Multi-Omic, Clinomic and Digitomic Attributes of Major Depression for Integrative Analytics

Inclusion Criteria: * Participated in the BROWNIE study. * DSM-5 diagnostic criteria are met for unipolar, non-psychotic MDD (excluding controls). * A score of \> 10 on the QIDS-C and QIDS-SR (equivalent to 13 or greater on HAM-D17) given that when medication exceeds the effect of placebo in primary care participants have a HAM-D17 \>12 (excluding controls). * Antidepressant treatment is deemed appropriate by a study clinician (excluding controls). * Smart watch wear time is at least 70% during their participation in the BROWNIE study. Exclusion Criteria: * Subjects with medical contraindications that preclude treatment with study drugs will be excluded. * Patients with schizophrenia, schizoaffective disorder, or who have bipolar I or II disorder (or another specified or unspecified bipolar spectrum disorder) will be excluded because they have a primary psychiatric condition that requires a different initial treatment. * Subjects currently on antidepressant medication with subtherapeutic results in terms of depression management will undergo a medication taper and discontinuation prior to initiation of a new study medication. The subject will be closely monitored by the study clinician during the medication taper and discontinuation phase. The medication taper is left up to the study clinician's discretion. Study subjects who cannot be safely tapered from their medication or experience adverse effects during the taper will be excluded from the study. * Subjects who have an active substance use disorder will be excluded. An active substance use disorder will be defined as meeting DSM-5 diagnostic criteria for any active substance use disorder. Persons meeting DSM-5 diagnostic criteria for a substance use disorder in full remission (\>12 months) and a negative urine drug of abuse screen at the screening visit or before the baseline study visit will be considered eligible. Persons with a positive urine drug of abuse screen may participate in the study if they do not meet DSM-5 diagnostic criteria for a substance use disorder. * Subjects unable to give informed consent or who are unwilling or unable to comply with study requirements are excluded. * Pregnant subjects will be excluded. * Subjects who are currently breastfeeding and who plan to continue breastfeeding will be excluded. * Subjects who are psychiatrically hospitalized or in a mental health crisis requiring urgent care or psychiatric hospitalization. * Study subjects currently on antipsychotic medications (e.g., typical, and atypical antipsychotic drugs) taken for primary psychotic illness or affective psychosis will be excluded. * Study subjects taking mood stabilizing agents (e.g., lithium, carbamazepine, valproate, lamotrigine, gabapentin, or other anticonvulsants) taken specifically for bipolar spectrum disorders are not eligible for participation.