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...
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...
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...
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...
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...
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...
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...
Frontostriatal disconnectivity plays a crucial role in the pathophysiology of major depressive disorder. However, whether the baseline functional connectivity of the frontostriatal network could predict the treatment outcome of low-dose ketamine infusion remains unknown. In total, 48 patients with treatment-resistant depression were randomly divided into 3 treatment groups (a single-dose...
Increasing evidence suggests that infusion of a subanesthetic dose of ketamine exerts antidepressant and antisuicidal effects in patients with treatment-resistant depression (TRD). In this investigation, we used the resting functional connectivity magnetic resonance imaging (fcMRI) to determine the effects of ketamine on the functional connectivity (FC) of prefrontal cortex (PFC)-related...
Clinical and animal studies have reported conflicting results regarding the effect of ketamine on cognitive function, although increasing evidence supports a rapid and sustained antidepressant effect of a subanesthetic dose of ketamine infusion for patients with treatment-resistant depression (TRD). However, the cognitive function before and after ketamine infusion was rarely investigated in...
Increasing evidence supports the rapid antidepressant effect of a low-dose ketamine infusion in treatment-resistant depression (TRD). Proinflammatory cytokines play a crucial role in the pathophysiology of TRD. However, it is unknown whether the rapid antidepressant effect of ketamine is related to the rapid suppression of proinflammatory cytokines. Seventy-one patients with TRD were randomized...
This study explores the responses to ketamine in patients with treatment-resistant depression (TRD) using a wearable forehead electroencephalography (EEG) device. We recruited fifty-five outpatients with TRD who were randomised into three approximately equal-sized groups (A: 0.5 mg/kg ketamine; B: 0.2 mg/kg ketamine; and C: normal saline) under double-blind conditions. The ketamine responses...
A single low-dose ketamine infusion exhibited a rapid antidepressant effect within 1h. Despite its short biological half-life (approximately 3h), the antidepressant effect of ketamine has been demonstrated to persist for several days. However, changes in brain function responsible for the persistent antidepressant effect of a single low-dose ketamine infusion remain unclear METHODS: Twenty-four...
The antidepressant effects of ketamine are thought to depend on brain-derived neurotrophic factor (BDNF) genotype and dose. The purpose of this study was to characterize the dose-related antidepressant effects of ketamine in patients with treatment-resistant depression drawn from a Chinese population predominately possessing lower activity BDNF genotypes (Val/Met, Met/Met). We conducted a...