Background: Posttraumatic stress disorder (PTSD) is a severe and frequent affection that is highly comorbid to major depressive disorder. Comorbid PTSD and depression increase the risk of treatment-resistant depression (TRD), with a high risk of functional impairment and suicide. Esketamine nasal spray is a recent validated treatment for TRD, but its efficacy on comorbid TRD-PTSD remains...
Treatment-resistant depression (TRD) remains a major clinical challenge in psychiatric practice and affects a substantial proportion of patients with major depressive disorder (MDD). It is commonly defined as failure to achieve remission after at least two adequately conducted antidepressant trials. TRD is associated with persistent functional impairment, increased morbidity, reduced quality of...
Extant literature suggests that anhedonia, defined as a loss of the ability to feel pleasure or interest, is subserved by dysregulation of reward processing in the central nervous system. Dextromethorphan (DXM), an uncompetitive N-Methyl-d-Aspartate (NMDA) receptor antagonist and sigma-1 (σ1) receptor agonist, is a glutamatergic modulator with antidepressant properties. The effect of DXM on...
Major Depressive Disorder (MDD) and chronic pain are independently debilitating conditions that frequently co-occur. This comorbidity poses a significant clinical challenge, resulting in greater symptom severity, higher disability, and worse prognosis than either condition alone. Current therapies often address each disorder in isolation, leaving individuals with comorbid MDD and chronic pain...
Borderline personality disorder (BPD) is often comorbid with major depressive disorder (MDD), and there has been a suggestion in the literature that this comorbidity may interfere with MDD treatment response. Our objective was to conduct a pilot study of psilocybin in adults with BPD and MDD. Adults aged 18 to 65 years with a DSM-5 diagnosis of MDD and BPD were enrolled in an open-label pilot...
Introduction: Treatment-resistant depression (TRD) represents a significant clinical challenge, particularly when associated with suicidal ideation. Intranasal esketamine has emerged as an effective therapeutic option in refractory cases, while monoamine oxidase inhibitors (MAOIs) remain relevant in the management of severe and resistant conditions. Objective: To describe the clinical course of...
Human Immunodeficiency Virus (HIV) infection remains a complex psychological and social challenge, particularly for women in the postpartum period. This case study aimed to illustrate the effectiveness of a mindfulness-based cognitive therapy (MBCT) within the biopsychosocial framework in reducing psychological distress in an HIV-positive housewife who had been diagnosed with a depressive...
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...
Background: Depression is a significant mental health condition affecting numerous individuals worldwide, leading to disability within society and posing a heightened risk of suicide, thereby diminishing overall quality of life. Depression, often a contributing factor in suicides, is associated with various prevalent medical conditions such as obesity, diabetes, stroke, Parkinson's disease, and...
PsychopathologyMarch 27, 2026Xiaoran 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 ReportsMarch 27, 2026Gianmauro 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 AdvancesMarch 27, 2026Thomas 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...
Objective: This study aimed to investigate the intervention effects of cognitive behavioral therapy (CBT) combined with mindfulness training on emotional regulation ability and sleep quality in adolescents with depressive disorders, providing evidence for optimizing non-pharmacological intervention strategies for adolescent depression in clinical settings. Methods: A total of 200 adolescent...
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...
PsyArXivMarch 25, 2026Sam Malins, Cosmin Manolescu, Tim Sweeney et al.
preprint
Mindfulness-Based Cognitive Therapy is a group psychological therapy that prevents relapse amongst people with recurrent depression. However, many people who attend MBCT do not fully benefit. This study assessed the feasibility, acceptability and initial clinical utility of personalised smart-messaging as an adjunct to remote Mindfulness-Based Cognitive Therapy (rMBCT) for recurrent depression...
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...
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...
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...
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...
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,...