Home-Based Spaced Transcranial Direct Current Stimulation for Treatment-Resistant Depression: A Feasibility and Safety Study
DOI: Pending DOI
Synopsis
We evaluated the feasibility of home-based spaced tDCS (5 sessions/day × 10 weekdays, 50 sessions) for treatment-resistant depression (TRD). Adults with TRD (MADRS ≥20; ATHF-SF ≥3) self-administered spaced tDCS using a code-activated device with continuous videoconference oversight. Of 10 enrolled, 8 initiated treatment and completed the 50-session protocol (1 withdrew during follow-up for reasons unrelated to tDCS); 2 are scheduled to begin at the time of submission. MADRS decreased from 25.9 at baseline to 10.8 at the 4-week post-treatment follow-up (response 75.0%, remission 62.5%). No SAEs; AEs were mild and self-limited. Home-based spaced tDCS appears feasible, well-tolerated, and merits sham-controlled evaluation.
Background
Major depressive disorder (MDD) is the leading cause of disability worldwide, and between 30-55% of patients develop treatment-resistant depression (TRD).[1] Existing neuromodulation options for TRD, such as electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS), are effective but limited by cost, infrastructure requirements, and the need for daily in-clinic visits, creating significant access barriers, particularly for patients in rural or underserved areas.
Transcranial direct current stimulation (tDCS) is non-invasive, low-cost, portable, and amenable to self-administration, positioning it as a candidate for scalable home-based delivery.[2] However, conventional once-daily tDCS protocols have produced mixed results in TRD, likely reflecting suboptimal stimulation dosing.[3] Preclinical and human motor cortex studies indicate that spaced tDCS, delivered as multiple sessions separated by short intersession intervals, engages late long-term potentiation and produces more durable plasticity than single sessions.[4,5]
We previously reported the first open-label trial of clinic-based spaced tDCS (50 sessions over 2 weeks) in 30 participants with TRD, demonstrating retention 93.3%, adherence 99.7%, and clinically meaningful symptom reduction.[6] Building on this, the present study evaluates whether the same spaced protocol can be delivered at home under remote supervision. Such a delivery model, if successful, would address the access barriers outlined above while preserving safety and treatment fidelity.
Methods
Design: Prospective, single-arm, open-label feasibility study at UC San Diego (NCT07217223). Target enrollment: 10 adults with TRD.
Participants: Adults aged 18–85 with a current major depressive episode, MADRS ≥20, and treatment resistance defined by ATHF-SF ≥3. Exclusions included bipolar disorder, psychotic disorders, moderate/severe substance use within 3 months, clinically significant suicidality, contraindications to tDCS, prior failed ECT, and prior non-response to >15 rTMS sessions or >4 ketamine sessions.
Intervention: 50 tDCS sessions delivered as 5 sessions/day × 10 consecutive weekdays. Each session: 2 mA, 20 minutes, with 30-second ramp-up/down and 20-minute intersession intervals (3 hours/day total). Anode F3 / cathode F4 (international 10-20 system) via Soterix Medical mini-CT device with SNAPpad sponge electrodes. The first session was conducted in clinic for training; subsequent sessions were self-administered at home under continuous videoconference supervision by a clinical research coordinator, with code-gated device activation preventing unsupervised use.
Assessments: MADRS and PHQ-9 were administered at baseline, after sessions 5 and 10, and at 1-, 2-, 3-, 4-, 8-, and 12-week post-treatment follow-up. Adverse events were monitored daily, including remote skin inspection. The primary analysis was descriptive (recruitment, retention, adherence, SAEs, and AE frequency). The secondary analysis evaluated change in MADRS and PHQ-9 scores, response rate, and remission rate at each reassessment throughout the study.
Results
Recruitment and retention: Recruitment began in November 2025. To date, 64 participants have been referred, 35 underwent phone screening, 12 proceeded to in-person screening, 12 consented, and 10 were enrolled and initiated treatment. At the time of submission, 8 participants had completed treatment and 2 were about to begin. Of these 8 participants, 7 had reached at least the 4-week post-treatment follow-up, and 1 withdrew after the 3-week post-treatment assessment, yielding a preliminary retention rate of 7/8 (87.5%). All 8 participants who initiated treatment completed the full 50-session protocol (adherence 100%).
Baseline characteristics: The average age of participants was 55.2 years (SD=12.8), and 87.5% were female. The onset of the first depressive episode occurred on average at 14.0 years old (SD=11.3). On average, participants had previously experienced 6.4 depressive episodes (SD=5.3). Mean ATHF-SF score was 3.1 (SD=0.7) for the current episode and 3.9 (SD=0.4) lifetime, consistent with moderate-to-severe treatment resistance.
Safety and tolerability: No serious adverse events were reported. Consistent with our prior clinic-based cohort, the most frequent AEs were transient sensations during stimulation (tingling/itching/burning, 8/8) and post-stimulation skin erythema (8/8), all mild and self-limited. Mild contact dermatitis under the anode emerged in all participants, on average during the second treatment week, and resolved by the 1-week follow-up. This side effect was not treatment-limiting and did not require any specific intervention.[7] Headache was reported by 3/8 (37.5%) of participants. No other side effects were reported and no participant required treatment interruption for tolerability.
Clinical outcomes: Mean MADRS scores decreased from 25.9 (SD=8.3) at baseline to 14.4 (SD=10.0) at end-of-treatment (day 10), 16.1 (SD=11.2) at 1-week follow-up, and 10.8 (SD=9.3) at 4-week follow-up. This corresponded to a 46.8% (SD=30.5%) improvement at end-of-treatment, 38.0% (SD=42.2%) at 1 week, and 61.8% (SD=25.0%) at 4 weeks. Response (≥50% MADRS reduction) was 62.5% at end-of-treatment, 37.5% at 1 week, and 75.0% at 4 weeks; remission (MADRS ≤10) was 50.0% at end-of-treatment, 37.5% at 1 week, and 62.5% at 4 weeks. PHQ-9 followed a similar trajectory.
Discussion
This study provides preliminary evidence that an intensive 50-session spaced tDCS protocol can be delivered safely at home, under remote supervision, to adults with TRD, with high adherence, acceptable tolerability, and encouraging clinical effects. For reference, our prior clinic-based cohort showed 4-week response 46.4% and remission 32.1%[6], suggesting that home-based delivery does not appear to compromise efficacy. To our knowledge, this is the first evaluation of a home-based spaced tDCS protocol for depression, as prior home-tDCS trials have used conventional once-daily dosing.
Several design elements likely contributed to the high protocol fidelity observed: code-gated device activation prevented unsupervised use, and continuous videoconference supervision allowed real-time correction of electrode placement and contact quality issues. The dermatological side-effect profile reproduces what we previously described in clinic.[7]
Limitations include the small sample size (N=10) and the single-arm open-label design. Without sham control, specific neuromodulatory effects cannot be distinguished from nonspecific benefits of intensive remote contact, and unblinded MADRS administration may have introduced rater bias inflating observed response rates. Clinical outcomes should therefore be interpreted as preliminary signals to inform a sham-controlled trial, not as evidence of efficacy.
These findings support advancing home-based spaced tDCS into an adequately powered sham-controlled randomized trial. If confirmed, this delivery model could substantially expand access for TRD patients unable to engage with daily clinic-based neuromodulation.
Disclosures
This research was enabled by the generous support of the Kreutzkamp Family Foundation. The funder had no role in study design, data collection, analysis, interpretation, or manuscript preparation. No author has any conflict of interest to disclose.
References
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