Acceptance and Committment Therapy Combined With Ketamine in Difficult-to-Treat Depression.

Inclusion Criteria:

To participate in this study, individuals must be eligible for and enrolled in the Ketamine Intervention Program (KIP) at UBC Hospital, an ongoing clinical program for difficult-to-treat depression, which has the following inclusion criteria:

1. Be of age 18 or older.
2. Have a DSM-5-TR diagnosis of major depressive disorder (MDD) or bipolar disorder (BD), in a current major depressive episode.
3. If diagnosed with MDD, have failed adequate trials of at least 2 antidepressants and 1 adjunctive medication(s); if BD, having failed adequate trials of at least 3 agents for bipolar depression.
4. Have a referral from a community psychiatrist who agrees to follow the patient throughout the entire trial.
5. Have the ability to provide informed consent.

Exclusion Criteria:

Individuals will not be eligible for the K-ACT study if they are deemed ineligible for enrollment with the KIP at UBC Hospital due to meeting any of the following existing exclusion criteria:

1. They are experiencing active psychosis.
2. They have: any of history of ketamine use disorder; a history of alcohol or other substance use disorder in the past 6 months; dementia or delirium; unstable medical conditions; uncontrolled hypertension; a history of seizures in the past 6 months; a history of elevated intracranial pressure/aneurysmal disease/arteriovenous malformation/intracranial hemorrhage.
3. They are currently pregnant or breastfeeding.
4. They have an allergy to ketamine.

Exclusion criteria specific to the K-ACT study include:

1. Currently undergoing ACT.
2. Past ACT within last 12 months.
3. Currently undergoing non-ACT structured psychotherapy (e.g., cognitive-behavioural therapy).