Mood-altering compounds hold promise for the treatment of many psychiatric disorders, such as depression, but connecting their molecular, circuit, and behavioral effects has been challenging. Here we find that, analogous to effects in rodent learned helplessness models, ketamine pre-exposure persistently suppresses futility-induced passivity in larval zebrafish. While antidepressants are...
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...
ObjectivesMelancholic depression may respond differently to certain treatments. The aim of this study was to compare the antianhedonic effects of six intravenous injections of 0.5 mg/kg ketamine in patients with melancholic and non-melancholic depression, which remain largely unknown.MethodsIndividuals experiencing melancholic (n = 30) and non-melancholic (n = 105) depression were recruited and...
Ketamine can produce rapid-acting antidepressant effects in treatment-resistant patients with depression. Although alterations in glutamatergic and GABAergic neurotransmission in the brain play a role in depression, the precise molecular mechanisms in these neurotransmission underlying ketamine's antidepressant actions remain largely unknown. Mice exposed to FSS (forced swimming stress) showed...
Military MedicineDecember 20, 2022Grace Vitek, R. Langenfeld, R. Walters et al.
INTRODUCTION Major depressive disorder is a serious, recurrent, and disabling psychiatric illness. Despite many proven treatments with multiple medications or therapies, approximately 30% of patients fail to achieve remission and are considered to have treatment-refractory depression (TRD). Recently, there has been a growing interest in the use of intravenous (IV) ketamine for the treatment of...
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...
Ketamine is an N-methyl-d-aspartate antagonist which is increasingly being researched and used as a treatment for depression. In low doses, it can cause a transitory modification in consciousness which was classically labelled as ‘dissociation’. However, ketamine is also commonly classified as an atypical psychedelic and it has been recently reported that ego dissolution experiences during...
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...
Chronic pain often leads to depression, increasing patient suffering and worsening prognosis. While hyperactivity of the anterior cingulate cortex (ACC) appears to be critically involved, the molecular mechanisms underlying comorbid depressive symptoms in chronic pain remain elusive. T cell lymphoma invasion and metastasis 1 (Tiam1) is a Rac1 guanine nucleotide exchange factor (GEF) that...
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,...
Abstract Background Clinical trials have demonstrated rapid antidepressant effects with intravenous (IV) ketamine for major depressive disorder, with relatively less research specifically for bipolar depression. Herein, we describe the real‐world effectiveness of repeated ketamine infusions for treatment‐resistant bipolar depression. Methods This study was conducted in a community clinic in...
Background: Ketamine may be effective in treating symptoms of anxiety, but the time profile of ketamine’s anxiolytic effect is ill-defined. This systematic review and meta-analysis investigated the anxiolytic effect of ketamine at different time points across a range of clinical settings. Methods: Electronic databases were searched to capture randomised control trials measuring the anxiolytic...
Disease and DiagnosisDecember 7, 2022Farah Moayedi, Ali Massoudifar, Sholeh Namazi et al.1 citation
Background: Major depressive disorder (MDD) generally occurs together with depression in patients with no history of manic, mixed, or hypomanic episodes. The suicidal ideation in MDD patients is very common and can potentially be considered an emergency circumstance in many cases. Among the developed drugs and medicines, ketamine (KET) is a potential option to treat patients with MDD. This...
Classical psychedelics with 5-hydroxytryptamine-2A receptor (5-HT2AR) agonism have rapid antidepressant actions in patients with depression. However, there is an ongoing debate over the role of 5-HT2AR in the antidepressant-like actions of psychedelics. In this study, we compared the effects of DOI (2,5-dimethoxy-4-iodoamphetamine: a hallucinogenic psychedelic drug with potent 5-HT2AR agonism),...
BACKGROUND Intravenous (IV) ketamine is an effective therapy for treatment-resistant depression. A large data base is confirmatory and steadily expanding. Qualitative studies can inform best practices and suggest new research directions. As part of a clinical trial designed to identify biomarkers of ketamine response, a qualitative study was conducted to characterize experiences with: receiving...
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...
Background: Ketamine is a widely used anesthetic agent. Although the potential adverse effects of ketamine use in juvenile age are uncertain, certain studies reported that children exposed to recurrent anesthesia could face an increased risk of neurodevelopmental deficits in motor function and behavioral risks. We aimed to investigate the long-term effects of repeated exposure to various...
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: Evidence-based treatment options for late-life treatment-resistant depression (TRD) are limited. Ketamine is a promising treatment for TRD; however, there is a paucity of data on its safety and efficacy in older adults. Methods: In this pilot clinical trial, 25 adults aged ≥60 years with TRD received IV ketamine openly twice a week for 4 weeks; partial responders at the end of this...