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

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.