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.
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
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