INTRODUCTION Dysfunction in amygdala networks has been implicated in major depressive disorder (MDD). Pharmacological treatments, such as esketamine and sertraline, are believed to exert their antidepressant effects by modulating amygdalar activity. This study aimed to investigate the relationship between changes in dynamic functional connectivity (dFC) within amygdala subregions and treatment...
INTRODUCTION Treatment-Resistant Depression (TRD) remains a major challenge in the management of Major Depressive Disorder (MDD). Esketamine, the S-enantiomer of ketamine and a glutamatergic modulator, has been approved by the FDA and EMA for TRD in 2019. Beyond its rapid antidepressant effects, esketamine may enhance neuroplasticity, facilitating the reconnection with emotional and cognitive...
Treatment-resistant depression (TRD) remains a relevant issue in psychiatric practice, driving the exploration of innovative therapeutic alternatives. Ketamine and its enantiomer, esketamine, are emerging as treatments known for their effectiveness as rapid-acting antidepressants. Although previous comparative studies have highlighted some differences in their effects, they did not concurrently...
Ketamine has been widely used since its discovery, and in addition to its anesthetic effects, in recent years it has been found to exhibit rapid and sustained antidepressant effects in rodent models and in patients with treatment-resistant depression (TRD) at subanesthetic doses. The antidepressant mechanism of ketamine has also been intensively studied, involving glutamate receptors such as...
Intranasal (IN) esketamine represents a novel add-on treatment for treatment-resistant depression (TRD) with reported favourable effects on insomnia. IN esketamine treatment might similarly reduce the incidence of insomnia as an adverse event (AE). The present meta-analysis therefore investigated whether IN esketamine relative to placebo is associated with a lower incidence of insomnia as an AE...
AIMS: This study aims to investigate the safety profile of Esketamine, with a particular focus on comparing adverse events (AEs) between adults (< 65 years) and older adults (≥ 65 years) using data from the FDA Adverse Event Reporting System (FAERS). METHODS: We conducted a comprehensive analysis of FAERS data from 2019 to 2024, identifying 6,452 Esketamine-related AE reports. After removing...
Esketamine has been shown to produce a major antidepressant response in patients with treatment-resistant depression (TRD). We evaluated the factors associated with achieving remission in these individuals. The study was carried out across four psychiatry departments in Madrid, Spain. Patients aged over 18 years were included if they received esketamine as an augmentation treatment for TRD....
This study aims to investigate the protective effects of esketamine on lung injury in rat models of chronic obstructive pulmonary disease (COPD) under mechanical ventilation. The focus is on serum exosome miRNA profiles through RNA sequencing and bioinformatics analysis. Male Sprague-Dawley rats were categorized into four groups: Control (C), COPD model (M), COPD model + saline (MS), and COPD...
Abstract Background Low dose ketamine has been shown, in animal studies, to enhance firing activity of norepinephrine neurons in the locus coeruleus, and burst as well as population activity of dopamine neurons in the ventral tegmental area [1]. These brainstem monoamine nuclei densely innervate the PFC, where clinical studies have shown a facilitation of glutamatergic neurotransmission in the...
This multicenter, randomized, placebo-controlled, clinical trial was designed to investigate the efficacy and safety of esketamine (ESK) for smoking cessation. The study enrolled a sample of 236 patients diagnosed with lung cancer and major depression disorder (MDD). Treatment included intranasal delivery of ESK or placebo once a week for 8 sessions. The primary outcomes were self-reported and...
Chronic stress is a risk factor for depression and may contribute to treatment resistance. This historical cohort study examined the association between baseline perceived stress, measured with the Perceived Stress Scale (PSS), and response to (es) ketamine in treatment-resistant depression (TRD). Adult TRD patients who received intravenous racemic ketamine or intranasal esketamine were...
OBJECTIVE To evaluate the safety of esketamine in bipolar depression, focusing on suicide-related outcomes and manic switch across timeframe and demographic subgroups. METHODS This retrospective cohort study was conducted in May 2025 using data from the TriNetX global collaborative network. Adults with bipolar depression treated with esketamine plus a mood stabilizer were propensity...
Frontiers in PsychiatryAugust 4, 2025Fernando Mora, J. Ramos-Quiroga, Enrique Baca-García et al.5 citations
Introduction Depression is a highly prevalent disease that severely impacts the life of patients. Inadequate response to at least two antidepressants despite adequacy of treatment and adherence is known as treatment-resistant depression (TRD), which entails a higher social and economic burden than non-resistant major depression. The lack of consensus on the definition of TRD and other aspects...
Ketamine has emerged as a promising treatment for major depression, though its efficacy and safety remain incompletely characterized in older adults. This systematic review synthesizes current evidence for ketamine in geriatric depression. A search of PubMed, EMBASE, and PsycINFO was conducted. Prospective clinical trials were included, with age restriction to participants ≥60 years applied at...
Background & Aims Esketamine, a promising treatment for treatment-resistant depression, has shown potential advantages over traditional antidepressants. However, its mechanisms remain unclear. This study explores how esketamine alleviates depressive behaviors through activation of the BDNF/TrkB/PI3K/AKT signaling pathway. Methods Using a Chronic Unpredictable Mild Stress (CUMS) rat model,...
The rapid and clinically meaningful antidepressant effects of ketamine and esketamine are well-established in major depressive disorder (MDD) and treatment-resistant depression (TRD) as evidenced by improvement in clinician- and patient-reported depression measures. However, there remains a need to determine how these agents affect patient-reported quality of life (QoL). Herein, we aimed to...
Ketamine and its enantiomers, esketamine and arketamine, have emerged as promising treatments for treatment-resistant depression (TRD). This cross-sectional study evaluates the regulatory alignment of 40 clinical trials listed on ClinicalTrials.gov, focusing on the methodological challenges. The study highlights methodological inconsistencies, particularly around the challenges of functional...
Pharmacological ResearchJuly 31, 2025C. Pisanu, R. Carvalho Silva, Mattia Meattini et al.6 citations
Treatment-resistant depression (TRD) remains a challenge in psychiatry, necessitating novel therapeutic strategies beyond traditional monoaminergic antidepressants. Ketamine and its S-enantiomer esketamine have demonstrated rapid and robust antidepressant effects in TRD, probably through mechanisms involving glutamatergic modulation, neuroplasticity, and anti-inflammatory properties. However,...
Objective: This study examines the durability (defined as time between treatments) of intravenous ketamine (IV-KET) and intranasal esketamine (IN-ESKET) for treatment-resistant depression (TRD), in a real-world clinical setting with repeated ketamine/esketamine maintenance therapy. Methods: This was a single-center, observational study of adults with TRD who completed acute-phase treatment...
Importance Psilocybin has demonstrated rapid and sustained antidepressant efficacy, with acute-phase effect sizes often more than double those for conventional antidepressants. However, concerns have been raised that high rates of functional unblinding in combination with trial participants with positive expectations of psychedelic use might bias treatment outcomes. Objective To compare...