The International Journal of Neuropsychopharmacology
November 1, 2024
Randall L. Morrison, Jaskaran Singh, Ella Daly et al.
9 citations
While esketamine is effective in treatment-resistant depression (TRD), detailed information about the effect of esketamine on cognition is relatively scarce. This analysis assessed the effect of short-term (3 double-blind [DB] studies: DB1, DB2, and DB4) or long-term maintenance treatment (DB3) with esketamine nasal spray (ESK) compared with a placebo (PBO) combined with active-comparator, on...
Health and Quality of Life Outcomes
May 8, 2023
Carol Jamieson, Vanina Popova, Ella Daly et al.
18 citations
BACKGROUND: Patients with treatment-resistant depression (TRD) report significant deficits in physical and mental health, as well as severely impaired health-related quality of life (HRQoL) and functioning. Esketamine effectively enhances the daily functioning in these patients while also improving their depressive symptoms. This study assessed HRQoL and health status of patients with TRD, who...
Psychiatry Research
March 15, 2023
Ibrahim Turkoz, J. Craig Nelson, Samuel T. Wilkinson et al.
19 citations
This exploratory post hoc analysis of two pooled 4-week, phase 3, double-blind, placebo- and active-controlled studies that compared esketamine nasal spray plus a newly initiated oral antidepressant (ESK+AD; n = 310) with a newly initiated oral AD plus placebo nasal spray (AD+PBO; n = 208) in patients with treatment-resistant depression (TRD) examined baseline patient demographic and...
The International Journal of Neuropsychopharmacology
December 14, 2022
David Williamson, Ibrahim Turkoz, Ewa Wajs et al.
11 citations
BACKGROUND: "Dissociation" comprises distinct phenomena, some of which are associated with esketamine treatment and some may overlap with positive symptoms of psychosis. Relationships between dissociation and psychotic symptoms assessed by -clinician report vs conventional rating scales were investigated in a post hoc analysis of data from the initial treatment session in an -open-label,...
Journal of Psychopharmacology
February 25, 2022
Francis M. Dijkstra, Aurora JAE van de Loo, Smedra Abdulahad et al.
16 citations
Background: Intranasal esketamine demonstrates rapid improvement of depressive symptoms. However, transient adverse effects (dissociation, sedation and dizziness) may occur, which could impact driving performance. Aims: To evaluate the effects of 84 mg intranasal esketamine on driving performance in unipolar major depressive disorder (MDD) or persistent depressive disorder (PDD) patients....
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.
The Journal of Clinical Psychiatry
July 16, 2021
Ibrahim Turkoz, Ella Daly, Jaskaran Singh et al.
21 citations
) and treatment-resistant depression (TRD) who did not meet response criteria within the first week of treatment. The current study is a pooled post hoc analysis of two phase 3, double-blind, active-controlled studies, conducted between August 2015 and February 2018, comparing ESK + AD with an oral antidepressant plus placebo (AD + PBO). Early treatment response was defined as a ≥ 50% decrease...
Journal of Affective Disorders
November 14, 2020
Stacie Hudgens, Lysbeth Floden, Michael Blackowicz et al.
77 citations
Patients with major depressive disorder who do not respond to ≥2 different pharmacological treatments within the current depressive episode are considered to have treatment resistant depression (TRD). This analysis determined meaningful change thresholds (MCT) of the Patient Health Questionnaire (PHQ-9) and Montgomery-Åsberg Depression Rating Scale (MADRS) using anchor-based methods and...
Clinical Pharmacology & Therapeutics
August 29, 2020
Eva G. Katz, David Hough, Teodora Doherty et al.
35 citations
This post hoc analysis assessed the benefit-risk profile of esketamine nasal spray + oral antidepressant (AD) induction and maintenance treatment in patients with treatment-resistant depression (TRD). The Benefit-Risk Action Team framework was utilized to assess the benefit-risk profile using data from three induction studies and one maintenance study. Benefits were proportion of remitters or...
Scientific Reports
July 28, 2020
Qingqin S. Li, Ewa Wajs, Rachel Ochs-Ross et al.
49 citations
Abstract To elucidate the genetic underpinnings of the antidepressant efficacy of S-ketamine (esketamine) nasal spray in major depressive disorder (MDD), we performed a genome-wide association study (GWAS) in cohorts of European ancestry (n = 527). This analysis was followed by a polygenic risk score approach to test for associations between genetic loading for psychiatric conditions, symptom...
International Journal of Neuropsychopharmacology
May 5, 2020
Ziad S. Saad, D. Hibar, Maggie Fedgchin et al.
43 citations
Abstract Background At ketamine and esketamine doses at which antidepressant doses are achieved, these agents are relatively selective, noncompetitive, N-methyl-D-aspartate receptor antagonists. However, at substantially higher doses, ketamine has shown mu-opioid receptor (MOR–gene symbol: OPRM1) agonist effects. Preliminary clinical studies showed conflicting results on whether naltrexone, a...
The Journal of Clinical Psychiatry
April 20, 2020
Ewa Wajs, Leah Aluisio, Richard Holder et al.
288 citations
OBJECTIVE: To evaluate long-term safety and efficacy of esketamine nasal spray plus a new oral antidepressant (OAD) in patients with treatment-resistant depression (TRD). METHODS: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse...
The International Journal of Neuropsychopharmacology
April 7, 2020
Michel Nijs, Ewa Wajs, Leah Aluisio et al.
21 citations
BACKGROUND: Esketamine nasal spray was recently approved for treatment-resistant depression. The current analysis evaluated the impact of symptom-based treatment frequency changes during esketamine treatment on clinical outcomes. METHODS: This is a post-hoc analysis of an open-label, long-term (up to 1 year) study of esketamine in patients with treatment-resistant depression (SUSTAIN 2). During...
CNS Spectrums
April 1, 2020
Leslie Citrome, Allitia DiBernardo, Jaskaran Singh
Abstract: Background: Targeting of glutamate receptors is a novel approach for the treatment of major depressive disorder (MDD). This study aimed to review the usefulness for esketamine nasal spray for the management of treatment-resistant depression (TRD) using the tools of evidence-based medicine: number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed...
The International Journal of Neuropsychopharmacology
July 9, 2019
Maggie Fedgchin, Madhukar H. Trivedi, Ella Daly et al.
593 citations
BACKGROUND: About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants and are considered to have treatment-resistant depression. METHODS: This Phase 3, double-blind, multicenter study enrolled adults with moderate-to-severe depression and nonresponse to ≥2 antidepressants in the current depression episode. Eligible patients (N = 346)...
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...
American Journal of Psychiatry
April 16, 2018
Carla M. Canuso, Jaskaran Singh, Maggie Fedgchin et al.
666 citations
OBJECTIVE: The authors compared the efficacy of standard-of-care treatment plus intranasal esketamine or placebo for rapid reduction of symptoms of major depression, including suicidality, among individuals at imminent suicide risk. METHOD: In a double-blind, multicenter, proof-of-concept study, 68 participants were randomly assigned to receive esketamine (84 mg) or placebo twice weekly for 4...
Psychopharmacology
February 1, 2018
Randall L. Morrison, Maggie Fedgchin, Jaskaran Singh et al.
72 citations
BACKGROUND: The effect of intranasal esketamine on cognitive functioning in healthy participants is assessed in this study. METHODS: computerized test battery assessed at 1 h predose and 40 min, 2, 4, and 6 h postdose. Secondary measures included the Mental Effort Scale, Karolinska Sleepiness Scale (KSS), and safety. RESULTS: Esketamine was associated with significant cognitive performance...
CNS Spectrums
February 1, 2018
Abigail I. Nash, M. Shawi, Jaskaran Singh et al.
Abstract Background Recognizing the importance not only of the clinician’s opinion but also of the patient’s experience and perspective, Sequenced Treatment Alternatives to Relieve Depression (STAR*D) utilized both clinician-reported and patient-reported outcomes in a large-scale multi-step study on antidepressant effectiveness in real-world settings. Both approaches indicate that <17% of Major...
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,...
Translational Psychiatry
September 20, 2016
Daniel M. Rotroff, Daniel Corum, Alison A. Motsinger‐Reif et al.
99 citations
Ketamine, at sub-anesthetic doses, is reported to rapidly decrease depression symptoms in patients with treatment-resistant major depressive disorder (MDD). Many patients do not respond to currently available antidepressants, (for example, serotonin reuptake inhibitors), making ketamine and its enantiomer, esketamine, potentially attractive options for treatment-resistant MDD. Although...
American Journal of Psychiatry
April 8, 2016
Jaskaran Singh, Maggie Fedgchin, Ella Daly et al.
530 citations
OBJECTIVE: Ketamine, an N-methyl-d-aspartate glutamate receptor antagonist, has demonstrated a rapid-onset antidepressant effect in patients with treatment-resistant depression. This study evaluated the efficacy of twice- and thrice-weekly intravenous administration of ketamine in sustaining initial antidepressant effects in patients with treatment-resistant depression. METHOD: In a...
Biological Psychiatry
November 4, 2015
Jaskaran Singh, Maggie Fedgchin, Ella Daly et al.
466 citations
BACKGROUND: The purpose of this study was to assess the efficacy and safety and to explore the dose response of esketamine intravenous (IV) infusion in patients with treatment-resistant depression (TRD). METHODS: This multicenter, randomized, placebo-controlled trial was conducted in 30 patients with TRD. Patients were randomly assigned 1:1:1 to receive an IV infusion of .20 mg/kg or .40 mg/kg...
CNS Neuroscience & Therapeutics
April 12, 2013
Giacomo Salvadore, Jaskaran Singh
80 citations
Several recent studies have shown that a single intravenous subanesthetic dose of ketamine, a NMDA receptor antagonist, exerts rapid antidepressant effects in patients with treatment refractory mood disorders and reduces suicidal ideation. Those insights have fueled tremendous excitement in the efforts to elucidate the mechanism underlying ketamine's antidepressant properties in animal models...