A Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression

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.