Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention

Inclusion Criteria:

• Participants are eligible for the study if they meet all the following criteria:

1. Written informed consent before any study procedures are performed

2. Meeting criteria for inpatient admission for suicidal ideation or attempt atone of the study sites

3. Recommended by a physician for esketamine treatment

4. Males or females ages 18 through 65 years of age

5. Diagnosis of major depressive disorder as confirmed by the MINI (inpatient) orthe HAM-D-17 (outpatient)

6. Willing to adhere to a reliable form of contraception throughout the trial andfor one month following completion of the trial (for subjects who are sexuallyactive)

7. In the opinion of the investigator, the patient is willing and able to complywith scheduled visits, treatment plan, and other trial procedures for theduration of the study

Exclusion Criteria:

• Participants are excluded if they meet any of the following criteria:

1. Active substance use disorder (except tobacco) within 6 months of screeningdate

2. Meets DSM-5 criteria for bipolar disorder, schizophrenia, schizophreniformdisorder, schizoaffective disorder, or pervasive development disorder

3. Dementia or other cognitive disorder or intellectual disability that wouldimpair the subject's ability to meaningfully engage in CBT (per investigatorjudgment)

4. Any other medical or psychiatric comorbidity that the investigator judges wouldput the participant at additional undue risk due to study participation orwould impair subject's ability to participate in the study.

5. Current or planned participation in a formal CBT program defined by thefollowing characteristics, each session has an agenda, a homework assignment isgiven at each session, and the homework assignment from the previous session isreviewed at the following appointment.

6. Previous Esketamine or ketamine treatment that did not produce a clinicalresponse as outlined below.

• 6 treatments with Esketamine at a dose of 56 mg or more with no clinicalresponse
• 6 treatments of IV ketamine at a dose between 0.4 mg/kg and 0.7mg /kg withno clinical response Patients must not have received Esketamine orketamine treatment within the past 12 weeks of time of enrollment.

7. The patient is pregnant or breastfeeding

8. Unable to give informed consent

9. Was previously enrolled/randomized into the trial

10. Patients who have a contraindication to receiving Esketamine including any ofthe following:

• aneurysmal vascular disease
• arteriovenous malformation
• history of intracerebral hemorrhage
• hypersensitivity to esketamine or ketamine