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Re: Re: Acupuncture treatment in irritable bowel syndrome

Dear Editor,

There is still substantial debate about the exact nature of the Streitberger needle and if indeed it is a “true placebo”: i.e. without any of the specific therapeutic effect associated with real acupuncture(1,2). Patients perceive Streitberger differently to real acupuncture which certainly would not be the case in a conventional drug trial with a tableted placebo.

Streitberger generates needling sensation, an acupuncture specific sensation thought to be associated with the efficacy of acupuncture. As we are not sure how acupuncture works, we cannot therefore be certain that the Streitberger needle is a true placebo(3). It is therefore important that each study using the Streitberger needle evaluates equipoise and the patient perceived credibility of both real and “placebo” treatment. This did not occur in Schneider et al’s study.

Furthermore this paper contains some interesting observations about placebo predictors. Research into the predictors of placebo outcome need to be treated with caution as a common conclusion from research conducted over the last 30 years is that there is too much inconsistency between studies to draw any definitive conclusion(4,5). Contrary to the claim make by Schneider et al., their findings on placebo predictors does not add to this research. Predictors of outcome should be independent of the outcome measures themselves. If that is not the case, then the correlations can result from two types of bias: regression to the mean and severity effects. Because the outcome data are statistically related to the same scales that are used as predictors, the predictor results do not provide useful information.

References

1. Lewith GT, White P. Rapid responses to article by Kaptchuk in BMJ. 3 February 2006 and 8 February 2006.

2. Lewith GT, White PJ, Kaptchuk T. Developing a research strategy for acupuncture. (In press - Clinical Journal of Pain).

3. White P, Lewith GT, Hopwood V, Prescott P. The placebo needle, is it a valid and convincing placebo for use in acupuncture trials? A randomised, single blind, cross-over trial. Pain. 2003; 106 (3): 401-409.

4. Brody, H. (2000). The placebo response. New York: HarperCollins.

5. Moerman, D. (2002). Meaning, medicine, and the 'placebo effect'. Cambridge Cambridge Univ Press.

George T. Lewith
Reader in Complementary Medicine,
University of Southampton.
Email: gl3@soton.ac.uk

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Re: Authors' reply

Dear Editor,

Re: Stratification by gender and subgroup is necessary for RCT on IBS by Prof. Bian

Thank you for the communication of your interesting study results. Your findings highlight a problem especially for acupuncture research. Many experimental trials are pointing out the efficacy of acupuncture, also regarding problems of the gastrointestinal tract.[1-4] However, many of these trials are not always controlled by appropriate placebo. Thus it is difficult to explain the positive result with specific effects.

Acupuncture and placebo-acupuncture seem to have the same positive effect in many RCTs.[5-8] That does not mean that an acupuncture effect is always a placebo effect. Especially in musculoskeletal diseases acupuncture seem to be stronger than placebo.[9-12] Indeed, in functional diseases the efficacy of acupuncture seems to rely on placebo effects. In our study, we placed the “Streitberger-needle”[13] 2 cm apart the real points to avoid acupressure effects. Nevertheless, we had definitive effects of the placebo acupuncture.[14] Thus, it seems that the identified physiological effects seem to play an ancillary role. Our results are supported by another recently published trial.[15] They used a sham acupuncture on non-acupuncture-points. As a consequence, it was not sure if the effects are due to some unspecific effects. The sham acupuncture trials have the disadvantage that the unspecific effect could always be due to some hypothesized unspecific needling effects. It will be always questioned: “Was that really a non-acupuncture point? How do you know that a sham acupuncture will not cause any effect?”. This is excluded with our study design.

The question arises why placebo-acupuncture and placebo in general[16] are so effective in irritable bowel syndrome. And the second question is whether the results of experimental trials are really due to specific effects. And if they are: why is this not reflected in clinical trials? What role does the cognitive processing play in this context? Further research is required to shed light on this phenomenon. It was not possible to do a subgroup analysis from a statistical point of view as we had only 9 males in our study. This is the same for the clinical subgroups. However, the placebo-effect was so strong that almost 526 patients would be necessary to prove some effect. Such an effect could be interesting, but it must be questioned if it is clinically relevant.

References:

(1) Cui KM, Li WM, Gao X et al. Electro-acupuncture relieves chronic visceral hyperalgesia in rats. Neurosci Lett 2005;376(1):20-3.

(2) Jin HO, Zhou L, Lee KY et al. Inhibition of acid secretion by electrical acupuncture is mediated via beta-endorphin and somatostatin. Am J Physiol 1996;271(3 Pt 1):G524-G530.

(3) Li P, Rowshan K, Crisostomo M et al. Effect of electroacupuncture on pressor reflex during gastric distension. Am J Physiol Regul Integr Comp Physiol 2002;283(6):R1335-R1345.

(4) Li Y, Tougas G, Chiverton SG et al. The effect of acupuncture on gastrointestinal function and disorders. Am J Gastroenterol 1992;87(10):1372-81.

(5) Linde K, Jobst K, Panton J. Acupuncture for chronic asthma. Cochrane Database Syst Rev 2000;(2):CD000008.

(6) Linde K, Streng A, Jürgens S et al. Acupuncture for Patients with Migraine. JAMA 2005;293:2118-25.

(7) Melchart D, Streng A, Hoppe A et al. Acupuncture in patients with tension-type headache: randomised controlled trial. BMJ 2005;331(7513):376 -82.

(8) White AR, Rampes H, Ernst E. Acupuncture for smoking cessation. Cochrane Database Syst Rev 2002;(2):CD000009.

(9) Kleinhenz J, Streitberger K, Windeler J et al. Randomised clinical trial comparing the effects of acupuncture and a newly designed placebo needle in rotator cuff tendinitis. Pain 1999;83(2):235-41.

(10) Manheimer E, White A, Berman B et al. Meta-analysis: acupuncture for low back pain. Ann Intern Med 2005;142(8):651-63.

(11) White P, Lewith G, Prescott P et al. Acupuncture versus placebo for the treatment of chronic mechanical neck pain: a randomized, controlled trial. Ann Intern Med 2004;141(12):911-9.

(12) Witt C, Brinkhaus B, Jena S et al. Acupuncture in patients with osteoarthritis of the knee: a randomised trial. Lancet 2005;366(9480):136- 43.

(13) Streitberger K, Kleinhenz J. Introducing a placebo needle into acupuncture research. Lancet 1998;352(9125):364-5.

(14) Schneider A, Enck P, Streitberger K et al. Acupuncture treatment in irritable bowel syndrome. Gut 2005. Epub ahead of print.

(15) Forbes A, Jackson S, Walter C et al. Acupuncture for irritable bowel syndrome: a blinded placebo-controlled trial. World J Gastroenterol 2005;11(26):4040-4.

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Re: Stratification by gender and subgroup is necessary for RCT on IBS

Dear Editor,

We read with great interest the paper by Antonius Schneider et al. assessing acupuncture treatment in irritable bowel syndrome (IBS).[1] They successfully recruited 43 patients with IBS according to Rome II criteria, and randomly assigned them to receive either acupuncture (n=22) (AC) or sham acupuncture (n=21) (SAC) using the so-called "Streitberger needle". Treatment duration was 10 sessions with an average of two acupuncture sessions per week, and primary endpoint was improvement of quality of life (QOL) using the Functional Digestive Diseases Quality of Life Questionnaire (FDDQL) and a general Quality of Life Questionnaire (SF -36),compared to baseline assessment. They found that both the AC as well as the SAC group improved significantly in global QOL by the FDDQL at the end of treatment (p=0.022), with no differences between both groups. This observation led authors to conclude that acupuncture in IBS is primarily a placebo response.

This result supported the conclusion of studies by Fireman et al.[2] and Forbes A et al.[3] Interestingly, we have recently finished one study with conclusion that acupuncture can attenuate chronic visceral hypersensitivity in rats.[4] Results showed that acupuncture has immediate and cumulative effects on chronic visceral pain induced by colorectal distention stimuli in rats with chronic visceral hypersensitivity. This result supported the findings in previous report[5], and really matched the phenomena of our clinical practice that IBS sufferers did get benefits from acupuncture treatment. We also found acupuncture can modulate the expression of corticotropin-releasing factor in the limbic system and concentration of serotonin in the colon[4], not just modulate the endorphin system via central processing of pain.[6,7]

In evidence, placebo effect cannot explain the efficacy of acupuncture on the rats with chronic visceral hypersensitivity. Furthermore, some trials did provide evidences that acupuncture have treatment effect on patients with IBS. In one open-design pilot study [8], after a 4-week course of acupuncture treatment, seven patients with IBS showed an improvement in overall well-being and bloating but not abdominal discomfort or defecation frequency. One study of seven patients with diarrhoea-predominant IBS showed that transcutaneous electrical acustimulation (TEAS) at acupoints PC6 and ST36 significantly increased the threshold of rectal sensation of gas, desire to defecate, and pain, but had no effects on rectal tone or compliance.[9]

Why evidences from clinical trials are so confusing? How to unfasten this sticking point? One study showed that gender is one factor to affect the manifestations of IBS. Male IBS patients have more significant decreased parasympathetic tone and increased sympathetic activity with altered autonomic nervous system responsiveness to a visceral stimulus than that of IBS female patients[11], and these differences may be due to gender difference in cortico-limbic processing of visceral stimuli. In another study with treatment scheme of twice per week for 2 months, transcutaneous electrical acustimulation( TEAS ) at LI 4 and ST36 improved the abnormal rectal sensation and related symptoms in patients with diarrhea-predominant IBS (n=24), but not in those with constipation- predominant IBS (n=20) and functional constipation (n=30).[10] This result indicates that there are characteristic differences between diarrhea- and constipation-predominant IBS patients.

Because of different characteristics of male and female patients with IBS, and diarrhea- and constipation-predominant IBS, we think it is not appropriate to mix the gender[1, 2,3,8,9,10,11] and subgroup of IBS[1,2,3, 8,9,11] for assessing the therapeutic effect of acupuncture on IBS. In fact, it threatened the internal validity of clinical trial results. Future randomized, double blind and placebo-controlled study with acupuncture on IBS should stratify patients by gender and subgroups in randomization and assessment, and we believe it is essential too for studies on IBS with drug therapy.

References

1. Schneider A, Enck P, Streitberger K, Weiland C, Bagheri S, Witte S, Friederich HC, Herzog W, Zipfel S. Acupuncture treatment in irritable bowel syndrome. Gut. 2005, September 22, in press.

2. Fireman Z, Segal A, Kopelman Y, Sternberg A, Carasso R. Acupuncture treatment for irritable bowel syndrome. A double-blind controlled study. Digestion. 2001; 64: 100-3.

3. Forbes A, Jackson S, Walter C, Quraishi S, Jacyna M, Pitcher M. Acupuncture for irritable bowel syndrome: a blinded placebo-controlled trial. World J Gastroenterol. 2005; 11: 4040-4.

4. Z.-X.Bian, X-G. Hu, R-A.Qin, X.-J. Zhang, L. Liu. Electro- acupuncture attenuates behavioral hyperalgesia and relieves stress-induced defecation in rats with chronic visceral hypersensitivity. unpublished data 2005.

5. Cui KM, Li WM, Gao X, Chung K, Chung JM, Wu GC. Electro- acupuncture relieves chronic visceral hyperalgesia in rats. Neurosci Lett. 2005 Mar 7; 376(1): 20-3.

6. Han JS. Acupuncture and endorphins. Neurosci.Lett. 2004; 361: 258- 61.

7. Hui KK, Liu J, Makris N, Gollub RL, Chen AJ, Moore CI et al. Acupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from fMRI studies in normal subjects.Hum.Brain Mapp. 2000; 9: 13-25.

8. Diehl DL. Chan J, Carr I, Mayberry JF. The role of acupuncture in the treatment of irritable bowel syndrome: a pilot study. Hepatogastroenterology. 1997; 44: 1328-30.

9. Xing J, Larive B, Mekhail N, Soffer E. Transcutaneous electrical acustimulation can reduce visceral perception in patients with the irritable bowel syndrome: a pilot study. Altern Ther Health Med. 2004; 10: 38-42.

10. Xiao WB, Liu YL. Rectal hypersensitivity reduced by acupoint TENS in patients with diarrhea-predominant irritable bowel syndrome: a pilot study. Dig Dis Sci. 2004; 49: 312-9.

11. Tillisch K, Mayer EA, Labus JS, Stains J, Chang L, Naliboff BD. Sex specific alterations in autonomic function among patients with irritable bowel syndrome. Gut. 2005; 54: 1396-1401.