International Journal of Neuropsychopharmacology
September 1, 2026
W. Cubała, K. Doolin, F. Ryan et al.
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...
International Journal of Neuropsychopharmacology
September 1, 2026
B. T. Baune, T. Benway, D. Gregory et al.
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...
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
July 17, 2026
Allan H. Young, Bernhard T Baune, Beatrice Benatti et al.
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...
The British Journal of Psychiatry
July 6, 2026
Nick Glozier, Richard W. Morris, Elizabeth Stratton et al.
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...
European Psychiatry
June 1, 2026
Eduard Vieta, Bernhard T Baune, N. Cardoner et al.
Introduction 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...
Archives of suicide research : official journal of the International Academy for Suicide Research
May 9, 2026
Gregory Carter, Maree Hackett, Stevan Nikolin et al.
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...
JAMA Psychiatry
March 25, 2026
Wiesław Jerzy Cubała, Malek Bajbouj, Michael Bauer et al.
3 citations
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...
BMC Psychiatry
March 17, 2026
Bernhard T Baune, Kevin Rosemann, Dimitri Hefter et al.
2 citations
Intranasal esketamine: real-world clinical practice in treatment-resistant depression and factors associated with treatment response.
Journal of Affective Disorders
October 15, 2025
Mary Lou Chatterton, Johana Kevin Perez, Thao Thai et al.
2 citations
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...
Pharmacological Research
July 31, 2025
C. 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,...
European Archives of Psychiatry and Clinical Neuroscience
July 1, 2025
Erhan Kavakbasi, Kevin Rosemann, Mert Yilmaz et al.
2 citations
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...
The British journal of psychiatry : the journal of mental science
January 7, 2025
Natalie T Mills, Stevan Nikolin, Nick Glozier et al.
3 citations
Retracted
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...
European Psychiatry
August 27, 2024
Erhan Kavakbasi, M. Yilmaz, Ö. Bulut et al.
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...
Der Nervenarzt
May 1, 2024
Bernhard T Baune, Sarah E Fromme, Maximilian Kiebs et al.
1 citation
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...
World Psychiatry
September 15, 2023
Roger S McIntyre, Mohammad Alsuwaidan, Bernhard T Baune et al.
712 citations
Treatment‐resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision‐making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a...
British Journal of Psychiatry
July 14, 2023
Colleen Loo, N. Glozier, David Barton et al.
70 citations
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,...
European Psychiatry
June 1, 2022
Bernhard T Baune, Z. Susam, V. Falcone et al.
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...