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...
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...
Psychopharmacology Bulletin
June 5, 2026
Michael E. Thase, Brian Brennan, Rachael Macisaac et al.
Approximately 30% of patients treated for major depressive disorder develop treatment-resistant depression (TRD). The STAR*D study demonstrated remission rates decline progressively with each antidepressant failure (37%, 31%, 14%, and 13%, respectively). A single-day individualized dosing regimen of GH001 (synthetic mebufotenin for inhalation) produced rapid, large improvements in depressive...
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...
The Journal of Clinical Psychiatry
May 4, 2026
Samuel T. Wilkinson, Brandon Kitay, Matthew Macaluso et al.
Background: Suicide is a public health crisis in the US, with limited evidence demonstrating efficacy of treatments for high-risk patients due in part to their exclusion from most clinical trials. This clinical trial evaluates the feasibility and efficacy of adjunctive cognitive behavioral therapy (CBT) with esketamine in patients with major depression and suicidal ideation (MDSI). Methods:...
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...
Biological Psychiatry Global Open Science
July 1, 2025
Stephen A Murata, Zachary B Madaj, Colt D Capan et al.
1 citation
Treatment-resistant depression (TRD) remains a challenge, but intravenous racemic ketamine offers rapid antidepressant effects. Reliable biomarkers are needed. In this study, we examined kynurenine pathway metabolites and inflammatory cytokines as predictors of ketamine response. The Bio-K study was a multicenter, open-label trial of 74 patients with TRD who received 3 ketamine infusions over...
Psychopharmacology Bulletin
March 4, 2024
Timothy Whitaker, Kimberly F Farrand, Michael E. Thase
249 citations
Despite the prevalence of Major Depressive Disorder (MDD) and the propensity of affected individuals to eventually die by suicide, there is no therapeutic approved specifically for suicidal ideation and behavior (SI/B) in MDD. The NMDA receptor antagonist ketamine has been investigated for the treatment of depression and shown to have a rapid effect on symptoms. Spravato® (esketamine) is...
The Journal of Clinical Psychiatry
August 14, 2023
Michael E. Thase
9 citations
Among the greatest unmet needs in major depressive disorder (MDD) is a lack of effective pharmacotherapies for patients who do not respond to first- and second-line antidepressant medications. After decades of muted progress, optimism regarding the future of MDD therapy rose after scientists serendipitously uncovered the antidepressant effects of ketamine. The discovery of ketamine's...
Depression and Anxiety
July 22, 2021
E. Daly, Ibrahim Turkoz, Giacomo Salvadore et al.
Comorbid anxiety is generally associated with poorer response to antidepressant treatment. This post hoc analysis explored the efficacy of esketamine plus an antidepressant in patients with treatment‐resistant depression (TRD) with or without comorbid anxiety.
American Journal of Psychiatry
March 17, 2021
Roger S McIntyre, Joshua D. Rosenblat, Charles B. Nemeroff et al.
694 citations
Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent...
JAMA Psychiatry
June 5, 2019
Ella Daly, Madhukar H. Trivedi, Adam Janik et al.
766 citations
Importance: Controlled studies have shown short-term efficacy of esketamine for treatment-resistant depression (TRD), but long-term effects remain to be established. Objective: To assess the efficacy of esketamine nasal spray plus an oral antidepressant compared with an oral antidepressant plus placebo nasal spray in delaying relapse of depressive symptoms in patients with TRD in stable...
American Journal of Psychiatry
May 21, 2019
Vanina Popova, Ella Daly, Madhukar H. Trivedi et al.
879 citations
OBJECTIVE: About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants. This study compared the efficacy and safety of switching patients with treatment-resistant depression from an ineffective antidepressant to flexibly dosed esketamine nasal spray plus a newly initiated antidepressant or to a newly initiated antidepressant (active...
JAMA Psychiatry
December 27, 2017
Ella Daly, Jaskaran Singh, Maggie Fedgchin et al.
708 citations
Importance: Approximately one-third of patients with major depressive disorder (MDD) do not respond to available antidepressants. Objective: To assess the efficacy, safety, and dose-response of intranasal esketamine hydrochloride in patients with treatment-resistant depression (TRD). Design, Setting, and Participants: This phase 2, double-blind, doubly randomized, delayed-start,...
Journal of Clinical Psychiatry
2017
Anup Sharma, M. Barrett, A. Cucchiara et al.
Objective To evaluate feasibility, efficacy and tolerability of Sudarshan Kriya yoga (SKY) as an adjunctive intervention in patients with major depressive disorder (MDD) with inadequate response to antidepressant treatment. Method Patients with MDD (defined by DSM-IV-TR) depressed despite ≥8 weeks of antidepressant treatment were randomized to SKY or a waitlist control (delayed yoga) arm for 8...