Ketamine With Dialectical Behavioural Therapy (DBT) for Suicidality in Individuals With Treatment-Resistant Depression and Borderline Personality Disorder (KET-DBT) (KET-DBT)

Inclusion Criteria:

1. Adults between the age of 18 to 70, inclusive;
2. Meets criteria for BPD, as determined by clinical assessment by a psychiatrist or psychologist and confirmed by the International Personality Disorder Examination (IPDE);
3. Meets DSM-5 criteria for MDD or BD (I or II), currently experiencing a MDE without psychotic features, as diagnosed by a study psychiatrist or psychologist. Diagnosis will be confirmed using the Mini- International Neuropsychiatric Interview (MINI);
4. Current MDE must be moderate to severe, as determined by the MADRS score >20 with an inadequate response to two or more guideline-concordant treatment trials as defined by the Antidepressant Treatment History Form-Short Form (ATHF- SF);
5. No changes in pharmacotherapy for MDD/BD in the last month or changes in psychotherapy in the past month;
6. Baseline SI as shown by two consecutive MSSI scores > 10 two weeks apart.

Exclusion Criteria:

1. Past or current history of a psychotic disorder as determined by clinical assessment and MINI;
2. Current or recent (within the past 3 months) manic or hypomanic episode as determined by clinical assessment via YMRS (score > 12) and the MINI;
3. Meeting criteria for Moderate to Severe Alcohol or substance use disorders currently or within the past 3 months;
4. Lifetime history of ketamine use disorder or illicit ketamine use.
5. Acute suicide risk requiring involuntary inpatient treatment under the Mental Health Act (MHA).
6. Presence of a relative or absolute contraindication to ketamine or midazolam, including a drug allergy, lifetime history of stroke, uncontrolled hypertension (Systolic BP > 160 or Diastolic BP > 100), low or labile blood pressure (Systolic BP < 100 or Diastolic BP < 60), recent (within the past 6 months) myocardial infarction, severe coronary artery disease (ascertained through participant's medical history), or moderate to severe renal (GFR scores ≤ 44) or hepatic impairment (A Child-Pugh score of ≥ 7);
7. Currently pregnant or breastfeeding or planning on getting pregnant within the first two months of the trial or planning on getting someone else pregnant within the first two months of trial. Participants who are sexually active must agree to use a highly effective contraceptive method (please see exhaustive list in Section 3.6.1);
8. Current use of prohibited concomitant medications, including other forms of ketamine or esketamine, high dose daily benzodiazepines (greater than 4 mg lorazepam equivalent daily) or monoamine oxidase inhibitors;
9. Currently engaged (or completed within the past year) in DBT treatment. NOTE: Individuals who have received only DBT skills training in the past year will be considered eligible to participate;
10. Those engaged in other forms of psychotherapy must be willing to discontinue for the duration of the 6-month DBT intervention (standard for DBT). There should be no changes in psychotherapy 30 days prior to baseline (i.e., Screening Visit 2).