INTRODUCTION: Acute suicidal ideation in major depressive disorder (MDD) is a psychiatric emergency requiring rapid risk assessment, containment, and treatment. Conventional monoaminergic antidepressants have delayed onset, leaving an interval during which severe depressive distress persists. Intranasal esketamine, a rapid-acting N-methyl-D-aspartate receptor antagonist, is approved for MDD...
Ketamine has been established as an anesthetic agent for decades. Around the turn of the millennium initial clinical studies demonstrated that subanesthetic doses of ketamine can exert antidepressant effects in treatment-resistant depression. These findings established the concept of an effective glutamatergic antidepressant treatment and initiated a paradigm shift. For many years, intravenous...
August 17, 2026Tychique T. Wasolua, Morgan S. Hardy, Tanner J. Bommersbach et al.
INTRODUCTION: Approximately 30-40% of patients with major depressive disorder fail to respond to conventional antidepressants. Ketamine and esketamine are increasingly used, yet synthesized data on cumulative safety remain limited. This systematic review evaluated long-term safety of both agents. METHODS: MEDLINE, PsycINFO, Embase, and Cochrane Library were searched from inception through...
BACKGROUND: Ketamine is an effective rapid-acting treatment for treatment-resistant depression (TRD), producing antidepressant effects within hours of administration. Because it induces states of heightened neuroplasticity and psychological openness, psychotherapy may enhance its therapeutic effects. METHODS: This exploratory, nonrandomized, open-label clinical trial evaluated the adjunctive...
This quality improvement project examined the impact of shared decision-making–guided music intervention integrated into esketamine treatment on depressive symptoms and quality of life in 10 adults with treatment-resistant depression at a private psychiatric clinic. Over 4 months, patients collaborated with their providers to select and listen to music during each session. Depressive symptoms...
Abstract Introduction Major depressive disorder (MDD) is characterized by dysfunction in higher-order cortical regions involved in emotional and cognitive processes; however, its neurobiological basis remains unclear. Pharmacological treatments, including esketamine and sertraline, produce rapid antidepressant effects. We investigated the local intrinsic neural dynamics underlying these...
This narrative review examines barriers to Danish patients' timely access to new treatments for treatment-resistant depression, focusing on controversies around esketamine. Delays arise from regulatory complexity, economic constraints and scientific debate over novel psychotropics. The review advocates evidence-based, faster implementation pathways for new treatments to alleviate the overall...
Background: Major depressive disorder (MDD) is highly prevalent and associated with significant disability and mortality. Treatment-resistant depression (TRD), defined as inadequate response to ⩾2 antidepressant lines, remains a major therapeutic challenge. Esketamine nasal spray, approved in 2019 for TRD, demonstrated efficacy and safety in randomized trials, but real-world evidence remains...
Trigeminal neuralgia (TN) is a debilitating orofacial pain condition frequently complicated by anxiety and depression, forming a self-reinforcing pain-affect cycle with limited therapeutic options. A TN mouse model with anxiety-like behavior was established using partial infraorbital nerve transection (pIONT). Esketamine (ES) (5 or 10 mg/kg) was administered intraperitoneally from postoperative...
This study evaluated the long-term comparative effectiveness and safety of esketamine versus injectable ketamine and esketamine versus oral antidepressants for major depressive disorder (MDD). This emulated target trial utilized observational data from a cohort of U.S. adults with MDD between 2018 and 2024. Patients were categorized into those receiving esketamine, injectable R,S-ketamine, and...
Ketamine and esketamine have been increasingly used as adjunctive treatments for treatment-resistant depression (TRD), yet evidence on pharmacological interactions with commonly prescribed psychotropic medications remains limited. This study evaluated the association between concomitant lamotrigine, lithium, and benzodiazepine use and antidepressant outcomes during subcutaneous esketamine...
Objectives: This article reviews the clinical status and treatment challenges of cancer-related depressive states, clarifies the mechanism of action of esketamine-a novel rapid-acting antidepressant-compares its efficacy with traditional drugs, evaluates safety and tolerability, and summarizes clinical evidence to support clinical practice and research. Methods: By searching databases such as...
This is a case report of a 52 year old female with ECT-refractory bipolar depression who was treated with esketamine nasal spray, leading to a noticeable improvement in her depressive symptoms. She experienced a relapse after a reduction in her maintenance treatment in conjunction with psychosocial stressors, but improved once again after returning to her induction regimen. She tolerated the...
Background Depression remains a leading cause of disability and suicide worldwide, with treatment-resistant depression (TRD) affecting nearly 30% of individuals diagnosed with major depressive disorder. Esketamine nasal spray (NS) and quetiapine extended-release (XR) are both approved as adjunctive therapies for TRD; however, direct head-to-head comparisons are limited. Method A systematic...
Treatment-resistant depression (TRD) is a heterogeneous condition in which symptoms such as anhedonia, rumination, and anxiety contribute to persistent disability. Esketamine nasal spray (ESK-NS), accelerated repetitive transcranial magnetic stimulation (arTMS), and adjunctive brexpiprazole represent novel therapeutic options with distinct mechanisms, though their domain-specific effects in...
Major depressive disorder (MDD) is a leading cause of disability worldwide, and current antidepressants are limited by delayed onset and incomplete efficacy. Esketamine produces antidepressant effects more rapidly than conventional treatments, but its underlying mechanisms remain unclear. We examined whether cannabinoid type 1 receptor (CB1R) signaling is associated with hippocampal...
This scoping review maps literature for use of ketamine or esketamine with psychotherapy for depression or depressive symptoms. Forty-seven studies were identified including 4/47 (9%) randomized controlled trials, 4/47 (9%) open label trials, 27/47 (57%) observational or retrospective studies, and 12/47 (26%) individual case reports. Studies were categorized as Ketamine/Esketamine Combined with...
Esketamine has been approved for the treatment of treatment-resistant depression. However, there is an unmet clinical need to extend the duration of esketamine's action to reduce the high recurrence rate after drug withdrawal and the potential side effects of repeated esketamine use. Here, we found that increasing extracellular signal-regulated kinase (ERK) activity by pharmacologically...