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Traditional Chinese Medicine (TCM) is popular for treatment of fibromyalgia (FM) although there is a lack of comprehensive evaluation of current clinical evidence for TCM's therapeutic effect and safety.
To review systematically the beneficial and harmful effects of TCM therapies for FM.
We searched six English and Chinese electronic databases for randomized clinical trials (RCTs) on TCM for treatment of FM. Two authors extracted data and assessed the trial quality independently. RevMan 5 software was used for data analyses with an effect estimate presented as mean difference (MD) with a 95% confidence interval (CI).
Twenty-five RCTs were identified with 1516 participants for this review. Seven trials (28%) were evaluated as having a low risk of bias and the remaining trials were identified as being as unclear or having a high risk of bias. Overall, ten trials were eligible for the meta-analysis, and data from remaining 15 trials were synthesized qualitatively. Acupuncture reduced the number of tender points (MD, –3.21; 95% CI –4.23 to –2.11; p<0.00001, I2=0%), and pain scores compared with conventional medications (MD, –1.78; 95% CI, –2.24 to –1.32; p<0.00001; I2=0%). Acupuncture showed no significant effect, with a random-effect model, compared with sham acupuncture (MD, –0.55; 95% CI, –1.35–0.24; p=0.17; I2=69%), on pain reduction. A combination of acupuncture and cupping therapy was better than conventional medications for reducing pain (MD, –1.66; 95% CI, –2.14 to –1.19; p<0.00001; I2=0%), and for improving depression scores with related to FM (MD, –4.92; 95% CI, –6.49 to –3.34; p<0.00001; I2=32%). Other individual trials demonstrated positive effects of Chinese herbal medicine on pain reduction compared with conventional medications. There were no serious adverse effects reported that were related to TCM therapies in these trials.
TCM therapies appear to be effective for treating FM. However, further large, rigorously designed trials are warranted because of insufficient methodological rigor in the included trials.
Fibromyalgia (FM) is nonspecific rheumatism in which typical symptoms are chronic widespread musculoskeletal pain and stiffness with accompanying fatigue, anxiety, sleep disorder; and/or irritable bowel syndrome.1 Experts in the United States and Canada have developed diagnostic criteria for identifying this disease for the American College of Rheumatology (ACR),2 which are also commonly used in China. This disease appears to affect increasing numbers of people, with a disabling outcome on their quality of life (QoL).3
As the cause of FM is unknown, it is characterized and diagnosed by its symptoms of chronic widespread pain and multiple tender points associated to some degree of facilitation by the central nervous system.4 There are two important goals for treating these symptoms.4 The first goal is reduction of pain, and the second goal is restoring functionality. Many peer-reviewed articles about the treatment of FM have been published involving different pharmacologic agents including nonsteroidal anti-inflammatory drugs (NSAIDs), opioid and nonopioid analgesics, anticonvulsants, antidepressants, α-adrenergic agonists, muscle relaxants, topical agents, local anesthetics, N-methyl-d-aspartate (NMDA) receptor antagonists, and botulinum toxin. None of these medications have proven to be effective for the entire scope of symptoms and disabilities associated with FM.4 One recent systematic review5 concluded that antidepressants are associated with improvements in pain, depression, fatigue, sleep disturbances, and health-related QoL in people with FM, with large effect sizes for tricyclic and tetracyclic antidepressants (TCAs; standard mean difference [SMD]=–1.64; 95% confidence interval [CI], –2.57 to –0.71). Uceyler et al.6 came to similar conclusions about amitriptyline. Tofferi et al.7 suggested that cyclobenzaprine offered some benefit to patients with FM, with 1 of 5 patients experiencing improvements, while Moore et al.8 showed that pregabalin had proven efficacy for relieving neuropathic pain and FM, although many patients experienced trivial benefit or discontinued treatment because of adverse effects.
Antidepressants have been shown to have some effect, whereas NSAIDs, steroids, and calcitonin have not. Cyclobenzaprine, alprazolam, tramadol, and SAM-e have shown some benefit to patients in small studies.7 Many medications produce significant sedation and physical dependence as well as causing psychologic dependence.4
A systematic review9 of randomized clinical trials (RCTs) of nonpharmacologic interventions concluded that, although significant differences between groups occurred, the varying combinations of intervention in the studies studies and the wide range of outcome measures used made it hard to form clear conclusions across studies. The interventions included education, relaxation therapy, cognitive–behavioral therapy, acupuncture, and hydrotherapy, and there was some preliminary support for aerobic exercise.
In Traditional Chinese Medicine (TCM) theory, FM is mainly caused by emotional upsets, which affect the Liver. Stagnation of qi activity leads to the stasis of Blood, which causes pain. The principle of treatment is regulating the qi and Blood, combined with dispelling Cold and removing Damp.10 TCM is a whole system that uses a range of therapies to treat FM; these include acupuncture, moxibustion, herbal medicine, and massage. Two systematic reviews have suggested that acupuncture alone is effective for treating FM; one analysis involved three RCTs and four cohort studies and the other analysis included three positive RCTs and two negative RCTs.11,12 No systematic review reported the effect of herbal medicine or other TCM therapies for FM, but a review published in 200513 suggested that “many of the herbs and other dietary supplements used by our patients are known to have potential adverse effects and may pose a risk to the patient.” This current systematic review aims to update the evidence from RCTs to evaluate the therapeutic effect and safety of TCM, including Chinese herbal medicine for FM.
We included parallel-group RCTs of any kind of TCM treatment, including acupuncture, herbal medicine, massage, and/or cupping compared with no treatment, placebo, and/or conventional medication in patients with FM. We also included combined therapy with TCM and other interventions compared with other interventions in RCTs, or combined therapy of two kinds of TCM compared with medication or other interventions. FM was diagnosed according to recognized criteria. Outcome measures included reduction in severity of pain or depression, improvement of QoL, and reduction of relapse rate. When multiple publications reported the same groups of participants, we only included the primary publication and excluded the duplicated publications. There was no limitation on language and publication type.
We searched the China Network Knowledge Infrastructure (CNKI; 1979–2009), Chinese Scientific Journal Database VIP (1989–2009), Wan Fang Database (1985–2009), Chinese Biomedicine (CBM) database (1978–2009), PubMed (1966–2009) and Cochrane Library (Issue 3, 2009). All searches ended at August 2009. The search terms included fibromyalgia, fibrosis, fibrositis, myofascitis, ormyofibrositis, combined with traditional Chinese medicine, TCM, herbal, acupuncture, massage, cupping, or Tui Na. Two authors (Cao H and Liu JP) selected studies for eligibility and checked against the inclusion criteria independently.
Two authors (Cao H and Liu JP) extracted the data from the included trials independently. The methodological quality for RCTs was assessed, using criteria from the Cochrane Handbook for Systematic Reviews of Interventions, Version 22.214.171.124 The quality of trials was categorized into low risk of bias, unclear risk of bias, or high risk of bias according to the risk for each important outcome within included trials, including adequacy of generation of the allocation sequence, allocation concealment, blinding, whether there were incomplete outcome data (“Describe the completeness of outcome data for each main outcome, including attrition and exclusions from the analysis. State whether attrition and exclusions were reported, the numbers in each intervention group [compared with total randomized participants], reasons for attrition/exclusions where reported, and any reinclusions in analyses performed by the review authors”),14 or selective outcome, or other sources of bias.
Data were summarized using risk ratio (RR) with 95% CIs for binary outcomes or mean difference (MD) with a 95% CI for continuous outcomes. We used Revman 5.0.2 software from the Cochrane Collaboration for data analyses. Meta-analysis was used if the trials had acceptable homogeneity of study design, participants, interventions, controls, and outcome measures. Statistical heterogeneity was tested by examining I2square15 or p-value; an I2>50% or a p-value<0.1 indicates the possibility of statistical heterogeneity. Both a fixed-effect model and a random-effects model were used if there was a possibility of statistical heterogeneity among the trials. If the I2 was <50%, or the p-value was >0.1, only a fixed-effect model was used for meta-analysis. Publication bias was explored via a funnel-plot analysis.
After primary searches in six databases, 883 citations were identified. The majority was excluded because of obvious ineligibility, and full-text papers of 35 studies were retrieved. Finally, 2516–38 randomized trials were included in this review, two trials39,40 were excluded as duplicated publications, and eight trials41–48 were excluded because the diagnosis criteria were not specified (Fig. 1). The characteristics of included trials are listed in Table 1. Of the included trials, two were unpublished postgraduate student dissertations.*,†
The twenty-five RCTs involved a total of 1516 patients with FM. The participants were ages 17–77, and the disease duration was from 3 months to 20 years. Twenty-three trials used ACR 1990 as the diagnostic criteria, one trial31 used the International Academy of Soreness Research (IASR)53 for diagnosing FM, and one trial26 made diagnoses according to the subjects' symptoms. The interventions included acupuncture (electroacupuncture, auricular acupuncture), cupping, herbal medicine (decoctions, capsules, and external preparations), massage, moxibustion, and combinations of acupuncture and cupping, or acupuncture and herbal medicine. The controls included no treatment, sham acupuncture, or conventional medications. The treatment duration ranged from 12 days to 12 weeks. Changes in visual analogue scale (VAS) scores as the major outcome measurement were reported in 15 trials. Seven trials18,23,27,31,33,34,† calculated the change of number of tender points, and used the McGill Pain Questionnaire (MPQ), Present Pain Intensity (PPI), or Fibromyalgia Impact Questionnaire (FIQ) for assessing intensity of pain. Four trials20,25,28,* used the Hamilton Depression Scale (HAMD) or Hamilton Anxiety Scale (HAMA) to assess depression or anxiety. Three trials16,24,34 used the Short-Form–36 (SF-36) and QoL scale (QoLS) for measuring QoL. Six trials used four categories to evaluate treatment effects including cure (symptoms disappeared and no tender points existed), markedly effective (symptoms reduced more than >50%), effective/reduced (symptoms reduced between 25% and 50%), and ineffective (symptoms reduced <25%). The combined rates of the markedly effective and effective treatments were used to calculate a total effective rate, which was the main outcome measure in some trials.
According to our predefined quality assessment criteria, seven 16,19,24,28,32,34,† of the 25 trials (28%) were evaluated as having a low risk of bias, and another 18 included trials were evaluated as having an unclear risk of bias (Table 2). The sample size varied from 10 to 38 participants, with an average of 25 patients per group. None of the trials reported prior sample-size calculation, 11 trials16,19,21,24,25,28,32,34,35,37 described randomization procedures (using a random number table, computer generation of random numbers, or a drawing), but only two trials19,24 reported adequate allocation concealment. Four trials19,24,32,34 blinded both patients and outcome assessors, one trial16 only blinded patients, and three trials28,33,* blinded the outcome assessors. Nine trials16,17,19,21,24,28,32,34,* reported the number of dropouts, and three trials16,32,34 used intention-to-treat analysis.
Twelve trials16,19,22–24,26,31–34,38,† tested acupuncture for treating FM. Six trials 16,19,24,26,32,33 compared acupuncture or electroacupuncture with sham acupuncture or sham electroacupuncture, and another six trials22,23,31,34,38,† compared acupuncture with conventional medications.
A pooling analysis of four trials16,19,24,32 showed a significant effect of acupuncture compared to sham acupuncture for reducing pain according to VAS scores after treatment (MD, –1.24; 95% CI, –1.47 to –1.01; p<0.00001). However, this effect became nonsignificant (MD, –0.55; 95% CI, –1.35–0.24, p=0.17) when using a random-effects model because of significant heterogeneity (I2=69%). Three trials23,31,† compared acupuncture with conventional medications, and the pooling results showed that acupuncture was significantly better than conventional medications for reducing pain (MD, –1.78; 95% CI –2.24 to –1.32, p<0.00001; I2=0%) and number of tender points (MD, –3.21; 95% CI, –4.23 to –2.11; p<0.00001; I2=0 %).
Two trials22,23 reported the relapse rate after 6 months, suggesting that acupuncture (including transcutaneous electrical nerve stimulation [TENS] and electroacupuncture) was significantly better than amitriptyline for preventing relapse (RR 0.28; 95% CI, 0.11–0.67; p=0.005; I2=0%).
As a result of the insufficient number of included trials in one meta-analysis, a meaningful funnel plot analysis was not feasible.
Six trials20,21,25,30,36,37 tested herbal medicine against Western medicine for FM. Three trials20,36,37 tested herbal decoctions, two trials25,30 tested a Chinese patent medicine, and one trial21 tested active components of an herbal medicine. As a result of the variation of herbal medicines, the data were not combined. The main findings of the six trials are presented in Table 4.
Only one small trial17 tested massage for treatment of FM and showed no significant difference between “connective tissue” massage and no treatment for reducing pain according to VAS scores after treatment (MD, –0.58; 95% CI, –1.76–0.60; p=0.34).
Six trials17,27–29,35,* tested the therapeutic effect of combination TCM therapies for treating FM. Three trials18,28,* compared acupuncture plus cupping therapy with medications, one trial29 compared acupuncture plus computerized intermediate frequency treatment with amitriptyline, one trial35 compared acupuncture plus laser treatment with amitriptyline, and one trial27 compared acupuncture plus herbal medicine with Western medications.
Two trials18,28 showed that a combination of acupuncture and cupping therapy plus medications was significantly better than conventional medications alone for reducing pain (MD, –1.66, 95% CI, 2.14 to –1.19, p<0.00001, I2=0%) and HAMD scores (MD, –4.92, 95% CI, –6.49 to –3.34, p<0.00001, I2=32%).
An outcome of adverse events was described in 11 trials.16,20,21,25,27,29,30,34,36,*,† Adverse effects from eight trials16,21,25,29,30,34,*,† were related to TCM therapies, including four16,29,34,†related to acupuncture, three to herbal medicine, and one* to cupping therapy. The adverse effects of acupuncture were bruising, nausea, fainting, discomfort at the sites of needle insertions or simulated needle insertions, and temporary edema of the hand. Nausea, fainting, dry mouth, bimalleolar edema, and skin rash were reported as adverse effects of herbal medicines. One trial* reported that 1 patient had mild scalding on the skin after being included in a cupping group (n=33).
Lethargy, nausea, fainting, dry mouth, fatigue, blurred vision, hyperhydrosis, and constipation were reported adverse effects of conventional medications.
No serious adverse event was reported in any of the included trials.
The data from the 25 RCTs that were analyzed demonstrate that, acupuncture, acupuncture combined with cupping therapy, or acupuncture combined with cupping and conventional medication were significantly more effective than conventional medication alone for reducing pain and number of tender points in subjects with FM. The therapeutic effect of acupuncture appears to be similar to sham acupuncture for pain reduction, but more data are needed to prove this finding. The therapeutic effects of herbal medicine and massage are uncertain due to limited numbers of clinical trials.
There are several limitations in this review. The quality of the included studies is generally poor, which indicates an unclear risk of bias resulting from insufficient reporting of methodological components in the trials. There were unclear descriptions of randomization procedures and lack of blinding in the majority of trials, which may have created potential performance biases and detection biases, as patients and researchers might have been aware of the therapeutic interventions. Intention-to-treat analysis was not applied in most of the included trials, and although it was not possible to perform a meaningful funnel-plot analysis because of the insufficient number of included trials in the meta-analysis, there remained the possible existence of publication bias. To the ability to perform meta-analysis was limited because of the heterogeneity of the interventions among the included trials and the variance of composite outcome measures used in 15 of the included trials. This was particularly relevant to the outcome classifications as cure, markedly effective, effective or ineffective, which were used in six trials and but was not validated; thus the findings were hard to interpret. Consequently, interpretation of these positive findings should be cautious, and the study methodology needs to be improved for future confirming studies.
The searches conducted in the present study identified four systematic reviews of acupuncture for treating FM. The latest one50 published in 2009 included only six trials, which were all included in this systematic review. In this systematic review five high-quality trials compared acupuncture with sham acupuncture, which may not be appropriate as a placebo against which to evaluate the therapeutic effect of real acupuncture.51 There were 12 trials evaluating acupuncture for FM in this review, but only two of them used syndrome-differentiation for acupuncture-point selection. The data suggesting that acupuncture is effective for FM should be taken as being tentative and further randomized trials are warranted. Control interventions in such trials should be carefully selected, as, at the present time, there is not a proper “acupuncture placebo.”
Nine of the included trials16,17,22,23,25,32–34,38 reported the results of follow-up. One trial34 followed all the patients for 2 years, reporting that the acupuncture group was significantly better than the control group with respect to numbers of tender points after 6 months, but, at 2 years, noting that there was no significant difference in any outcomes. One trial32 followed all patients for 7 months and showed no difference between acupuncture and sham acupuncture for pain reduction. Assefi et al.16 followed all patients for 6 months, suggesting that the observed effect was probably driven by the higher mean score in the simulated-acupuncture group compared with the sham-needling group. Another trial17 followed patients for up to6 months and showed no statistically significant differences between massage and no treatment for the tested parameters at 3 and 6 months. Two trials22,23 followed the patients for 6 months, suggesting that acupuncture was significantly better than amitriptyline for preventing relapse after treatment, although the number of patients who were followed was too small for substantial statistical analysis. There is no evidence for a long-term effect of herbal medicine or cupping therapy.
Most of the existing trials are of small size and have an unclear risk of bias or a high risk of bias. Further rigorously designed trials are needed to confirm the effectiveness of TCM therapy for treating FM. Randomization methods need to be described clearly and reported fully. Although blinding of patients and practitioners might be very difficult for acupuncture or herbal medicine, blinding of outcome assessors should be attempted as far as possible to minimize performance and assessment biases. Choosing outcome measures should be based on an international consensus and should include continuous data and daily average pain scores from baseline to study completion. Analysis of outcomes based on the intention-to-treat principle is vital as is the application of well-defined diagnostic criteria, such as ACR 1990, thus, increasing comparability between trials. Reporting of trials should follow Consolidated Standards of Reporting Trials (CONSORT)52 standards to explain the processes involved explicitly and in a transparent manner.
The preliminary conclusions of the current study suggest that patents with FM might benefit from TCM treatment. FM is a chronic disease and better, larger trials will be the basis for demonstrating the effectiveness and long-term effects of TCM therapies.
This is a full-text article of a presentation for the 5th International Congress on Complementary Medicine Research, Tromsø, Norway, May 19–21, 2010.
*Fu XY, Li CD. Clinical randomized controlled trial on combination of acupuncture, cupping and medicine for treatment of fibromyalgia syndrome [dissertation for Master's degree from Chengdu University of Traditional Chinese Medicine, Chengdu, China]. 2004.
†Guo Y, Sun YZ. Clinical observation of therapeutic effect of penetration needling at the back in treating with fibromyalgia syndrome [dissertation for Master's degree from Heilongjiang University of Traditional Chinese Medicine, Heilongjiang, China]. 2005.
No competing financial conflicts exist.
H.J. Cao and Liu JP were supported by a grant from the National Basic Research Program of China (“973” Program, No. 2006CB504602) and an international cooperation project from the Ministry of Science and Technology of China (2009DFA31460). Liu JP was in part supported by the Grant Number R24 AT001293 from the National Center for Complementary and Alternative Medicine (NCCAM) of the U.S. National Institutes of Health. Lewith GT was supported by the Rufford Maurice Laing Foundation.