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.