This study is testing two medicines, AXS-05 and bupropion, to see which one better stops the return of depression symptoms. Depression symptoms are feelings of sadness or hopelessness. AXS-05 is a new medicine being tested, while bupropion is a medicine already used for depression. The study is randomized, meaning that participants are chosen by chance to take one of the medicines. It is also double-blind, meaning neither the participants nor the researchers know who is taking which medicine during the study. Everyone will first take AXS-05 for 10 weeks. If they feel better, they will then continue with either AXS-05 or switch to bupropion for about 26 weeks. Participants must have had depression for at least four weeks and cannot have been in a similar study before. They also should not have taken any experimental treatments recently. The study will last for a total of 36 weeks, including time on both medications.

• Study lasts up to 36 weeks.
• Participants must follow all study rules.
• Participants must have had depression for at least 4 weeks.