Virtual Reality-Based Mindfulness as an Adjunct to Treatment as Usual in Treatment-Resistant Depression

NCT07422519 | Recruiting

• 1 other identifier: PR(AG)494/2024
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of this study is to evaluate the efficacy and tolerability of a combined Virtual Reality (VR)-based mindfulness intervention and pharmacological treatment compared with pharmacological treatment alone in reducing depressive symptoms in patients with Treatment-Resistant Depression (TRD). Secondary questions this study aims to address include:

1. 1.Does the combined intervention lead to changes in inflammatory blood parameters compared with pharmacological treatment alone?
2. 2.Does the addition of a VR-based mindfulness intervention prolong remission of depressive symptoms six months after treatment completion?
3. 3.Is the combined treatment with mindfulness and esketamine well-tolerated, and how does its adverse effect profile compare with esketamine treatment alone?
4. 4.Is there an association between changes in mindfulness trait levels, assessed using the FFMQ-SF, and reductions in depressive symptom severity?

Conditions

Depression Disorder; Depression - Major Depressive Disorder; Depression Chronic; Treatment-Resistant Major Depressive Disorder

Keywords

Treatment-Resistant Depression; Major Depressive Disorder; Mindfulness-Based Intervention; Virtual Reality; Esketamine

Outcome Measures

Primary Outcomes (1)

• Severity in depressive symptoms as assessed by Montgomery-Åsberg Depression Rating Scale (MADRS)

  The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated, 10-item scale used to evaluate the severity of depressive symptoms. Each item is scored from 0 to 6, yielding a total score ranging from 0 to 60, with higher scores indicating greater depression severity.

  Baseline (Week 0), Week 4 (end of the induction phase), Week 30 (end of the maintenance phase), and Week 54 (follow-up)

Secondary Outcomes (7)

• Clinical Global Impressions - Improvement (CGI-I) and Severity (CGI-S)

  Baseline (Week 0), Week 4 (end of induction), Week 30 (end of maintenance), and Week 54 (follow-up)

• Self-reported depressive symptoms as assessed by the Beck Depression Inventory (BDI)

  Baseline (Week 0), Week 4 (end of induction), Week 30 (end of maintenance), and Week 54 (follow-up)

• Global functioning as assessed by Global Assessment of Functioning (GAF)

  Baseline (Week 0), Week 4 (end of induction), Week 30 (end of maintenance), and Week 54 (follow-up)

• Functional impairment as assessed by Sheehan Disability Scale (SDS)

  Baseline (Week 0), Week 4 (end of induction), Week 30 (end of maintenance), and Week 54 (follow-up)

• Dissociative symptoms as assessed by the Clinician-Administered Dissociative States Scale (CADSS)

  During the induction phase, approximately 1.5 hours after each dose, through Week 4 (end of induction phase).

Other Outcomes (1)

• Treatment resistance severity assessed by Maudsley Staging Method (MSM)

  Baseline (Week 0)

Study Arms (2)

Control Arm: Esketamine Treatment as Usual (ESK)

OTHER

Participants allocated to the control arm will receive conventional pharmacological treatment with intranasal esketamine for treatment-resistant depression.

Drug: Esketamine Treatment as Usual (ESK)

Experimental Arm: Esketamine Plus Mindfulness (ESK-MIND)

EXPERIMENTAL

Participants allocated to the experimental arm will receive intranasal esketamine in combination with a mindfulness-based intervention delivered via virtual reality. Induction Phase (Weeks 1-4): Participants will receive the same intranasal esketamine induction regimen as the control arm. In addition, participants will receive a 10-minute session of virtual reality-based mindfulness therapy immediately prior to each esketamine administration during the induction phase. The mindfulness intervention will be standardised and delivered using immersive virtual environments with guided audio content. Maintenance Phase (Weeks 5-30): Following the induction phase, participants will continue with the same esketamine maintenance regimen as the control arm: once-weekly administration for four weeks, followed by once every two weeks until treatment completion. Doses of 56 mg or 84 mg will be administered according to clinical response and tolerability, with adjustments based on clinical course.

Behavioral: Virtual-Reality-based mindfulness intervention; Drug: Esketamine Treatment as Usual (ESK)

Interventions

Virtual-Reality-based mindfulness intervention BEHAVIORAL

The mindfulness-based intervention will be delivered using a virtual reality (VR) platform (Sunrise Serenity) developed by XRHealth. The intervention consists of a 10-minute guided mindfulness meditation presented in a 360-degree immersive virtual environment depicting a seaside scene at sunrise. Participants will use a Pico Neo 2 VR headset with handheld controllers. The intervention software will be pre-installed on the device to ensure standardised delivery. Prior to the first intervention session, participants will complete a 5-minute familiarisation period with the VR equipment to ensure comfort and proper use. The VR-based mindfulness session will be administered immediately before each intranasal esketamine treatment during the induction phase (weeks 1-4; 8 sessions in total). The software used is patented and certified for medical use, with regulatory approval from the U.S. Food and Drug Administration (FDA) and CE marking.

Experimental Arm: Esketamine Plus Mindfulness (ESK-MIND)

Esketamine Treatment as Usual (ESK) DRUG

The treatment with intranasal esketamine for treatment-resistant depression includes two phases. Induction Phase (Weeks 1-4): Following diagnosis of treatment-resistant depression, participants will receive intranasal esketamine twice weekly for four weeks. At the first treatment session, a total dose of 56 mg (two 28 mg devices) will be administered. In subsequent sessions, the dose may be adjusted according to individual tolerability and clinical judgement. Maintenance Phase (Weeks 5-30): After completion of the induction phase, participants will enter a maintenance phase in which esketamine will be administered once weekly for four weeks, followed by administration once every two weeks until the end of the treatment period. Doses of 56 mg or 84 mg will be administered based on clinical response and tolerability, with dose adjustments made according to clinical evolution.

Control Arm: Esketamine Treatment as Usual (ESK); Experimental Arm: Esketamine Plus Mindfulness (ESK-MIND)

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 74 years, inclusive
• Diagnosis of treatment-resistant Major Depressive Disorder (MDD), single or recurrent episode, in accordance with DSM-5 diagnostic criteria.
• Inadequate response to two or more oral antidepressants during the current depressive episode
• Inadequate response to at least one pharmacological combination or augmentation strategy
• Ability and willingness to provide written informed consent for participation and data collection

You may not qualify if:

• Presence of any contraindication to esketamine administration according to the approved product label
• Current participation in another interventional clinical study involving antidepressant medication
• Any medical, psychiatric, or other condition that, in the opinion of the investigator, could: (a) compromise participant safety or well-being, or (b) interfere with, limit, or confound study assessments or outcomes

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead

Study Sites (1)

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Central Study Contacts

Dr. J. Antoni Ramos-Quiroga

CONTACT

+3493 274 6087; antoni.ramos@vallhebron.cat

Júlia Vendrell-Serres

CONTACT

+3493 274 60 87; julia.vendrell@vallhebron.cat

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2026
• First Posted: February 20, 2026
• Study Start: September 18, 2025
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)