Investigating the Efficacy and Mechanisms of Individualized tACS Targeting Anhedonia in Late-Life Depression

Efficacy and Mechanisms of Personalized tACS Targeting Anhedonia in Late-Life Depression

This project focuses on clinical translational research into personalized transcranial alternating current stimulation (tACS) for treating anhedonia in late-life depression (LLD). Key components include: (1) Optimizing individualized tACS treatment parameters through randomized, double-blind, controlled trials and establishing precise treatment protocols using deep learning algorithms; (2) Assessing the short-term (2 weeks) and long-term (3 months) efficacy of tACS on depressive symptoms and anhedonia using scales such as the HAMD, SHAPS, and DARS, while monitoring safety; (3) Integrating multimodal detection technologies (64-channel EEG, inflammatory factors/neurotransmitters, etc.) to elucidate the mechanisms by which tACS alleviates anhedonia through modulating prefrontal neural oscillations (y-band), improving synaptic plasticity (increased BDNF), and regulating neurotransmitters (5-HT, DA). This study will establish, for the first time, an individualized parameter system for tACS treatment of LLD, providing a novel non-pharmacological intervention strategy for clinical practice.

Study Overview

• Status: Recruiting
• Conditions: Anhedonia; Late-Life Depression
• Intervention / Treatment: Device: Transcranial Alternating Current Stimulation (tACS); Device: shame tACS

Detailed Description

This project aims to explore effective treatment strategies and mechanisms of action for personalized transcranial alternating current stimulation (tACS) targeting anhedonia in late-life depression (LLD). Late-life depression has a high prevalence, with 70% of patients exhibiting symptoms of anhedonia, which is

. Current pharmacological treatments face challenges such as poor response rates and significant side effects, creating an urgent need for novel intervention strategies. As a non-invasive neurostimulation technique, tACS can improve depressive symptoms by modulating brain oscillatory activity; however, personalized treatment protocols and mechanisms specifically targeting anhedonia in LLD remain unclear. By optimizing tACS parameters, validating clinical efficacy, and elucidating the underlying neural mechanisms, this project will fill a research gap in this field. The findings will not only provide safe and effective non-pharmacological treatment options for patients with geriatric depression, thereby reducing suicide risk, but will also advance the application of tACS technology in precision medicine for mental disorders, holding significant clinical value and social implications.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Daliang Sun Da liang Sun, Doctor; Phone Number: +86 88188876; Email: 474929588@qq.com

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300222
      • Recruiting
      • Tianjin Anding Hospital
      • Contact: Daliang Sun, Doctor; Phone Number: +86 88188876; Email: 474929588@qq.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• (1) Patients were interviewed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) - Clinical Version (SCID-5-CV) to confirm that they met the DSM-5 diagnostic criteria for "major depressive disorder"; (2) Age ≥ 60 years; gender not restricted; (3) Hamilton Depression Scale (HAMD)-17 score > 24

Exclusion Criteria:

- (1) History of severe head trauma or serious neurological conditions such as epilepsy; (2) Any brain devices or implants, including cochlear implants and aneurysm clips; treatments such as transcranial direct current stimulation (tDCS).

(3) Individuals who have undergone other physical modulation therapies within the past 8 weeks, including but not limited to non-convulsive electroconvulsive therapy, repetitive transcranial magnetic stimulation, and transcranial direct current stimulation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: active; The peak-to-peak amplitude was 1 mA at 40 Hz (tACS), with a frequency and a sinusoidal stimulation waveform. The stimulation sites were located in the prefrontal cortex (F3 and F4) based on the 10-20 international EEG electrode placement system, with CZ serving as the return electrode.	Device: Transcranial Alternating Current Stimulation (tACS); divided into a real-stimulus group and a sham-stimulus group
Sham Comparator: shame; The peak-to-peak amplitude was 1 mA at 40 Hz (tACS), with a frequency and a sinusoidal stimulation waveform. The stimulation sites were located in the prefrontal cortex (F3 and F4) based on the 10-20 international EEG electrode placement system, with CZ serving as the return electrode, shame arm is not biologically active.	Device: shame tACS; The sham tACS group received 40 Hz tACS with a peak-to-peak amplitude of 1 mA, a frequency of y, and a sinusoidal waveform. The stimulation sites were located in the prefrontal cortex (F3 and F4) based on the 10-20 system of international EEG electrode placement, with CZ serving as the return electrode, which did not generate stimulation pulses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dimensional Anhedonia Rating Scale (DARS)	The Dimensional Anhedonia Rating Scale (DARS) assesses the degree of anhedonia in patients.	12 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Scale，HAMD -17	The severity of a patient's depressive symptoms is assessed using the Hamilton Depression Scale (HAMD)-17. This scale consists of 17 items that comprehensively evaluate a patient's depressive symptoms; the higher the score, the more severe the depressive symptoms.	12 week

Collaborators and Investigators

• Sponsor: Jie Li

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 29, 2026
• First Submitted That Met QC Criteria: June 9, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: transcranial alternating current stimulation; anhedonia; late-life depression; Brain function
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Anhedonia; Therapeutics; Behavioral Disciplines and Activities; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Transcranial Direct Current Stimulation
• Other Study ID Numbers: tACS-MDD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Recruitment for this study is currently underway, and we are unable to disclose specific experimental data at this time.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No