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Antidepressant Monotherapy and Combination Therapy with Acupuncture in Depressed Patients: A Resting-State Functional Near-Infrared Spectroscopy (fNIRS) Study


Depression is a common psychiatric illness affecting over 300 million people globally. Acupuncture has been reported to be a safe complementary treatment for depression. This study is aimed to investigate the efficacy and mechanism of combining acupuncture with antidepressants in treating depression compared to the sole use of antidepressants. Seventy depression patients were randomly assigned to the treatment group (n = 50) and control group (n = 20). The treatment group received acupuncture combined antidepressants treatment for 3 weeks, while the control group took antidepressants monotherapy for 3 weeks. Among the 70 patients, 40 participants (20 control; 20 treatment) were randomized for studying functional connectivity (FC) of the dorsolateral prefrontal cortex (DLPFC) measured by the functional near-infrared spectroscopy. The primary outcome was HAMD-17 and secondary outcomes were PHQ-9, and the relationships of resting-state FC (rsFC) with the depression severity. PHQ-9 and HAMD-17 scores in the treatment group were significantly lower than those in the control group at Week 3 (p = 0.01) with effect sizes of −0.4 and −0.61 respectively. The rsFC in F1, F3, AF3, AF7, FC3, FC5 (left DLPFC, 10–20 system), AF8, and F6 (right DLPFC) in the treatment group had significant temporal correlation (p < 0.05, FDR corrected) in DLPFC compared to the channels in the control group. No significant correlation was found between the changes of rsFC and depression severity. In conclusion, depressed patients receiving acupuncture combined with antidepressants have improvement of depressive symptoms and the stronger rsFC in the DLPFC compared to those using antidepressants alone.

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Major Depressive Disorder


Analysis of variance


Dorsolateral prefrontal cortex


Resting-state functional connectivity


Functional near-infrared spectroscopy


Institutional Review Board


Treatment group


Control group


Patient Health Questionnaire 9


Hamilton Depression Rating Scale 17 items


Montgomery-Asberg Depression Rating Scale


Pittsburgh Sleep Quality Index


36-Item Short Form Survey


False Discovery Rate




Cognitive Control Network


dorsal Anterior Cingulate Cortex


dorsal/posterior Parietal Cortex


Electroconvulsive therapy


Liver Qi stagnation


Heart and Spleen deficiency


Intention To Treat


Missing at random






Total hemoglobin


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The authors acknowledge the generous advice and equipment support from Dr. Susan M. Bridges (GRF ref. 17100514). It is thankful to Dr. Lo lo Yam and Mr. Chi Wing Tam for providing acupuncture treatment, and to Miss Mei Yan Chan for performing clinical assessment and data collection. This study is funded by the HKU SEED Funding (ref: 201505159005).

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Authors and Affiliations



ZJZ, JMW, FZ, NZ, QZ, and HYC were involved in the conception, design of the study, and critical comments on the manuscript. YKW, GDZ, and ZSQ conducted data analysis. ZZJ, ZSQ, and YKW conducted re-examination and re-analysis of the data set. JMW and HYC carried out acupuncture treatment. YKW drafted the manuscript. ZJZ, HYC, XJY, FZ, and JMW revised manuscript.

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Correspondence to Haiyong Chen or Zhang-Jin Zhang.

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Wong, Y.K., Wu, J.M., Zhou, G. et al. Antidepressant Monotherapy and Combination Therapy with Acupuncture in Depressed Patients: A Resting-State Functional Near-Infrared Spectroscopy (fNIRS) Study. Neurotherapeutics 18, 2651–2663 (2021).

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  • Acupuncture
  • Antidepressant
  • Depression
  • Functional near-infrared spectroscopy
  • Clinical trial