Lumateperone for Late-Life Depression

Inclusion Criteria:

* Age \>=60
* Current unipolar non-psychotic major depression determined by SCID-5
* MADRS score \>=20 at screening and \>=18 at baseline
* Treatment-resistance defined as documented history of non-response to at least two oral medications of adequate dose and duration in this episode or previous episode, OR clinician determination that treatment augmentation is appropriate
* Currently taking oral antidepressant prescribed at least minimum therapeutic dose and for at least six weeks duration
* MMSE score of \>/=24

Exclusion Criteria:

* Dementia
* High risk for suicide, defined as a 4 or 5 on C-SSRS (indicating active suicidal ideation with current or recent intent or plan), and unable to be managed safely in the clinical trial. Urgent psychiatric referral will be made in these cases.
* High risk alcohol use: defined as a score of 6 or more on the AUDIT-C
* Medically inappropriate for participation as determined by PIs.