Transcranial Electrical Stimulation for Comorbid Depression and Chronic Pain
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-65
SponsorShanghai Mental Health Center
About this trial
This clinical trial aims to investigate a novel non-pharmacological intervention, transcranial electrical stimulation (tES), for the treatment of comorbid depression and chronic 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 one of four interventions: (1) anodal tDCS unilateral hemispheric concurrent dual-site stimulation (a-tDCS UHCDS) targeting the left DLPFC and M1; (2) single-target anodal tDCS over the left DLPFC; (3) 40 Hz gamma transcranial alternating current stimulation (tACS); or (4) 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-17) and pain intensity (e.g., NRS, BPI) across groups to evaluate the efficacy. Secondary outcomes include pain perception, quantitative sensory testing (QST), fMRI, MEG, metabolic markers, neurotransmitter and inflammatory 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Aged 18-65 years;
Meet the diagnostic criteria for a depressive episode according to DSM-5, with current mild-to-moderate depressive symptoms (HAMD-17 score ≥8 and ≤23);
Report persistent pain lasting ≥3 months and score ≥4 on item 5 of the Brief Pain Inventory (BPI);
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;
Disqualifiers
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.
Active suicidal ideation, defined as a score of 4 on item 3 of the HAMD-17.
Severe or treatment-resistant depression (HAMD-17 score ≥23, with current depressive episode lasting at least 2 years or failure to respond to two or more antidepressant treatments during the current episode).
Substance use disorder within the past 3 months.
Trial design
Design model
Parallel
Treatments tested in this trial
Dual-target a-tDCS UHCDS
DeviceParticipants receive active anodal transcranial direct current stimulation (tDCS) delivered via a unilateral hemispheric concurrent dual-site stimulation (UHCDS) montage. Two anodal electrodes (5 × 5 cm) are placed over the left dorsolateral prefrontal cortex (DLPFC, F3) and the left primary motor cortex (M1, C3), with a common cathodal reference electrode (5 × 7 cm) placed over the contralateral supraorbital area (Fp2). A constant current of 2 mA is applied for 20 minutes per session, with a 30-second ramp-up and ramp-down period. The intervention is administered once daily for 2 weeks (total of 10 sessions).
Single-target a-tDCS
DeviceParticipants receive active single-target anodal transcranial direct current stimulation (tDCS). The anodal electrode (5 × 5 cm) is placed over the left dorsolateral prefrontal cortex (DLPFC, F3), and the cathodal electrode (5 × 7 cm) is placed over the contralateral supraorbital area (Fp2). A constant current of 2 mA is applied for 20 minutes per session, with a 30-second ramp-up and ramp-down period. The intervention is administered once daily for 2 weeks (total of 10 sessions).
10 Hz alpha-tACS
DeviceParticipants receive active 10 Hz transcranial alternating current stimulation (tACS). Three 5 × 5 cm electrodes are placed as follows: target electrode over F3, counter electrode over F4, and reference electrode over Cz. A sinusoidal alternating current at 10 Hz frequency (alpha band) is applied with the following intensity parameters: 1 mA (zero-to-peak) at F3 and F4 electrodes, and 2 mA (zero-to-peak) at the Cz reference electrode. Stimulation duration is 40 minutes per session, including 30-second ramp-up and ramp-down periods. The intervention is administered once daily, 5 days per week, for 2 weeks (total of 10 sessions).
Sham tES
DeviceParticipants receive sham transcranial electrical stimulation (tES) using the same electrode montage as the corresponding active groups. To maintain blinding, the stimulator delivers current only during the initial 30-second ramp-up period, followed by an immediate ramp-down, and a final 30-second ramp-up at the end of the stimulation session. This mimics the initial sensation of active stimulation without delivering sufficient current to induce neural modulation. For the tACS sham condition, the 40-minute session includes only the ramp-up/ramp-down sequences at the beginning and end. Participants are randomly assigned to one of the three sham montages (dual-target tDCS, single-target tDCS, or tACS) in parallel with the active groups.
Treatment groups
240 Participants
are divided into 4 treatment groupsGroup A: Dual-target a-tDCS UHCDSExperimental treatment 1 intervention
Group B: Single-target a-tDCSExperimental treatment 1 intervention
Group C: 10 Hz alpha-tACSExperimental treatment 1 intervention
Group D: Sham tESSham comparator 1 intervention
Trial outcomes
Primary outcomes
1
Brief Pain Inventory (BPI) - Pain Intensity Subscale
Description: The BPI is a validated self-administered questionnaire that assesses the severity of pain and its impact on daily functioning. The pain intensity subscale consists of four items rating pain at its "worst," "least," "average," and "current" (right now). Each item is rated on a 0 to 10 numeric rating scale. Higher scores mean a worse outcome. The Minimal Clinically Important Difference (MCID) is defined as a reduction of ≥ 1 point from baseline in the BPI pain intensity score. The outcome is the proportion of participants in each group who achieve this MCID threshold at each follow-up time point.
Time frame
Baseline, 1 week, 2 weeks, 6 weeksSecondary outcomes
1
Hamilton Depression Rating Scale-17 (HAMD-17) - Mean Percentage Reduction from Baseline
The HAMD-17 is a 17-item clinician-rated scale assessing depression severity. Items are rated on 3- or 5-point scales, with total scores ranging from 0 to 52. Higher scores mean a worse outcome (greater depression severity). The outcome is the percentage reduction in HAMD-17 total score from baseline at each follow-up time point, calculated using the formula: \[(Baseline score - Follow-up score) / Baseline score\] × 100% A positive percentage indicates improvement (reduction in depressive symptoms).
Time frame
Baseline, 1 week, 2 weeks, 6 weeks2
Quantitative Sensory Testing (QST) - Change from Baseline
QST is a standardized psychophysical method used to assess somatosensory function, including pain perception. The testing battery includes thermal (cold and warm detection thresholds, cold and heat pain thresholds) and mechanical (mechanical detection threshold, mechanical pain threshold, wind-up ratio) modalities, following the protocol of the German Research Network on Neuropathic Pain (DFNS). For each QST parameter, the change from baseline is calculated as: Follow-up value - Baseline value. The interpretation of higher or lower scores depends on the specific parameter (e.g., increased pain thresholds indicate reduced pain sensitivity, which is a better outcome; decreased mechanical detection thresholds may indicate improved sensory function).
Time frame
Baseline, 2 weeks3
Pain Catastrophizing Scale (PCS) - Mean Percentage Reduction from Baseline
The PCS is a 13-item self-report scale (0-52, higher scores = worse outcome) assessing catastrophic thoughts about pain across three domains: rumination, magnification, and helplessness. The outcome is the percentage reduction from baseline: \[(Baseline - Follow-up)/Baseline\] × 100%.
Time frame
Baseline, 1 week, 2 weeks, 6 weeks4
Generalized Anxiety Disorder Scale-7 (GAD-7) - Mean Percentage Reduction from Baseline
The GAD-7 is a 7-item self-report scale (0-21, higher scores = worse outcome) assessing anxiety symptoms over the past two weeks. The outcome is the percentage reduction from baseline: \[(Baseline - Follow-up)/Baseline\] × 100%.
Time frame
Baseline, 1 week, 2 weeks, 6 weeksSponsors and contacts
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Shanghai Mental Health Center
Lead sponsor
Shanghai 10th People's Hospital
Collaborator
Shanghai Tongji Hospital, Tongji University School of Medicine
Collaborator
Source ClinicalTrials.gov
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