Multitarget Transcranial Direct Current Stimulation for Comorbid Depression and Chronic Pain: A Multicenter Randomized Controlled Trial

Shanghai Mental Health Center

Status: Not yet enrolling

Conditions: Chronic Pain; Depression Disorder

Treatments: Device: tDCS

Study type: Interventional

Funder types: Other

Identifiers

NCT07334561

2025-80

Details and patient eligibility

About

This clinical trial aims to investigate a novel non-pharmacological intervention, transcranial direct current stimulation (tDCS) for the treatment of comorbid depression and pain. The primary objectives are to optimize neurostimulation parameters through a multicenter randomized controlled design and to elucidate the underlying neural circuit-immune interaction mechanisms of this comorbidity. Participants with comorbid depression and chronic pain will be randomly assigned to receive active multi-target tES or sham stimulation. The intervention period will last for 2 weeks, followed by a series of post-treatment follow-up assessments. Researchers will compare the changes in depression severity (e.g., assessed by HAMD-24) and pain intensity (e.g., NRS, BPI) across groups to evaluate the efficacy. Secondary outcomes include pain perception, quuatitive sensory test, fMRI, MEG, metabolic markers, neurotransmitter and inflammation biomarkers. This study aims to provide a precise, individualized therapeutic strategy, reduce reliance on pharmacotherapy, and promote the development of domestic high-end medical devices.

Enrollment: 144 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Aged 18-65 years;
2. Meet the diagnostic criteria for a depressive episode according to ICD-11, with current mild-to-moderate depressive symptoms (HAMD-24 score ≥8 and ≤34);
3. Report persistent pain lasting ≥3 months and score ≥4 on item 5 of the Brief Pain Inventory (BPI);
4. Maintain a stable anti-depression drug and psychological treatment plan (including dosage, drug type, or therapeutic approach) for at least four weeks prior to enrollment;
5. Right-handed, with normal hearing, vision, or corrected vision;
6. Able to voluntarily provide written informed consent to participate in the study and willing and capable of complying with all study procedures.

Exclusion criteria

1. Diagnosed with other psychiatric disorders, including schizophrenia spectrum disorders, bipolar I disorder (due to potential risk of manic episodes and contraindication of lithium or anticonvulsants), primary anxiety disorders, depression associated with severe somatic illness, etc.
2. Active suicidal ideation, defined as a score of 4 on item 3 of the HAMD-24.
3. Severe or treatment-resistant depression (HAMD-24 score ≥35, with current depressive episode lasting at least 2 years or failure to respond to two or more antidepressant treatments during the current episode).
4. Substance use disorder within the past 3 months.
5. Experience of malignant pain due to cancer pain syndrome, visceral pain (e.g., gastric pain), or referred pain (e.g., back pain from pancreatitis).
6. Neurological disorders associated with structural brain abnormalities (e.g., traumatic brain injury, recent stroke, brain tumor).
7. Having undergone neuromodulation treatments within the past 3 months, including electroconvulsive therapy (MECT), repetitive transcranial magnetic stimulation (rTMS), or transcranial electrical stimulation (tES).
8. Contraindications to transcranial electrical stimulation (e.g., intracranial metal implants, cardiac pacemaker, cochlear implant, skin lesions at stimulation sites, personal or family history of epilepsy).
9. Current or within the past 1 month use of medications affecting central nervous system excitability or pain, such as anticonvulsants, lithium, opioids, nonsteroidal anti-inflammatory drugs, and antipsychotics. Occasional as-needed use of acetaminophen as rescue medication is permitted but must be documented in detail in the study diary.
10. Signs of dementia or other severe cognitive impairment (MoCA score <17).
11. Severe or unstable somatic diseases, including but not limited to: neurological disorders (e.g., epilepsy, stroke, migraine, history of cranial surgery); cardiovascular diseases (e.g., uncontrolled hypertension, heart failure, arrhythmia, myocardial infarction); respiratory disorders (e.g., severe sleep apnea syndrome); malignancy or immunocompromised status; uncontrolled diabetes (fasting blood glucose >12 mmol/L).
12. Pregnancy or lactation.
13. Concurrent participation in another clinical trial, participation in any clinical trial within the past 90 days, or planned participation in another trial during the study period.
14. Any contraindications to magnetic resonance imaging (e.g., metal implants, claustrophobia, respiratory or motor impairments).
15. Inability to cooperate with study assessments.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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144 participants in 3 patient groups

tDCS-DLPFC group

Active Comparator group

Description:

They receive actual tDCS on purpose brain targets (DLPFC).

Treatment:

Device: tDCS

Device: tDCS

Device: tDCS

Sham Group

Sham Comparator group

Description:

They receive fake tDCS (no current) on purpose brain targets.

Treatment:

Device: tDCS

Device: tDCS

Device: tDCS

tDCS-M1-DLPFC

Experimental group

Description:

They receive actual tDCS on purpose brain targets (M1+DLPFC).

Treatment:

Device: tDCS

Device: tDCS

Device: tDCS