Virtual Reality-Augmented At-Home tDCS for Major Depression

Effectiveness of Virtual Reality-Based Relaxation as an Adjunctive Therapy to Optimize At-Home Transcranial Direct Current Stimulation (tDCS) for Depression: A Randomized Controlled Trial

The goal of this clinical trial is to investigate the efficacy of combining Virtual Reality (VR)-based relaxation and Transcranial Direct Current Stimulation (tDCS) for treating Major Depression.

The main questions this study aims to answer are:

1. Does the combination of VR Relaxation and tDCS at-home result in significantly greater symptom improvement in depression than tDCS alone?
2. Are there differences in treatment effectiveness depending on demographic characteristics (e.g., age, gender)?
3. Feasibility: What is the level of acceptance and adherence to the combined VR and tDCS therapy compared to tDCS alone?

In a randomized controlled trial, patients will be assigned to either a tDCS + VR group or a tDCS-only group.

The study protocol is the following:

• On the first day, patients complete baseline questionnaires and are then randomly assigned to either the tDCS-only group or the tDCS + VR group.
• Both groups perform home-based treatment five times per week for four weeks, with each session lasting 30 minutes.
• After two weeks, patients return for a follow-up visit to complete questionnaires and assess adherence, side effects, and clinical progress.
• At the end of the four-week treatment period, a final assessment is conducted, including questionnaires and patient feedback.
• After 12-16 weeks (i.e. 2 to 3 months after the last tDCS session) Follow Up Assessment (BDI, MADRS, HDRS, GCI, GAF)

Participant Recruitment:

Patients with unipolar or bipolar depression will be recruited from inpatient wards at Klinikum rechts der Isar and outpatient services. After screening for eligibility and obtaining informed consent, participants will be randomized into two groups (1:1), stratified by depression severity (MADRS > or < 30):

Active Group: 4-week home-based combination therapy of tDCS and VR-based relaxation

Control Group: 4-week home-based tDCS without VR relaxation

Treatment Protocol:

at-home tDCS: 2 mA for 30 minutes, electrodes at F3/F4 (bifrontal, over DLPFC), daily Monday to Friday, total 20 sessions. Optional MRI before/after treatment.

VR Relaxation: Nature exposure via VR headset, 30 minutes daily parallel to tDCS, Monday to Friday, 20 sessions.

Assessment Schedule:

Baseline Visit (Visit 1): Informed Consent, demographics, medical history, vital signs, and baseline scales (BDI, MADRS, HDRS, GCI, GAF, CTQ, EHI, FTND). First session in-clinic with training for home use. Up to 5 additional sessions may be conducted in-clinic.

Mid-Treatment (Visit 2): After 2 weeks: vital signs, questionnaires (BDI, MADRS, HDRS, GCI, GAF), therapy adherence (according to number of conducted sessions), side effects, treatment adjustments if needed.

Final Assessment (Visit 3): After 4 weeks: final vitals, questionnaires (BDI, MADRS, HDRS, GCI, GAF), patient satisfaction survey, therapy experience interview.

Follow Up Assessment (Visit 4): After 12-16 weeks: questionnaires (BDI, MADRS, HDRS, GCI, GAF)

Technical data on tDCS use (automatic logging) including time, adherence, etc., will also be recorded.

Inclusion Criteria:

• At least a moderate depressive episode (MADRS baseline score ≥ 20).
• Patients aged between 18 and 65 years.
• Sufficient cognitive abilities to understand study requirements and instructions (MMSE ≥ 27).
• Stable antidepressant/psychiatric medication for at least two weeks prior to study entry.

Exclusion Criteria:

• Currently clinically relevant Axis II disorders.
• Other relevant Axis I disorders (except anxiety disorders).
• Substance use disorders within the last 3 months prior to study entry (excluding nicotine and caffeine dependence).
• Skin lesions at the site of tDCS electrode placement.