The purpose of this open-label, multicenter study is to assess the long term safety and efficacy of intranasal esketamine plus an oral antidepressant in participants with treatment-resistant depression (TRD).
This is an open-label (the researchers and participants know the treatment the participant is receiving), multicenter (more than 1 study site), long-term safety and efficacy study of intranasal esketamine plus an oral antidepressant in participants with treatment-resistant depression (TRD). Participants will enter the study either directly (direct-entry participants) or after completing the Double-Blind Induction Phase of ESKETINTRD3005 (transferred-entry participants). The study consists of 4 phases: Screening Phase (4 weeks), Open-Label Induction Phase (4 weeks), Open-Label Optimization/Maintenance phase (48 weeks), and Follow up Phase (4 weeks). Transferred entry non-responders in the ESKETINTRD3005 may enter study at the Open-Label Induction Phase and responders in the ESKETINTRD3005 may enter Optimization/Maintenance phase. In the Open-Label Induction Phase, participants will self-administer flexibly-dosed intranasal esketamine (participants who are less than (\<) 65 years old self-administer 56 mg or 84 mg dose, participants who are greater than or equal to (\>=) 65 years old self-administer 28 mg, 56 mg or 84 mg dose) twice weekly for 4 weeks. The starting dose for all participants \>= 65 years old will be 28 mg. In addition, each direct-entry participants will be assigned to receive 1 of 4 selected oral antidepressant medications (escitalopram or sertraline or duloxetine or venlafaxine extended release \[XR\]), initiated on Day 1 of the open-label induction phase and continued through the duration of the study. Transferred-entry participants will continue their same antidepressant from ESKETINTRD3005 through the duration of this study. Participants who are responders at the end of the Open-Label Induction phase and transferred-entry responder participants (from study ESKETINTRD3005) will enter the Optimization/Maintenance Phase where intranasal esketamine treatment sessions will be reduced from that in the induction phase (twice weekly) to weekly for the first 4 weeks of this phase, and then individualized to either once weekly or once every other week based on the severity of depressive symptoms. Participants' safety and depressive symptoms will be assessed and monitored throughout the study.
Open-Label Induction Phase: Participants will self-administer esketamine intranasally twice per week for 4 weeks as a flexible dose regimen (56 mg or 84 mg for those \< 65 years; 28 mg, 56 mg or 84 mg for those \>= 65 years). Participants \>= 65 years old will start at a dose of 28 mg on Day 1. Optimization/Maintenance Phase: Participants will self-administer esketamine intranasally (56 mg or 84 mg for those \< 65 years; 28 mg, 56 mg or 84 mg for those \>= 65 years) once weekly then individualized to either once weekly or once every other week based on the severity of depressive symptoms. Transferred-entry responder participants from ESKETINTRD3005 \>= 65 years old will start at a dose of 28 mg in Week 5.
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. The minimum therapeutic dose is 10 mg/day. Participants \>= 65 years of age will be titrated up to 20 mg/day, but can lower the dose to 10 mg/day for tolerability.
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 up to a dose of 150 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 for participants \< 65 years of age up to a dose of 225 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 150 mg/day. For participants \>= 65, it can be titrated up to a dose of 150 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 75 mg/day.
Banfield, Argentina
Buenos Aires, Argentina
Córdoba, Argentina
La Plata, Argentina
Mendoza, Argentina
Rosario, Argentina