Cognitive Behavioral Therapy to Sustain the Antidepressant Effects of Ketamine in Treatment-Resistant Depression: A Randomized Clinical Trial.
Samuel T Wilkinson, Taeho Greg Rhee, Jutta Joormann...
https://pubmed.ncbi.nlm.nih.gov/34186531Actively Recruiting
Phase 4
Age: 21Years - 65Years
All Genders
ID07369102
Esketamine With or Without Psychedelic Preparation and Integration for Treatment-Resistant Depression: A Randomized Controlled Trial
Led by University of Puerto Rico · Updated on 2026-01-27
20
Participants Needed
2
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the effects of esketamine (Spravato®), an FDA-approved nasal spray, on adults with treatment-resistant depression (TRD). The study aims to determine if adding therapeutic support sessions before and after esketamine doses can improve mood, functioning, and overall treatment experience. This is a randomized controlled trial comparing esketamine with and without these additional support sessions. All participants will receive intranasal esketamine twice weekly during an acute 4-week phase, then weekly or biweekly during a maintenance phase lasting up to 8 weeks based on clinical response. One group will also receive brief, structured preparation and integration therapy sessions before and after each dose, designed to support emotional processing and meaning-making. The other group will receive standard clinical monitoring without extra psychotherapeutic support. During the 8-week study, participants will attend dosing sessions with monitoring for at least two hours after each dose. Researchers will assess depression severity using the Montgomery-Åsberg Depression Rating Scale (MADRS) along with measures of emotional regulation, treatment acceptability, and safety. Follow-up assessments will monitor treatment response, remission, relapse, and suicidal thoughts. The study is conducted under clinical supervision with informed consent and ethical approval.
CONDITIONS
Brief Title
Esketamine With or Without Integration Therapy for Treatment-Resistant Depression
Who Can Participate
Age: 21Years - 65Years
All Genders
Eligibility Criteria
You may qualify if you...
- Adults aged 21 to 65 years
- Current diagnosis of Major Depressive Disorder confirmed by Structured Clinical Interview for DSM5 (SCID-5)
- Treatment-resistant depression defined as failure to achieve remission with at least two antidepressants of adequate dose and duration
- Baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score of 30 or higher
- Participants with passive or active suicidal ideation may be included if clinically stable for outpatient care
- Ability to understand and voluntarily provide written informed consent
- Willingness to use effective contraception during the study and for one month after final dose if of reproductive potential
- Willingness and ability to attend all study sessions and complete procedures
- Demonstrated psychological readiness to engage in preparation and integration therapy sessions
You will not qualify if you...
- Immediate need for inpatient psychiatric hospitalization due to acute suicide risk
- Current diagnosis of bipolar I disorder (manic phase), schizophrenia, schizoaffective disorder, or other primary psychotic disorders
- Active moderate to severe substance use disorder (except nicotine) in past 6 months
- Intellectual disability, dementia, or cognitive/developmental disorders impairing participation in therapy sessions
- Medical conditions posing undue risk during esketamine administration (e.g., vascular disease, hypersensitivity to esketamine)
- Current pregnancy or breastfeeding
- Participation in formal psychotherapy involving structured weekly sessions in past 3 months unless stabilized for at least 8 weeks
- Six or more prior esketamine or IV ketamine sessions without clinical response
- Ketamine or esketamine use in past 12 weeks
- Inability to provide informed consent
- Prior participation in this study
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - 8 weeks
Participants receive FDA-approved intranasal esketamine twice weekly during the first 4 weeks (acute phase), then weekly or biweekly during weeks 5 to 8 (maintenance phase). Participants in the integration arm also receive brief, structured therapeutic preparation and integration sessions before and after each dosing to support emotional processing and meaning-making.
Twice-weekly visits for 4 weeks, then weekly or biweekly visits for 4 weeks
Trial Site Locations
Total: 2 locations
1
Pravan Foundation
San Juan, Puerto Rico, 00909
Actively Recruiting
2
University of Puerto Rico, Department of Psychiatry
San Juan, Puerto Rico, 00936
Actively Recruiting
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Research Team
P
Paulina D Rullan-Farinacci, MD
K
Karen G Martinez-Gonzalez, MD, MSc
How is the study designed?
Study Type
INTERVENTIONAL
Masking
SINGLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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Published Research Related To This Trial
Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy.
Jennifer Dore, Brent Turnipseed, Shannon Dwyer...
https://pubmed.ncbi.nlm.nih.gov/30917760Psychedelic Harm Reduction and Integration: A Transtheoretical Model for Clinical Practice.
Ingmar Gorman, Elizabeth M Nielson, Aja Molinar...
https://pubmed.ncbi.nlm.nih.gov/33796055Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study.
Carla M Canuso, Jaskaran B Singh, Maggie Fedgchin...
https://pubmed.ncbi.nlm.nih.gov/29656663Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study.
Vanina Popova, Ella J Daly, Madhukar Trivedi...
https://pubmed.ncbi.nlm.nih.gov/31109201Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial.
Ella J Daly, Madhukar H Trivedi, Adam Janik...
https://pubmed.ncbi.nlm.nih.gov/31166571