By the end of radiotherapy for head and neck cancers, more than 50% of patients experience radiation-induced xerostomia (RIX), a condition manifested by a long-lasting perception of dry mouth. Radiation-induced xerostomia is associated with a series of complications, such as difficulty sleeping and speaking, dysgeusia, and dysphagia, that significantly affect patients’ quality of life. A 2019 review of clinical trials1 compiled several strategies against RIX and reported that sialogogue medications, sparing parotid glands by intensity-modulated radiation therapy, and salivary gland transfer have been shown to be effective but at the cost of adverse events or persistent symptoms after treatment. A 2015 randomized clinical trial2 demonstrated that patients with RIX who received acupuncture-like transcutaneous electrical nerve stimulation had marginally better responses and significantly fewer adverse events compared with patients who received oral pilocarpine. This trial suggested that acupuncture may be a promising approach to prevent RIX.
In the study by Garcia et al,3 results of a 2-center, phase 3, randomized, sham-controlled clinical trial for the treatment and prevention of RIX with acupuncture are presented. Interestingly, one center was situated in the United States, and the other was in China. A classic 3-arm study design was used to compare true acupuncture (TA) and sham acupuncture (SA) with a standard care control (SCC). Compared with SCC, TA resulted in significantly lower xerostomia scores and lower incidence of clinically significant xerostomia 1 year after treatment, while the SA was not significantly associated with improved xerostomia scores. However, no significant difference between TA and SA xerostomia scores was observed, and both acupuncture groups combined showed significantly lower xerostomia scores compared with SCC. This phenomenon is often found in acupuncture trials and may be resolved by the increase of the overall sample sizes or, at least, by the disproportionate increase of the size of the TA group to detect differences between TA and SA.
One of the significant and exciting findings in the study by Garcia et al3 is the differences between the US and Chinese study sites. Among US patients, only the SA group showed a significantly better xerostomia score compared with the SCC group, while no differences were observed between the TA and SCC groups. In contrast, among Chinese patients, TA significantly improved the xerostomia scores compared with SA and SCC, while the SCC and SA had very similar efficacy. In other words, the Chinese study population clearly showed a hypothesis-confirming result, while the US study population seemed to have been more susceptible to SA. This finding coincides with the opposite tendency of the expectation scores during the course of the treatment: in the Chinese patients, confidence in the sham treatment decreased, while US patients built more confidence in the sham treatment through time. In China, most patients are well aware that without the de qi sensation, acupuncture treatment does not work. Acupuncture service has a very low price and is widely available in most community health care centers and hospitals in China.4 Therefore, Chinese acupuncturists have to have proficient needle manipulation skills to quickly elicit strong and long-lasting de qi sensations; otherwise, patients may switch to other acupuncturists. This may also explain the larger effect size of TA in the study site in China.
Usually in acupuncture trials, SA consists of using real acupuncture needles and inserting them superficially at non–acupuncture points (minimal acupuncture). In this study, SA consisted of a mixture of real and nonpenetrating placebo needles and a mixture of real and sham points. In addition, in the informed consent process, patients were told that 2 different acupuncture approaches would be used but that 1 approach might not target dry mouth symptoms. Although this aspect of the informed consent process was intended to maximize confidence in both acupuncture approaches, apparently in the Chinese setting characterized by a long cultural background of traditional Chinese medicine (TCM), SA was experienced differently compared with TA. In this setting, Chinese clinicians are deeply familiar with TCM and acupuncture. Therefore, they may have felt more irritated using the SA procedure, a suggestion that they may have carried over to their patients. In contrast in Western societies, TCM and acupuncture are much less deeply rooted, which likely resulted in more uncertainties on specific acupuncture treatments. Given the nature of SA, it might be a reasonable way to use the same acupoints as in TA but manipulate needles in a countertreatment manner. For example, if the treatment protocol requires “tonifying energy” in an acupoint, the SA could “sedate energy” at the same acupoint. However, this is unethical for acupuncturists, as they believe that such treatment would worsen the condition being treated.
Findings in the study by Garcia et al3 support the idea that acupuncture exerts its effects not only or not mainly by needle site activity and specific neurophysiological mechanisms but also by expectations, conditioning, and suggestibility of clinicians and patients.5 The effects of these unspecific factors may be quite large. Together with many other 3-arm acupuncture trials in Western countries, results of the study by Garcia et al3 has disclosed what is referred to in the literature as the efficacy paradox,6 that is, even though TA and SA were similarly effective, the size of overall effect of any acupuncture was superior to standard therapy.
In a previous randomized, single-blind, placebo-controlled, multifactorial, mixed-methods clinical trial on chronic pain, the personality of individual practitioners (not the empathic behavior) and patient’s beliefs about treatment veracity independently had significant effects on outcomes.7 However, patients and acupuncturists are embedded in a larger cultural context in which acupuncture appears to support the therapeutic ritual of the patient in a unique way and plays a crucial role in the therapeutic outcome of the patient. In support of this, recent research has shown that these complex, ritual-induced biochemical and cellular changes in a patient’s brain are very similar to those induced by drugs.8
With these ideas in clinical acupuncture trials in mind, the cultural background should increasingly move to the center of attention. What was predicted in a small interview among patients with back pain came true: “In China, outcomes of active acupuncture will be still better than the outcomes of sham acupuncture.”9
Published: December 6, 2019. doi:10.1001/jamanetworkopen.2019.16929
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Karst M et al. JAMA Network Open.
Corresponding Author: Matthias Karst, MD, PhD, Department of Anesthesiology, Pain Clinic, Hannover Medical School, Carl-Neuberg-Str 1, 30625 Hannover, Germany (email@example.com).
Conflict of Interest Disclosures: None reported.
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Karst M, Li C. Acupuncture—A Question of Culture. JAMA Netw Open. 2019;2(12):e1916929. doi:10.1001/jamanetworkopen.2019.16929
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