Additional Study Information: We are currently enrolling individuals with Major Depressive Disorder (MDD) to participate in this research study. This is a one-year open-label study to evaluate the long-term safety and tolerability of an investigational drug called REL-1017 (esmethadone) when taken alone (monotherapy) or when taken with other antidepressants (adjunctive therapy). Study visits will include physical examination, vital signs, electrocardiograms, blood collection, urine collection, and psychological assessments. Participants may be enrolled in the study for up to 13 months, consisting of 12 months of treatment and a 1-month post-treatment follow-up visit. Telephone contact will be made throughout the study.