RecruitingPhase 4NCT07369102

Esketamine With or Without Integration Therapy for Treatment-Resistant Depression

Esketamine With or Without Psychedelic Preparation and Integration for Treatment-Resistant Depression: A Randomized Controlled Trial

Sponsor

University of Puerto Rico

Enrollment

20 participants

Start Date

Feb 1, 2026

Study Type

INTERVENTIONAL

Conditions

Treatment Resistant Depression (TRD)

Summary

This study will explore the effects of esketamine (Spravato®), an FDA-approved nasal spray, on adults diagnosed with treatment-resistant depression (TRD). All participants will receive esketamine as prescribed by a healthcare professional in a clinical setting. The purpose of this research is to understand whether adding therapeutic support in the form of preparation and integration sessions - before and after the esketamine doses - can enhance the treatment experience and lead to longer-lasting improvements in mood and functioning. Participants will be randomly assigned to one of two groups: Esketamine with therapeutic support sessions (integration group) Esketamine without additional support (standard care group) Both groups will receive standard monitoring and psychiatric evaluation during the study. The support sessions offered in the integration group are designed to help participants prepare for their treatment sessions and make sense of their experiences afterward, using a structured, evidence-based approach. The study will last approximately 8 weeks per participant, with follow-up assessments. The goal is to learn whether integration therapy can improve treatment outcomes, safety, and satisfaction for individuals with depression that hasn't responded to other treatments.

Eligibility

Min Age: 21 YearsMax Age: 65 Years

Plain Language Summary

Simplified for easier understanding

This study is comparing two treatment approaches for adults with treatment-resistant depression (TRD) — depression that hasn't improved despite trying at least two antidepressants: esketamine infusions alone versus esketamine combined with a psychological integration therapy session to help process the experience. **You may be eligible if...** - You are between 21 and 65 years old - You have been diagnosed with major depressive disorder (MDD) and have not achieved remission after at least two adequate courses of antidepressants - Your depression symptoms are currently severe (MADRS score of 30 or above) - You may include people with passive or active suicidal thoughts, provided you are clinically stable for outpatient care **You may NOT be eligible if...** - You have a history of psychosis, bipolar disorder, or schizophrenia - You have an active substance use disorder - You are currently at imminent risk of suicide requiring hospitalization - You are pregnant or breastfeeding - You have uncontrolled high blood pressure or conditions that make ketamine unsafe Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGEsketamine hydrochloride (intranasal)

Intranasal esketamine (Spravato®), administered under medical supervision in accordance with FDA guidelines for treatment-resistant depression. Dosing schedule includes twice-weekly administration during weeks 1-4 (acute phase), followed by weekly or biweekly administration during weeks 5-8 (maintenance phase), based on clinical response and tolerability. All dosing occurs in a clinical setting with standard monitoring for at least two hours post-administration.

BEHAVIORALIntegration Therapy

Brief, structured psychotherapeutic sessions delivered before and after each esketamine dose, based on psychedelic-assisted therapy principles. Sessions are designed to support emotional safety, preparation for the treatment experience, and integration of psychological content that may arise. Conducted by trained clinicians following a standardized framework developed for this study. Only participants in the experimental arm receive this intervention.