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

Conditions studied

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

About this study

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. Does the combined intervention lead to changes in inflammatory blood parameters compared with pharmacological treatment alone? 2. Does the addition of a VR-based mindfulness intervention prolong remission of depressive symptoms six months after treatment completion? 3. Is the combined treatment with mindfulness and esketamine well-tolerated, and how does its adverse effect profile compare with esketamine treatment alone? 4. Is there an association between changes in mindfulness trait levels, assessed using the FFMQ-SF, and reductions in depressive symptom severity? Participants will be recruited from a Treatment-Resistant Depression Programme and randomly assigned to receive either VR-based mindfulness intervention in addition to treatment as usual or treatment as usual alone. The mindfulness intervention will last one month and include a total of 8 sessions. All participants will undergo comprehensive assessments at baseline and at predefined follow-up time points to evaluate clinical outcomes, inflammatory markers, tolerability, and remission duration.

Interventions

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

Primary outcomes

• Severity in depressive symptoms as assessed by Montgomery-Åsberg Depression Rating Scale (MADRS) (Baseline (Week 0), Week 4 (end of the induction phase), Week 30 (end of the maintenance phase), and Week 54 (follow-up))

Eligibility information

Study locations

• Hospital Universitari Vall d'Hebron, Barcelona, 08035 Spain