Accelerated High-Dose tDCS for Depression

Accelerated High-Dose tDCS for Depression: An Open-Label Outpatient Pilot Study

In this study, investigators are testing whether a higher dose of a non-invasive brain stimulation technique, called transcranial direct current stimulation (tDCS), can be safely used in people with depression. Participants will come to the Brain Stimulation Lab and receive mild electrical stimulation through electrodes placed on their scalp.

The study begins with a safety run-in, where the first few participants will receive stimulation at gradually increasing levels (2, 4, and 6 milliamps) while being closely monitored. If no serious side effects are found, later participants will receive repeated 6 milliamp sessions for 5 days total. Investigators will check skin comfort, mood, and overall tolerability after each session.

Study Overview

• Status: Recruiting
• Conditions: Major Depression; Major Depression Disorders
• Intervention / Treatment: Device: Transcranial Direct Current Stimulation (tDCS)

Detailed Description

Major depressive disorder (MDD) remains one of the leading causes of disability worldwide, with many patients experiencing inadequate response to currently available treatments. Transcranial direct current stimulation (tDCS) has shown promise as a non-invasive, well-tolerated neuromodulation technique for depression, but nearly all prior studies have used lower current intensities (≤2 mA). Preliminary modeling and experimental work suggest that higher current dosing may be necessary to achieve sufficient engagement of cortical targets and produce stronger clinical effects.

The present study is designed to address this gap by systematically evaluating the safety, tolerability, and feasibility of high-dose tDCS delivered at 6 mA in adults with MDD. Establishing safety at this higher intensity is a critical step before pursuing larger efficacy trials. By carefully monitoring adverse events and skin integrity during an initial run-in phase, this study provides an evidence base for whether 6 mA tDCS can be safely implemented in a clinical population.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Recruiting
      • MUSC Brain Stimulation Lab
      • Contact: Elisabeth Collins, BS; Phone Number: 8437928292; Email: brainstimlab@musc.edu
      • Contact: Clayton Olash, MD; Phone Number: 5023778275; Email: olash@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ages 18-70.
• Current MDD diagnosis (MINI v7).
• Baseline PHQ-9 > 9.
• Capacity to consent
• Fluent English.

Exclusion Criteria:

• Bipolar or psychotic disorder
• Primary anxiety disorders without concomitant major depression as defined above
• Current significant suicidal ideation or behaviors require a higher level of care.
• Use of neuromodulation therapies (e.g., ECT, TMS, VNS) within the past 6 months.
• History of seizures, implanted cranial/ cardiac metal, or neurosurgery.
• Use of medications that significantly reduce seizure threshold
• Frequent/severe HA
• Personal history of head trauma, concussion, or TBI
• Catatonic or otherwise unable to perform the consent process
• Current alcohol or substance-use disorder (moderate-severe).
• Any non-uniformities in the skin under the electrode site, including eczema, severe rashes, hyperhidrosis, communicable skin disorders, sensitive skin (ex. eczema, severe rashes), blisters, open wounds, burns including sunburns, cuts or irritation (e.g. due to shaving), or other skin defects or lesions, as determined by clinical personnel
• Pregnancy (urine test required for women of childbearing potential).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental: High-Dose tDCS Intervention; Participants in this single-arm, open-label pilot study will receive high-dose transcranial direct current stimulation (tDCS) for major depressive disorder. Each participant undergoes twice-daily 20-minute sessions at 6 mA for five consecutive weekdays (total of 10 sessions). The first three participants complete an in-lab dose-escalation safety run-in (2 mA → 4 mA → 6 mA on Day 1) with a Day 2 skin integrity check before continuing at 6 mA twice daily for the remaining days. All participants complete baseline, post-intervention, and 4-week follow-up assessments of depressive symptoms, cognition, and tolerability.

Device: Transcranial Direct Current Stimulation (tDCS); Participants receive transcranial direct current stimulation (tDCS) using a high-dose (6 mA) protocol delivered twice daily for five consecutive weekdays (10 sessions total). The first three participants complete a Day 1 in-lab dose-escalation (2 mA → 4 mA → 6 mA) with a Day 2 skin integrity check before continuing at 6 mA. All sessions last 20 minutes and are followed by adverse-event monitoring.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Device-Related Serious Adverse Events	Defined as events requiring hospitalization or emergency care during the stimulation period.	Up to 7 days
Number of Participants Completing All Scheduled Sessions Without Discontinuation	Up to 5 days	Completion of all planned stimulation sessions without dropout due to adverse effects.
Mean Score on Adverse Event Questionnaire	Average Likert-scale ratings of discomfort, headache, or skin irritation.	Daily during treatment (Days 1-5)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Depression Severity Score From Baseline to Post-Treatment	Self-reported depression severity using a validated scale.	Baseline to Day 5
Change in Cognitive Function Score From Baseline to Post-Treatment	Subjective cognitive performance measured via standardized instrument.	Baseline to Day 5
Change in Mindfulness Score From Baseline to Post-Treatment	Self-reported mindfulness using a validated scale.	Baseline to Day 5
Change in Depression Severity Score From Baseline to 4-Week Follow-Up	Longitudinal assessment of symptom durability.	Baseline to 4 weeks post-treatment
Electric Field Intensity in Target Brain Regions Based on MRI Modeling	Retrospective modeling of intracerebral current flow using structural MRI.	Within 30 days of MRI scan

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Study Director: Clayton Olash, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: November 4, 2025
• First Submitted That Met QC Criteria: November 5, 2025
• First Posted (Actual): November 10, 2025

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Depression; tDCS; Interventional; Brain Stimulation; Nervous System; Transcranial Direct Stimulation
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Behavioral Symptoms; Mood Disorders; Depressive Disorder; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Neurologic Manifestations; Depression; Depressive Disorder, Major; Therapeutics; Behavioral Disciplines and Activities; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Transcranial Direct Current Stimulation
• Other Study ID Numbers: Pro00146983; R25DA020537 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes