Ketamine for Depression: Advances in Clinical Treatment, Rapid Antidepressant Mechanisms of Action, and a Contrast with Serotonergic Psychedelics.

The approval of ketamine for treatment-resistant depression has created a model for a novel class of rapid-acting glutamatergic antidepressants. Recent research into other novel rapid-acting antidepressants - most notably serotonergic psychedelics (SPs) - has also proven promising. Presently, the mechanisms of action of these substances are under investigation to improve these novel treatments, which also exhibit considerable side effects such as dissociation. This chapter lays out the historical development of ketamine as an antidepressant, outlines its efficacy and safety profile, reviews the evidence for ketamine's molecular mechanism of action, and compares it to the proposed mechanism of SPs. The evidence suggests that although ketamine and SPs act on distinct primary targets, both may lead to rapid restoration of synaptic deficits and downstream network reconfiguration. In both classes of drugs, a glutamate surge activates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) throughput and increases in brain-derived neurotrophic factor (BDNF) levels. Taken together, these novel antidepressant mechanisms may serve as a framework to explain the rapid and sustained antidepressant effects of ketamine and may be crucial for developing new rapid-acting antidepressants with an improved side effect profile.

Covid-19: Involvement of the nervous system. Identifying neurological predictors defining the course of the disease.

The main objective of this study was to analyse neurological symptoms during a Covid-19 infection and determine the pattern of symptoms by comparing outpatients with inpatients. A further goal was to identify possible predictors, such as pre-existing conditions and neurological symptoms. We recorded the clinical data of 40 inpatients and 42 outpatients in this retrospective, cross sectional study. Of them, 68 patients (83%), evenly distributed between the two groups, suffered from neurological symptoms. We identified the onset of neurological symptoms and the related time ranges in 41 patients (36 outpatients and 5 inpatients). Of these, 63.4% reported neurological symptoms on the first or second day of illness. 49 patients (72%) showed combinations of at least two to a maximum of seven different neurological symptoms. A more severe course of disease was correlated with age and male sex, but age was not identified as a predictor for the occurrence of neurological symptoms. Women suffered from central and neuromuscular symptoms more often than men (p = 0,004). The most common symptoms were fatigue (54%), headache (31%), loss of taste (31%), and loss of smell (27%). Pre-existing dementia was associated with increased lethality; similarly, pre-existing stroke was associated with a more severe course of Covid-19 infection. Hallucinations and confusion were related to an increased likelihood of death. The present data demonstrate the importance of comprehensive neurological support of inpatients and outpatients affected by Covid-19.