Accelerated high-capacity 6 mA transcranial direct current stimulation for major depression: an open-label pilot study

Home-based 2 mA transcranial direct current stimulation (tDCS) was recently approved by the US Food and Drug Administration for depression, but tDCS amplitude has been limited largely by skin tolerance, and higher-intensity, accelerated dosing may be more efficacious or faster-acting. Using a novel high-capacity tDCS (HC-tDCS) stimulator and hydrogel electrodes, we evaluated the safety, tolerability and feasibility of accelerated HC-tDCS (20-minute bifrontal 6 mA sessions, twice daily for five days) in 20 patients with major depressive disorder. A Safety Review Committee reviewed data from the first three participants, who completed a within-day escalation to 6 mA, before the remaining 17 were enrolled. Retention and adherence were 100% (203 of 203 sessions), and 19/20 tolerated the full 6 mA amplitude without dose reduction. There were no serious adverse events. The most common symptoms were fatigue (49% of sessions), burning (46%) and tingling (43%) at the electrode, and difficulty concentrating (40%). Electrode-site erythema occurred in all participants, with no severe reaction or skin breakdown. At 1 week, 7 of 20 reported a residual skin change, mostly peeling or redness, none painful; at 1 month, hyperpigmentation at the electrode site persisted in 2 participants, both Black. At the end of the five-day course, PHQ-9 scores decreased from 15.8 to 7.2 (Hedges g = 1.62); 50% of participants responded, 45% remitted, and improvement was maintained at 1-month follow-up. Accelerated HC-tDCS was feasible, well tolerated, and warrants a sham-controlled trial.