PharmaceuticalsDecember 26, 2022Lorena Catarina Del Sant, Luciana Maria Sarin, Ana Cecília Lucchese et al.
Esketamine has been approved by the US Food and Drug Administration (FDA) as an adjunctive treatment for use in conjunction with an oral antidepressant for patients with treatment-resistant depression (TRD), but dissociative symptoms are common adverse effects. A retrospective analysis of 394 subcutaneous esketamine injections given to 70 patients with TRD that were administered once a week...
Esketamine is a novel treatment for treatment resistant depression (TRD) and was approved by the FDA in early 2019. It antagonizes the NMDA receptor providing rapid improvement in symptoms with a complex mechanism of action primarily mediated through glutamatergic activation. Significant barriers exist to widespread use of esketamine including durability of response, particularly in the...
Alcohol use disorder (AUD) is especially prevalent among individuals with major depressive disorder (MDD) and is associated with higher morbidity, mortality, disability, and risk for suicide. Intranasal esketamine has been documented to be a safe and effective option for treatment resistant MDD and received US FDA approval in 2019. However, the availability of esketamine is limited due to...
BACKGROUND: "Dissociation" comprises distinct phenomena, some of which are associated with esketamine treatment and some may overlap with positive symptoms of psychosis. Relationships between dissociation and psychotic symptoms assessed by -clinician report vs conventional rating scales were investigated in a post hoc analysis of data from the initial treatment session in an -open-label,...
Pharmacological magnetic resonance imaging (phMRI) is a noninvasive method used to evaluate neural circuitry involved in the behavioral effects of drugs like ketamine, independent of their specific biochemical mechanism. The study was designed to evaluate the immediate effect of esketamine, the S-isomer of (±) ketamine on brain activity in awake mice using blood oxygenation level dependent...
Ketamine has demonstrated rapid and significant antidepressant effects in patients with treatment resistant depression (TRD). Herein, we conducted a systematic review to determine ketamine's efficacy as a function of the stage of treatment resistance (e.g., number of failed treatments) among individuals with TRD. A systematic search of PubMed and Scopus from inception to August 2021 was...
Objective: To evaluate the efficacy and safety of esketamine + antidepressant in treatment-resistant depression. Methods: We searched PubMed, Web of Science, Embase, CNKI, and Wanfang databases to obtain published information on esketamine + antidepressant from inception to July 2022. We searched for randomized controlled studies on the treatment of depression with a double-blind induction...
There is a pressing need to identify biological indicators of major depression to help guide proper diagnosis and optimize treatment. Animal models mimicking aspects of depression constitute essential tools for early-stage exploration of relevant pathways. In this study, we used the Flinders Sensitive and Resistant Line (FSL/FRL) to explore central and peripheral transcriptional changes in...
To present the first real-world data of patients with treatment-resistant depression (TRD) treated with esketamine through a French cohort Temporary Authorisation for Use (ATUc) programme. In 2019, the French Health Authorities exceptionally granted the first ATUc in psychiatry for TRD patients. Clinical characteristics, safety and efficacy data were reported by physicians. The ATUc ended ∼6...
Since a significant body of studies supports the involvement of glutamatergic neurotransmission in the neurobiology of obsessive-compulsive disorder (OCD). Ketamine, a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist with rapid and sustained antidepressant effect, raises as a potential new anti-OCD drug. Evidence from pre-clinical studies indicates that female mice are more sensitive...
Over the past two decades, ketamine has emerged as a novel effective and safe rapid-acting antidepressant. While the vast majority of studies on ketamine have focused on its ability to reduce the severity of depression broadly, its effectiveness in specific domains such as cognition, anhedonia, suicidality, and workplace/social/scholastic functionality has been neglected. Similarly, current...
This article presents a mechanism of action hypothesis to explain the rapid antidepressant effects of esmethadone (REL-1017) and other uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists and presents a corresponding mechanism of disease hypothesis for major depressive disorder (MDD). Esmethadone and other uncompetitive NMDAR antagonists may restore physiological neural plasticity in...
This publication discusses two compounds belonging to the psychoactive substances group which are studied in the context of depression treatment—psilocybin and esketamine. The former is a naturally occurring psychedelic. The latter was invented in the laboratory exactly 60 years ago. Although the substances were controversial in the past, recent studies indicate the potential of those...
bioRxiv Preprint ServerSeptember 6, 2022Tommaso Di Ianni, Matine M. Azadian, Sedona N. Ewbank et al.2 citations
preprint
Subanesthetic ketamine rapidly and robustly reduces depressive symptoms in patients with treatment-resistant depression. While it is commonly classified as an N-methyl D-aspartate receptor (NMDAR) antagonist, our picture of ketamine’s mechanistic underpinnings is incomplete. Recent clinical evidence has indicated, controversially, that a component of the efficacy of ketamine in depression may...
OBJECTIVE The aim of this study was to estimate the cost-effectiveness of esketamine nasal spray relative to intravenous ketamine for patients with treatment-resistant depression (TRD) in the US. METHODS We used a Markov model with a 1-month cycle length, and we estimated quality-adjusted life years (QALYs), costs (2020 USD), and incremental cost-effectiveness ratios (ICER) of esketamine...
INTRODUCTION: Esketamine is the S-enantiomer of racemic ketamine and has been approved by the Food and Drug Administration for the management of treatment resistant depression, demonstrating effective and long-lasting benefits. The objective of this observational study is to elucidate the association of intranasal (IN) esketamine with beneficial and negative outcomes in the management of...
OBJECTIVE N-methyl D-aspartate Receptor (NMDAR) antagonist antidepressants have known potential for abuse liability. The aim of this study was to evaluate the abuse liability of D-cycloserine (DCS), using a self-administration paradigm in which DCS was tested in its efficacy in substituting for ketamine in ketamine-dependent rats.
Background Intranasal esketamine has been recently approved for the treatment of resistant depression. It is the only form of ketamine approved. The formulation costs around $600 per dose while plain injected ketamine, on which most research has been done, costs less than $20 per dose. Research shows that intranasal esketamine is less effective and has more unwanted effects than injected...
Abstract Objective To assess the likelihood of attaining response/remission of depressive symptoms with esketamine nasal spray (ESK) plus standard of care (SoC) vs placebo nasal spray (PBO) plus SoC at 4 weeks in patients with major depressive disorder and active suicidal ideation with intent (MDSI) without early response. Methods A post hoc analysis of pooled data from ASPIRE I and ASPIRE II...
IntroductionAbout one third of patients with major depressive disorder (MDD) have treatment resistant depression (TRD). The difficulty of treating TRD especially in those with suicidal ideation and psychotic features demands treatments that are fast-acting, safe, and effective. Limited access, lack of viable options, and incomplete characterization of rapid-acting antidepressants has prevented...