Conditions: Depressive Disorder, Major
Keywords: Escitalopram Major depressive disorder Non-inferiority Bupropion
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 534
Healthy volunteers: no

Brief summary:
This multi-centre study will follow a randomised, double-blind, parallel-group, active-controlled design and will evaluate the efficacy, safety and tolerability of bupropion extended-release (XL) (300 mg/day) compared with escitalopram (10-20 mg/day) in outpatients and inpatients with major depressive disorder (MDD). The total duration of the study will be 11 weeks consisting of three phases. The screening phase (phase I) will be lasting for 0-14 days, subjects will be randomised to bupropion XL or escitalopram in a 1:1 ratio for acute phase treatment phase (phase II) for 8 weeks. There are 3 dose levels during this acute treatment phase. The 3-dose level plan is designed to ensure each drug is titrated according to the prescribing information and to reach an optimal clinical dose. Finally patients will enter the taper phase (phase III) for up to 1 week to assess and reduce the possible withdrawal symptoms.

In China almost all existing antidepressants are available on the market, but bupropion XL has not yet been approved. This Phase III clinical trial will be used for the purpose of registering bupropion XL in China.

Detailed description:

Arms:
arm 1: Subject will receive bupropion in 3 dose levels along with escitalopram matching placebo to maintain the blind in acute treatment phase. At dose level 1 (Week 0 to Week 1), Subjects will receive bupropion XL 150 milligram (mg) per day for a week. At dose level 2 (Week 1 to Week 4), bupropion XL dose will be increased to 300mg/day for further 3 weeks. At dose level 3 (Week 4 to Week 8), bupropion XL dose will be maintained at 300mg/day. Subjects intolerable to dose level 3 will be allowed to down titrate to dose level 2 at anytime, and maintain the dose until the end of acute treatment phase (Week 8, Visit 7). At the end of acute treatment phase, the dose of bupropion XL will be reduced to 150mg/day for 1 week before discontinuation. arm 2: Subject will receive escitalopram in 3 dose levels along with bupropion matching placebo to maintain the blind in acute treatment phase. At dose level 1 (Week 0 to Week 1), Subjects will receive escitalopram 10mg/day for a week. At dose level 2 (Week 1 to Week 4), escitalopram dose will be maintained at 10mg/day for further 3 weeks. At dose level 3 (Week 4 to Week 8), escitalopram dose will be increased to 20mg/day. Subjects intolerable to dose level 3 will be allowed to down titrate to dose level 2 at anytime, and maintain the dose until the end of acute treatment phase (Week 8, Visit 7). At the end of acute treatment phase, the dose of escitalopram 20mg/day, the dose will be reduced to 10 mg/day for 1 week before discontinuation, while those receiving 10mg/day will discontinuation directly.

Interventions: intervention 1: Bupropion intervention 2: Bupropion Matching Placebo intervention 3: Escitalopram intervention 4: Escitalopram Matching Placebo
Intervention descriptions: intervention 1: Bupropion is an extended-release plain creamy white colored tablet which contains bupropion hydrochloride equivalent to 150 mg of bupropion. intervention 2: Bupropion hydrochloride matching placebo tablets will be supplied to maintain blinding intervention 3: Escitalopram is available as a Swedish orange capsule containing escitalopram oxalate equivalent to 10 mg of escitalopram. intervention 4: Escitalopram oxalate matching placebo tablets will be supplied to maintain blinding

Protocol document: