Effect of Non-invasive Spinal Cord Stimulation in Unmedicated Adults with Major Depressive Disorder: A Pilot Randomized Controlled Trial and Induced Current Flow Pattern

Background Converging theoretical frameworks suggest a role and a therapeutic potential for spinal interoceptive pathways in major depressive disorder (MDD). We aimed to evaluate the antidepressant effects and tolerability of transcutaneous spinal direct current stimulation (tsDCS) in MDD. Methods This was a double-blind, randomized, sham-controlled, parallel group, pilot clinical trial in unmedicated adults with moderate MDD. Twenty participants were randomly allocated (1:1 ratio) to receive “active” 2.5 mA or “sham” anodal tsDCS sessions with a thoracic (anode; T10)/right shoulder (cathode) electrode montage 3 times/week for 8 weeks. Change in depression severity (MADRS) scores (prespecified primary outcome) and secondary clinical outcomes were analyzed with repeated measures ANOVA models. An E-Field model was generated using the active tsDCS parameters. Results Compared to sham (n=9), the active tsDCS group (n=10) showed a greater baseline to endpoint decrease in MADRS score with a large effect size (−14.6± 2.5 vs −21.7±2.3, p=0.040, d=0.86). Additionally, compared to sham, active tsDCS induced a greater decrease in MADRS “reported sadness” item (−1.8 vs − 3.2, p=0.012), and cumulatively decreased pre/post tsDCS session diastolic blood pressure. Statistical trends in the same direction were observed for MADRS “pessimistic thoughts” item, and CGI-I scores. No group differences were observed in adverse events (AEs) and no serious AEs occurred. The current flow simulation showed electric field at strength within the neuromodulation range (max. ∼0.45 V/m) reaching the thoracic spinal gray matter. Conclusions These preliminary results suggest that tsDCS is feasible, well-tolerated, and shows therapeutic potential in MDD. The underlying mechanisms warrant further study. Clinicaltrials.gov registration NCT03433339 URL: https://clinicaltrials.gov/ct2/show/NCT03433339