Additional Study Information: We are currently enrolling individuals with Major Depressive Disorder (MDD) to participate in this research study. The main goals of this study are to assess the safety and efficacy of an investigational drug called REL-1017 as an adjunctive treatment for MDD. The study includes a 30-day screening period and a 28-day treatment period for a total of 58 days. Eligible participants will be randomly assigned to receive either REL-1017 (esmethadone) or a placebo (a pill without active study drug). Participants will also continue taking their regularly prescribed antidepressant medication. Study visits will include physical examination, vital signs, electrocardiograms, blood collection, urine collection, and assessments. Participants will be compensated for their time and reimbursed for travel expenses to and from the clinic.