BACKGROUND

Fibromyalgia

Fibromyalgia is a syndrome with features that include chronic, widespread musculoskeletal pain and stiffness and associated with fatigue, poor sleep and the presence of discrete tender points. Fibromyalgia affects ~3.7 million people in the U.S.; 75% of patients are women between the ages of approximately 35 to 55 .1 One small survey estimated that approximately 20% of fibromyalgia patients treated at a university-based clinic in the United States tried acupuncture within 2 years of diagnosis.2

Description of Acupuncture

In its original form acupuncture was based on the principles of traditional Chinese medicine .3-5 The general theory of acupuncture is based on the premise that there are patterns of energy flow through the body that are essential for health. Traditional acupuncturists understand health in terms of a vital force of energy called Qi which circulates between the organs along channels called meridians. The traditional Chinese medicine acupuncture practitioner seeks to identify the
1
nature of any imbalance in Qi, and then selects the appropriate acupuncture points from among approximately 360 points distributed along the meridians.4, 6, 7

Acupuncture involves the stimulation of the specific acupuncture points (acupoints) on the skin, usually by the insertion of needles ranging in length from 1 cm to 10 cm. Between 5 and 15 needles are used in a typical treatment, with the point combinations varying during a course of sessions. The acupoints can be chosen based on a standardized "formulary" involving a fixed menu of consistent points for each disease or condition or selected for each patient individually based on a patient’s specific symptoms and Qi balance. Depth of puncture can be up to 5 cm.
Other forms of acupuncture include electroacupuncture, heat (including moxibustion), pressure, and laser-generated light.5, 6, 8 A glossary of these procedures is found in Appendix A. Generally, studies have addressed either manual needling or electroacupuncture because the stimulation parameters of these procedures are easiest to control.4, 6, 7

FDA's Role

The U.S. Food and Drug Administration (FDA) regulates devices used for acupuncture, such as the needles. Since 1973, the FDA considered acupuncture devices, including needles, as investigational medical devices. 9 In December of 1994, petitions were filed with the FDA to approve the needles as treatment for five medical conditions: pain, nausea and vomiting, substance abuse, asthma and other respiratory problems, and stroke and paralysis.10 As a result of these events, FDA undertook an extensive review of the available evidence regarding the effectiveness of acupuncture.6, 10 FDA announced on March 29, 1996 that acupuncture needles had been reclassified from Class III (experimental) medical devices to Class II (non-experimental but regulated) medical devices for "general acupuncture use" by licensed, registered or certified practitioners.11 As part of this reclassification, FDA determined that the "investigational use" labeling requirements no longer applied. However, the FDA determined that acupuncture needles must comply with the following special controls:

(1) Labeling for single use only and conformance to the requirements for prescription devices set out in 21 CFR 801.109,
(2) Device material biocompatibility, and,
(3) Device sterility.
Class II devices involve less stringent controls by FDA that include good manufacturing procedures and proper labeling. However, clinical data demonstrating clinical effectiveness is not required. To receive marketing clearance as a class II device, acupuncture devices must go through the FDA’s 510 (k) process.12
The FDA requires manufacturers of acupuncture needles to label them for single use only. Acupuncture needles must also bear a prescription labeling statement which restricts their use to qualified practitioners as determined by the states. Manufacturers also have to provide information about device material bio-compatibility and sterility.13

Adverse events associated with acupuncture

Serious adverse events associated with acupuncture include transmission of infectious disease, pneumothorax, other problems associated with organ punctures, spinal lesions, cardiac tamponade, and broken needles with remnants migrating to other locations.7, 8 Minor adverse events include forgotten needles, exacerbation of symptoms, minor bleeding, hematoma, fatigue, sweating, severe nausea, fainting, and headache.4, 7, 8 Adverse events may be associated with practitioner competence and training.4, 14, 15

There have been several studies quantifying the rates of adverse events. A few studies compiled case reports. One Japanese systematic review of case reports found 25 cases of pneumothorax, 18 cases of spinal cord injury, 11 cases of acute hepatitis B and two fatalities from infections.16 This study and other similar studies establish that serious adverse events are possible, but they were not able to measure the frequency of these complications.17

Two large prospective studies in the U.K. provided estimates of the rates of adverse events. White and colleagues conducted a prospective survey of 32000 treatments and found that the rate of “significant” events were 14 per 10,000 acupuncture visits. 18 None of these were deemed to be serious. A total of 671 minor events (such as bleeding or needling pain) per 10,000 acupuncture visits were reported in this study. MacPherson? and colleagues conducted a prospective survey of 34000 treatments and found that there were no reports of serious adverse events that required hospital admission or led to permanent disability or death. 19 Minor adverse events such as severe nausea and vomiting occurred in 1.3 out of 1000 visits. Mild transient reactions such as pain or bleeding occurred in 15% of the visits.

METHODOLOGY

• We reviewed two recent Technology Assessments to provide a synopsis of systematic reviews as of 2001 (Table 1).
• We updated the initial review by searching and listing systematic reviews and other reviews on the use of acupuncture for fibromyalgia from 2000 to the present (Table 2).
• We further updated the review by searching for all RCTs published since the last systematic review.
• We reviewed the abstracts of all RCTs identified.
• We searched for ongoing acupuncture clinical trials to treat fibromyalgia from the clinicaltrials.gov web site (Table 3).
The search strategy used to identify studies listed in all Tables is summarized in Appendix D.

RESULTS

Literature search

To evaluate the current evidence for the efficacy of acupuncture in treating fibromyalgia we identified two recent methodologically sound Technology Assessments:

“Alberta”: Alberta Health Technology Assessment, Acupuncture: Evidence from Systematic Reviews and Meta-analyses (2002) 8
“NHS”: United Kingdom National Health Service Center for Reviews and Dissemination: Effective Health Care on Acupuncture (2001) 7

These reviews systematically assessed available systematic reviews and meta-analyses on acupuncture. Both of these cited only a single systematic review on fibromyalgia by Berman and colleagues.20 The Alberta report rated the Berman systematic review as “Satisfactory” (on a 3 point rating system from “Good” to “Poor”). The Alberta report criticized the Berman systematic review because it failed to identify the style of acupuncture (e.g. whether the points were individualized to the patient or chosen based on a formula), appropriateness of treatment, or the qualification of the practitioner.

In order to find more recent literature, we searched for reviews or RCTs published since 2000. Two reviews were found: Berman and Bandolier; these did not include any new RCTs. 21,22 There were no RCTs identified in our search that were published since the last systematic review.
We searched the clinicaltrials.gov website to find current clinical trials on the use of acupuncture for fibromyalgia. Two clinical trials are currently underway (Table 3).

Issues in evaluating acupuncture for fibromyalgia

In addition to standard design issues such as the number of patients needed for adequate statistical power, the randomization procedures, and the appropriateness of outcome measures, the Alberta report summarized specific issues in designing a study for acupuncture including:

• Selection of control technique: Placebo or “sham” acupuncture in studies of acupuncture typically use non-traditional acupuncture points, superficial puncturing of the skin, or for electroacupuncture, the use of electrical stimulators without connecting the cables. Some researchers believe that inserting a needle anywhere in the body or applying pressure to any site evokes a response.

• Complexities of acupuncture: There are many choices in designing a study including different types of acupuncture, different systems for choosing sites and variability in the technique of needle insertion and manipulation.
In addition, it is important to consider that fibromyalgia is a chronic disease characterized by recurring pain over a period of many months or longer. Long term follow-up would be critical to determine the effectiveness of the treatment.

Clinical data

The Berman review, which is the basis for all the other reviews of acupuncture for fibromyalgia, cites 7 primary studies 23-29 , of which 3 are RCTs (Table 4). 25, 27, 28

Berman and colleagues considered the Deluze RCT to be the only one of high methodological quality. 28 The other two RCTs were considered to be of lower quality because the designs precluded the ability to blind patients to group assignment and the method of randomization concealment was unclear.

The NHS report included fibromyalgia together with the use of acupuncture for other types of chronic pain, and criticized the literature based on three points:

• Quality of the studies was related to study outcomes: lower quality studies were more likely to favor acupuncture.
• Most RCTs of acupuncture in chronic pain have few patients and may be underpowered.
• Active acupuncture and sham techniques may be inadequate; including too few numbers of points, too few treatment sessions, and placement of sham needles in the same body segment as the active needles.
Deluze and colleagues studied 70 patients with electroacupuncture compared to sham. They found statistically significant improvements on several outcome measures such as pain relief. They did not, however, follow patients beyond the three week study period. The two other RCTs had longer term follow-up. Berman et al. reviewed the results of the Lautenschlager et al. study of 50 patients and stated that no significant difference of effect was found between acupuncture and placebo at 3 month follow-up (the translation of the abstract is ambiguous and we could not therefore confirm this statement by Berman et al.) Berman et al. also noted that the data from the RCT was combined with data from a nonrandomized pilot study.27 Cassisi and colleagues studied 21 patients and found a long term pain relief benefit at 6 months, but this benefit was quantitatively less than the initial pain relief.25

CONCLUSIONS

There is only one RCT (Deluze et al. 28) on the use of acupuncture for fibromyalgia that was considered to be of high quality by Berman et al, the primary reviewer of fibromyalgia. This study of 70 patients found statistically significant benefits for acupuncture using several outcome measures such as pain relief. This study used electroacupuncture rather than the more traditional needling technique. More importantly, however, Deluze et al. only followed patients for three weeks. Studies of lower methodological quality include two other randomized studies and several other nonrandomized studies.

The reviews interpret the strength of this body of evidence somewhat differently (Table 1 and 2). None of the reviews concluded that the evidence was sufficient to use acupuncture as a first line treatment, although two concluded that the evidence supported the use of acupuncture as adjunctive or second line treatment for fibromyalgia. Even though the study by Deluze et al. found a statistically significant benefit for acupuncture, it only followed patients for three weeks, which is not long enough to draw conclusions about health outcomes for patients with this long-term chronic condition. Longer term studies are necessary to determine the benefit of any treatment for fibromyalgia.

 
At this time, therefore, there is insufficient evidence to conclude that acupuncture has efficacy for the treatment of fibromyalgia. Two randomized controlled clinical trials with a follow-up of at least 13 weeks are currently underway and should provide more useful data about this treatment for fibromyalgia.