Ketamine for Older Adults Pilot

1. Community-living men and women age 65 years and older;
2. Treatment-resistant depression: defined as unipolar major depressive disorder, non-delusional (diagnosed by SCID-5) that persists despite ≥ 2 adequate antidepressant trials of different classes in the current episode; including at least one evidence-based second-line treatment in the current episode (including serotonin norepinephrine reuptake inhibitors, bupropion, tricyclics, monoamine oxidase inhibitors, or augmentation with an atypical antipsychotic, stimulant, bupropion, lithium, or triiodothyronine
3. Persistent moderate to severe depressive symptoms determined by Patient Health Questionnaire 9-item (PHQ-9)26 score ≥15 at baseline
4. Able to provide informed consent.

Exclusion Criteria:

1. Dementia per history, score \< 24 on the Montreal Cognitive Assessment (MoCA), or determined by clinical interview with geriatric psychiatrist to have high likelihood of dementia;
2. Psychotic spectrum or bipolar disorder or severe personality disorder that at the PIs discretion would interfere with safe participation. Anxiety disorders are not an exclusion.
3. Unstable medical conditions such that IV ketamine is not safe or tolerated or that would interfere with participation in a long-term study (i.e., poorly controlled hypertension, life expectancy \< 1 year because of terminal illness, unstable angina).
4. Baseline systolic BP > 165 systolic or 100 diastolic at evaluation.
5. Current alcohol or substance use disorder or lifetime recreational ketamine use or other dissociative agent (e.g., PCP).
6. Use of naltrexone, memantine, or any medication that could be considered contraindicated with ketamine.
7. Taking more than 2 adequately-dosed oral antidepressants.
8. High acute risk for suicide and unable to be managed safely in the clinical trial.