A Systematic Review and Meta-analysis of Efficacy, Cost-effectiveness, and Safety of Selected Complementary and Alternative Medicine for Neck and Low-back Pain
SOURCE: Evid Based Complement Alternat Med [Epub 2011 Nov 24]
Andrea D. Furlan, Fatemeh Yazdi, Alexander Tsertsvadze, * Anita Gross, Maurits Van Tulder, Lina Santaguida, Joel Gagnier, Carlo Ammendolia, Trish Dryden, Steve Doucette, Becky Skidmore, Raymond Daniel, Thomas Ostermann, and Sophia Tsouros
Clinical Epidemiology Methods Centre, Ottawa Hospital Research Institute, University of Ottawa Evidence-Based Practice Center, Box 208, Ottawa, ON, Canada K1H 8L6
Background: Back pain is a common problem and a major cause of disability and health care utilization.
Purpose: To evaluate the efficacy, harms, and costs of the most common CAM treatments (acupuncture, massage, spinal manipulation, and mobilization) for neck/low-back pain.
Data Sources: Records without language restriction from various databases up to February 2010.
Data Extraction: The efficacy outcomes of interest were pain intensity and disability.
Data Synthesis: Reports of 147 randomized trials and 5 non-randomized studies were included. CAM treatments were more effective in reducing pain and disability compared to no treatment, physical therapy (exercise and/or electrotherapy) or usual care immediately or at short-term follow-up. Trials that applied sham-acupuncture tended towards statistically non-significant results. In several studies, acupuncture caused bleeding on the site of application, and manipulation and massage caused pain episodes of mild and transient nature.
Conclusions: CAM treatments were significantly more efficacious than no treatment, placebo, physical therapy, or usual care in reducing pain immediately or at short-term after treatment. CAM therapies did not significantly reduce disability compared to sham. None of the CAM treatments was shown systematically as superior to one another. More efforts are needed to improve the conduct and reporting of studies of CAM treatments.
Back pain is a general term that includes neck, thoracic, and lower-back spinal pain. In the majority of cases, the aetiology of back pain is unknown and therefore is considered as “nonspecific back pain”. Back pain is considered “specific” if its aetiology is known (e.g., radiculopathy, discogenic disease). Although back pain is usually self-limited and resolves within a few weeks, approximately 10% of the subjects develop chronic pain, which imposes large burden to the health-care system, absence from work, and lost productivity . In a recent study, the direct costs of back pain related to physician services, medical devices, medications, hospital services, and diagnostic tests were estimated to be US$ 91 billion or US$ 46 per capita . Indirect costs related to employment and household activities were estimated to be between US$ 7 billion and US$ 20 billion, or between US$25 and US$ 71 per capita, respectively [3–5]. One study published in 2007 showed that the 3-month prevalence of back and/or neck pain in USA was 31% (low-back pain: 34 million, neck pain: nine million, both back and neck pain: 19 million) .
The prevalence of back pain and the number of patients seeking care with complementary and alternative medicine (CAM) therapies in the US has increased over the last two decades . The most prevalent CAM therapies for back and neck pain in the US are spinal manipulation, acupuncture, and massage . The exact mechanisms of action of CAM therapies remain unclear. Recently, many randomized controlled trials (RCTs) have been conducted to study the effects of CAM therapies for back pain. The results of many systematic reviews [8–12], meta-analyses , and clinical practice guidelines [14–17] regarding the effectiveness of CAM therapies for back pain relative to no treatment, placebo, or other active treatment(s) in reducing pain and disability have been inconsistent.
The agency for healthcare research and quality (AHRQ) and the national center for complementary and alternative medicine (NCCAM) commissioned the University of Ottawa Evidence-based Practice Center (UO-EPC) to review and evaluate evidence regarding the effectiveness, cost-effectiveness, and safety of the most prevalent CAM therapies (i.e., acupuncture, manipulation, mobilization, and massage) used in the management of back pain. This technical report can be viewed at the AHRQ website (http://www.ahrq.gov/) . The present paper summarizes the evidence from this technical report with a focus on a subset of studies reporting pain, disability, and harms outcomes compared between CAM therapies and other treatment approaches deemed relevant to primary care physicians (i.e., waiting list, placebo, other CAM therapies, pain medication, and physical therapy including exercise, electrotherapy and/or other modalities). The specific aims of this study were to systematically review and compare the efficacy, cost-effectiveness, and safety of acupuncture, manipulation, mobilization, and massage in adults (18 years or older) with neck or low-back pain.
This paper identified a large amount of evidence on comparative effectiveness of single mode CAM interventions for management of low-back and neck pain in subjects with a wide spectrum of causes of pain.
The benefits of CAM therapies were limited mostly to immediate and short-term posttreatment periods when compared to inactive treatments (no treatment or placebo). The observed benefits were more consistent for the measures of pain intensity than disability. Trials that applied sham-acupuncture tended to produce negative results (i.e., statistically nonsignificant) compared to trials that applied other types of placebo (e.g., TENS, medication, laser) between acupuncture and placebo groups. One explanation for the beneficial effect of sham acupuncture is the diffuse noxious inhibitory controls (DNIC) where neurons in the dorsal horn of the spinal cord are strongly inhibited when a nociceptive stimulus is applied to any part of the body, distinct from their excitatory receptive fields . Another explanation could be the nonspecific effects of attention and beliefs in a potentially beneficial treatment.
The results were less consistent regarding comparison of CAM therapies to other active treatments (e.g., other CAM therapy, physiotherapy, pain medication, usual care). The degree of clinical importance for the differences in pooled pain intensity observed between the treatment groups for low-back pain was small (acupuncture versus placebo; mobilization versus physical modalities), medium (acupuncture versus no treatment; massage versus relaxation), or large (acupuncture versus manipulation, in favour of manipulation; massage versus physical modalities).
Due to the small number of economic evaluations, inconsistent standards of comparison, and substantial heterogeneity as well as different healthcare payment systems used in the countries these trials were conducted, it was not possible to apply these findings globally or to reach clear conclusions about the cost-effectiveness of any of these CAM treatments. Acupuncture was cost-effective relative to usual care or no treatment in subjects with back pain. Evidence for massage and mobilization was insufficient.
We identified 4 systematic reviews of acupuncture: one for LBP  and 3 for neck pain [195–198]. The LBP review found either acupuncture being superior (1 trial) or no different from sham acupuncture (3 trials). Although the present paper included a much wider range of trials, its results for neck pain were consistent with those of the three reviews [195, 197, 198] in finding acupuncture moderately more beneficial compared to no treatment or placebo immediately or the short-term after treatment.
There were 2 reviews that evaluated manipulation and/or mobilization for acute, subacute, or chronic LBP [199, 200]. The first review  found manipulation more beneficial than sham but similar to general practitioner care, physical therapy, or exercise. The other review , indicated that manipulation did not differ from NSAIDs but was more beneficial than mobilization, general practitioner care, detuned diathermy, or physical therapy.
The results are similar across the three systematic reviews with respect to the superiority of manipulation and mobilization compared to no treatment of placebo for the various duration of LBP. The discrepancies lie when comparing manipulation or mobilization to other treatments. One review  concludes that manipulation or mobilization is equally effective compared to all other treatments, while the other  generally finds manipulation more effective than most other forms of therapy, but mostly in the short-term.
In our paper, manipulation and mobilization effectiveness is variable depending on symptom duration, outcome, comparator, whether there is exercise or general practitioner care and followup period. Although this variability can be considered as “inconsistent findings”, the overall evidence suggests that manipulation and mobilization are an effective treatment modality compared to other therapies. The three systematic reviews also differ significantly on definition of SMT: the review by Assendelft et al.  lumps spinal manipulation and mobilization together and also allows for cointerventions). The synthesis methods were different, one has more language restrictions  and uses best evidence methodology, while the other uses meta-analysis for all included trials and includes patients with leg pain . In addition, they only included RCT published prior to 2002. All these reasons can explain differences in the findings and conclusions.
The findings of this paper regarding the effects of manipulation on neck pain were consistent with those of other reviews [9, 201–203]. While some differences in results between this and other two reviews can be explained by the inclusion criteria and grading of trials, the major results in findings were similar. Two other reviews [204, 205] assessed multimodal interventions (mobilization and manipulation combined with other interventions) and therefore were outside the scope of this review. One Cochrane review  found massage to be more beneficial than placebo or no treatment for chronic nonspecific LBP at short or long-term followup.
One of the strengths of this paper is that it identified a large amount of relevant evidence. The reviewers used systematic, comprehensive, and independent strategies to minimize the risk of bias in searching, identifying, retrieving, screening, abstracting, and appraising the primary studies. The search strategy, not restricted by the language or year of publication, was applied to multiple electronic sources. Further strength of this paper is the inclusion of only those trials from which an effect of a single CAM therapy could be isolated. Moreover, the results of individual trials were stratified by spine region (e.g., low-back, neck), duration of pain (acute, subacute, chronic, mixed, and unknown), and cause of pain (specific or nonspecific).
This paper has its limitations. The reviewed evidence was of low to moderate grade and inconsistent due to substantial methodological and/or clinical diversity, as well as small sample size of many trials, thereby rendering some between-treatment comparisons inconclusive. The differences in the therapy provider’s experience, training, and approaches (e.g., deep or superficial massage, choice of trigger points, needling techniques) may have additionally contributed to heterogeneous results. Evidence for acute, subacute, and mixed specific pain was sparse relative to that for chronic nonspecific pain. Quantitative subgroup analyses exploring the effects of age, gender, race, type of treatment provider, or dose of treatment could not be performed due to lack or insufficient data. Poorly and scarcely reported harms data limited our ability to meaningfully compare rates of adverse events between the treatments. This paper focused on manipulation or mobilization to estimate the efficacy. Results from these studies may not be readily applicable to various combinations of interventions used in today’s practice. However, the assessment of a single intervention is the first step in teasing out which therapeutic item is more effective in reducing pain and improving function.
This paper assessed the extent of publication bias using a visual inspection of the funnel plot and the Egger’s regression-based technique . Although the visual inspection method is not very reliable, it conveys some general idea as to how symmetrical the dispersion of individual trial effect estimates is around more precise effect . The funnel plot of acupuncture placebo-controlled trials showed some degree of asymmetry which may have arisen due to publication bias. Publication bias, if present, may have led to overestimation of the treatment effect of acupuncture compared to placebo in reducing pain intensity.
In future, results from long-term large head-to-head trials reporting clinically relevant and validated outcomes are warranted to draw more definitive conclusions regarding benefits and safety of CAM treatments relative to each other or to other active treatments. More research is needed to determine which characteristics of CAM therapies (e.g., mode of administration, length of treatments, number of sessions, and choice of spinal region/points) are useful for what conditions. Future studies should also examine the influence treatment-, care provider-, and population-specific variables on treatment effect estimates. It is clear that strong efforts are needed to improve quality of reporting of primary studies of CAM therapies.