steps to "breakthrough" approaches in clinical challenges. Pharmacokinetic/pharmacodynamic (PK/PD) models have incorporated recirculation, ketamine metabolites, drug-drug interaction, and covariates such as age. Ketamine-induced relief from treatment-resistant depression has been explained by "disinhibition" of gamma-aminobutyric acid-ergic interneurons and synaptogenic mechanisms requiring neurotrophic signals. Neuroimaging/electroencephalographic investigations have shown an increase in gamma spectral power in healthy volunteers and patients with depression, but also opposite changes in functional network connectivity after subanesthetic ketamine. Volunteer data may not be transferable to clinical conditions. Altered states of consciousness induced by subanesthetic ketamine have been described by disruption of resisting-state functional networks and frontoparietal connectivity with preservation of multisensory and sensor-motor networks. This has been interpreted as a "disconnected consciousness". More precise PK/PD models may improve the ketamine use regimen. The findings from research on depression are an important discovery because ketamine's impact on neuronal plasticity and synaptogenesis in human brain disease has directly been documented. Psychic adverse effects with subanesthetic ketamine are related to a "disconnected consciousness". Overall, progress has been made, but the "breakthrough" still has to come.
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 31
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- GABA interneurons are the cellular trigger for ketamine's rapid antidepressant actions. Journal of Clinical Investigation November 19, 2019
- Ketamine Has Distinct Electrophysiological and Behavioral Effects in Depressed and Healthy Subjects Molecular Psychiatry February 27, 2018
- Ketamine: A tale of two enantiomers Journal of Psychopharmacology November 6, 2020
- Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Journal of Neuroscience August 19, 2015
and 26 more in the library