A Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Adult Participants With Treatment-resistant Depression
SUSTAIN-1
A Randomized, Double-blind, Multicenter, Active-Controlled Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Treatment-resistant Depression
3 other identifiers
interventional
719
14 countries
147
Brief Summary
The purpose of this study is to assess the efficacy of intranasal esketamine plus an oral antidepressant compared with an oral antidepressant (active comparator) plus intranasal placebo in delaying relapse of depressive symptoms in participants with treatment-resistant depression (TRD) who are in stable remission after an induction and optimization course of intranasal esketamine plus an oral antidepressant.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2015
147 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 13, 2015
CompletedFirst Posted
Study publicly available on registry
July 10, 2015
CompletedStudy Start
First participant enrolled
October 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 15, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
February 16, 2018
CompletedResults Posted
Study results publicly available
May 21, 2019
CompletedApril 29, 2025
April 1, 2025
2.4 years
May 13, 2015
March 29, 2019
April 25, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Time to Relapse in Participants With Stable Remission (Maintenance Phase)
Relapse is defined as any of following: Montgomery-asberg depression rating scale (MADRS) total score greater than or equal to (\>=) 22 for 2 consecutive assessments separated by 5-15 days and/or hospitalization for worsening depression or any other clinically relevant event to be suggestive of a relapse of depressive illness such as suicide attempt/completed suicide/hospitalization for suicide prevention; If hospitalized, start date of hospitalization will be date of relapse, if not hospitalized date of event will be used. MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal-severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. Stable remission: MADRS total score less than or equal to (\<=) 12 for at least 3 of last 4 weeks of OP phase, with 1 excursion total score greater than (\>) 12 or one missing assessment at OP week 13 or 14.
Time from randomization to the first relapse during the maintenance phase (up to 92 Weeks)
Secondary Outcomes (17)
Time to Relapse in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
Time from randomization to the first relapse during the maintenance phase (up to 92 Weeks)
Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in PHQ-9 Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
Baseline and Endpoint (Up to 92 Weeks)
- +12 more secondary outcomes
Study Arms (2)
Intranasal Esketamine plus oral antidepressant
EXPERIMENTALOpen-Label Induction Phase: Direct-entry participants will self-administer esketamine intranasally twice per week for 4 weeks as a flexible dose regimen in the Open-label Induction Phase. Participants will initiate a new oral antidepressant on Day 1 of this phase. Optimization Phase: Direct-entry and transferred-entry participants will self-administer intranasal esketamine (same dose) at weekly treatment sessions for the first 4 weeks of this phase, then individualized to either once weekly or once every other week based on depressive symptoms. Participants continue same oral antidepressant treatment from induction phase. Maintenance Phase: Direct-entry and transferred-entry participants assigned to esketamine will self-administer intranasal esketamine (same dose) once weekly or once every other week based on depressive symptoms. Participants continue same oral antidepressant treatment from induction phase.
Placebo Plus Oral Antidepressant
EXPERIMENTALOptimization Phase: Transferred-entry participants will self-administer intranasal placebo at weekly treatment sessions for the first 4 weeks of this phase, then individualized to either once weekly or once every other week based on depressive symptoms. Participants continue same oral antidepressant treatment from induction phase. Maintenance Phase: Direct-entry and transferred-entry participants assigned to intranasal placebo will self-administer intranasal placebo once weekly or once every other week based on depressive symptoms. Participants continue same oral antidepressant treatment from induction phase.
Interventions
Open-label induction phase: Direct entry participants start at a dose of 56 mg on Day 1. On Day 4, the dose may be increased to 84 mg or remain at 56 mg. From Day 8 to 22, dose may be increased to 84 mg, remain the same or be reduced to 56 mg from 84 mg per protocol, at investigator's discretion based on efficacy and/or tolerability. On Day 25, a dose reduction from 84 mg to 56 mg is permitted but no dose increase is permitted. Optimization Phase: Direct-entry and transferred-entry participants will self-administer intranasal esketamine (same dose) for first 4 weeks, then individualized to either once weekly or once every other week based on depressive symptoms. Maintenance Phase: All participants assigned to esketamine will self-administer intranasal esketamine once weekly or once every other week based on depressive symptoms.
Optimization Phase: Transferred-entry participant will self-administer intranasal placebo at weekly treatment sessions for the first 4 weeks of this phase, then individualized to either once weekly or once every other week based on depressive symptoms. Maintenance Phase: Direct-entry and transferred-entry participants assigned to placebo will self-administer matching intranasal placebo once weekly or once based on depressive symptoms.
Duloxetine could be selected as the oral antidepressant medication by the investigator based on review of Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and relevant prior antidepressant medication information. The minimum therapeutic dose is 60 milligram per day (mg/day).
Escitalopram could be selected as the oral antidepressant medication by the investigator based on review of MGH-ATRQ and relevant prior antidepressant medication information. Escitalopram will be titrated upto a maximum dose of 20 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 10 mg/day.
Sertraline could be selected as the oral antidepressant medication by the investigator based on review of MGH-ATRQ and relevant prior antidepressant medication information. Sertraline will be titrated upto a maximum dose of 200 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 50 mg/day.
Venlafaxine Extended Release could be selected as the oral antidepressant medication by the investigator based on review of MGH-ATRQ and relevant prior antidepressant medication information. Venlafaxine Extended Release will be titrated upto a maximum dose of 225 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 150 mg/day.
Eligibility Criteria
You may qualify if:
- For Direct-Entry Participants
- At the time of signing the informed consent form (ICF), participant must be a man or woman 18 (or older if the minimum legal age of consent in the country in which the study is taking place is greater than \[\>\]18) to 64 years of age, inclusive - At the start of the screening/prospective observational phase, participant must meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) (if single-episode MDD, the duration must be greater than or equal to \[\>=\] 2 years) or recurrent MDD, without psychotic features, based upon clinical assessment and confirmed by the Mini-International Neuropsychiatric Interview (MINI)
- At the start of the screening/prospective observational phase, participant must have an Inventory of Depressive Symptomatology-Clinician rated ( IDS-C30) total score of greater than or equal to (\>=) 34
- At the start of the screening/prospective observational phase, participants must have had nonresponse (less than or equal to 25 percent \[%\] improvement) to greater than or equal to (\>=1) but less than or equal to (\<=) 5 oral antidepressant treatments taken at adequate dosage and for adequate duration, as assessed using the Massachusetts General Hospital (MGH-ATRQ )
- MGH-ATRQ and documented by medical history and pharmacy/prescription records, for the current episode of depression. In addition, the participant is taking different ongoing oral antidepressant treatment (on the MGH-ATRQ) for at least the previous 2 weeks at or above the minimal therapeutic dose
- The participant's current major depressive episode, depression symptom severity (Week 1 MADRS total score \>=28 required), and treatment response to antidepressant treatments used in the current depressive episode (retrospectively assessed) must be deemed valid for participation in a clinical study based on a Site-Independent Qualification Assessment For Transferred-Entry Participants
- The participant must have completed the double-blind induction phase in ESKETINTRD3001 or ESKETINTRD3002 and must have demonstrated response at the end of that phase (\>=50% reduction in the MADRS total score from baseline \[Day 1 pre-randomization\] at the end of the 4-week double-blind induction phase)
You may not qualify if:
- Participants who have previously demonstrated nonresponse of depressive symptoms to esketamine or ketamine in the current major depressive episode, to all 4 of the oral antidepressant treatment options available for the double-blind induction phase (ie, duloxetine, escitalopram, sertraline, and venlafaxine extended release \[XR\]) in the current major depressive episode (based on MGH-ATRQ), or an adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT
- Participant has received vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression
- Participant has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychotic features, bipolar or related disorders (confirmed by the MINI), obsessive compulsive disorder (current only), intellectual disability (DSM-5 diagnostic codes 317, 318.0, 318.1, 318.2, 315.8, and 319), autism spectrum disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, or narcissistic personality disorder
- Participant has homicidal ideation/intent, per the investigator's clinical judgment, or has suicidal ideation with some intent to act within 6 months prior to the start of the screening/prospective observational phase, per the investigator's clinical judgment or based on the Columbia Suicide Severity Rating Scale (C-SSRS)
- Participants with history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (155)
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Birmingham, Alabama, United States
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Little Rock, Arkansas, United States
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Anaheim, California, United States
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Garden Grove, California, United States
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Glendale, California, United States
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Oakland, California, United States
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San Diego, California, United States
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Hartford, Connecticut, United States
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Bradenton, Florida, United States
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Gainesville, Florida, United States
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Miami, Florida, United States
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Orlando, Florida, United States
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Atlanta, Georgia, United States
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Chicago, Illinois, United States
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Hoffman Estates, Illinois, United States
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Joliet, Illinois, United States
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Maywood, Illinois, United States
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Schaumburg, Illinois, United States
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Skokie, Illinois, United States
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Prairie Village, Kansas, United States
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Wichita, Kansas, United States
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Lake Charles, Louisiana, United States
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Baltimore, Maryland, United States
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Gaithersburg, Maryland, United States
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Boston, Massachusetts, United States
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New Bedford, Massachusetts, United States
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Quincy, Massachusetts, United States
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Watertown, Massachusetts, United States
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Worcester, Massachusetts, United States
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Rochester Hills, Michigan, United States
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Minneapolis, Minnesota, United States
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O'Fallon, Missouri, United States
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Saint Charles, Missouri, United States
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Omaha, Nebraska, United States
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New York, New York, United States
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Durham, North Carolina, United States
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Hickory, North Carolina, United States
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Oklahoma City, Oklahoma, United States
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Media, Pennsylvania, United States
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Philadelphia, Pennsylvania, United States
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Scranton, Pennsylvania, United States
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Lincoln, Rhode Island, United States
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Providence, Rhode Island, United States
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Dallas, Texas, United States
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Houston, Texas, United States
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Charlottesville, Virginia, United States
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Waukesha, Wisconsin, United States
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Aalst, Belgium
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Bruges, Belgium
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Brussels, Belgium
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Heusden-Zolder, Belgium
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Liège, Belgium
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Yvoir, Belgium
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Belo Horizonte, Brazil
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Curitiba, Brazil
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Fortaleza, Brazil
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Goiânia, Brazil
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Itapira, Brazil
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Passo Fundo, Brazil
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Porto Alegre, Brazil
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Rio de Janeiro, Brazil
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Santo André, Brazil
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São José do Rio Preto, Brazil
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São Paulo, Brazil
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Calgary, Alberta, Canada
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Vancouver, British Columbia, Canada
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Kingston, Ontario, Canada
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Ottawa, Ontario, Canada
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Toronto, Ontario, Canada
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Montreal, Quebec, Canada
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Brno, Czechia
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Hostivice, Czechia
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Klecany, Czechia
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Kutná Hora, Czechia
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Litoměřice, Czechia
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Pilsen, Czechia
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Prague, Czechia
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Strakonice, Czechia
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Pärnu, Estonia
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Tallinn, Estonia
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Tartu, Estonia
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Clermont-Ferrand, France
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Douai, France
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Nantes, France
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Paris, France
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Poitiers, France
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Toulon, France
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Berlin, Germany
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Cham, Germany
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Gelsenkirchen, Germany
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Halle, Germany
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Mainz, Germany
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Mittweida, Germany
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Pfaffenhofen, Germany
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Prien am Chiemsee, Germany
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Balassagyarmat, Hungary
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Budapest, Hungary
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Guadalajara, Mexico
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León, Mexico
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Mexico City, Mexico
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Monterrey, Mexico
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San Luis Potosí City, Mexico
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Bełchatów, Poland
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Torun, Poland
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Tuszyn, Poland
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Warsaw, Poland
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Bratislava, Slovakia
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Liptovský Mikuláš, Slovakia
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Rimavská Sobota, Slovakia
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Rožňava, Slovakia
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Svidník, Slovakia
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Alcorcón, Spain
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Barcelona, Spain
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Ponferrada, Spain
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Vitoria-Gasteiz, Spain
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Lund, Sweden
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Solna, Sweden
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Stockholm, Sweden
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Adana, Turkey (Türkiye)
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Ankara, Turkey (Türkiye)
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Bursa, Turkey (Türkiye)
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Denizli, Turkey (Türkiye)
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Istanbul, Turkey (Türkiye)
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Izmir, Turkey (Türkiye)
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Kucukcekmece/Istanbul, Turkey (Türkiye)
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Manisa, Turkey (Türkiye)
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Oanakkale, Turkey (Türkiye)
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Sakarya, Turkey (Türkiye)
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Samsun, Turkey (Türkiye)
Related Publications (7)
Kern Sliwa J, Naranjo RR Jr, Turkoz I, Petrillo MP, Cabrera P, Trivedi M. Effects of esketamine nasal spray on depressive symptom severity in adults with treatment-resistant depression and associations between the Montgomery-Asberg Depression Rating Scale and the 9-item Patient Health Questionnaire. CNS Spectr. 2024 Jun;29(3):176-186. doi: 10.1017/S1092852924000105. Epub 2024 Apr 1.
PMID: 38557430DERIVEDCastro M, Wilkinson ST, Al Jurdi RK, Petrillo MP, Zaki N, Borentain S, Fu DJ, Turkoz I, Sun L, Brown B, Cabrera P. Efficacy and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Who Completed a Second Induction Period: Analysis of the Ongoing SUSTAIN-3 Study. CNS Drugs. 2023 Aug;37(8):715-723. doi: 10.1007/s40263-023-01026-3. Epub 2023 Aug 9.
PMID: 37558912DERIVEDWilliamson DJ, Gogate JP, Kern Sliwa JK, Manera LS, Preskorn SH, Winokur A, Starr HL, Daly EJ. Longitudinal Course of Adverse Events With Esketamine Nasal Spray: A Post Hoc Analysis of Pooled Data From Phase 3 Trials in Patients With Treatment-Resistant Depression. J Clin Psychiatry. 2022 Sep 19;83(6):21m14318. doi: 10.4088/JCP.21m14318.
PMID: 36149841DERIVEDChen G, Chen L, Zhang Y, Li X, Lane R, Lim P, Daly EJ, Furey ML, Fedgchin M, Popova V, Singh JB, Drevets WC. Relationship Between Dissociation and Antidepressant Effects of Esketamine Nasal Spray in Patients With Treatment-Resistant Depression. Int J Neuropsychopharmacol. 2022 Apr 19;25(4):269-279. doi: 10.1093/ijnp/pyab084.
PMID: 35022754DERIVEDDoty RL, Popova V, Wylie C, Fedgchin M, Daly E, Janik A, Ochs-Ross R, Lane R, Lim P, Cooper K, Melkote R, Jamieson C, Singh J, Drevets WC. Effect of Esketamine Nasal Spray on Olfactory Function and Nasal Tolerability in Patients with Treatment-Resistant Depression: Results from Four Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Studies. CNS Drugs. 2021 Jul;35(7):781-794. doi: 10.1007/s40263-021-00826-9. Epub 2021 Jul 7.
PMID: 34235612DERIVEDKatz EG, Hough D, Doherty T, Lane R, Singh J, Levitan B. Benefit-Risk Assessment of Esketamine Nasal Spray vs. Placebo in Treatment-Resistant Depression. Clin Pharmacol Ther. 2021 Feb;109(2):536-546. doi: 10.1002/cpt.2024. Epub 2020 Oct 13.
PMID: 32860422DERIVEDDaly EJ, Trivedi MH, Janik A, Li H, Zhang Y, Li X, Lane R, Lim P, Duca AR, Hough D, Thase ME, Zajecka J, Winokur A, Divacka I, Fagiolini A, Cubala WJ, Bitter I, Blier P, Shelton RC, Molero P, Manji H, Drevets WC, Singh JB. Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2019 Sep 1;76(9):893-903. doi: 10.1001/jamapsychiatry.2019.1189.
PMID: 31166571DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Director, Clinical Research
- Organization
- Janssen Research & Development, LLC
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 13, 2015
First Posted
July 10, 2015
Study Start
October 1, 2015
Primary Completion
February 15, 2018
Study Completion
February 16, 2018
Last Updated
April 29, 2025
Results First Posted
May 21, 2019
Record last verified: 2025-04