**Study Summary:** This study wants to find out if a medicine called AXS-05 works better than another medicine, bupropion, in stopping depression from coming back in people with major depressive disorder (MDD). **Major depressive disorder (MDD)** is a mental health condition that makes people feel very sad or lose interest in things they usually like. In this study, people will first take AXS-05 for 10 weeks. If they feel better, they will then be chosen randomly to either keep taking AXS-05 or switch to bupropion for up to 26 more weeks. **Randomized** means they are chosen by chance, like flipping a coin. **Double-blind** means neither the doctors nor the patients know which medicine they are taking, to make sure the results are fair. - You will first take AXS-05 for 10 weeks and then possibly switch to bupropion. - The study will last up to 36 weeks, and you'll need to visit the study site for check-ups. - Only join if you have MDD, haven’t tried AXS-05 before, and can follow study rules. Please talk to your doctor to understand if this study is right for you.