KET-RO Plus RO DBT for Treatment Resistant Depression

Inclusion Criteria:

• Males and females aged 18-65

• Moderate to severe persistent depression [treatment resistant depression - TRD] (exhibiting 2+ unipolar major depression episodes (non-delusional) with priortreatment non-response to antidepressant or psychosocial treatment

• Treatment-resistant depression: defined as unipolar major depressive disorder,non-delusional (diagnosed by SCID-5, Structured Clinical Interview for the DSM )that persists despite ≥ 2 adequate antidepressant trials of different classes in thecurrent episode; including at least one evidence-based second-line treatment in thecurrent episode (including serotonin norepinephrine reuptake inhibitors, bupropion,tricyclics, monoamine oxidase inhibitors, or augmentation with an atypicalantipsychotic, stimulant, bupropion, lithium, or Triiodothyroinine) higherproportion of OC (over controlled) words endorsed compared to UC (Under controlled)words on the Word Pairs Checklist

• no current or past psychosis

• English speaking

• Able to attend in-person behavioral sessions and ketamine/therapy visits

• Willingness to have RO DBT-A as only psychosocial treatment engaged in (medicationtreatment may continue-but see below for exclusion)

Exclusion Criteria:

• Outside age range

• Significant neurological condition (i.e., seizure, stroke, severe head injury) ormental retardation (IQ<70)

• Current or recent substance use disorder, actively suicidal or homicidal (e.g.,requires hospitalization)

• Use of naltrexone, memantine or medication considered contraindicated with ketamine

• Baseline systolic BP > 150 systolic or 90 diastolic at evaluation. Participants whoinitially present with elevated blood pressure may be re-assessed; and if needed,referred to their healthcare provider for hypertension management

• Taking more than 2 adequately-dosed oral antidepressants

• Inability to understand, speak and read English sufficiently

• Not be pregnant or at risk of becoming pregnant

• Medical conditions or medication usage that in the judgement of the investigatorsputs the patient at unreasonable safety risk

• First degree relative with a psychotic diagnosis involving hallucinations,delusions, or disorganized thinking and speech (e.g. schizophrenia, schizoaffectivedisorder, etc)