Evan McCarvill, 1012268 Women's Health Research Paper March 7th, 2011 Womens Health Research Paper: Acupuncture

for the treatment of Pain in Women with Fibromyalgia Introduction: Fibromyalgia is an often debilitating syndrome of as yet unknown aetiology (Alacron and Bradley, 1998; Merck manual, 2006), frequently presenting with symptoms such as chronic fatigue, cognitive dysfunction, sleep disorder, morning stiffness, anxiety and depression. It's most prominent and distinctive symptom is widespread muskuloskeletal pain, lasting longer than 3 months, with multiple tender points that are widely and symmetrically distributed throughout the body. Diagnosis is clinical (Merck manual, 2006; Merskey and Bogduk, 1994). For most patients, this syndrome has a significant negative impact on quality of life and performance (Henriksson et al, 1992). It is estimated that the prevalence of this syndrome ranges from 2 to 4 percent of the population in the industrialized world (Buskila and Cohen, 2007). It occurs much more frequently in women than in men, with 3.4% women being affected and only 0.5% of men being affected (Wolfe et al, 1995). A wide range of therapies are employed to treat these symptoms, including pharmaceutical interventions and physical therapies (Abeles et al, 2008; Clauw, 2008), but results have been less than desired. Consequently, a high proportion of fibromyalgia patients seek out complimentary and alternative therapies as well (Pioro-Boisset et al, 1996). One promising alternative therapy is acupuncture. The National Institute of Health issued a consensus statement concluding that acupuncture may be of benefit in the treatment of fibromyalgia as an adjunctive therapy (NIH, 1998). However, lack of controlled studies weakened the conclusion. The purpose of this paper is to provide a review of the more recent available research, to demonstrate the evidence supporting the use of acupuncture for the treatment of pain in women with fibromyalgia, and to discuss the strengths and limitations of that evidence, so as to be able to advise patients on the clinical use of acupuncture.

Results: Targino et al (2008) conducted a randomized controlled trial on fifty eight women, diagnosed with fibromyalgia according to the 1990 American College of Rheumatology (ACR) classification criteria (Wolfe et al, 1990). This trial compared the effectiveness of acupuncture in combination with standard care, with the effectiveness of standard care alone. For outcome measures, patients were asked to report pain intensity according to a visual analogue scale (VAS). Mean pressure pain threshold over all 18 fibromyalgia points was also evaluated by a blinded assessor. Patients in the acupuncture group received 20 treatment sessions in total, administered twice weekly, each lasting about 20 minutes. This treatment was given in addition to standard care, which consisted of tricyclic antidepressants, as well as oral instruction to follow a regimen of brisk walking, deep breathing and stretching. Patients in the control group received this standard care without acupuncture. Outcome assessments were made at baseline, and at 3, 6, 12, and 24 months after the first evaluation. At 3 months, the main outcome measure of pain, using the VAS, showed that acupuncture added to standard care was more effective than standard care alone (P<0.001). VAS scores at 6, 12 and 24 months follow-up were not statistically significant. Pain pressure threshold was significantly better in the acupuncture group at 3 months (P<0.001), and at 6 months (P = 0.016), but not at 12 months or later. Patients in the acupuncture group showed VAS scores and pain pressure threshold values significantly improved from baseline values at all follow-ups, including at 24 months (P<0.005). No significant changes (P>0.05) were noted in the standard care group at any time. The sample size in the above study (Targino et al, 2008) was fairly large, which is a major strength. Another strength was the use of pain pressure threshold as an outcome measure, in addition to the more subjective Visual Analogue Acale (VAS). The near empirical nature of pain pressure threshold data is good evidence against a placebo effect. Incidentally, one weakness of this study was the lack of a placebo group, although it did make an effective demonstration of the additive effect of acupuncture to standard therapy. Other weaknesses included the fact that patients were not blinded to their treatment

group, and adherence to the antidepressants, exercise, stretching, and deep breathing protocols of standard care could only be based on the patients' reports. Another weakness was the fact that the VAS was not disease specific, which limits the value of the resulting data. One final strength however, was the fact that there were follow-up evaluations up to 24 months after treatment, which provides a very useful long-term perspective on the effectiveness of acupuncture, versus standard care alone. Deluze et al (1992) conducted a randomized controlled trial of 70 patients, 54 of whom (77%) were women, who had been diagnosed with fibromyalgia according to the criteria of the American College of Rheumatology (Wolfe et al, 1990). They compared electroacupuncture therapy to a sham acupuncture procedure. Pain outcome measures included pain threshold, number of analgesic tablets used, regional pain score, and pain recorded on a Visual Analogue Scale (VAS). Treatment consisted of 6 sessions of electroacupuncture, given over the course of 3 weeks. Outcome measures were evaluated before the first session and after treatment, by the same blinded physician for all patients. Patients in the electroacupuncture group improved significantly in all parameters from baseline, whereas there was no such improvement in the control group. Compared to the control group, the electroacupuncture group showed significantly improved outcomes for pain threshold (P = 0.0303), pain according to VAS (P = 0.0246), but not number of analgesic tablets used (P = 0.0945), or regional pain score (P = 0.0570). In particular, the pain threshold, thought to be the most significant, improved by 70% from baseline in the electroacupuncture group, but by only 4% in the control group. The above study (Deluze et al, 1992) had a strong sample size, which is encouraging. They also appeared to have a satisfactory placebo procedure, which is another major strength. Yet another strength was the use of near empirical outcome measures, such as pain threshold and number of analgesic tablets used. Patients were asked afterward which group they thought they were in, and it was shown that they seemed quite unaware. This assurance of blinding is certainly a notable strength. The only major weakness of this study was the fact that it was very short. There were only two evaluations; before and after treatment. There was no follow-up, due to practical limitations.

Martin et al (2006) conducted a prospective, partially blinded, controlled, randomized clinical trial, comparing the effectiveness of true acupuncture with simulated acupuncture. Fifty patients, diagnosed with fibromyalgia according to the criteria of the American College of Rheumatology (Wolfe et al, 1990), were randomized evenly between these two treatment groups. All patients were female, except for one in the control group; not a statistically significant gender difference. The Fibromyalgia Impact Questionnaire (FIQ), a widely accepted, standardized and validated tool for fibromyalgia research (Burckhardt et al, 1991), was used to measure clinical outcomes, such as pain, physical function, work status, depression, anxiety, sleep, stiffness, fatigue and well-being on a 0-to-10 point scale. The Multidisciplinary Pain Inventory (MPI), a more generalized measure of chronic pain and its impact (Turk, 1990), was also used to measure pain severity, interference with daily life, life control, affective distress, and general activity level. The MPI has proven use for chronic pain and fibromyalgia (Turk et al, 1998). Standardized bilateral acupuncture points were chosen for application to all patients. In the true acupuncture group, patients were seated, and the procedure was kept out of view with a tray below the chin. In the control group, providing simulated acupuncture, patients were positioned identically,

with the procedure hidden from view. At the end of both true and simulated treatments, patients were left to relax in a darkened room with quiet music for 20 minutes. A total of 6 sessions were completed. The blinded study coordinator collected the surveys at baseline, after treatment, and at 1 and 7 months after treatment. The overall FIQ group effect of acupuncture was significantly superior to the control group (P = 0.01). The greatest difference was at 1 month (P = 0.007). Significant subscale results were seen for fatigue and anxiety. The MPI group effect showed significant improvement in pain (P = 0.03) up to 1 month after treatment, but was no longer a significant difference at 7 months (P = 0.05). The above study (Martin et al, 2006) determined their sample size based on other trials that studied fibromyalgia. Therefore, although the sample size is not particularly strong, it is directly comparable to results of other studies of fibromyalgia for this reason. Another strength was the use of a creative form of simulated acupuncture as an effective placebo, and it was determined that patients were blind to

which treatment group they had been assigned. Such blinding is essential for quality acupuncture research and it is an important strength of this study. Although this study did not employ the relatively objective pain pressure threshold as an outcome measure, it did employ a validated standardized questionnaire, the FIQ, which is specific to studying fibromyalgia. The use of such standardized statistical tools is certainly a major strength. The use of the MPI, although not disease-specific, was still a strength, as it provided another independent outcome measure. Finally, the patient sample was near homogeneous in gender, diagnosis, and severity of symptoms, due to their recruitment through a prior fibromyalgia treatment program, which minimizes the confounding factors that might obscure the observed effect of acupuncture. Itoh and Kitakoji (2010) conducted a preliminary randomized controlled trial involving 16 patients (13 women and 3 men), diagnosed with fibromyalgia by specialists according to the criteria of the American College of Rheumatology (Wolfe et al, 1990). Patients were randomized to either group A, which received 5 weeks of acupuncture, after 5 weeks of a prior control period without acupuncture, and to group B, which received continuous acupuncture for a full 10 weeks. Acupuncture treatments were provided once per week, and each session lasted for 30 minutes, consisting of 15 minutes of electroacupuncture and 15 minutes of trigger point acupuncture. Patients in group A were examined once or twice per week by a fibromyalgia specialist prior to the five-week intervention period. Outcome measures included pain intensity, quantified with a 10cm visual analogue scale (VAS), and also pain disability, pain, sleep, fatigue, stiffness, anxiety and depression, as measured by the Fibromyalgia Impact Questionnaire (FIQ) (Burckhardt et al, 1991). The VAS and FIQ questionnaires were completed by patients before each treatment, and analyzed at baseline and at 5 weeks and 10 weeks after the first treatment. The median VAS score and the FIQ score were both unchanged in group A at week 5, but had decreased by week 5 in group B, which had been receiving acupuncture treatment. The VAS and FIQ scores of group A began to decrease after week 5, when acupuncture treatment began. The difference in VAS score between groups A and B at week 5 was significant (P =

0.022), while there was no significant difference at baseline (P = 0.566), nor at the tenth week after both groups had been receiving acupuncture (P = 0.252). There was a significant difference in FIQ score between the groups at week 5 (P = 0.026), while there was also no difference at baseline (P = 0.616) and at week 10 (P = 0.086). The above study (Itoh and Kitakoji, 2010) is a randomized trial of only 16 patients. Clearly, this is a very small sample size, which is a major weakness. Another weakness was the lack of a placebo group, although one group was treated to a 5-week standard-treatment period for comparison, while the other received 10 weeks of continuous treatment. This means that lack of blinding could be a major weakness of this study as well. Nevertheless, this study finds strength in it's use of the standardized and validated Fibromyalgia Impact Questionnaire, in addition to the pain intensity VAS scores. Although questionnaires are somewhat subjective, the ability to standardize the data should allow for ease of comparison with other trial results. Duncan et al (2007) conducted an uncontrolled observational study of the effectiveness of acupuncture for fibromyalgia in tertiary care. Patients were included if they met the usual fibromyalgia criteria and had a pain score of at least 30 on a 100mm Visual Analogue Scale (VAS). They were not permitted to introduce new treatments during the study, though they could continue ongoing treatments. Acupuncture was provided with a Western approach, according to a protocol determined by consensus. Patients were offered 8 treatments in 8 weeks. Outcome measures were pain intensity, as indicated by VAS, as well as the Fibromyalgia Impact Questionnaire. Measurements were taken before and after treatment, and at 14, 20 and 34 weeks after initiation of the study. Fourteen out of 24 patients completed the course of treatment, within approximately 10 weeks. Compliance was poor, and completion of outcome measures was variable. Five patients scored a minimum of 20% reduction in the FIQ, and two of these scored a 50% reduction. This was considered a clinically relevant improvement. Duncan et al (2007) conducted an uncontrolled observational study. The fact that this study was

not placebo controlled immediately weakens the value of its results. Furthermore, the acupuncture treatment was determined by consensus, with a Western approach, so its comparability to traditionally applied acupuncture can be called into question. Compliance was poor and only 14 patients completed the study. This leaves a very small sample size with little statistical value. Although the results were deemed clinically significant, it was not clear on what basis this was determined. Contrarily, strengths of this study include the use of the statistically validated FIQ tool for fibromyalgia research, as well as the follow-up evaluations for up to 34 weeks. Discussion: The purpose of this research review was to become able to inform and advise a female patient suffering from pain due to fibromyalgia syndrome, on how she might relieve some of that pain and improve her quality of life. From the results outlined above, it seems apparent that acupuncture treatment can provide benefit, additive to standard fibromyalgia treatment (Targino et al, 2008; Itoh and Kitakoji, 2010), which is superior to placebo (Deluze et al, 1992; Martin et al, 2006). It is important to note from Martin et al (2006) and Targino et al (2008), that the benefit given by acupuncture treatment was relatively transient, with the statistically significant difference between treatment groups diminishing after a few weeks to months of cessation of treatment. This indicates that acupuncture would likely need to be administered continuously over an extended period, in order to maintain benefit to the patient. Despite the relatively small sample sizes of most of the studies, the positive results appear to be consistent and statistically significant. This was true whether the trials used objective outcomes such as pain pressure threshold (Targino et al, 2008; Deluze et al, 1992), or exclusively questionnaire data (Martin et al, 2006; Itoh and Kitakoji, 2010). It should be noted that the FIQ is a statistically validated tool for use in studies of fibromyalgia, and that positive results with this tool can be taken as valid and can easily be compared with the results of other fibromyalgia studies. This can likely be taken as good evidence in favour of the use of acupuncture for treatment of pain in women with fibromyalgia.

There are however, some weaknesses to this research. Most of the trial subjects were women, which of course was the focus of this paper, but this also limits the applicability of these results to male fibromyalgia patients. In addition, positive results hold greater weight if they are based on larger sample sizes than those employed in these reviewed studies. The studies were also variable in the quality of their blinding techniques, and in the form of placebo control, if any, that they employed. There is still some debate as to the best methods of creating placebo controls for acupuncture trials (Streitberger et al, 1998; Goddard et al, 2005). An alternative to a placebo group is to take pretreatment measurements for an extended period for comparison, as with Itoh and Kitakoji (2010), or to simply compare adjunctive acupuncture with standard care alone, as with Targino et al (2008). There are advantages to this proposal, such as the elimination of possible confounding effects of sham acupuncture, and disadvantages, such as possible lack of blinding. Although there remain some weaknesses to the available research for acupuncture in the treatment of pain for fibromyalgia, the evidence appears clear enough to warrant acupuncture as an adjunctive treatment to standard care. Of note is that standard care includes exercise, relaxation, and stretching (Targino et al, 2008), which all fall within the scope of Naturopathic practice. Acupuncture points typically used in the reviewed studies included LI4, St36, Lv3, GB34, Sp6, Pc6, and Ht7 (Martin et al, 2006; Targino et al, 2008), and should be considered when designing an acupuncture protocol. It should be emphasized that the treatment will need to be applied weekly or bi-weekly over an extended period, likely several months, in order to sustain benefit (Martin et al, 2006; Targino et al, 2008). In conclusion, it seems quite clear that acupuncture would be a safe, effective and cost-efficient addition to the standard approach to fibromyalgia treatment. Given the complexity of fibromyalgia syndrome, monotherapies are not recommended, and so acupuncture should be indicated as one of a series of interventions that should be employed. It is likely that application of acupuncture therapy will synergistically enhance the pain-reducing benefit of other interventions and help to further improve and maintain quality of life.

Works Cited Abeles M, Solitar BM, Pillinger MH, Abeles AM. (2008) Update on fibromyalgia therapy. American Journal of Medicine; 121(7): 555-561. Alacron GS, Bradley LA. (1998) Advances in the treatment of fibromyalgia: Current status and future directions. American Journal of Medical Science; 315: 397-404. Beers MH, Porter RS, Jones TV, Kaplan JL, Berkwits M (2006). Fibromyalgia. In E. (Ed. 18) The Merck Manual. Whitehouse Station, NJ: Merck Research Laboratories. Burckhardt CS, Clark SR, Bennett RM. (1991) The fibromyalgia impact questionnaire: development and validation. Journal of Rheumatology. 18: 728-733. Buskila D, Cohen H. (2007). Comorbidity of fibromyalgia and psychiatric disorders. Current Pain and Headache Reports; 11(5): 333-338. Clauw DJ. (2008) Pharmacotherapy for patients with fibromyalgia. Journal of Clinical Psychiatry; 69(Suppl 2): 25-29. Deluze C, Bosia L, Zirbs A, Chantraine A, Vischer TL. (1992) Electroacupuncture in fibromyalgia: results of a controlled trial. British Medical Journal; 305: 1249-1252. [FULL TEXT AVAILABLE UPON REQUEST] Duncan B, White A, Rahman A. (2007) Acupuncture in the treatment of fibromyalgia in tertiary care a case series. Acupuncture Med; 25(4): 137-147. Goddard G, Shen Y, Steele B, Springer N (2005). A controlled trial of placebo versus real acupuncture. J Pain 6: 237-242. Henriksson C, Gundmark I, Bengtsson A, Ed AC. (1992) Living with fibromyalgia. Consequences for everyday life. Clinical Journal of Pain; 8: 138-144. Itoh K, Kitakoji H. (2010) Effects of acupuncture to treat fibromyalgia: A preliminary randomized controlled trial. Chinese Medicine; 5:11 [FULL TEXT AVAILABLE UPON REQUEST] Martin DP, Sletten CD, Williams BA, Berger IH. (2006) Improvement in fibromyalgia symptoms with acupuncture: Results of a randomized controlled trial. Mayo Clinic Proceedings; 81(6): 749-757. [FULL TEXT AVAILABLE UPON REQUEST] Merskey H, Bogduk N, editors. (1994) Classification of chronic pain. Description of chronic pain syndromes and definitions of terms. Seattle: IASP Press; p. 45. NIH Consensus Conference. (1998) Acupuncture. JAMA; 280: 1518-1524. Pioro-Boisset M, Esdaile JM, Fitzcharles MA. (1996) Alternative medicine use in fibromyalgia syndrome. Arthritis Care Res; 9(1): 13-17.

Streitberger K, Kleinhenz J (1998). Introducing a placebo needle into acupuncture research. Lancet 352: 364-365. Targino RA, Imamura M, Kaziyama HHS, Souza LPM, Hsing WT, Furlan AD, Imamura ST, Neto RSA. (2008) A randomized controlled trial of acupuncture added to usual treatment for fibromyalgia. Journal of Rehabilitation Medicine; 40: 582-588. [FULL TEXT AVAILABLE UPON REQUEST] Turk DC. (1990) Customizing treatment for chronic pain patients: who, what, and why. Clinical Journal of Pain. 6: 255-270. Turk DC, Okifuji A, Sinclair JD, Starz TW. (1998) Differential responses by psychosocial subgroups of fibromyalgia syndrome patients to an interdisciplinary treatment. Arthritis Care Res. 11: 397-404. Wolfe F, Ross K, Anderson J, Russell IJ. (1995) Aspects of fibromyalgia in the general population: sex, pain threshold, and fibromyalgia symptoms. Journal of Rheumatology; 22: 151-156. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, Fam AG, Farber SJ, Fiechtner JJ, Franklin CM, Gatter RA, Hamaty D, Lessard J, Lichtbroun AS, Masi AT, McCain GA, Reynolds WJ, Romano TJ, Russell IJ, Sheon RP. (1990) The american college of rheumatology 1990 criteria for the classification of fibromyalgia. Report of the multicenter criteria committee. Arthritis and Rheumatism; 33(2): 160-172.