Abstract Background Treatment-resistant depression (TRD) represents a particularly challenging form of major depressive disorder (MDD), defined by an inadequate response to at least two antidepressants given at adequate dose and duration within the current depressive episode. TRD affects nearly one-third of individuals with MDD and is consistently linked to greater psychiatric and medical...
Abstract Background Treatment-resistant depression (TRD) is a chronic condition affecting approximately 30% of patients with major depressive disorder, posing a significant unmet need for safe and effective treatments. GH001, an inhaled formulation of mebufotenin (5-MeO-DMT), has shown good tolerability and safety in early stage clinical trials in healthy volunteers and patients with TRD. Aims...
Esketamine nasal spray (NS) is an established treatment for patients with treatment resistant depression (TRD). To further optimise real-world outcomes, consensus is needed regarding strategies to enhance patient outcomes and decision-making factors for pivotal timepoints in esketamine NS treatment. This modified Delphi panel (3 rounds) established expert consensus (≥80% agreement) from 30...
BACKGROUND: Longer-term outcome and safety data of repeated subcutaneous racemic ketamine for treatment-resistant depression (TRD) is lacking, as is knowledge of the impact of prior ketamine treatment on subsequent response. AIMS: To evaluate the effectiveness and safety of a 4-week course of subcutaneous racemic ketamine over 6 months and investigate whether prior ketamine treatment influences...
Treatment-resistant depression (TRD), a persistent condition impacting up to 30% of patients with major depressive disorder, carries substantial personal and economic burden. There remains an unmet need for therapies that provide both rapid and durable improvements in TRD. Preliminary clinical trials indicate that GH001, a synthetic, inhalable formulation of mebufotenin, has the potential for...
Ketamine has disputed effects on suicidal ideation scores in depressed populations. This study assessed effectiveness of ketamine in adults with treatment resistant depression, examining a secondary outcome of suicidal ideation. Phase III, double-blind, randomized, active-controlled, multicenter trial. Participants were randomized to twice-weekly subcutaneous racemic ketamine or midazolam for 4...
Importance: Few pharmacotherapies are approved for treatment-resistant depression, and many patients do not achieve remission following treatment with those therapies. Objective: To examine the efficacy and safety of single-day treatment with a synthetic formulation of inhaled mebufotenin (GH001) vs placebo in patients with treatment-resistant depression. Design, Setting, and Participants: This...
BACKGROUND: Intranasal esketamine has recently emerged as an innovative treatment option for treatment-resistant depression (TRD). This retrospective, uncontrolled study aimed to evaluate the real-world effectiveness of esketamine in an naturalistic inpatient setting and explore demographic and clinical factors associated with treatment response. METHODS: We conducted a chart review of 101...
Ketamine is effective for treatment resistant depression (TRD); but cost-effectiveness evidence remains limited. To evaluate the cost-effectiveness of subcutaneous ketamine for TRD from health sector and societal perspectives. A cost-utility analysis alongside the KADS randomised controlled trial (RCT) involved 174 participants receiving ketamine or midazolam (active control) twice weekly for 4...
Clinical response and remission may not fully reflect patient priorities in treatment-resistant depression (TRD). Health-related quality-of-life (HRQoL) outcomes should be assessed to comprehensively capture treatment benefits. ESCAPE-TRD (NCT04338321) was a 32-week randomized, phase IIIb trial comparing esketamine nasal spray (NS) versus quetiapine extended release (XR), both alongside an...
Pharmacological ResearchJuly 31, 2025C. Pisanu, R. Carvalho Silva, Mattia Meattini et al.6 citations
Treatment-resistant depression (TRD) remains a challenge in psychiatry, necessitating novel therapeutic strategies beyond traditional monoaminergic antidepressants. Ketamine and its S-enantiomer esketamine have demonstrated rapid and robust antidepressant effects in TRD, probably through mechanisms involving glutamatergic modulation, neuroplasticity, and anti-inflammatory properties. However,...
Intranasal esketamine (ESK) is a novel therapy option in patients with treatment-resistant depression (TRD). Patients with a history of electroconvulsive therapy (ECT) non-response (ECT+) in the current episode have usually been excluded from previous studies. Data on the effectiveness of ESK in ECT non-responders are sparse. In this retrospective study, we investigated the effectiveness of...
Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties. To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD. The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active...
Introduction Esketamine intranasal spray has been approved in both the USA and EU as a novel treatment in patients with treatment-resistant major depression (TRD) and for the management of acute depressive emergencies during the course of major depressive disorder (MDD). Real-world data on the effectiveness and safety of esketamine nasal spray in clinical use are limited. Objectives To...
Treatment-resistant depression (TRD) is a complex disorder. Although no standardized definition has been established to date, there are promising and well-established treatment options for the condition. Looking at the current pharmacological and neuromodulatory strategies, there is an urgent need for fast-acting and well-tolerated treatment options. The search for new mechanisms of action goes...
Background Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. Aims To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. Method This phase 3,...
IntroductionNMDA-Receptor antagonists have rapid antidepressant and antisuicidal properties. However, the antidepressant effect is short lasting raising the question of best maintenance strategy, which is unanswered so far. Invasive vagus nerve stimulation (VNS) as a treatment option for refractory and chronic major depression was shown to reduce the need of maintenance treatment sessions in...
Introduction Psychiatric emergencies in Major Depressive Disorder (MDD) are characterised by multiple types of symptoms including risk of self-harm and suicidal ideation. S-ketamine intranasally (Spravato) has recently been shown to help alleviate symptoms during depressive emergencies. In this case-series, we detail the clinical effects and usability of S-ketamine applied intranasally in a...