This study is testing a new medicine called SPT-300 (GlyphAllo) for people with major depressive disorder (MDD), with or without anxious distress. MDD is a condition where a person feels very sad for a long time. The study aims to see if SPT-300 helps with these feelings and if it is safe. Participants will randomly be given either SPT-300 or a placebo (a dummy treatment), and neither the participant nor the doctor will know which one they are getting. This is called a double-blind study.

Eligibility: You must be between 18 and 65 years old, have MDD, and have had a depressive episode for at least 4 weeks. You cannot participate if you have certain mental health conditions, substance abuse, or are pregnant or breastfeeding.

• The study requires multiple visits over an 18-month period.
• Eligible participants must agree to use birth control if they can become pregnant.
• Participants should avoid using drugs of abuse.