Evidence Trace, complete trial record
In plain terms
In plain terms: Transcranial Direct Current Stimulation shows early signals in human research but the evidence is limited -- small trials, surrogate endpoints, or not yet independently replicated. It is an emerging area, not yet a proven one.
Transcranial Direct Current Stimulation
C
Limited: small, mixed or unreplicated trials
The endpoint this grade is based on: Validated scale scored by a clinician blinded to treatment
The evidence as the record states it
Razza et al. (Br J Psychiatry, 2026; PMID 41498282): individual patient data meta-analysis of 18 sham-controlled trials and 1,246 patients; Hedges' d 0.24, response odds ratio 1.33, remission not significant, with larger trials showing smaller differences. Positive trials: Brunoni et al. (JAMA Psychiatry, 2013; PMID 23389323), SELECT-TDCS, 120 patients in a factorial design with sertraline, tDCS alone better than placebo on MADRS; Brunoni et al. (N Engl J Med, 2017; PMID 28657871), ELECT-TDCS, 245 patients, tDCS beat placebo by 3.2 HDRS points but failed noninferiority to escitalopram, with more skin redness, tinnitus and nervousness and two cases of new-onset mania; Woodham et al. (Nat Med, 2025; PMID 39433921), 174 patients, 10 weeks of home-based tDCS with remote supervision, 2.3 HDRS points better than sham, funded in part by the device's maker. Null trials: Burkhardt et al. (Lancet, 2023; PMID 37414064), DepressionDC, 160 patients at eight German hospitals, triple-blind, tDCS added to an SSRI, no difference on MADRS at 6 weeks and more mild adverse events with active stimulation; Loo et al. (Brain Stimul, 2018; PMID 29111077), 130 patients in an international multisite trial, no difference from sham in unipolar or bipolar depression, with more remitters on sham in the unipolar group; Borrione et al. (JAMA Psychiatry, 2024; PMID 38170541), 210 patients, fully unsupervised home use with or without a digital intervention, no difference from sham, one nonfatal suicide attempt in the active arm. Ren et al. (JAMA Netw Open, 2025; PMID 40531534): meta-analysis of 88 trials; tDCS alone not significant in major depressive disorder, significant combined with medication. Li et al. (Pain Ther, 2026; PMID 42435147): network meta-analysis restricted to chronic musculoskeletal pain, where depressive symptoms were a secondary outcome; it does not test depression as a disorder and does not carry this grade. Grade C: positive pooled analyses alongside null multicenter trials is inconsistent evidence.
PMID 42435147 PMID 41498282 PMID 23389323 PMID 28657871 PMID 37414064 PMID 29111077 PMID 38170541 PMID 39433921 PMID 40531534
Evidence by specific use
Depressive symptoms in major depression, clinic-administered
Grade C
Razza et al. (2026; PMID 41498282) pool 18 sham-controlled trials: d 0.24, smaller in larger trials. SELECT-TDCS (Brunoni et al., 2013; PMID 23389323) and ELECT-TDCS (Brunoni et al., 2017; PMID 28657871) were positive against placebo, the latter failing noninferiority to escitalopram with two cases of new-onset mania. DepressionDC (Burkhardt et al., 2023; PMID 37414064; 160 patients, add-on to an SSRI) and the international trial (Loo et al., 2018; PMID 29111077; 130 patients) were null. Ren et al. (2025; PMID 40531534) find tDCS alone not significant in major depressive disorder. Inconsistent: C.
PMID 41498282 PMID 23389323 PMID 28657871 PMID 37414064 PMID 29111077 PMID 40531534
Depressive symptoms in major depression, home-based
Grade C
Two trials disagree. Woodham et al. (2025; PMID 39433921): 174 patients, remotely supervised, 2.3 HDRS points better than sham over 10 weeks, part-funded by the device's maker. Borrione et al. (2024; PMID 38170541): 210 patients, fully unsupervised, no difference from sham at 6 weeks, with one nonfatal suicide attempt in the active arm. One positive and one null: C.
PMID 39433921 PMID 38170541
Why Grade C and not Grade B
Grade C reflects early or limited human evidence -- small trials, surrogate endpoints, or preliminary findings not yet independently replicated. The evidence points in a promising direction but does not yet meet the standard for Grade B. A single well-powered, independently replicated trial with a meaningful endpoint would move this to Grade B or higher.
What this grade covers and what it does not
Grade C on depressive symptoms in major depression, clinic-administered or home-based. Pooled sham-controlled data are positive but small: an individual patient data meta-analysis of 18 trials and 1,246 patients found Hedges' d 0.24, with larger trials showing smaller effects (Razza et al., 2026; PMID 41498282). Positive trials include SELECT-TDCS (Brunoni et al., 2013; PMID 23389323), ELECT-TDCS, which beat placebo but failed noninferiority to escitalopram (Brunoni et al., 2017; PMID 28657871), and a remotely supervised home-based trial part-funded by the device maker (Woodham et al., 2025; PMID 39433921). Large independent sham-controlled trials were null: DepressionDC at eight hospitals (Burkhardt et al., 2023; PMID 37414064), the international multisite trial (Loo et al., 2018; PMID 29111077), and fully unsupervised home use (Borrione et al., 2024; PMID 38170541). Positive meta-analyses alongside null multicenter trials is inconsistent evidence, so C. WHAT THIS GRADE DOES NOT COVER: tDCS as monotherapy, which a 2025 meta-analysis of 88 trials found not significant in major depressive disorder (Ren et al., 2025; PMID 40531534), a reading under which the letter would be D on Route 2; cognitive enhancement in healthy adults; pain and anxiety, where the cited network meta-analysis found its robust effects for TMS rather than tDCS (Li et al., 2026; PMID 42435147); and TMS, graded separately. Safety signals from the trials: more mild adverse events with active stimulation, two cases of new-onset mania in ELECT-TDCS, and one nonfatal suicide attempt in the active arm of the unsupervised home-use trial.
What would move this grade
A well-powered randomized trial with an objective, clinically meaningful primary endpoint and at least one independent replication would support Grade B or higher.
How to track whether this is working
A clinician-rated depression scale (HAM-D or MADRS) at baseline and after the course, as the trials used. Electrode placement, current (mA), session duration and montage at every session.