Study: NCT02422186

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Esketamine
Description: All participants will start with first dose (Day 1 as 28 milligram \[mg\]); second dose (Day 4) is either 28 or 56 mg. All subsequent doses may be 28, 56 or 84 mg. After the first dose, all dosing decisions are determined by the investigator based on efficacy and tolerability.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Placebo
Description: Participants will self-administer matching placebo, intranasally, twice per week for 4-weeks as a flexible dose regimen in the Double-Blind Induction Phase.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Duloxetine (Oral Antidepressant)
Description: 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).

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Duloxetine (Oral Antidepressant)
Description: 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).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Escitalopram (Oral Antidepressant)
Description: 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 given at a dose of 10 mg/day throughout the Double-Blind Induction Phase. This dose (10 mg/day) is the also the minimum therapeutic dose.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Escitalopram (Oral Antidepressant)
Description: 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 given at a dose of 10 mg/day throughout the Double-Blind Induction Phase. This dose (10 mg/day) is the also the minimum therapeutic dose.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Sertraline (Oral Antidepressant)
Description: 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 may 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.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Sertraline (Oral Antidepressant)
Description: 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 may 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Venlafaxine Extended Release (XR) (New Antidepressant)
Description: 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 may 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.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Venlafaxine Extended Release (XR) (New Antidepressant)
Description: 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 may 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.