Antidepressant treatments, including conventional antidepressants and (es)ketamine, may reverse default mode network (DMN) resting-state functional connectivity (rsFC) alterations related to major depressive disorder (MDD). Despite these agents having distinct initial action mechanisms, both likely share downstream effects that lead to structural and functional adaptations in MDD-related neural...
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...
Oral esketamine is a potentially effective and well-tolerated treatment for treatment-resistant depression (TRD). However, around 50% of TRD individuals treated with oral esketamine do not achieve response, and this variation in response may be accounted for by interindividual differences between patients. Efforts to develop effective and personalized depression treatment strategies are...
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...
Summary This case report presents the case of a 25-year-old woman who developed ketamine addiction following a single sub-anaesthetic dose of intranasal ketamine in a pilot study investigating intranasal racemic ketamine for acute suicidality. She had a history of depression, obsessive–compulsive disorder, autism spectrum disorder and anorexia nervosa, and she had sporadically used alcohol and...
Ketamine has been shown to decrease suicidality in patients with depression. However, little is known about tolerability and efficacy in heterogenous, acutely suicidal patients in emergency settings. This pilot study aimed to assess the feasibility, acceptability, and safety of generic intranasal racemic ketamine (75 mg) in the treatment of acute suicidality regardless of the underlying...
Ketamine-assisted psychotherapy (KAP) is considered a promising treatment strategy in psychiatric disorders, combining psychotherapeutic interventions with the rapid-acting pharmacological effects of ketamine towards enhancing outcomes. Although KAP has been practiced for many years across different diagnoses, evidence regarding optimal treatment methods and working mechanisms remains limited...
Suicidality is a transdiagnostic entity in patients with and without psychiatric disorders. Ketamine is a novel treatment for treatment-resistant depression with favorable effects on related suicidality in this population. Little is known about the effects of ketamine on suicidality as a distinct phenomenon. To assess whether a dose of 75 mg intranasal (IN) ketamine reduces acute suicidality...
Intranasal (IN) esketamine represents a novel add-on treatment for treatment-resistant depression (TRD) with reported favourable effects on insomnia. IN esketamine treatment might similarly reduce the incidence of insomnia as an adverse event (AE). The present meta-analysis therefore investigated whether IN esketamine relative to placebo is associated with a lower incidence of insomnia as an AE...
Oral esketamine has relatively low and variable bioavailability, which may complicate broader use as an antidepressant. This study aimed to investigate associations between different pharmacokinetic outcomes and change in depressive symptoms following oral esketamine administration in patients with treatment-resistant depression. Understanding such associations may inform dosing and...
Oral esketamine for patients with treatment-resistant depression (TRD) could offer certain advantages over other routes, such as intravenous or intranasal, but it has not been systematically studied in a real-world setting. Here we present results from a relatively large naturalistic study to evaluate the effectiveness, tolerability, and safety of oral esketamine in patients with TRD. One...
Background: Esketamine is a rapidly acting antidepressant with robust efficacy in treatment-resistant depression (TRD). Diminishing therapeutic effects and attenuated side effects have been reported after long-term use. This study aimed to investigate its long-term pharmacokinetics and factors that may contribute to reduced efficacy over time in patients with TRD by evaluating the potential...
Accumulating evidence supports the efficacy of (es)ketamine in the treatment of major depressive disorder (MDD), particularly treatment-resistant depression (TRD). Yet around 50% of the individuals with TRD do not respond to (es)ketamine. Elucidating predictors of response and remission could improve treatment outcomes at the individual level by defining subpopulations that are most likely to...
This study investigates repeated oral esketamine as a substitution strategy for maintenance electroconvulsive therapy (M-ECT) in eight patients with treatment-resistant depression (TRD). In a 6-week dosing phase, esketamine was titrated from 0.5 or 1.0 mg/kg to a maximum of 3.0 mg/kg twice weekly. Outcomes included 6-week change in Inventory of Depressive Symptomatology - Self-rated (IDS-SR),...
Psilocybin represents a novel therapeutic approach for individuals with major depressive disorder (MDD) who do not respond to conventional antidepressant treatment. Investigating the influence of psilocybin on the pathophysiological processes involved in MDD could enhance our neurobiological understanding of the presumed antidepressant action mechanism. This systematic review aims to summarize...
About one-third of patients with depression do not achieve adequate response to current treatment options. Although intravenous and intranasal administrations of (es)ketamine have shown antidepressant properties, their accessibility and scalability are limited. We investigated the efficacy, safety, and tolerability of generic oral esketamine in patients with treatment-resistant depression (TRD)...
Abstract Psilocybin is the most researched classic psychedelic for Treatment-Resistant Depression (TRD). While optimizing set and setting are considered essential for efficacy and safety, patient perspectives on these aspects have rarely been investigated. To address this knowledge gap, the current paper explored the experiences of 11 TRD patients (8 women, 3 men) participating in a...
Ketamine and its enantiomers are widely researched and increasingly used to treat mental disorders, especially treatment-resistant depression. The phenomenology of ketamine-induced experiences and their relation to its psychotherapeutic potential have not yet been systematically investigated. To describe the phenomenology of patient experiences during oral esketamine treatment for...
Psilocybin is being studied for use in treatment-resistant depression. In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the...
Ketamine has rapid yet often transient antidepressant effects in patients with treatment-resistant depression. Different strategies have been proposed to prolong these effects. Maintenance ketamine treatment appears promising, but little is known about its efficacy, safety, and tolerability in depression. We searched Pubmed, Embase, and the Cochrane Library and identified three randomised...
Objective: Ketamine is increasingly prescribed for treatment-resistant depression (TRD), often as add-on to regular antidepressants. Augmentation of ketamine to monoamine oxidase inhibitors (MAOIs) is advised against, as this practice might increase blood pressure or cause serotonin syndrome. Despite the potential relevance for patients, little is known about actual side effects of combined...
Introduction: Small-scale clinical studies with psychedelic drugs have shown promising results for the treatment of several mental disorders. Before psychedelics become registered medicines, it is important to know the full range of adverse events (AEs) for making balanced treatment decisions. Objective: To systematically review the presence of AEs during and after administration of...
Ketamine and its enantiomer esketamine represent promising new treatments for treatment-resistant depression (TRD). Esketamine induces acute, transient psychoactive effects. How patients perceive esketamine treatment, and which conditions facilitate optimal outcomes, remains poorly understood. Understanding patient perspectives on these phenomena is important to identify unmet needs, which can...
Objective: Ketamine shows rapid and robust antidepressant effects in clinical studies. Psychotic features are an exclusion criterion in most ketamine treatment studies based on the assumption that psychosis will increase with ketamine administration. As patients with treatment-resistant depression (TRD) often have psychotic features, and treatment-resistant depressive symptoms are also common...
Abstract Background The use of ketamine for depression has increased rapidly in the past decades. Ketamine is often prescribed as an add-on to other drugs used in psychiatric patients, but clear information on drug-drug interactions is lacking. With this review, we aim to provide an overview of the pharmacodynamic interactions between ketamine and mood stabilizers, benzodiazepines, monoamine...