European Psychiatry
June 1, 2026
O. Vasiliu, D. G. Vasiliu
Introduction Hopes related to esketamine have been raised by its approval for treatment-resistant major depression (TRD) in the sense that this antidepressant, with a novel mechanism of action, will be useful for patients with bipolar depression (BD), too. The need to find more evidence-based pharmacological approaches to both TRD and BD is acute due to the high rates of partial response or...
European Psychiatry
June 1, 2026
Nawfel Ayad, Samer Makhoul, F. Alkhaja
Introduction Treatment-resistant depression remains a major clinical challenge, with many patients experiencing relapse despite advances in medication and psychotherapy. Esketamine offers rapid relief from depressive symptoms, while psychotherapy helps patients build lasting skills to manage their condition. Despite their individual effectiveness, little is known about how these treatments work...
European Psychiatry
June 1, 2026
E. D. Cindik-Herbrueggen, A. S. Kucukali
Introduction Adult attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with mood and anxiety disorders (Sandstrom et al. Acta Psychiatr Scand 2021;143 380–391), and when major depressive disorder (MDD) is present, it often follows a treatment-resistant course (Thapar et al. J Child Psychol Psychiatry 2023;64 4–15). Intranasal esketamine, a non-competitive NMDA-receptor...
European Psychiatry
June 1, 2026
Jesús García-Jiménez, S. Posik, B. Herrejón et al.
Introduction Treatment-resistant depression (TRD) is highly burdensome. Intranasal esketamine is effective, yet hospital-centric delivery adds travel and continuity barriers that may hinder adherence and outcomes. We hypothesize that community outpatient, patient-proximal delivery —often with the patient’s usual psychiatrist—improves effectiveness, engagement and acceptability, consistent with...
European Psychiatry
June 1, 2026
M. P. Rapagnani, L. Veronesi, F. Sartini
Introduction In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments of antidepressants. Esketamine (the S-enantiomer of ketamine) nasal spray, administered in combination with either a selective serotonin reuptake inhibitor (SSRI) or a serotonine-norepinephrine reuptake inhibitor (SNRI), is the only treatment approved in Europe...
European Psychiatry
June 1, 2026
I. C. Mândraș, A. L. Comșa
Introduction Suicidality represents a major clinical and public health challenge, particularly among patients with treatment-resistant depression (TRD), who carry a disproportionately high risk of suicide. Traditional antidepressants often have delayed onset and limited efficacy in reducing suicidal ideation in this high-risk population, highlighting the need for rapid-acting interventions....
The Brown University Psychopharmacology Update
June 1, 2026
A two‐year extension of a trial of esketamine nasal spray in patients with treatment‐resistant depression has found no new safety concerns associated with long‐term use of the drug. The overall relapse rate across both the original trial and the extension was 6.9%.
European Psychiatry
June 1, 2026
Introduction Treatment-resistant depression (TRD) represents a major challenge in psychiatry. Nearly one-third of patients with major depressive disorder fail to achieve remission despite adequate antidepressant therapy, and about 30% attempt suicide during their lifetime. Given this elevated risk, identifying treatments that rapidly reduce depressive symptoms and suicidality while improving...
International Journal of Psychiatry in Clinical Practice
June 1, 2026
Damian Swieczkowski, Aleksander Kwaśny, Michal Pruc et al.
To explore sex, racial and ethnic disparities in esketamine clinical trials for mental health disorders registered on ClinicalTrials.gov. We conducted a registry-based cross-sectional analysis of interventional esketamine trials with results posted on ClinicalTrials.gov (cut-off date: 10 February 2025). Using predefined eligibility criteria, two investigators independently extracted and...
European Neuropsychopharmacology
June 1, 2026
Andreas Reif, Yağcıoğlu Ae Anıl, Istvan Bitter et al.
3 citations
Optimising patient outcomes in treatment resistant depression (TRD) requires treatments which provide sustained remission, without relapse, and tolerability in the long term. ESCAPE-LTE (NCT04829318) was a phase IV, single-arm, 2-year (104 weeks) long-term extension of ESCAPE-TRD (NCT04338321; 32 weeks), a rater-blinded, randomised, active-controlled trial, which evaluated the safety,...
Journal of Psychiatric Research
June 1, 2026
Ludovic Samalin, Maud Rothärmel, Lila Mekaoui et al.
In patients with treatment-resistant depression (TRD), the efficacy and tolerance of intranasal esketamine (ESK) spray, alone or combined with oral antidepressants, has been supported by clinical trials and observational studies. The French real-world ESKALE study assessed the benefit of ESK in 157 patients with TRD. In this post-hoc analysis of the ESKALE study we aimed to describe the...
British Journal of Pharmacology
June 1, 2026
Szabolcs Koncz, Dóra Pothorszki, Noémi Papp et al.
2 citations
Ketamine consists of two enantiomers, (R)-ketamine and (S)-ketamine, which exhibit distinct pharmacological properties. Currently, only the (S)-enantiomer has been approved for the treatment of major depressive disorder, whereas recent clinical studies have failed to demonstrate an antidepressant effect for (R)-ketamine. The quantitative electroencephalography (qEEG) gamma-enhancing effect of...
Asian Journal of Psychiatry
June 1, 2026
Fabiola Raffone, Filippo Mazzoni, Arianna De Ciechi et al.
3 citations
Suicidal ideation and deliberate self-harm are frequent and persistent in treatment-resistant depression (TRD), particularly when comorbid borderline personality disorder (BPD) is present. Real-world evidence on antisuicidal outcomes during intranasal esketamine in this population remains limited. In this multicentre prospective observational study, 90 outpatients with TRD received intranasal...
Biomedicines
June 1, 2026
Masaru Tanaka
Major depressive disorder remains a leading cause of disability, and decades of monoamine-centered pharmacology have yielded delayed and often incomplete relief. Rapid-acting antidepressants reshaped the field by linking swift symptom improvement to glutamatergic plasticity, yet durable benefit depends on how newly reconfigured circuits are stabilized and tuned. This review synthesizes evidence...
medRxiv Preprint Server
May 31, 2026
Yves Martins Varela, Patrícia Cavalcanti-Ribeiro, Geovan Menezes de Sousa et al.
preprint
Background Ketamine has emerged as an effective rapid-acting treatment for treatment-resistant depression (TRD), producing significant antidepressant effects within hours of administration. Given ketamine’s capacity to induce states of heightened neuroplasticity and psychological openness, psychotherapy may represent a meaningful complement to its pharmacological effects — facilitating...
Research Square
May 27, 2026
Tychique T. Wasolua, Tanner J. Bommersbach, Roger S McIntyre et al.
preprint
Abstract Ketamine and esketamine are increasingly used as rapid-acting antidepressants, yet concerns remain regarding potential structural neurotoxicity, particularly with chronic or high-dose exposure. Despite expanding clinical use, no comprehensive systematic review has integrated neurotoxicity evidence across preclinical and human studies while formally evaluating methodological quality....
Therapeutic Advances in Psychopharmacology
May 22, 2026
Liliana Patarroyo-Rodriguez, Vanessa K. Pazdernik, Jennifer L. Vande Voort et al.
Background: Ketamine and esketamine ((es)ketamine) rapidly reduce depressive symptoms and suicidal ideation (SI) in treatment-resistant depression (TRD), but whether early SI improvement during the acute phase of the treatment predicts reduced suicide-associated emergency department (SAED) visits over the longer term remains unclear. Objectives: To examine whether early improvements in SI,...
Therapeutic Advances in Psychopharmacology
May 19, 2026
correction
[This corrects the article DOI: 10.1177/20451253261437597.].
Behavioral Sciences
May 14, 2026
Fabiola Raffone, Carlo Ignazio Cattaneo, Enrico Pessina et al.
Trauma-related autobiographical memories can manifest as involuntary, vivid, emotionally charged intrusions that perpetuate avoidance, negative emotions, and functional impairment. While these memories are central to post-traumatic stress disorder (PTSD), they also occur across diagnoses and are often reported in depressive disorders, including treatment-resistant depression (TRD). Although...
Fortschritte der Neurologie · Psychiatrie
May 13, 2026
Cornelius Schüle, Anna Sobieraj, Helena Rogg
1 citation
Abstract: Esketamine is an NMDA receptor antagonist and was approved as a nasal spray in March 2019, initially in the USA and then in December 2019 in Europe, as an adjunct to antidepressant pharmacotherapy for the treatment of treatment-resistant major depression or for rapid symptom reduction in psychiatric emergency situations in patients with major depression. In addition, esketamine nasal...