Journal of Affective Disorders - The Consciousness Library

Clinical correlates of anhedonia non-response to ketamine in treatment-resistant depression.

Journal of Affective Disorders August 15, 2026 Michał Walaszek, Wiesław Jerzy Cubała, Zofia Kachlik et al.

Anhedonia, a core symptom of major depressive disorder (MDD), is associated with illness severity, suicide risk, poor functioning, and predicts poor response to antidepressants. While no treatments are approved, ketamine and esketamine show promise in reducing anhedonia. This study examines clinical and sociodemographic features linked to anhedonia treatment response in treatment-resistant...

DOI: 10.1016/j.jad.2026.121762 Full text Ketamine Treatment-resistant depression Anhedonia Psychopharmacology

Exploratory non-randomized clinical trial of subcutaneous esketamine in treatment-resistant depression: Effects of ketamine-assisted psychotherapy

Journal of Affective Disorders August 10, 2026 Yves Martins Varela, Patrícia Cavalcanti-Ribeiro, Geovan Menezes de Sousa et al.

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...

DOI: 10.1016/j.jad.2026.122369

The role of therapeutic alliance in psilocybin treatment for treatment-resistant depression: A post hoc path analysis.

Journal of Affective Disorders August 1, 2026 Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al. 2 citations

The contribution of patient support to psilocybin's antidepressant effects remains uncertain. Relationships between therapeutic alliance (Scale to Assess Therapeutic Relationship-Patient version; STAR-P), psychedelic experience (Five-Dimensional Altered States of Consciousness Questionnaire and Emotional Breakthrough Inventory; 5D-ASC and EBI) and clinical outcomes (Montgomery-Åsberg Depression...

DOI: 10.1016/j.jad.2026.121662 Full text Psilocybin Treatment-resistant depression Psychedelic experience Psychological support +1

Psilocybin-assisted therapy for major depressive disorder: Perspective from meta-analysis.

Journal of Affective Disorders August 1, 2026 Taro Kishi, Kenji Sakuma, Masakazu Hatano et al.

This systematic review and meta-analysis of six randomized controlled trials aimed to investigate the temporal changes in the efficacy and safety of psilocybin treatment for major depressive disorder (MDD). Separate meta-analyses were conducted for standard-dose psilocybin (25 mg/session, or 20-30 mg/70 kg/session) and low-dose psilocybin (10 mg/session or 15.05 mg/70 kg/session) subgroups....

DOI: 10.1016/j.jad.2026.121675 Full text Depression Psilocybin Meta-analysis Randomized controlled trial +1

Comparative effectiveness and safety of esketamine versus injectable racemic ketamine and oral antidepressants for major depressive disorder: A population-based target trial emulation.

Journal of Affective Disorders August 1, 2026 Ching-Hua Julie Lee, Yunzhe Qian, Weiqun Yu et al.

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...

DOI: 10.1016/j.jad.2026.121487 Full text Esketamine Major depressive disorder Treatment-resistant depression Outcomes +1

Role of concomitant benzodiazepines, lithium, and lamotrigine in modulating the antidepressant effects of subcutaneous esketamine in patients with treatment-resistant depressive episodes: A retrospective naturalistic study.

Journal of Affective Disorders August 1, 2026 João Paulo Atidio, Rodrigo Simonini Delfino, Igor Saque Garios et al.

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...

DOI: 10.1016/j.jad.2026.121721 Full text Esketamine Treatment-resistant depression Benzodiazepine Lamotrigine +3

Serum brain-derived neurotrophic factor following oral esketamine in treatment-resistant depression: Results from a randomized placebo-controlled trial.

Journal of Affective Disorders July 16, 2026 Sara Massetti, Sanne Y Smith-Apeldoorn, Jolien K E Veraart et al.

Ketamine and its enantiomer esketamine are efficacious in 30-35% of the patients with treatment-resistant depression (TRD). Increased serum brain-derived neurotrophic factor (BDNF) following treatment has been proposed as a potential biomarker of antidepressant response. This is based on studies evaluating single intravenous ketamine treatment. BDNF expression at different treatment schedules...

DOI: 10.1016/j.jad.2026.122265 Full text Esketamine Major depressive disorder Brain-derived neurotrophic factor Clinical trial

Predictors of responsiveness to ketamine: An updated systematic review of neuroimaging findings.

Journal of Affective Disorders July 15, 2026 Iman Kiani, Giulia Cattarinussi, Fabio Sambataro et al.

Major depressive disorder (MDD) is a leading cause of disability worldwide, with a significant portion of patients experiencing treatment-resistant depression (TRD). Ketamine, a rapid-acting antidepressant, has shown promise in alleviating symptoms of TRD and suicidality, but variability in treatment response remains a challenge. Identifying neuroimaging biomarkers that predict responsiveness...

DOI: 10.1016/j.jad.2026.121521 Full text Ketamine Major depressive disorder Neuroimaging Suicidality

Sequential influences of emotion regulation and rumination in trait mindfulness-depression relationships.

Journal of Affective Disorders July 1, 2026 G. B. Maruthy, Lyndahl M. Himes, Nicholas A. Hubbard et al.

Depression is a common mental health disorder affecting millions worldwide. Pharmacotherapies are partially effective, but numerous side effects often make them unfavorable. Recent investigations show that mindfulness meditation effectively mitigates depression-symptoms but the underlying mechanisms remain elusive. Here, we examined the sequential influence of emotion regulation (ER) and...

DOI: 10.1016/j.jad.2026.122331

Intrinsic excitation-inhibition imbalance in major depressive disorder.

Journal of Affective Disorders June 29, 2026 Yao Ge, Lijuan Chen, Yu Shen et al.

Major depressive disorder (MDD) ranks among the foremost contributors to disability worldwide, yet its neurophysiological mechanisms remain poorly understood. Excitation-inhibition (E/I) imbalance has been implicated in MDD pathophysiology, but cortex-wide E/I ratio and its molecular substrates in MDD remain unknown. Resting-state functional magnetic resonance imaging data from 254 MDD patients...

DOI: 10.1016/j.jad.2026.122164 Full text Depression Ketamine Excitation-inhibition balance Hurst exponent

Increased morning cortisol after ketamine treatment for suicidal depression: Exploratory report from a randomized trial.

Journal of Affective Disorders June 25, 2026 Tse-Hwei Choo, Hanga C Galfalvy, John G Keilp et al.

Depression and its severe outcomes, suicidal ideation and behavior, are exacerbated by stress. A broad literature links dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) stress response system to depression, suicidal ideation and behavior. Our midazolam-controlled clinical trial of subanesthetic, intravenous ketamine infusion for suicidal depressed patients found rapid reduction...

DOI: 10.1016/j.jad.2026.122175 Full text Depression Ketamine Cortisol Resilience +2

Psilocybin-assisted cognitive behavioral therapy for major depressive disorder: A pilot trial.

Journal of Affective Disorders June 15, 2026 Marc J. Weintraub, Jessica K Jeffrey, Megan Ichinose et al.

Psilocybin-assisted therapy has emerged as a promising treatment for major depressive disorder, but little attention has been paid to the psychotherapy that adjoins psilocybin. Providing an adjunctive psychotherapy that is manualized and evidence-based may make psilocybin treatment more acceptable, effective, and disseminable. We examined the acceptability, feasibility, and clinical outcomes of...

DOI: 10.1016/j.jad.2026.121423 Full text Depression >psychotherapy Cbt Pat +4

The effect of a mindfulness-based stress reduction program on stress and quality of life in mothers of children with physical disabilities: A single-blind randomized controlled trial.

Journal of Affective Disorders June 15, 2026 Cengiz Taşkaya, Leyla Sezgin, Necmettin Çiftci

Mothers of children with physical disabilities often experience caregiving-related stress that may negatively affect their psychological well-being and quality of life. Mindfulness-based interventions may help reduce stress by improving awareness and emotional regulation. This study aimed to examine the effect of a mindfulness-based stress reduction (MBSR) program on parental stress,...

DOI: 10.1016/j.jad.2026.122131 Full text Mindfulness Disability Mothers Quality of life +1

Prescribing bias and adverse outcomes of esketamine in major depression comorbid substance.

Journal of Affective Disorders June 8, 2026 Dian‐jeng Li, Tien-Wei Hsu, Te-Chang Changchien et al.

Little is known about esketamine's effectiveness for patients with major depressive disorder (MDD) comorbid substance use disorders (SUD). We conducted a retrospective cohort study using the TriNetX US Collaborative Network, including adults aged ≥18 years with MDD. Three propensity-score-matched (1:1) cohorts were defined based on treatment: esketamine, antidepressant-only, and repetitive...

DOI: 10.1016/j.jad.2026.122106 Full text Esketamine Major depressive disorder Substance use disorder Mortality +1

Comparing transcranial magnetic stimulation and esketamine treatment response trajectories in resistant depression.

Journal of Affective Disorders June 7, 2026 Lindsay L Benster, Jordan N Kohn, Benjamin Wade et al.

Repetitive transcranial magnetic stimulation (rTMS) and intranasal esketamine are FDA-approved for treatment-resistant depression (TRD), yet comparative real-world data on response trajectories and predictors of outcomes remain limited. A retrospective analysis was performed using electronic medical records from UC San Diego Health. Adults with TRD treated with rTMS (n = 279) or intranasal...

DOI: 10.1016/j.jad.2026.122107 Full text Esketamine Treatment-resistant depression Rtms

Changes in anxiety, quality of life, and functioning following psilocybin-assisted therapy in veterans with treatment-resistant depression.

Journal of Affective Disorders June 4, 2026 Carlton M Kelly, Mathieu Fradet, Catherine Bostian et al.

Psilocybin has demonstrated promise for improving depressive symptoms in treatment-resistant depression, but its effects on anxiety, quality of life, functioning, and posttraumatic stress symptoms are less well studied. This study reports exploratory findings from an open-label trial in Veterans with TRD. Participants received a single 25-mg dose of psilocybin administered with psychological...

DOI: 10.1016/j.jad.2026.122063 Full text Anxiety Psilocybin Treatment-resistant depression Posttraumatic stress disorder +1

Unpacking the role of psychopathology in the state-to-trait mindfulness transition: A longitudinal structural equation modeling study.

Journal of Affective Disorders June 2, 2026 Veronica L O'Brien, Nicolette P. Rickert

Research has established that higher trait mindfulness is inversely associated with psychopathology in cross-sectional and longitudinal studies, and research has also demonstrated that mindfulness-based interventions increase trait mindfulness over time. The present study sought to investigate the trajectory of mindfulness development by examining whether repeated practice of state mindfulness...

DOI: 10.1016/j.jad.2026.122062 Full text Mindfulness-based stress reduction Psychopathology State mindfulness Trait mindfulness

Effects of ketamine on sleep and circadian rhythmicity in major depressive disorder and bipolar disorder: A systematic review.

Journal of Affective Disorders May 6, 2026 Rutger Boesjes, Claudia Oosterveld, Jeanine Kamphuis et al. 1 citation

Ketamine, including its enantiomers (S)-ketamine (esketamine) and (R)-ketamine (arketamine), has demonstrated rapid antidepressant effects in major depressive disorder (MDD) and bipolar disorder (BD), yet clinical responses vary widely, highlighting the need to identify mechanisms underlying treatment efficacy and related potential predictors. Growing evidence suggests that alterations in sleep...

DOI: 10.1016/j.jad.2026.121915 Full text Depression Ketamine Major depressive disorder Bipolar disorder +3

Is there an independant anti-suicidal effect of esketamine in treatment resistant depression?

Journal of Affective Disorders May 1, 2026 Michel Danon, Gabriela Ostronoff, Anne-Cécile Petit et al.

Regulatory approvals for intranasal esketamine in treatment-resistant depression (TRD) differ with respect to its indication for suicidal ideation. While rapid antidepressant effects are well documented, whether esketamine exerts an anti-suicidal effect independent of mood improvement remains unclear. In this two-center observational study, 261 adults with moderate-to-severe TRD at Sainte-Anne...

DOI: 10.1016/j.jad.2026.121181 Full text Depression Esketamine Suicide

Ketamine-related neural changes in treatment-resistant depression: A multimodal synthesis of fMRI and PET studies.

Journal of Affective Disorders April 28, 2026 Nesreen Sedeek, Carley Rivers, Lucas Williamson et al.

Ketamine produces rapid antidepressant effects in a subset of patients with treatment-resistant depression, yet neuroimaging findings have been difficult to integrate because studies differ in imaging modality, analytic approach, task context, and post-infusion timing. To address this, we conducted a multimodal synthesis of functional magnetic resonance imaging (fMRI) and positron emission...

DOI: 10.1016/j.jad.2026.121891 Full text Ketamine Brain networks Multimodal synthesis PET +2

A systematic review of ketamine and esketamine-induced long-term potentiation and synaptic scaling: Do the molecular and synaptic plasticity effects inform dosing intervals?

Journal of Affective Disorders April 15, 2026 Gia Han Le, Sabrina Wong, Danica E. Johnson et al. 4 citations

Ketamine and esketamine exhibit rapid antidepressant effects in persons with treatment-resistant depression (TRD) and bipolar depression (TRBD). However, the synaptic mechanisms governing dose, frequency, and durability of response remain unclear. This review aims to evaluate the dosing parameters, including minimum dose and optimal dosing intervals, that reliably induce or maintain long-term...

DOI: 10.1016/j.jad.2025.121081 Full text Depressive disorder Ketamine Drug administration schedule Long-term potentiation +2

Comparison of rTMS and esketamine for treatment-resistant depression: A target trial emulation.

Journal of Affective Disorders April 15, 2026 Jen-Ping Chen, Chih-Wei Hsu, Yi-Ting Chen et al.

Repetitive transcranial magnetic stimulation (rTMS) and esketamine are FDA-approved treatments for treatment-resistant depression (TRD), yet head-to-head comparative effectiveness data remain limited. Our study compared the effectiveness and safety profiles of rTMS versus esketamine in adults with TRD. This cohort study used target trial emulation with 1:1 propensity score matching on 50...

DOI: 10.1016/j.jad.2025.121132 Full text Esketamine Treatment-resistant depression Target trial emulation

The effect of dextromethorphan on reward-related behaviors: A systematic review of preclinical and clinical evidence.

Journal of Affective Disorders April 1, 2026 Kayla M Teopiz, Gia Han Le, Sabrina Wong et al.

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...

DOI: 10.1016/j.jad.2025.120836 Full text Depression Major depressive disorder Anhedonia Anticipatory +9

Inflammatory response to repeated subcutaneous esketamine in treatment-resistant depression: The role of baseline C-reactive protein.

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...

DOI: 10.1016/j.jad.2025.120877 Full text Esketamine Treatment-resistant depression Antidepressant response C-reactive protein +2

Does number of dosing sessions and type of adjunctive psychotherapy affect outcomes in psychedelic-assisted-psychotherapy for depressive disorders and anxiety disorders? A systematic review and meta-analysis.

Journal of Affective Disorders February 15, 2026 Tomas Lindegaard, Anton Käll

Although there is increasing evidence of the efficacy of psychedelic-assisted psychotherapy (PAP) for depressive and anxiety disorders, less is known regarding how different methodological aspects affect outcomes. This study investigated the moderating impact of one or multiple dosing sessions and type of adjunctive psychotherapy on the efficacy of PAP in depression and anxiety populations....

DOI: 10.1016/j.jad.2025.120732 Full text Anxiety Depression Psychedelic-assisted psychotherapy Meta-analysis +1

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