Psychotherapy Combined With Intranasal Esketamine for the Treatment of Suicidal Ideation (PIK-SI)

Combined Intranasal Esketamine and Brief Cognitive Behavioral Therapy for Suicidal Ideation - A Randomized Controlled Trial

The purpose of this study is to examine the effects of combined intranasal esketamine with brief cognitive behavioral therapy for suicide prevention (BCBT-SP) for suicidal ideation (SI) in patients with treatment- resistant depression (TRD). The secondary aim is to identify the biological targets of treatment response using combined transcranial magnetic stimulation and electroencephalography (TMS-EEG). In this project we will recruit patients between the ages of 18 and 70, diagnosed with a major depressive episode with ongoing suicidal ideation present who have failed (or not shown signs of improvement) after at least one prior treatment. The null hypothesis is that there will be no difference in reductions in suicidality at 1-week post-treatment between the combined treatment group and the ketamine only treatment group. The alternative hypothesis is that the combined treatment will result in a greater reduction in suicidal ideation at 1-week post-treatment.

Study Overview

• Status: Enrolling by invitation
• Conditions: Suicidal Ideation
• Intervention / Treatment: Other: Naturalistic Intranasal Esketamine; Behavioral: Brief Cognitive Behavioral Therapy for Suicide Prevention

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92127
      • UC San Diego Health - 4S Ranch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. All genders
2. Ages 18 to 70 years
3. Physician order of intranasal esketamine in the UCSD Interventional Psychiatry Clinic
4. Treatment resistant depression diagnosis confirmed by the ordering physician (treatment failure defined as the lack of clinically meaningful response in depression following an antidepressant trial)
5. Ongoing SI present beyond the screening phase of the study (confirmed with Beck SSI score ≥4).
6. Pass the TMS adult safety screening (TASS) questionnaire
7. Voluntary outpatients capable to consent to treatment and seen at the UC San Diego Health Interventional Psychiatry program.
8. Able to adhere to the treatment schedule.

Exclusion Criteria:

1. Previously undergone the Brief Cognitive Behavioral Therapy for Suicide Prevention (BCBT-SP) protocol
2. Currently undergoing an evidence based psychotherapy treatment (according to the policies by the American Psychological Association)
3. Presence of SI prompting emergent hospital stay (SI in which the participant can maintain voluntary and capable as an outpatient, as well as recent suicide attempt, will not be exclusionary)
4. Not capable to consent to treatment or not suitable for outpatient treatment
5. Have a cardiac pacemaker or implanted medication pump; any history of seizure except those therapeutically induced by ECT or a febrile seizure of infancy, cerebral aneurysm, significant head trauma with loss of consciousness for greater than 5 minutes; Have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed.
6. Based on eligibility for Intranasal Esketamine in the UCSD IPP clinic: Lifetime diagnosis of bipolar I or II disorder or schizophrenia spectrum disorder or current diagnosis of a substance use disorder or cognitive disorder documented in the electronic medical records

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intranasal Esketamine; Naturalistic Intranasal Esketamine	Other: Naturalistic Intranasal Esketamine; Naturalistic Intranasal Esketamine is administered in accordance with psychiatrist recommendations
Experimental: BCBT-SP + Intranasal Esketamine; Brief Cognitive Behavioral Therapy for Suicide Prevention combined with Intranasal Esketamine	Other: Naturalistic Intranasal Esketamine; Naturalistic Intranasal Esketamine is administered in accordance with psychiatrist recommendations; Behavioral: Brief Cognitive Behavioral Therapy for Suicide Prevention; 12 session evidence based psychotherapy protocol with weekly 50 minute sessions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Beck Scale for Suicidal Ideation	1-week post treatment
TMS-EEG N100 peak	1-week post treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Suicidal Ideation Attributes Scale (SIDAS)	1-week post treatment
Columbia Suicide Severity Scale (C-SSRS)	1-week post treatment

Collaborators and Investigators

• Sponsor: University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: February 1, 2026
• First Submitted That Met QC Criteria: February 1, 2026
• First Posted (Actual): February 9, 2026

Study Record Updates

• Last Update Posted (Actual): February 9, 2026
• Last Update Submitted That Met QC Criteria: February 1, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Self-Injurious Behavior; Suicide; Behavior; Suicidal Ideation
• Other Study ID Numbers: 813122

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No