JMIR Publications

ABSTRACT

Background:

Major depressive disorder (MDD) affects over 280 million people globally, with significant treatment gaps despite available interventions. Transcranial direct current stimulation (tDCS) has emerged as a promising non-invasive brain stimulation technique, with recent developments in home-based delivery addressing accessibility barriers.

Objective:

To systematically review and meta-analyze the efficacy, safety, and feasibility of remotely supervised tDCS for depression treatment.

Methods:

A comprehensive systematic search was conducted across MEDLINE (1946-June 2025), Embase (1974-July 2025), Web of Science (inception-July 2025), Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane. Database of Systematic Reviews using predefined search strategies combining three concept groups: intervention terms (transcranial direct current stimulation, tDCS, non-invasive brain stimulation), setting terms (home-based, remotely supervised, telemedicine, self-administered), and condition terms (depression, major depressive disorder, bipolar depression). Studies investigating home-based, remotely supervised, or self-administered tDCS for depression in adults were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2 tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies.

Results:

From 603 records identified across all databases (MEDLINE: 65, Embase: 255, Web of Science: 135, Cochrane databases: 148), 363 unique records remained after deduplication. Following systematic screening, 36 studies met inclusion criteria, comprising 8 randomized controlled trials, 15 observational studies, 8 feasibility/implementation studies, 3 qualitative studies, and 2 systematic reviews/meta-analyses. However, 11 studies were clinical trials or letters to the editor without complete data. Therefore, comprehensive data extraction and analysis was completed for 25 studies with published results (>1,500 participants, >8,000 treatment sessions). Meta-analysis stratified by supervision model demonstrated that real-time supervision produced significant therapeutic effects (standardized mean difference [SMD] = -0.35, 95% CI: -0.58 to -0.12, p = 0.003) with response rates of 55-60% and number needed to treat of 5. In contrast, unsupervised delivery showed no significant effect (SMD = +0.01, 95% CI: -0.23 to +0.25, p = 0.93). The landmark Nature Medicine randomized controlled trial (n=174) with real-time supervision showed response rates of 58.3% versus 37.8% (OR=2.31, 95% CI: 1.17-4.55, p=0.017). However, the largest trial (JAMA Psychiatry, n=210) using unsupervised delivery found no significant differences between active tDCS and sham controls. Safety analysis of >8,000 sessions revealed an excellent safety profile with no serious adverse events in properly supervised protocols. Common side effects included skin redness (18-64%, odds ratio vs sham = 3.12), mild headache (15-22%, OR = 1.58), and tingling sensations (12-36%, OR = 4.05), all of which were mild and self-limiting.

Conclusions:

Remotely supervised tDCS demonstrates clinically meaningful efficacy for treating major depressive disorder when implemented with real-time supervision and appropriate training protocols. Implementation quality, particularly supervision intensity, is the critical determinant of treatment success. Effect sizes are comparable to established depression treatments (SMD 0.31-0.38), with excellent safety and high patient acceptability (>90% satisfaction). Unsupervised delivery fails to produce therapeutic benefits, highlighting the essential role of human oversight in home-based brain stimulation. The evidence supports conditional recommendation for healthcare systems with adequate infrastructure to implement supervised home-based tDCS programs, prioritizing quality assurance over scalability.