Opioid use disorder (OUD) is a serious substance-related disorder resulting from abuse or misuse of opioids [
International guidelines recommend opioid substitution treatment (OST), namely, pharmacotherapy (buprenorphine, methadone, etc.); in addition, the primary clinical treatment for OUD also includes psychosocial treatment and acupuncture [
This study was performed according to the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0) [
We searched ten online databases, namely, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, ProQuest Dissertation and Theses, Allied and Complementary Medicine Database (AMED), Clinicaltrials.gov, and who.int/trialsearch, from inception to 23 December 2017, using search terms acupuncture, acupressure, point, opioid, heroin, morphine, and so on. There were no language restrictions. Special search strategies of the abovementioned databases are presented in online Appendix
Trials were included if they met the following criteria: Types of studies: clinical randomized controlled trials (RCTs) and quasi-RCTs except crossover trials and cluster RCTs. Types of participants: considering actual clinical conditions [ Types of interventions: experimental interventions included acupuncture therapies, and control interventions included no treatment or sham acupuncture or other therapies, such as psychosocial interventions, pharmacological interventions, and other conventional interventions.
Primary outcomes are
Secondary outcomes are
All articles identified through searches of the online databases were imported to the EndNote X8 (Clarivate Analytics, Pennsylvania, the United States) software. Two review authors (ZC and YW) independently screened all articles by reading theirs titles and abstracts and excluded articles which do not meet inclusion criteria. Afterwards, the two authors independently reviewed full-text of articles. If there is any controversy during the screening, the third review author (YR) read relevant information and decided whether or not to include the article.
Two review authors (ZC and YW) independently extracted data to a self-designed data extraction form, which included authors, publication data, study design, sample size, characteristics of participants, history of drug use, interventions, and outcomes. Two other review authors (RW and JX) independently checked extracted data to enhance the accuracy. Afterwards, data were imported to RevMan 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration) software.
The Cochrane risk of bias assessment tool [
The GRADE approach [
RevMan 5.3 was used to analyse data. For dichotomous outcomes, results were reported as risk ratios (RRs) with 95% confidence intervals (CIs). It should be noted that if there were no events in both groups, the study was excluded from the meta-analysis [
Nine studies [
Details of withdrawal scales.
| | | |
---|---|---|---|
Bearn et al. 2009 [ | Short Opiate Withdrawal Scale | 10 | 3 |
Hu et al. 2003 [ | Himmelsbach scoring table for withdrawal symptoms | 10 | One score for yawning, tear shedding, running nose and sweating separately; three scores for pupil dilation, trembling, gooseflesh, anorexia; five scores for restlessness and worry. |
Meade et al. 2010 [ | Subjective Opiate Withdrawal Scale | 21 | 4 |
Mu et al. 2010 [ | Withdrawal symptoms rating scale (created by Liu Chuang) | 10 | 3 |
Wen et al. 2005 [ | Score of abstinence symptoms | 17 | 15 |
Zong et al. 2001 [ | Himmelsbach scoring table for withdrawal symptoms | 13 | One score for yawning, tear shedding, running nose, sweating, heat vexation, hyperpnea, rise of systolic hypertension; three scores for pupil dilation, trembling, gooseflesh, anorexia; five scores for worry and emesis. |
Characteristics of included studies.
| | | | | | | | | | | | | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Bearn et al. 2009 [ | United Kingdom | RCT | 82 | 35.99 years | 62 males and 20 females | Not mentioned | Not mentioned | DSM-IV | Auricular acupuncture (n = 48); sham auricular acupuncture (n = 34) | 14 days (10 sessions) | 30 to 40 minutes | Before 14s-days acupuncture treatment, participants received 10 to 14 days decremental methadone therapy. | Intensity of withdrawal syndrome and craving. |
Hu et al. 2003 [ | Not mentioned | RCT | 96 | 30.4 years | 44 males and 52 females | 29.5 months | 1.16 g | Clinical assessment | Electroacupuncture (n = 20); (n = 28); Chinese herbs (n = 23); Acupuncture & Chinese herbs (n = 25) | 20 days (20 sessions) | 20 minutes | Not mentioned | Intensity of withdrawal syndrome. |
Meade et al. 2010 [ | America | RCT | 48 | 27.5 years | 33 males and 15 females | Not mentioned | Not mentioned | Clinical assessment | TEAS (n = 24); Sham TEAS (n = 24) | 4 days (12 sessions) | 30 minutes | Not mentioned | Intensity of withdrawal syndrome, carving, pain severity and interference; sleep quality. |
Mu et al. 2009 [ | China | RCT | 120 | 29.43 years | 48 males and 72 females | 4.78 years | 1.81 g | DSM-IV | Acupuncture group 1: electroacupuncture (n = 30); acupuncture group 2: electroacupuncture (n = 30); sham electroacupuncture (n = 30); no treatment (n = 30) | 10 weeks (30 sessions) | 20 minutes | Did not receive antipsychotic drugs in the previous week | Intensity of anxiety and depression |
Mu et al. 2010 [ | China | RCT | 120 | 29.84 years | 48 males and 72 females | 4.72 years | 1.78 g | DSM-IV and ICD-10 | Acupuncture group 1: electroacupuncture (n = 30); acupuncture group 2: electroacupuncture (n = 30); sham electroacupuncture (n = 30); no treatment (n = 30) | 10 weeks (30 sessions) | 20 minutes | Did not receive any detoxification treatment in the previous 3 months | Intensity of withdrawal syndrome, anxiety, depression, and Craving. |
Washburn et al. 1993 [ | America | RCT | 100 | 40.46 years | 68 males and 32 females | 16.8 years | Not mentioned | Clinical assessment | Auricular acupuncture (n = 55); sham auricular acupuncture (n = 45) | 21 days | 20 to 45 minutes | All Participants received counseling and discharge planning, and AIDS education | Urine examination |
Wen et al. 2005 [ | China | RCT | 220 | 33.8 years | 171 males and 49 females | 20.13 months | 0.83 g | DSM-IV | Manual acupuncture (n = 111); western medicine (n = 109) | 10 days (10 sessions) | 30 minutes | Did not receive any detoxification treatment in the previous 1 month | Intensity of withdrawal syndrome and anxiety |
Zhang et al. 2000 [ | Not mentioned | RCT | 181 | 26.54 years | Not mentioned | 3.27 years | 1.74 g | DSM-III | TEAS (n = 121); sham TEAS (n = 60) | 15 days (27 sessions) | Not mentioned | Not mentioned | Sleeping time; intensity of pain, anxiety, addiction. |
Zong et al. 2001 [ | China | RCT | 96 | 30.4 years | 44 males and 52 females | 15 months | 1.18 g | DSM-III-R | Electroacupuncture (n = 20); Chinese herbs (n=23); western medicine (n=28); acupuncture & Chinese herb (n = 25) | 20 days (20 sessions) | 20 minutes | Not mentioned | Intensity of withdrawal syndrome; urine examination. |
Flow chart of literature and screen process.
All included studies were described as RCTs. However, in random sequence generation, 1 study [
Summaries of findings for all comparisons and GRADE analyses are presented in Tables
Summary of findings: acupuncture versus no treatment.
| | | | |
---|---|---|---|---|
Craving for opioid | 1 | 90 | MD -2.18 (-3.10 to -1.26) | ⊕⊕ ⊝⊝ |
Anxiety | 2 | 180 | SMD -0.79 (-2.47 to 0.88) | ⊕ ⊝⊝⊝ |
Depression | 2 | 180 | SMD -1.50 (-1.85 to -1.15) | ⊕⊕ ⊝⊝ |
Retention of treatment | 2 | 180 | RR 1.00 (0.96 to 1.04) | ⊕⊕ ⊝⊝ |
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.
Summary of findings: acupuncture versus sham acupuncture.
| | | | |
---|---|---|---|---|
Number of positive urine samples for opioids | 1 | 13 | RR 2.22 (0.37 to 13.38) | ⊕⊕⊕⊝ |
Craving for opioid | 4 | 401 | SMD -0.66 (-1.97 to 0.64) | ⊕⊝⊝⊝ |
Pain | 2 | 229 | SMD -0.89 (-2.54 to 0.76) | ⊕⊝⊝⊝ |
Sleep quality | 1 | 48 | MD -1.14 (-3.58 to 1.30) | ⊕⊕⊕⊝ |
Sleeping time | 1 | 181 | MD 2.31 (1.97 to 2.65) | ⊕⊕⊕⊝ |
Anxiety | 3 | 361 | SMD -0.56 (-1.37 to 0.25) | ⊕⊝⊝⊝ |
Depression | 2 | 180 | SMD -1.07 (-1.88 to -0.25) | ⊕⊝⊝⊝ |
Retention of treatment | 3 | 235 | RR 1.03 (0.97 to 1.08) | ⊕⊕⊝⊝ |
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.
Summary of findings: acupuncture versus medication.
| | | | |
---|---|---|---|---|
Craving for opioid | 1 | 220 | MD -0.01 (-0.20 to 0.18) | ⊕⊕⊕⊝ |
Anxiety | 1 | 220 | MD -0.06 (-0.24 to 0.12) | ⊕⊕⊕⊝ |
Retention of treatment | 2 | 291 | RR 1.01 (0.95 to 1.07) | ⊕⊕⊕⊝ |
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.
Meta-analyses of the effects of acupuncture compared to no treatment in treating OUD.
Craving for opioid
Anxiety
Depression
Retention of treatment
Meta-analyses of the effects of acupuncture compared to sham acupuncture in treating OUD.
Number of opiate positive urine samples
Craving for opioid
Pain
Sleep score
Sleeping time
Anxiety
Depression
Retention of treatment
Meta-analyses of the effects of acupuncture compared to medication in treating OUD.
Craving for opioid
Anxiety
Retention of treatment
In fact, acupuncture studies have high clinical heterogeneity owing to different acupuncture styles, different stimulation modes, different courses of acupuncture treatment, different acupuncture dosages, different choices of points, different context of acupuncture treatment, and so on. For EA, the duration was 20 days or 10 weeks, the frequency was three times per week or one time per day, and each treatment session lasted 20 minutes; for AA, the duration was 14 days or 21 days, the frequency was one time per day, and each treatment session lasted from 20 to 45 minutes; for TEAS, the duration was 4 days or 15 days, the total course of treatment was 12 sessions or 27 sessions, and each treatment session lasted 30 minutes. Point selections of all studies were not identical. Sham acupuncture studies also have clinical heterogeneity due to different stimulation modes and different stimulate positions. Medication controlled studies have heterogeneity on accounts of different types of drugs and different drug dosages. Because the number of studies was too small, we did not conduct these subgroup analyses. It was proposed to conduct sensitivity analyses through excluding studies with “high risk of bias”; however, sensitivity analyses for most meta-analyses were not performed because most studies did not provide necessary data and the amounts of studies were small. We conducted one sensitivity analysis for comparison between acupuncture and sham acupuncture in craving for opioid. And there was no significant change in craving for opioid after the removal of one study with “high risk of bias”.
Owing to an insufficient number of included studies, we did not conduct analysis of reporting bias by funnel plot.
The objective of this study is to assess the efficacy of various modes of acupuncture in OUD through intensity of withdrawal syndrome; duration of treatment; urine examination; intensity of pain, anxiety, depression, insomnia, and other associated symptoms; retention of treatment; and nature and rate of adverse effect. This study included 9 studies involving 1063 participants. There was certain difference between acupuncture and comparators, namely, no treatment, sham acupuncture, and medication, in treating OUD.
For intensity of withdrawal syndrome, it is impossible to arrive at a firm conclusion, due to the small number and low quality of studies. Nevertheless, the included studies indicated that EA and MA are effective for treating OUD. Data showed that EA was more effective in alleviating withdrawal syndromes than no treatment/sham acupuncture [
Regarding secondary outcomes, EA could be effective in reducing craving for opioid and depression; TEAS could not improve sleep quality but could be effective in prolonging sleeping time; moreover, it was effective in reducing anxiety syndromes. The levels of evidence were very low to moderate, and most were very low to low. In addition, no data on adverse effects were available in all selected studies.
Although acupuncture could effectively treat OUD, considering of small sample sizes and low-quality studies, our findings warrant further high-quality studies with large samples size. Most studies were conducted in China, and the others were carried out in Kingdom and America. Acupuncture is applied in different countries through variable manners [
Overall, acupuncture could be effective in treating OUD, but the mechanism by which acupuncture alleviate OUD is not completely clear. The mechanism of acupuncture on OUD is probably related to opioid peptides, which are endogenous peptides with opiate-like activity. The three major classes currently recognized are dynorphins, enkephalins, and endorphins. Dynorphins can effectively suppress heroin withdrawal [
This study has several limitations. First, both the quantity of selected studies and the sample sizes of most studies were small. Second, some studies were of poor quality. Twenty-two percent of selected studies were assessed as “high risk of bias” [
Four previous meta-analyses and systematic reviews reported the effect of acupuncture on the treatment of OUD [
In this systematic review and meta-analysis, acupuncture could be effective in treating OUD, but there was insufficient evidence to suggest better effect of acupuncture compared to medication. These findings also showed EA could be effective in alleviating symptoms of craving for opioid and depression, and TEAS could be effective in improving insomnia and anxiety; nevertheless, the findings were insufficient to support clinical use of AA in treating OUD. The safety of acupuncture therapy in treating OUD was uncertain. To be noted, these results of the effects of acupuncture for OUD are limited by small number and low quality of selected studies.
No additional data were available.
The authors declare that they have no conflicts of interest.
Zhihan Chen and Yitong Wang contributed equally to this study. All authors participated in the design of this study. Zhihan Chen and Yitong Wang drafted this manuscript and Yulan Ren revised it. Zhihan Chen, Yitong Wang, and Yulan Ren participated the design of search strategies. Zhihan Chen, Yitong Wang, and Rui Wang conducted electronic search. Zhihan Chen and Yitong Wang completed screening of all articles. Zhihan Chen, Yitong Wang, Rui Wang, and Jin Xie participated data extraction. Zhihan Chen and Yitong Wang assessed the risk of bias and the quality of evidence. Zhihan Chen, Yitong Wang, and Jin Xie participated data analyses. Yulan Ren arbitrated any disagreements in the process of the study. All authors read and approved the final manuscript. Zhihan Chen and Yitong Wang are equal contributors.
This study is funded by Science & Technology Department of Sichuan Province (Grant no. 2018SZ0071).
Appendices 1. Search strategy: special search strategies of ten online databases, namely, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, ProQuest Dissertation and Theses, Allied and Complementary Medicine Database (AMED), Clinicaltrials.gov, and who.int/trialsearch. Appendices 2. PRISMA 2009 checklist: PRISMA 2009 is a guideline for reporting of systematic reviews, and we use the guideline to structure our manuscript.