According to the definition of chronic or persistent pain given by the International Association for the Study of Pain, if the pain lasts longer than 3 months or beyond the time period when an acute insult would have been expected to heal, it becomes a chronic condition [
Depression is prevalent around the world, affecting more than 350 million people worldwide [
As two of the most widespread disorders, studies suggested that pain and depression were closely related [
In view of the biopsychosocial aspects involved in chronic pain, a multimodal approach to management is essential [
Conventional treatment of depression mainly includes medication, psychotherapy, and physiotherapy. Taking antidepressants as the most preferred treatment of this disease, only a third of patients with depression respond fully to antidepressant medication [
In terms of management for chronic pain and depression comorbidity, there was a significant overlap in the pharmacological treatment [
Acupuncture, a unique therapeutic method of traditional Chinese medicine with a history of thousands of years, has become a widely recognized alternative and complementary therapy in clinical practice [
To date, there have been several systematic reviews of acupuncture in the treatment for chronic pain or for depression [
A comprehensive search for studies about the effectiveness of acupuncture for chronic pain with depression was conducted through the online database. The following electronic databases were searched from inception to March 17, 2020: the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese Biomedical Database (SinoMed), China National Knowledge Infrastructure (CNKI), and Wanfang database. The following terms were used: “chronic pain” OR “pain, chronic” AND “depression” OR “depressive disease” OR “depressive disorder” AND “acupuncture therapy” AND “random.” During searching Chinese databases, the similar search strategy with Chinese terms was adopted. The initial database search was done by 3 authors (Yan, Zhu, and Wang) independently to ensure reproducibility.
Trials were eligible if they were randomized controlled trials (RCTs) recruiting participants with chronic pain and depression comorbidity, regardless of whether there was single blind, double blind, or nonblind.
Patients diagnosed with chronic pain combined with depression or depression combined with chronic pain will be included. The main concern of studies cited must be chronic pain and depression, that is to say, the author must explain the definition or diagnostic criteria for chronic pain and depression. There will be no limits on the age, sex, and source of cases.
Patients in the experimental group were treated with acupuncture alone or in combination with other therapy, while those in the control group were subjected to other therapy without acupuncture for chronic pain with depression.
The primary outcomes of interest were the pain scores and depression severity, i.e., Visual Analog Scale (VAS): higher scores indicate more severe pain, and Hamilton Depression Scale (HAMD): higher scores indicate a greater degree of depression, and to observe the changes of indicators before and after intervention. The secondary outcomes included any adverse events, i.e., Treatment Emergent Symptom Scale (TESS) or Rating Scale for Side Effects (SERS).
In order to evaluate the independent effects of acupuncture, the following trials were excluded: (1) conference abstracts, review articles, animal studies, cadaveric studies, in vitro studies, or articles published in a form other than clinical trials; (2) any control group that included acupuncture therapies; (3) literatures without relevant indicators or quantitative data; (4) evaluation indicators include only chronic pain or only depression; (5) repeated published literature.
4 authors (Yan, Zhu, Wang, and Da) independently screened all potential eligible studies. Titles and abstracts were first screened to exclude irrelevant papers. Full text of all articles of potentially relevant abstracts were retrieved and screened according to the study inclusion and exclusion criteria. Final article selection was done independently by all four reviewers, and disagreements were resolved by consensus.
4 authors (Yan, Zhu, Wang, and Da) independently conducted the methodological quality of all included studies. Each article was quality appraised with the five-point Jadad Score [
Data were extracted into a prespecified data extraction table, with items including the authors’ names, the year of publication, total sample size, age, gender, detailed intervention information of two groups, outcome measures, and adverse reactions.
Review Manager 5.3, provided freely by the Cochrane cooperation net, was applied for statistical analysis. The primary outcomes, VAS and HAMD, were both continuous variables, and mean difference (MD) was used as effect values. The confidence internal was set as
A total of 521 references were retrieved after removing duplicates (Figure
Study flow diagram.
Basic information of 7 RCT studies.
No. | Author | Year | Sample (EG/CG) | Age (SD) | Gender (EG/CG) | Time since diagnosis (SD) (EG/CG) | |
---|---|---|---|---|---|---|---|
EG | CG | ||||||
1. [ | Wang | 2012 | 60 (30/30) | 51.5 (4.1) | 50.3 (4.7) | — | — |
2. [ | Xiao | 2015 | 48 (24/24) | 53.17 (9.89) | 50.58 (8.80) | 8/16 (M/F)/10/14 (M/F) | — |
3. [ | Ma | 2015 | 12 8 (64/64) | 39.93 (12.93) | 38.69 (14.19) | 27/37 (M/F)/29/35 (M/F) | 20.33 (12.76) m/20.00 (12.12) m |
4. [ | Luo | 2018 | 84 (42/42) | 57.15 (11.26) | 57.39 (11.58) | 22/20 (M/F)/23/19 (M/F) | 42.31 (8.75) m/41.92 (8.32) m |
5. [ | Liu | 2013 | 90 (45/45) | 47 (8) | 48 (8) | 15/30 (M/F)/16/29 (M/F) | 3.5 (1.8) m/3.2 (1.7) m |
6. [ | Cao | 2008 | 60 (30/30) | 20–70 | 23/37 (M/F) | 0.5–30 y | |
7. [ | Huang | 2000 | 65 (30/35) | 30.39 (7.01) | 25/40 (M/F) | — |
EG, experimental group; CG, control group; —, not available; m, month; y, year.
Detailed intervention information 1.
No. | Study type | Diagnosis | EG | CG | Duration (wks) |
---|---|---|---|---|---|
1 | RCT | Depression with chronic pain | Abdominal acupuncture | Deanxit | 4 |
2 | RCT | Migraine with depression | Acupuncture | Deanxit combined rizatriptan benzoate tablets | 4 |
3 | RCT | Depression with chronic pain | Acupuncture combined duloxetine | Duloxetine | 8 |
4 | RCT | Recurrent chronic trigeminal neuralgia accompanied by depression | Acupuncture combined traditional Chinese medicine | Traditional Chinese medicine | 4 |
5 | RCT | Depression with chronic pain | Acupuncture combined SSRI antidepressants | SSRI antidepressants | 4 |
6 | RCT | Chronic pain with depression | Acupuncture | Deanxit | 4 |
7 | RCT | Depression with chronic pain | Acupuncture | Amitriptyline | 6 |
EG, experimental group; CG, control group.
Detailed intervention information 2.
No. | EG | CG | ||||
---|---|---|---|---|---|---|
Intervention | Dose | Frequency | Intervention | Dose | Frequency | |
1 | Acupuncture | — | Once a day for 3 days, then performed every 3 days | Deanxit | Flupirtine, 0.5 mg/meritoxin 10 mg | Once a day |
2 | Acupuncture | — | Once a day for, 5 times a week | Deanxit | Flupirtine, 0.5 mg/meritoxin 10 mg | Once a day |
Rizatriptan benzoate tablets | 1 tablet | If necessary | ||||
3 | Acupuncture | — | 5 times a week | Duloxetine | 60 mg/d | Once a day |
Duloxetine | 60 mg/d | Once a day | ||||
4 | Acupuncture | — | Once a day | TCM | — | Once dose a day |
TCM | — | Once dose a day | ||||
5 | Acupuncture | — | Once every 2 days | SSRI antidepressants | — | Once a day for 1 week, then adjust the dosage |
SSRI antidepressants | — | Once a day for 1 week, then adjust the dosage. | ||||
6 | Acupuncture | — | 5 times a week | Deanxit | Flupirtine, 0.5 mg/meritoxin 10 mg | Twice a day for 10 days, then once a day |
7 | Acupuncture | — | 6 times a week | Amitriptyline | 25–150 mg | Once a day |
EG, experimental group; CG, control group; TCM, traditional Chinese medicine; —, not available.
A total of 6 studies assessed pain [
VAS scores in each study.
Author | Year | EG | CG | ||
---|---|---|---|---|---|
Before therapy mean (SD) | 4 w mean (SD) | Before therapy mean (SD) | 4 w mean (SD) | ||
Wang | 2012 | 7.0 (1.8) | 2.9 (1.0) | 6.8 (1.5) | 3.2 (1.0) |
Ma | 2015 | 7.33 (1.22) | 4.81 (1.25) | 7.28 (1.19) | 5.27 (1.32) |
Luo | 2018 | 7.92 (1.16) | 2.29 (1.01) | 7.86 (1.22) | 3.12 (1.25) |
Liu | 2013 | 3.68 (1.15) | 0.93 (0.78) | 3.70 (1.12) | 2.53 (1.09) |
Cao | 2008 | 7.50 (1.12) | 2.34 (1.43) | 7.48 (1.27) | 2.40 (1.45) |
EG, experimental group; CG, control group.
Forest plot depicting the VAS.
Forest plot depicting the VAS after sensitivity analysis.
In the eligible RCTs, all trials conducted the depression-related assessments, and HAMD was used in 6 of them [
HAMD scores in each study.
Author | Year | EG | CG | ||
---|---|---|---|---|---|
Before therapy mean (SD) | 4 w mean (SD) | Before therapy mean (SD) | 4 w mean (SD) | ||
Wang | 2012 | 18.5 (3.8) | 9.3 (3.9) | 19.4 (3.4) | 10.9 (4.9) |
Ma | 2015 | 23.88 (1.86) | 16.20 (2.40) | 23.91 (1.56) | 17.60 (2.29) |
Luo | 2018 | 11.09 (2.79) | 4.32 (1.41) | 11.23 (2.70) | 7.06 (2.59) |
Liu | 2013 | 24.08 (4.96) | 10.84 (3.86) | 25.13 (4.96) | 14.33 (4.12) |
Cao | 2008 | 25.87 (7.76) | 12.07 (6.92) | 26.43 (9.00) | 12.90 (6.01) |
Huang | 2000 | 26.71 (5.13) | — | 26.87 (4.25) | — |
EG, experimental group; CG, control group; —, not available.
Forest plot depicting the HAMD.
Forest plot depicting the HAMD after sensitivity analysis.
All studies recorded adverse events during treatment in both groups. Incidence of adverse events was recorded in 5 studies [
Side effect scores in each study.
No. | Adverse events | TESS score | SERS score | |||
---|---|---|---|---|---|---|
EG (%) | CG (%) | EG mean (SD) | CG mean (SD) | EG mean (SD) | CG mean (SD) | |
1 | 3 (10%) | 15 (50%) | — | — | — | — |
2 | 0 (0%) | 4 (16.67%) | — | — | — | — |
3 | 23 (35.94%) | 28 (43.75%) | 3.25 (1.55) | 3.77 (1.86) | — | — |
4 | 7 (16.67%) | 9 (21.43%) | — | — | — | — |
5 | — | — | — | — | 3.78 (2.67) | 6.48 (4.04) |
6 | 0 (0%) | 20 (66.67%) | — | — | — | — |
7 | — | — | 0 | 10.8 (2.88) | — | — |
EG, experimental group; CG, control group; —, not available.
The quality assessment of the trials was performed using the five-point Jadad Score (Table
Assessment of studies’ quality.
No. | Randomization | Blinding | Follow-up | Score |
---|---|---|---|---|
1 | 2 | 0 | 1 | 3 |
2 | 1 | 0 | 1 | 2 |
3 | 1 | 0 | 0 | 1 |
4 | 1 | 0 | 0 | 1 |
5 | 1 | 0 | 0 | 1 |
6 | 1 | 0 | 0 | 1 |
7 | 1 | 0 | 0 | 1 |
This study is a comprehensive systematic review of acupuncture in the treatment for chronic pain with depression. There were significant differences in the VAS score and HAMD, decreasing between the two groups after treatment, indicating that acupuncture used alone or in combination with medication therapy can relieve pain and depression better than medication. Patients in the experimental group had lower incidence of adverse events and side effect scores, which proved the safety of acupuncture. The above results suggested that acupuncture has not only a better clinical result on the treatment of chronic pain with depression but also has a higher security compared with medication therapy.
When it comes to acupuncture therapy, we found that different individual studies might utilize different acupoints, but from these prescriptions we could also find something in common. In practice, there are many ways to select acupoints during acupuncture treatment. Selection of local acupoints around the pain location was the main method to treat pain. In the treatment of depression, acupoints on the head were selected more frequently, such as Governor Vessel (GV) 20, GV 24, Extra-points of Head and Neck (EX-HN) 1, and EX-HN 3. In addition, some distal acupoints were also be selected, including Pericardium meridian of hand-jueyin (PC) 6, Heart meridian of hand-shaoyin (HT) 7, Spleen meridian of foot-taiyin (SP) 6, and Liver meridian of foot-queyin (LR) 3. According to traditional Chinese medicine theory, human emotional activities are closely related to the five internal organs, so this explains why acupoints on multiple meridians can be selected for the treatment of depression.
The treatment of chronic pain and depression comorbidity has always been a tough problem because of poorer response to the pharmacological treatment and long-term side effects of drugs. Acupuncture, as an effective, simple, and economical treatment, has been used in the treatment of many diseases in China. The results of the systematic review suggested that acupuncture has a promising application prospect due to its unique advantages for the treatment of chronic pain with depression, and it can be used in patients with poorer response to the medication or suffering from serious side effects.
Previous systematic reviews of acupuncture for chronic pain and depression comorbidity are not available. However, findings from other chronic pain reviews and depressive disorder reviews are consistent with this review and indicate that acupuncture used alone or in combination with other treatment measures has a better therapeutic effect to the control group [
There are many patients suffering from chronic pain with depression at present, and the findings of this systematic review provided a valuable alternative to these patients. However, most of the included articles had a quality score of no more than 2 points [
The design of future studies in this area can play an important role in improving the quality of evidence and address the lack of evidence to support acupuncture for the management of chronic pain and depression comorbidity. Hence, there are some recommendations to guide future research: (i) improving methodological quality; (ii) extending follow-up periods to include intermediate- and long-term follow-up; (iii) increasing sample sizes. High-quality studies should also include costs, risks, and synergistic values of combining acupuncture with drugs compared with monotherapy otherwise.
Acupuncture has a promising application prospect due to its unique advantages for the treatment of chronic pain with depression comorbidity, which can be used in patients suffering from some certain chronic pain with depression comorbidity with poorer response to the conventional medication or suffering from serious side effects. High-quality RCTs are needed to support the current clinical application of acupuncture for the treatment of chronic pain with depression comorbidity and to broaden the clinical application.
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
The authors have no conflicts of interest.
Bin Yan, Shibai Zhu, Yu Wang, and Gula Da contributed equally to this work.