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...
Eur Neuropsychopharmacol
June 5, 2026
Andreas Reif, A. Elif Anıl Yağcıoğlu, Istvan Bitter et al.
Response to: Commentary on "Long-term treatment with esketamine nasal spray in patients with treatment resistant depression: Results from the ESCAPE-LTE study".
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
June 1, 2026
Andreas Reif, Yağcıoğlu Ae Anıl, Istvan Bitter et al.
3 citations
Optimising patient outcomes in treatment resistant depression (TRD) requires treatments which provide sustained remission, without relapse, and tolerability in the long term. ESCAPE-LTE (NCT04829318) was a phase IV, single-arm, 2-year (104 weeks) long-term extension of ESCAPE-TRD (NCT04338321; 32 weeks), a rater-blinded, randomised, active-controlled trial, which evaluated the safety,...
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...
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...
Pharmacological Research
October 1, 2025
Florian Freudenberg, Christine Reif-Leonhard, Gerard R Dawson et al.
Treatment-resistant depression (TRD) represents a major clinical challenge. Affecting about 30 % of major depressive disorder (MDD) patients, effective treatments for TRD are urgently needed. While depression research and antidepressant (AD) development have long centred on monoaminergic targets, research over the past 35 years has increasingly explored glutamatergic mechanisms. Here we present...
Biological Psychiatry
March 8, 2025
Jonathan Repple, Maximilian Bayas, Chiara Möser et al.
8 citations
After decades of limited progress in depression treatment, recent advancements have sparked renewed interest in developing novel antidepressants, particularly rapid-acting antidepressants (RAADs). Despite these promising developments, there remains a significant gap in research on bipolar depression. While several antipsychotics have been investigated for their efficacy in bipolar depression...
The British journal of psychiatry : the journal of mental science
February 1, 2025
Allan H. Young, Pierre-Michel Llorca, Andrea Fagiolini et al.
7 citations
In patients with treatment resistant depression (TRD), the ESCAPE-TRD study showed esketamine nasal spray was superior to quetiapine extended release. To determine the robustness of the ESCAPE-TRD results and confirm the superiority of esketamine nasal spray over quetiapine extended release. ESCAPE-TRD was a randomised, open-label, rater-blinded, active-controlled phase IIIb trial. Patients had...
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry
2025
Christine Reif-Leonhard, Shannon N Millard, Dorsa Ferdowssian et al.
3 citations
While neuropsychological effects of conventional antidepressants are well-documented, more research is needed for rapid-acting antidepressants. This study examines the effects of esketamine on emotion processing and cognitive functioning, both acutely and sub-chronically. Eighteen treatment-resistant depression (TRD) patients received repeated intravenous esketamine infusions. Mood state was...
European Archives of Psychiatry and Clinical Neuroscience
August 29, 2024
Florian Freudenberg, Christine Reif-Leonhard, Andreas Reif
10 citations
Changes in glutamatergic neuroplasticity has been proposed as one of the core mechanisms underlying the pathophysiology of depression. In consequence components of the glutamatergic synapse have been explored as potential targets for antidepressant treatment. The rapid antidepressant effect of the NMDA receptor antagonist ketamine and subsequent approval of its S-enantiomer (i.e. esketamine),...
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
August 1, 2024
Roger S McIntyre, Istvan Bitter, Jozefien Buyze et al.
30 citations
In ESCAPE-TRD (NCT04338321), esketamine nasal spray (NS) significantly increased the probability of remission at Week 8, and of being relapse-free through Week 32 after remission at Week 8, versus quetiapine extended release (XR) in patients with treatment resistant depression (TRD). Here, we explore the time course, burden and consequences of treatment emergent adverse events (TEAEs) in the...
New England Journal of Medicine
October 4, 2023
Andreas Reif, Istvan Bitter, Jozefien Buyze et al.
197 citations
BACKGROUND: In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with...
Neuropharmacology
January 6, 2023
Nicolas Singewald, Simone B. Sartori, Andreas Reif et al.
57 citations
Psychiatric disorders associated with psychological trauma, stress and anxiety are a highly prevalent and increasing cause of morbidity worldwide. Current therapeutic approaches, including medication, are effective in alleviating symptoms of anxiety disorders and posttraumatic stress disorder (PTSD), at least in some individuals, but have unwanted side-effects and do not resolve underlying...