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...
Stress worsens clinical outcomes in patients with major depressive disorder (MDD); however, timely accessible stress management tools remain limited. Digital interventions offer scalable adjunctive solutions early during pharmacological treatment. In this multicenter, assessor-blinded, randomized controlled crossover pilot trial, we conducted a preliminary evaluation of the short-term efficacy...
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...
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,...
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...
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...
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...
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...
Background: Off-label use of intravenous ketamine (IVK) for depression is a widespread practice with limited regulation in the United States. There is an urgent need for current, evidence-informed treatment guidelines to facilitate patient safety, clinical decision-making, and care quality in real-world contexts. Methods: The American Society of Ketamine Physicians, Psychotherapists and...
Major Depressive Disorder (MDD) affects millions globally, with approximately 30% of patients experiencing treatment-resistant depression (TRD). While ketamine has emerged as a rapid-acting intervention, response rates remain variable, underscoring the need to refine precision medicine approaches for ketamine treatment. Network theories of mental health disorders have been promoted as framework...
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...
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...
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...
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...
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...
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...
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...
Based on findings in cross-lagged panel network (CLPN) models, Ma et al. concluded prospective effects between indicators of mindfulness and mental health problems. Here, we used multiverse methodology and found discrepant increasing, decreasing, and null effects depending on the used model, and meta-analytic aggregations of these discrepant effects did not differ significantly from zero....
Objective: While inflammatory dysregulation is well-documented in major depressive disorder (MDD), its response to esketamine treatment in adolescents remains poorly understood. We aimed to examine the effects of esketamine on the inflammatory cytokines in adolescent MDD. Methods: This randomized, double-blind trial assigned 49 adolescents with MDD to receive three infusions of esketamine or...
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....
General anesthetics can exert significant adverse effects on the central nervous system. This study aimed to investigate whether repeated exposure to sevoflurane induces depression-like behaviors in postpartum rats. Pregnant rats were exposed to 3% sevoflurane for 2 h on gestational days 13-15. Emotional behaviors were assessed on postpartum days 1, 7, 14, and 21. Hippocampal protein levels...
Anhedonia, a core symptom of depression, is often resistant to conventional treatments and significantly impacts quality of life. This secondary analysis aimed to evaluate the effects of psilocybin-assisted psychotherapy (PAP) on anhedonia severity in individuals with treatment-resistant depression (TRD). Participants (n = 30) with TRD and a primary diagnosis of Major Depressive Disorder or...
Ketamine is known to be a rapid-acting antidepressant, but there is limited evidence regarding which types of patients are best-suited to this treatment and whether adjunctive psychotherapy improves outcomes. In a sample of 224 patients who received five ketamine infusions at a private clinic, this study uses Bayesian mixed modeling to examine the effects of early life stress (measured with the...
Australia recently became the first country to reschedule methylenedioxymethamphetamine (MDMA) to permit authorized prescribing for post-traumatic stress disorder (PTSD) outside of clinical trials. This study explored the direct experience of Australian clinicians, researchers, and patients regarding the use of MDMA-assisted psychotherapy (MDMA-AP) for PTSD to inform guideline development....
In recent years psychedelics have gained popularity and potential promise in the field of mental health, but for patients diagnosed with bipolar disorder (BD), fears of emerging manic or psychotic symptoms have caused investigators to exclude them from psychedelic research. In this observational study, we explore the motivations, expectations, and personality characteristics of individuals with...