Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2) in Major Depressive Disorder (MDD)

Inclusion Criteria:

• Provide written informed consent, as approved by the NYU Institutional ResearchEthic Board (IRB).

• Patients ages 18-65;

• Current/acute Major Depressive Disorder (MDD) diagnosis, per MINI psychiatricinterview;

• At least moderate severity of depression (Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 20 at initial screen);

Exclusion Criteria:

• DSM-5 diagnosis of Bipolar disorders, Cyclothymia, Schizoaffective disorder,Schizophrenia; any psychotic disorder or affective psychosis;

• Subjects that have had more than two failures of adequate anti-depressant trials inthe current MDD episode;

• Subjects on psychotropic medications other than SSRIs, NDRIs, SNRIs, or mirtazapine (occasional use of sleep agents, equivalent to lorazepam 1 mg or zolpidem 10 mg,will be allowed);

• Those that have previously been on SGLT2 inhibitors;

• A significant history of non-adherence to treatments;

• History of neurologic / seizure disorder;

• A significant history of non-adherence to treatments;

• History of dementia/cognitive dysfunction (MOCA < 22);

• A primary diagnosis of a personality disorder, in the opinion of the screeningclinician;

• DSM-5 substance use disorder (drug/alcohol) active within the past 12 months, orpositive urine toxicology at screening;

• History of diabetic ketoacidosis;

• History of recurrent genital mycotic infection;

• GFR <45;

• HgA1c.>8.0%

• History of an allergic reaction to an SGLT2 inhibitor.

• Pregnancy or lactation (women of reproductive age, ie <50 years old, should be onlicensed hormonal or barrier method contraception).

• Any known pancreatic disease resulting in insulin deficiency (T1D, history ofpancreatitis, pancreatic surgery);

• History of liver or kidney disease;

• Hypersensitivity to empagliflozin or any of the excipients in JARDIANCE.