Abstract In March 2019, the US Food and Drug Administration (FDA) approved a nasal spray formulation of esketamine for the treatment of resistant depression in adults. Esketamine is the S-enantiomer of ketamine, an FDA-approved anaesthetic, known to cause dissociation and, occasionally, hallucinations. While ketamine has not been approved for depression in the USA or in any other country, it...
A paradigm shift in the conceptualization of the neurobiology of depression and the serendipitous discovery of ketamine's rapid-acting antidepressant (RAAD) effects has ushered in a new era of innovative research and novel drug development. Since the initial discovery of ketamine's RAAD effects, multiple studies have supported its short-term efficacy for fast-tracked improvements in...
This narrative review aims to provide an overview of the current literature on the pharmacology, safety, efficacy and tolerability of intranasal esketamine, the S-enantiomer of ketamine, for the treatment of treatment-resistant depression (TRD). A literature search using Medline, Embase, PsycINFO and Cochrane Central was conducted (January 2000 to July 2019). Product information and...
Background: Ketamine’s defining side effects are dissociation and increased blood pressure/heart rate. An oral formulation with delayed absorption could minimize these effects. We recently reported safety and tolerability data for an extended release ketamine tablet in healthy volunteers. Methods: To assess safety, tolerability, efficacy, and pharmacokinetics of an extended release oral...
Ketamine, a drug introduced in the 1960s as an anesthetic agent and still used for that purpose, has garnered marked interest over the past two decades as an emerging treatment for major depressive disorder. With increasing evidence of its efficacy in treatment-resistant depression and its potential anti-suicidal action, a great deal of investigation has been conducted on elucidating ketamine’s...
There are many putative mechanisms by which ketamine has its effect and many unanswered questions about risks and benefits of long-term ketamine therapy. A research imperative is the identification of predictors of response to intravenous ketamine, especially a sustained response to maintenance ketamine. Temperament is an inherited aspect of personality and is a predictive factor for outcome in...
As a field, psychiatry is undergoing an exciting paradigm shift toward early identification and intervention that will likely minimize both the burden associated with severe mental illnesses as well as their duration. In this context, the rapid-acting antidepressant ketamine has revolutionized our understanding of antidepressant response and greatly expanded the pharmacologic armamentarium for...
Clinical and preclinical studies have demonstrated that depression, one of the most common psychiatric illnesses, is associated with reduced levels of neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), contributing to neuronal atrophy in the prefrontal cortex (PFC) and hippocampus, and reduced hippocampal adult neurogenesis....
The pharmacological modulation of functional connectivity in the brain may underlie therapeutic efficacy for several neurological and psychiatric disorders. Functional magnetic resonance imaging (fMRI) provides a noninvasive method of assessing this modulation, however, the indirect nature of the blood-oxygen level dependent signal restricts the discrimination of neural from physiological...
Clinical and preclinical researches have shown that sub-anesthetic ketamine elicits sustained antidepressant effects for up to 1-2 weeks. Pharmacokinetics studies (t1/2 = 23 min) in mice showed no ketamine residue at 24 h after sub-anesthetic or anesthetic ketamine administration. Therefore, this study aims to reveal the mechanism underlying these different biological functions at 24 h after...