Ketamine, an N-methyl-D-aspartate receptor antagonist, is a racemic mixture of esketamine and arketamine used to treat unipolar and bipolar depression. Preliminary reports indicate that it may be beneficial for depressed patients reporting symptoms of anhedonia. In this systematic review we aim to assess and analyze the existing body of evidence regarding the therapeutic effects of ketamine on the domain of anhedonia. Electronic databases (PubMed, APA Psycinfo and Web of Science) were searched from inception to November 2023. Protocol was registered in PROSPERO under the identifier CRD42023476603. A total of twenty-two studies, including four randomized-controlled trials and eighteen open-label trials were included. All studies reported alleviation of anhedonia symptoms following ketamine or esketamine administration, regardless of the number of infusions. Several important limitations were included, first and foremost low number of placebo-controlled randomized-controlled trials. This review indicates a potential anti-anhedonic effect of ketamine in patients with depression. Several trials used neuroimaging techniques which confirm ketamine's effect on functional connectivity correlating with the improvement in anhedonia. Despite considerable variations in methodology and the specific brain regions investigated, these studies collectively point towards ketamine's neuroplastic effects in mitigating anhedonia.

2024-07-01·Folia Pharmacologica Japonica

Resolvin E1 as a potential lead for the treatment of depression

Article

作者: Kaneda, Katsuyuki ; Minami, Masabumi ; Deyama, Satoshi

Typical monoamine-based antidepressants have significant limitations, including a time lag for therapeutic response and low efficacy (more than one-third of depressed patients fail to respond to multiple antidepressant medications and are considered treatment-resistant). Conversely, ketamine, an N-methyl-D-aspartate receptor antagonist, exhibits rapid and sustained antidepressant actions in patients with treatment-resistant depression. However, clinical use of ketamine is limited due to its serious side effects. Thus, there is a significant need to develop novel ketamine-like antidepressants with fewer side effects. We previously demonstrated that intracerebroventricular infusion of resolvins (RvD1, RvD2, RvE1, RvE2, and RvE3), specialized pro-resolving lipid mediators derived from docosahexaenoic and eicosapentaenoic acids, produce antidepressant-like effects in mouse models of depression. Among resolvins, RvE1 produces the most potent antidepressant-like effects likely via ChemR23 in several mouse models of depression. Local infusion of RvE1 into the medial prefrontal cortex (mPFC) or dorsal hippocampal dentate gyrus (DG) also produces antidepressant-like effects, suggesting that these brain regions are sites of action of RvE1. Additionally, intranasal (i.n.) administration of RvE1 produces antidepressant-like effects through mechanisms similar to ketamine: activity-dependent release of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), and subsequent mechanistic target of rapamycin complex 1 (mTORC1) activation in the mPFC play a crucial role in the rapid and sustained antidepressant-like actions of i.n. RvE1. Moreover, the antidepressant-like effects of i.n. RvE1 require BDNF and VEGF release, but not mTORC1 activation, in the dorsal DG. These findings suggest that RvE1 can be a promising lead for a novel rapid-acting antidepressant.

2024-06-01·Neurocritical Care

Ketamine to Prevent Endotracheal Intubation in Adults with Refractory Non-convulsive Status Epilepticus: A Case Series

Article

作者: Syed, Maryam J ; Muzammil, Syeda Maria ; Mohamed, Wazim ; Zutshi, Deepti

BACKGROUNDNon-convulsive status epilepticus (NCSE) is defined as status epilepticus (SE) with no obvious motor phenomenon and is diagnosed based on electroencephalogram (EEG). Refractory SE (RSE) is the persistence of seizures despite treatment with an adequately dosed first-line and second-line agents. Although guidelines for convulsive RSE include third-line agents such as intravenous anesthetic drugs (midazolam, propofol, or barbiturates), the therapeutic approach to NCSE is not well outlined. Treatment with traditional anesthetics invariably includes endotracheal intubation, which is associated with significant adverse events. Comparatively, ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist is not associated with significant cardiorespiratory depression and may help in avoiding intubation.OBJECTIVEIn this case series, we describe our experience with the early use of intravenous ketamine as the first anesthetic agent in patients with refractory NCSE to avoid endotracheal intubation.METHODSWe present a case series of nine patients managed in the Neurointensive Care Unit at a university-affiliated tertiary care hospital. The study was approved by the hospital and university institutional review boards and the requirement for informed consent was waived for retrospective analysis of existing data, per institutional policy. All cases of SE were identified from a prospective database, and a subsequent retrospective chart review identified all patients with a diagnosis of refractory NCSE in whom ketamine was used as the first anesthetic agent. The primary endpoint was the avoidance of endotracheal intubation while on ketamine infusion. The secondary endpoint was defined as cessation of both clinical and electrographic seizures recorded on continuous EEG within 24 h of ketamine administration.RESULTSA total of nine patients experiencing refractory NCSE were included in this case series, with a median age of 61 (range 26-72) years and seven patients were male. The primary endpoint, avoiding intubation, was achieved in five out of nine (55%) cases. Six patients experienced resolution of refractory NCSE with ketamine administration as the sole anesthetic agent. Four patients required endotracheal intubation and three patients had a failure of seizure cessation with ketamine. Hypersalivation and pneumonia were the most common ketamine associated adverse events. In non-intubated patients, no deaths occurred. One patient was discharged home, four to subacute rehabilitation, one to a long term acute care hospital, and one patient to hospice.CONCLUSIONThe use of ketamine as the primary anesthetic agent may be a reasonable option to avoid endotracheal intubation in a subset of patients with refractory NCSE. This study is limited by its small sample size, retrospective design, and reliance on information obtained from chart review.

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适应症	最高研发状态	国家/地区	公司	日期
疼痛	临床前	美国	Merck Research Laboratories Massachusetts LLC	2007-01-24
帕金森病	临床前	美国	Merck Research Laboratories Massachusetts LLC	2007-01-24