Several studies have reported entropy reductions in regions of the brain associated with affective-regulatory and reward- and motivation-related processes in patients with major depressive disorder. However, whether low-dose ketamine modulates this reduction remains unclear. We analyzed resting-state functional magnetic resonance imaging data from two single-infusion low-dose ketamine trials....
We examined symptom-level treatment effects and exploratory symptom networks after ketamine in treatment-resistant depression. This post hoc analysis pooled 132 participants assigned to ketamine 0.5 mg/kg or protocol-specific control (66 each) from saline-controlled 2017 and midazolam-controlled 2023 trials. Baseline- and trial-adjusted models assessed Montgomery-Åsberg Depression Rating Scale...
Background: Studies have demonstrated that subanesthetic-dose ketamine may modulate the functioning of specific depression-related brain regions, particularly the anterior cingulate cortex and prefrontal cortex. However, how subanesthetic-dose ketamine alters the global and regional graph theory metrics of resting-state functional connectivity in patients with treatment-resistant depression...
Emerging evidence shows that ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, can produce rapid anti-suicidal effects in treatment-resistant depression, yet its underlying neuropharmacological mechanisms remain elusive. The present study aimed at investigating the therapeutic effect of ketamine infusion on suicidal ideation by examining hemodynamic response changes in resting-state...
Intravenous ketamine demonstrates rapid efficacy for treatment-resistant depression (TRD). However, its impact on individual depressive symptoms and whether the degree of treatment resistance moderates these effects remain unclear. This study aimed to dissect symptom-specific trajectories and examine the moderating role of the degree of treatment resistance. We conducted a post-hoc analysis of...
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...
As accumulating evidence suggests the antisuicidal properties of ketamine, elucidating its underlying mechanisms and predictors of treatment response has become crucial. Whether a combination of clinical markers can enhance the prediction of the antisuicidal response to ketamine remains unclear.Using data from our previous randomized placebo-controlled and open-label trials, this post hoc...
Abstract This paper distinguishes the drug-centered view of psychedelics (DCP) and the drug-assisted view of psychedelics (DAP). While these approaches differ conceptually, both rely on the methodology of evidence-based medicine, using randomized controlled trials to validate therapeutic efficacy. Using MDMA-assisted psychotherapy as a case study of DAP, we reconstruct the causal reasoning...
Evidence suggests the crucial role of dysfunctional default mode (DMN), salience and frontoparietal (FPN) networks, collectively termed the triple network model, in the pathophysiology of treatment-resistant depression (TRD). Using the graph theory- and seed-based functional connectivity analyses, we attempted to elucidate the role of low-dose ketamine in the triple networks, namely the DMN,...
Low-dose ketamine is an N-methyl-D-aspartate receptor antagonist that exerts an antidepressant effect on patients with treatment-resistant depression (TRD). This antidepressant effect may extend beyond the glutamatergic hypothesis. Nevertheless, the roles of genes encoding other monoamine neurotransmitters (i.e., serotonin and dopamine) in the neuromechanism of low-dose ketamine remain unknown....
Ketamine is a dissociative drug used for the treatment of depression. However, the neurofunctional mechanism underlying the antidepressant effect of ketamine remains unknown. According to previous research, low-dose ketamine affects large-scale brain networks, including default-mode and salient networks. A total of 43 patients with treatment-resistant depression (TRD) and suicidal ideation (SI)...
Previous studies have shown an association between the thalamocortical dysconnectivity and treatment-resistant depression (TRD). Whether a single subanesthetic dose of ketamine may change thalamocortical connectivity among patients with TRD is unclear. Whether these changes in thalamocortical connectivity is associated with the antidepressant and antisuicidal effects of ketamine treatment is...
Low-grade inflammation (LGI) contributes to resistance against traditional antidepressants. However, whether the antidepressant and antisuicidal effects of ketamine on patients with treatment-resistant depression (TRD) differ between those with LGI and those without LGI remains unknown.This study included 167 patients with TRD, among whom 46 had LGI and 121 did not have LGI. The patients...
The concurrent rise in the prevalence of autism and youth suicide has drawn public health and professional attention. The renaissance of psychedelics in psychiatry occurred in the early 21st century and may suggest a hope for the therapeutic effect of psychedelics in autism and suicide. The psychedelics' molecular entities are the compounds that modulate the serotoninergic and glutamatergic...
Objective Psilocybin-assisted therapy has shown promising efficacy on clinical depressive symptoms. However, diverse psychological support or psychotherapy was performed with psilocybin treatment. This study aimed to explore the association of psychological protocols with the efficacy of psilocybin-assisted therapy for depressive symptoms. Method Five major databases were systemic searched for...
Background: Low-dose ketamine infusion has been demonstrated to exert antisuicidal effects on patients with treatment-resistant depression (TRD) and strong suicidal ideation. Although evidence suggests an association between hopelessness and suicidality, very few studies have investigated the antihopelessness effects of ketamine. Methods: This study included 84 patients with TRD and strong...
OBJECTIVE Previous studies have found an association between klotho, an anti-aging hormone, and major depressive disorder. However, whether low-dose ketamine infusion alters klotho levels among patients with treatment-resistant depression (TRD) remains unknown. METHODS In total, 48 patients with TRD and strong suicidal ideation were randomly assigned to a single 0.5 mg/kg ketamine or 0.045...
Whether pretreatment working memory and response inhibition function are associated with the rapid and sustained antisuicidal effect of low-dose ketamine among patients with treatment-resistant depression (TRD) and strong suicidal ideation is unclear. We enrolled 65 patients with TRD, comprising 33 who received a single infusion of 0.5 mg/kg ketamine and 32 who received a placebo infusion. The...
BACKGROUND Evidence indicates that vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) influence the pathophysiology of depression. However, whether low-dose ketamine regulates VEGF and MMP-9 levels and whether changes in VEGF and MMP-9 levels are associated with the antidepressant and antisuicidal effects of ketamine remained unclear. METHODS Forty-eight patients...
Abstract Background The benefits of low-dose ketamine for patients with treatment-resistant depression (TRD) and prominent suicidal ideation require further investigation. The effects of treatment refractoriness, the duration of the current depressive episode, and the number of prior antidepressant failures on ketamine efficacy also require clarification. Methods We recruited 84 outpatients...
BACKGROUND Whether cortical excitation and inhibition functions differ between patients with treatment-resistant depression (TRD) and strong suicidal ideation (SI) and healthy subjects and whether 0.5 mg/kg ketamine infusion can modulate cortical excitation and inhibition functions among patients with TRD-SI remain unclear. METHODS A total of 29 patients with TRD-SI and 35 age- and sex-matched...
Evidence has suggested that the modulation of N-methyl-d-aspartate receptors (NMDARs) and 5-hydroxytryptamine receptors (5-HTRs) via the psychedelic drugs, such as ketamine and psilocybin, rapidly alters the state of consciousness and the neuroplasticity. The United State Food and Drug Administration approved the indications of esketamine for treatment-resistant depression (TRD) in 2019 and...
Abstract Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar...
BACKGROUND This posthoc analysis compared the antidepressant and antisuicidal effects of low-dose ketamine infusion with those of repetitive transcranial magnetic stimulation (rTMS) on treatment-resistant depression (TRD). METHODS In the ketamine infusion trial, 48 patients with TRD were randomized to receive a single infusion of 0.5 mg/kg ketamine or normal saline. In the rTMS trial, 105...
AbstractBackgroundThe antidepressant effect of low-dose ketamine infusion on Taiwanese patients with anxious vs nonanxious treatment-resistant depression (ANX-TRD vs NANX-TRD) has remained unknown.MethodsIn total, 71 patients with TRD were randomized to three groups. Each group had participants who received saline infusions mixed with 0 (a normal saline infusion), 0.2, and 0.5 mg/kg of...