Efficacy and Safety of Transcranial Alternating Current Stimulation (tACS) Combined With Stable Medication in Adolescents With Depression: A Randomized, Double-Blind, Controlled Pilot Study

Overview

To evaluate the efficacy of tACS treatment. To determine whether tACS can accelerate symptom remission, improve clinical response rates, and facilitate the recovery of emotional and cognitive functions through standardized clinical assessments. To evaluate the safety of tACS treatment. To assess adverse events and side effects in both the intervention and control groups, ensuring the safety and tolerability of tACS in adolescent populations.

Detailed description

This randomized, double-blind, sham-controlled pilot trial will evaluate the efficacy and safety of transcranial alternating current stimulation (tACS) combined with stable pharmacotherapy in adolescents with major depressive disorder (MDD). Eligible participants are aged ≥8 years, meet DSM-5 criteria for a current depressive episode, have a CDRS-R score ≥40, and have been on stable antidepressant treatment for at least 4 weeks.

A total of 30 participants will be randomized 1:1 to receive either active tACS or sham stimulation, in addition to their ongoing medication. The active group will undergo 20 sessions over 4 weeks (5 sessions per week) using the NEXALIN ADI device (77.5 Hz, 15 mA, \~40 minutes per session). The sham device is identical in appearance but delivers no current. Both participants and operators will remain blinded.

The primary outcomes are changes in depressive symptoms measured by the CDRS-R and BDI. Secondary outcomes include anxiety (SCARED, HAMA), global improvement (CGI-S, CGI-I), suicide risk (C-SSRS), quality of life (PedsQL), sleep (PSQI), rumination (RRS), and cognition (THINC-it). Safety will be monitored through adverse events, vital signs, laboratory tests, and tolerability assessments.

This pilot study will provide preliminary evidence on the potential of tACS as an adjunctive treatment for adolescent depression and inform future large-scale trials.

Interventions

• Device tACS
  This intervention uses the NEXALIN ADI alternating current stimulation device from Beijing Naisilin Technology Co., Ltd., to deliver targeted stimulation to the prefrontal cortex and bilateral mastoid regions. The prefrontal cortex electrode directly stimulates the cerebral cortex, while the mastoid electrodes ensure the synchronized activation of bilateral neural pathways. Stimulation is applied at a frequency of 77.5 Hz and a current intensity of 15 mA, aiming to optimize brainwave synchroniza
• Device tACS
  In the sham stimulation group, participants will receive intervention using a sham device that is identical in appearance, operation, and stimulation protocol to the real tACS device, but does not deliver any current. Both participants and operators will be unable to distinguish between real and sham stimulation based on the device's appearance, sound, or tactile feedback. Device allocation will follow a randomized code generated in advance to ensure blinding and proper group assignment.

Primary outcome measures

• Change in CDRS-R (Children's Depression Rating Scale) scores from baseline [Time frame: Baseline of treatment period, 1 month; The follow-up period was 1 month, 3 months]

Secondary outcome measures (8)

• Change in BDI-II (Baker Depression Scale) scores from baseline [Time frame: Baseline of treatment period, 1 month; The follow-up period was 1 month, 3 months.]
• Change in SCARED (The Screen for Child Anxiety-Related Emotional Disorders) scores from baseline [Time frame: Baseline of treatment period, 1 month; The follow-up period was 1 month, 3 months.]
• Change in suicide risk from baseline on the C-SSRS (Columbia Suicide Severity Rating Scale) [Time frame: Baseline of treatment period, 1 month; The follow-up period was 1 month, 3 months.]
• Change in PSQI (Pittsburgh Sleep Quality Index) scores from baseline [Time frame: Baseline of treatment period, 1 month; The follow-up period was 1 month, 3 months]
• Change in PedsQL4.0 (The Pediatric Quality of Life Inventory) scores from baseline [Time frame: Baseline of treatment period, 1 month; The follow-up period was 1 month, 3 months]
• Change in CGI-S (Clinical Global Impressions-Severity Scales) scores from baseline [Time frame: Baseline of treatment period, 1 month; The follow-up period was 1 month, 3 months]
• Change in CGI-I (Clinical Global Impressions-Improvement Scales) scores from baseline [Time frame: Baseline of treatment period, 1 month; The follow-up period was 1 month, 3 months]
• Change in RSS (Ruminative Responses Scale) [Time frame: Baseline of treatment period, 1 month; The follow-up period was 1 month, 3 months]

Eligibility criteria

Inclusion criteria

• Age 12-18 years.
• Meet DSM-5 diagnostic criteria for a current depressive episode, as confirmed by the K-SADS-PL.
• Children's Depression Rating Scale-Revised (CDRS-R) score ≥40 at baseline.
• Stable psychotropic medication treatment for at least 4 weeks prior to enrollment and willingness to continue the same regimen throughout the study.

Exclusion criteria

• Psychiatric comorbidities other than anxiety disorders.
• Depression with psychotic features.
• Young Mania Rating Scale (YMRS) score >13.
• History of neurological disorders (e.g., epilepsy, traumatic brain injury) or severe physical illnesses (e.g., thyroid disease, lupus, diabetes, significant liver, kidney, or lung impairment, major trauma).
• Previous treatment with electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), tACS, or other neurostimulation therapies.
• Current use of antiepileptic drugs or high-dose benzodiazepines.
• History of alcohol or substance abuse or dependence.
• Pregnant or breastfeeding females.
• Contraindications to MRI.
• Current high suicide risk.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Chongqing Medical University — Chongqing

Publications

• Clancy KJ, Andrzejewski JA, You Y, Rosenberg JT, Ding M, Li W. Transcranial stimulation of alpha oscillations up-regulates the default mode network. Proc Natl Acad Sci U S A. 2022 Jan 4;119(1):e2110868119. doi: 10.1073/pnas.2110868119. PMID 34969856
• Jones KT, Johnson EL, Gazzaley A, Zanto TP. Structural and functional network mechanisms of rescuing cognitive control in aging. Neuroimage. 2022 Nov 15;262:119547. doi: 10.1016/j.neuroimage.2022.119547. Epub 2022 Aug 5. PMID 35940423
• Yan CG, Chen X, Li L, Castellanos FX, Bai TJ, Bo QJ, Cao J, Chen GM, Chen NX, Chen W, Cheng C, Cheng YQ, Cui XL, Duan J, Fang YR, Gong QY, Guo WB, Hou ZH, Hu L, Kuang L, Li F, Li KM, Li T, Liu YS, Liu ZN, Long YC, Luo QH, Meng HQ, Peng DH, Qiu HT, Qiu J, Shen YD, Shi YS, Wang CY, Wang F, Wang K, Wang L, Wang X, Wang Y, Wu XP, Wu XR, Xie CM, Xie GR, Xie HY, Xie P, Xu XF, Yang H, Yang J, Yao JS, Yao PMID 30979801
• Chai Y, Gehrman P, Yu M, Mao T, Deng Y, Rao J, Shi H, Quan P, Xu J, Zhang X, Lei H, Fang Z, Xu S, Boland E, Goldschmied JR, Barilla H, Goel N, Basner M, Thase ME, Sheline YI, Dinges DF, Detre JA, Zhang X, Rao H. Enhanced amygdala-cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation. Proc Natl Acad Sci U S A. 2023 Jun 27;120(26):e2214 PMID 37339227
• Wang J, Zhao W, Wang H, Leng H, Xue Q, Peng M, Min B, Jin X, Tan L, Gao K, Wang H. Brain-wide activation involved in 15 mA transcranial alternating current stimulation in patients with first-episode major depressive disorder. Gen Psychiatr. 2024 Mar 8;37(2):e101338. doi: 10.1136/gpsych-2023-101338. eCollection 2024. PMID 38476648
• Biackova N, Adamova A, Klirova M. Transcranial alternating current stimulation in affecting cognitive impairment in psychiatric disorders: a review. Eur Arch Psychiatry Clin Neurosci. 2024 Jun;274(4):803-826. doi: 10.1007/s00406-023-01687-7. Epub 2023 Sep 8. PMID 37682331
• Zhou J, Li D, Ye F, Liu R, Feng Y, Feng Z, Li R, Li X, Liu J, Zhang X, Zhou J, Wang G. Effect of add-on transcranial alternating current stimulation (tACS) in major depressive disorder: A randomized controlled trial. Brain Stimul. 2024 Jul-Aug;17(4):760-768. doi: 10.1016/j.brs.2024.06.004. Epub 2024 Jun 14. PMID 38880208
• Elyamany O, Leicht G, Herrmann CS, Mulert C. Transcranial alternating current stimulation (tACS): from basic mechanisms towards first applications in psychiatry. Eur Arch Psychiatry Clin Neurosci. 2021 Feb;271(1):135-156. doi: 10.1007/s00406-020-01209-9. Epub 2020 Nov 19. PMID 33211157

Identifiers

NCT: NCT07185451 · 1stChongqingMU__ZXY

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗