Zenodo (CERN European Organization for Nuclear Research)
March 30, 2026
Psilocybin-assisted therapy has emerged as a promising intervention for treatment-resistant depression (TRD), yet standardized and transparent therapeutic frameworks remain limited. This therapist manual was developed for the EPIsoDE trial, a phase IIb randomized clinical study investigating the efficacy and safety of psilocybin with adjunct psychotherapy in patients with TRD (NCT04670081). The...
Psychopathology
March 27, 2026
Xiaoran Ding, Yaping Wu, Juan Yang et al.
1 citation
Ketamine has emerged as a promising rapid-acting antidepressant with distinct advantages for the treatment of treatment-resistant depression (TRD). Its therapeutic effects are mediated through multi-target modulation of the glutamatergic system. Unlike conventional antidepressants, ketamine exerts a markedly faster onset of action; however, its long-term safety profile and potential risk of...
Scientific Reports
March 27, 2026
Gianmauro Palombelli, Valentina Zecca, Marta Boffa et al.
1 citation
Major depressive disorder is highly prevalent and disabling, and many patients do not respond to standard therapies, resulting in treatment-resistant depression (TRD). Progress in TRD requires preclinical models with poor response to conventional treatments. The Wistar-Kyoto rat exposed to chronic mild stress (WKY/CMS) offers a robust paradigm: it shows limited responsiveness to standard...
Medicine Advances
March 27, 2026
Thomas Edward Cutting, Richard Evans Hartman
ABSTRACT Numerous studies have demonstrated the efficacy of (R, S)‐ketamine as a treatment for post‐traumatic stress disorder (PTSD), treatment‐resistant depression, and comorbid occurrences of these conditions. The (R) and (S) stereoisomers of ketamine have also demonstrated efficacy in attenuating stress and depressive symptoms, with (R)‐ketamine demonstrating reduced abuse potential and side...
Mindfulness
March 26, 2026
Céline Stinus, Sophie Berjot
Abstract Objectives This randomized controlled trial examined mechanisms underlying meditation-induced changes in self-related processes and compared attentional and deconstructive meditation. The objectives were to (1) examine whether components of selflessness mediate the effects of meditation on dysfunctional attitudes, identity threat, and depressive symptoms, and (2) compare the effects...
PsyArXiv
March 25, 2026
preprint
The Feasibility and Acceptability of Personalised Smart-Messaging To Enhance Remote Mindfulness-Based Cognitive Therapy for Recurrent Depression
JAMA Psychiatry
March 25, 2026
Wiesław Jerzy Cubała, Malek Bajbouj, Michael Bauer et al.
3 citations
Importance: Few pharmacotherapies are approved for treatment-resistant depression, and many patients do not achieve remission following treatment with those therapies. Objective: To examine the efficacy and safety of single-day treatment with a synthetic formulation of inhaled mebufotenin (GH001) vs placebo in patients with treatment-resistant depression. Design, Setting, and Participants: This...
Frontiers in Cell and Developmental Biology
March 25, 2026
Mizuki Yamamoto, Haruka Hirakata, Koji Toda
5 citations
Major depressive disorder is a highly prevalent psychiatric condition that can affect individuals across the lifespan, yet its pathophysiology remains incompletely understood. Classical hypotheses, informed by preclinical and clinical studies, emphasized dysregulated monoaminergic neurotransmission and guided the development of widely prescribed antidepressants, including selective serotonin...
Journal of Clinical Psychopharmacology
March 24, 2026
Riccardo Guglielmo, Emma Laura Facchinetti, Daniele Cioci et al.
Treatment-resistant depression affects up to one third of patients with major depressive disorder and is frequently accompanied by persistent cognitive impairments that significantly hinder functional recovery. Emerging evidence suggests that sub-anesthetic esketamine does not appear to be associated with cognitive deterioration and may be associated with procognitive effects; however, no...
CNS Drugs
March 24, 2026
Mathieu Seynaeve, Fiona Dunbar, Chandni Hindocha et al.
Intranasal 5-MeO-DMT Concomitant with SSRI for Treatment-Resistant Depression: A Proof-of-Concept Trial.
Mini reviews in medicinal chemistry
March 24, 2026
Shivaputra A Patil, Holly C Hunsberger
Psilocybin, chemically known as (4-phosphoryloxy-N, N-dimethyltryptamine, 4-PODMT), is derived from the psychoactive mushroom genus, Psilocybe. Of the four active metabolites, psilocin readily enters systemic circulation. The psychoactive effects of psilocin are thought to arise through partial agonist effects at the 5-HT2A receptor. Psychedelic drugs, including psilocybin, are having a...
Journal of psychopharmacology (Oxford, England)
March 21, 2026
Jesús García-Jiménez, D Nuñez-arias, G Carretero Merelo et al.
The trajectory and predictors of response under routine clinical care of esketamine nasal spray (ESK NS) over treatment-resistant depression (TRD) require elucidation. This retrospective, longitudinal cohort study was conducted across three Spanish centers. Adults diagnosed with TRD who initiated ESK NS and completed at least the induction phase were included. Assessments occurred at baseline,...
Nan fang yi ke da xue xue bao = Journal of Southern Medical University
March 20, 2026
Zhuoning Zhang, Xinyu Hao, Fuyang Cao et al.
To investigate the regulatory role of glutamatergic neurons in the medial prefrontal cortex (mPFC) in the antidepressant effects of esketamine. A total of 150 male C57BL/6J mice were randomly divided into 15 groups (n=10). The mice subjected to the chronic restraint stress (CRS), and those exhibiting depressive-like behaviors following CRS received either esketamine or saline treatment, and...
The Journal of ECT
March 19, 2026
Jennifer Sjödin, Karin Zimmer, Max Bell et al.
Electroconvulsive therapy (ECT) is an established treatment of major depressive disorder (MDD), particularly in severe cases and in cases resistant to pharmacological interventions. Anesthesia plays an important role in optimizing patient tolerability during ECT but may attenuate the treatment effect, as anesthetic agents elevate the seizure threshold. This review aims to examine the impact of...
JAMA Psychiatry
March 18, 2026
Zachary J. Williams, Hannah Barnett, Balázs Szigeti
10 citations
Importance: Psychedelic-assisted therapy (PAT) trials have high levels of functional unblinding, which biases results when comparing PAT with blinded interventions. Because PAT is effectively always open label, treatment results should be compared with those of open-label traditional antidepressants (TADs), so potential benefits associated with patients knowing their treatment is equal between...
JAMA Psychiatry
March 18, 2026
Lea J. Mertens, Michael Koslowski, Felix Betzler et al.
9 citations
Importance: Psilocybin shows promise in treating depression, although limitations of previous research warrant further research. Objective: To investigate the efficacy and safety of oral psilocybin, 25 mg, with adjunct psychotherapy in treatment-resistant depression (TRD). Design, Setting, and Participants: This was a 2-center, triple-blinded (investigator, participant, rater), phase 2b, active...
BMC Psychiatry
March 17, 2026
Bernhard T Baune, Kevin Rosemann, Dimitri Hefter et al.
2 citations
Intranasal esketamine: real-world clinical practice in treatment-resistant depression and factors associated with treatment response.
Frontiers in Computer Science
March 16, 2026
Akey Sungheetha, R. Rajesh Sharma, Oluwasegun Julius Aroba et al.
Introduction This computational modeling study introduces a novel Explainable Artificial Intelligence (XAI) framework for optimizing single-dose psilocybin treatment protocols through personalized intervention modeling using publicly available mental health datasets. All results presented are derived from novel simulated data and predictive modeling only, not from real-time clinical...
Journal of Affective Disorders
March 15, 2026
Patrícia Cavalcanti-Ribeiro, Lara Carvalho Araújo Melo De Souza, Vagner Deuel O de Tavares et al.
Treatment-resistant depression (TRD) remains a major clinical challenge, with inflammation increasingly implicated in its pathophysiology. C-reactive protein (CRP), an accessible biomarker, has emerged as a potential predictor of antidepressant response. While intravenous and intranasal ketamine have shown anti-inflammatory effects, evidence linking inflammation and clinical outcomes remains...
Cureus
March 14, 2026
Suneha Shelke, Rusheeth Thummalapally
Treatment-resistant depression (TRD) presents a complex clinical challenge, particularly when comorbid with substance use disorders (SUDs) or other compulsive behaviors. With up to a third of major depressive disorder (MDD) patients failing to respond to standard antidepressant therapies, there is growing interest in interventions such as esketamine, a glutamatergic N-methyl-D-aspartate (NMDA)...
Clinics and practice
March 13, 2026
Alessandro Guffanti, Matteo Leonardi, Natascia Brondino et al.
Major depressive disorder (MDD) is a leading cause of disability worldwide and contributes significantly to the global burden of disease. Recent data show an increasing prevalence of treatment-resistant depression (TRD). Patients with autism spectrum disorder (ASD) often exhibit MDD as a comorbidity and it is often resistant to conventional treatments. ASD determines emotional dysregulation and...
arXiv Preprint Archive
March 12, 2026
Yuxin Zhu, Sahithi Lakamana, Masoud Rouhizadeh et al.
Treatment-resistant depression (TRD) is a severe form of major depressive disorder in which patients do not achieve remission despite multiple adequate treatment trials. Evidence across pharmacologic options for TRD remains limited, and trials often do not fully capture patient-reported tolerability. Large-scale online peer-support narratives therefore offer a complementary lens on how patients...
Int J Psychiatry Clin Pract
March 11, 2026
Michele Prato, Matteo Carminati, Filippo Frizzi et al.
1 citation
Fast-acting approaches for treatment-resistant depression: real-world comparative effectiveness of Intranasal Esketamine versus accelerated rTMS.
Pharmacological Reports
March 11, 2026
Benjamin D. Brody, Dora Kanellopoulos
1 citation
Recent retrospective analyses have shown that individuals with comorbid Substance Use Disorders (SUDs) are overrepresented among responders to ketamine for Treatment Resistant Depression (TRD). Ketamine is an effective treatment for depression and also a potential substance of misuse. The authors contrast a mechanistic pathway with a possible expectancy effect to account for these findings, and...