Clinical TrialTreatment-Resistant Depression (TRD)EsketaminePlaceboEsketamineRecruiting

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

This interventional trial (n=30) will evaluate the efficacy and tolerability of a virtual reality-based mindfulness intervention combined with intranasal esketamine treatment compared to esketamine treatment alone in patients with treatment-resistant major depressive disorder (TRD). Participants will be randomly assigned to receive either the combined treatment (esketamine plus mindfulness) or standard esketamine treatment as usual, with the primary aim of assessing reductions in depressive symptoms. During the 4-week induction phase, both groups will receive intranasal esketamine, with the experimental group also participating in a 10-minute virtual reality mindfulness session prior to each treatment. Following this, the maintenance phase will last from weeks 5 to 30, with participants continuing esketamine administration once weekly for four weeks, followed by biweekly sessions. Key outcome measures will include changes in depressive symptom severity, inflammatory blood parameters, tolerability, and the duration of remission, with assessments conducted at baseline, the end of the induction phase, and at 30 and 54 weeks post-treatment.

Target Enrollment
30 participants
Study Type
Phase NA interventional
Design
Randomized

Detailed Description

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.

Study Arms & Interventions

Control Arm: Esketamine Treatment as Usual (ESK)

experimental

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

Interventions

  • Esketamine

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.

Interventions

  • Placebo
    • 10-minute session before each esketamine administration during induction phase• 8 doses total

    Unmatched intervention: Virtual-Reality-based mindfulness intervention

  • Esketamine

Participants

Ages
18 – 74
Sexes
All

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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

Study Details

Study Team

Sponsors & Collaborators

Locations

Hospital Universitari Vall d'Hebron — Barcelona, Spain

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