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...
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,...
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...
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...
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...
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 PsychiatryMarch 8, 2025Jonathan 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...
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...
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...
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),...
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...
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...
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...