So it’s 2020, a new year and the dawn of a new decade. Unfortunately, new year or new decade or not, we will be continuing to deal with the same old topics. Don’t get me wrong. I’m sure that there will be new issues to deal with, new pseudomedicine to analyze, new attempts to legitimize quackery as we proceed through the 20s, but there are some forms of pseudomedicine that just never die. Worse, one of these, acupuncture, is, if anything, gaining more acceptance, as its proponents promote it as a “nonpharmacologic treatment for pain” and thus a powerful tool to combat the opioid addiction epidemic, even to the point of fooling gullible legislators to have Medicare and Medicaid fund it while forcibly tapering chronic pain patients from opioids they had been taking for a long time with success. Promoting acupuncture and other pseudomedicine as “nonpharmacologic treatments for pain” has been an explicit policy of the National Center for Complementary and Integrative Medicine (NCCIH) for at least four years now.
So, with the end of the last decade and the dawn of the new, the publication of a large new synthesis of systematic reviews for acupuncture for chronic pain conditions by Carol Paley and Mark Johnson of the National Health Service and Leeds Beckett University, respectively, is a welcome addition to the medical literature. Even better, they break down their analysis by several common chronic pain conditions. Spoiler alert: Paley and Johnson find that the evidence for the efficacy of acupuncture for chronic pain is “conflicting and inconclusive, due in part to recurring methodological shortcomings of RCTs”. They can’t say it, but I will, yet again: Acupuncture is nothing more than a theatrical placebo, to quote David Colquhoun and our very own Steve Novella.
While I like what Paley and Johnson have done, I can’t help but point out that they do fall for some of the common tropes about acupuncture:
Acupuncture is an age-old technique which became part of modern medicine in the 1970s. In modern medicine, traditional forms of acupuncture, based on the ancient Chinese concept of qi and meridians, have been superseded by acupuncture based on a neurophysiological model [5,6]. The unique identity of acupuncture lies in the process of inserting needles (‘acu’) in the skin (‘puncture’), although a modern definition should include the need to do this at specific points in accordance with known physiological or anatomical rationale [7].
Of course, acupuncture was and still is based on the concept of qi in traditional Chinese medicine, the needles being stuck into specific sites on specific “meridians” (or channels for the mystical magical life energy known as qi) supposedly “redirecting” the flow of that energy, to healing effect. Doctors who believe in acupuncture have twisted themselves into knots trying to come up with seemingly plausible physiologic mechanisms by which acupuncture could “work,” ranging from the local release of adenosine, to local opioid release, to interactions with connective tissue, to even a whole new “organ.”
Acupuncture is also a treatment with considerable—shall we say?—reinvention throughout history, or even, as I would put it, retconning and, today, promotion by the Chinese government. Indeed, contrary to how it’s sold (and how Paley and Johnson describe it), acupuncture as practiced now is not even ancient, but rather a practice that reached its current form roughly 90 years ago. Before that, it was a brutal practice, more akin to “ancient Western” medicine involving bloodletting. (Indeed, if you want to read what acupuncture was like over 100 years ago, read Harriet Hall’s review of a book by a Scottish surgeon Dugald Christie, who was stationed in China from 1883 to 1913. The descriptions feature children with needles left plunged deep in their bodies for days, including one who died.) Around 90 years ago a Chinese pediatrician named Cheng Dan’an (承淡安, 1899-1957) proposed that needling therapy be resurrected because (he thought then) its actions could be explained through neurology, which is why he also proposed moving the needling points away from blood vessels. He also replaced the previously used coarse needles with the fine filiform needles in use today, in part because he wanted to do acupuncture on children and babies. It’s amazing how even scientists who are skeptical that acupuncture has any value don’t know its true history and how that history has been extensively retconned.
An overview of the systematic review
Let’s dig into the review. The authors note in the introduction that by 2013 it was “estimated that over 3,000 clinical trials had been published with over one hundred systematic reviews (SRs) (some with meta-analyses) attempting to synthesise available evidence.” So you’d think that, with that many publications and clinical trials of acupuncture, we’d have a good idea of whether it works or not and for what conditions. You would, of course, be wrong:
In the face of conflicting evidence and continually changing guidance, it is unsurprising that acupuncture practitioners are finding that an intervention that, anecdotally at least, is often well received by patients in the clinic and appears to have good results, is rejected by commissioners and policy makers and regarded in some quarters as a ‘theatrical placebo’ [8,14]. One reason for this uncertainty may be related to the clinical research methodologies used to determine clinical efficacy.
Well, yes, most acupuncture studies are crap, poorly designed and prone to bias, particularly studies carried out in China, which are never negative. However, one thing we do know: The larger the study, the more well-controlled the study, the more rigorous the design, the less of an effect is seen, to the point where in the largest, best controlled studies, “true” acupuncture is indistinguishable from sham acupuncture.
Still, it’s worthwhile to evaluate the existing evidence base:
The aim of this review is to synthesise evidence from previously published SRs of RCTs evaluating the clinical efficacy of acupuncture to alleviate chronic pain from any source. We have made judgements from a Western medical perspective. Our approach is to outline research findings through commentary rather than a comprehensive objective appraisal of SRs. We appreciate that the non-systematic approach is vulnerable to selection and evaluation biases and opinion-orientated arguments. Nevertheless, our approach enables consideration of issues surrounding the quality and adequacy of the evidence, including RCT design, and provides practitioners and policy makers with a comprehensive source of SRs published to date.
To approach this issue, the authors did a search of the standard electronic databases (MEDLINE, the Database of Abstracts of Reviews of Effects (DARE) and the Cochrane Library) using the terms “acupuncture,” “chronic pain,” “analgesia,” “pain management,” “systematic review,” and/or “meta-analysis,” restricting their results to English language reviews. The inclusion criteria were systematic reviews with or without meta-analyses of studies using manual acupuncture, electroacupuncture, dry needling, or auriculotherapy (ear acupuncture) for any chronic pain condition. Reviews were also included in which acupuncture was compared with sham or placebo acupuncture, no treatment, or another intervention (pharmacological or non-pharmacological). Cochrane and non-Cochrane reviews and overviews were included as well. Reviews were excluded if they didn’t evaluate acupuncture involving actual needling (i.e., acupressure and laser acupuncture were excluded), as were reviews examining acupuncture for acute but not chronic pain and variants of acupuncture like bee venom acupuncture.
Then:
One review author (CAP) extracted information from reviews including type of pain, number of RCTs, treatments, conclusion and quality of evidence stated by the authors of each included review taken as a direct quote from the Conclusion, Abstract or Discussion sections of their manuscript. In addition, we ascribed a judgement of efficacy of each review according to whether the sample size met criteria based on the work of Moore et al. [16,17] and adopted by the Pain, Palliative and Supportive Care group from Cochrane Collaboration in their risk of bias assessment. They suggest that trial arms with fewer than 200 participants in RCTs or fewer than 500 participants in meta-analyses are at a high risk of bias, which seriously undermines confidence in findings. Thus, reviews were categorized as meeting our criteria for adequacy if they contained a pooled analysis of 500 events or at least one RCT with >200 participants in each arm of the trial. We categorised efficacy as: Sufficient evidence and in favour of acupuncture (+), sufficient evidence in favour of control/placebo (−), sufficient evidence but conflicting/inconclusive (=) and insufficient evidence to make a judgement (?).
The authors found a total of 177 reviews of acupuncture for the relief of chronic pain published over the last 30 years (1989-2019), including two overviews of Cochrane reviews, ten overviews of non-Cochrane reviews, and 145 non-Cochrane systematic reviews. That’s a lot of reviews. Let’s look at the results.
Acupuncture for chronic pain irrespective of etiology
Analyzing the literature, the authors note:
We found 20 SRs of acupuncture for chronic pain irrespective of aetiology or pathophysiology. In 2014, SRs reported that evidence supported the efficacy of wrist-ankle acupuncture and auricular acupuncture for alleviating chronic pain [30,31]. Since then, SRs were generally inconclusive because of methodological shortcomings and small sample sizes in primary studies [32,33,34,35,36]. In 2018, Vickers et al. concluded that evidence supported the efficacy of acupuncture for various chronic pain conditions associated with musculoskeletal disorders, headache and osteoarthritis, with beneficial effects persisting at long-term follow-up (39 RCTs, [37]). The long-term effects of acupuncture were consistent with evidence from an earlier SR by MacPherson et al. [38].
Evidence from SRs suggests that there are insufficient high-quality RCTs to judge the efficacy of acupuncture for chronic pain associated with various medical conditions.
We’ve discussed the original Vickers meta-analysis for acupuncture for osteoarthritis. I haven’t been impressed by his followup studies, but maybe I should do a summary sometime. In any event, I would phrase the conclusion differently: Inconclusive literature plus no plausible physiologic mechanism for acupuncture to work equal an ineffective treatment whose effects are nonspecific placebo effects.
Acupuncture for headache
Regarding the use of acupuncture for headache (including migraine headaches), the authors conclude:
The earliest SR was published in 1999 and judged there to be too few RCTs of sufficient methodological quality to determine efficacy of acupuncture for recurrent headache (22 randomised or ‘quasi’ randomised trials, Melchart [54]) or tension-type and cervicogenic headache (8 RCTs [47]). A similar pattern of ‘promising’ but not definitive evidence continued through the next decade (27 RCTs [53]; 8 RCTs [46]), including a Cochrane review of 26 RCTs of acupuncture for idiopathic headache [52]. Nevertheless, some reviewers have claimed that there is evidence that acupuncture is superior to sham for chronic headache (31 RCTs, only 2 RCTs were of high quality and adequately powered, Sun [48]), and a recent Cochrane review providing evidence of superiority of acupuncture over placebo for the prevention of tension-type headache ([44] 12 RCTs, including two adequately powered RCTs) and episodic migraine ([49], 22 RCTs, including two adequately powered RCTs). A systematic review published in 2016 is consistent with the latter finding that acupuncture was superior to sham acupuncture for migraine (10 RCTs [50]).
Evidence from the SRs suggests that acupuncture prevents episodic or chronic tension-type headaches and episodic migraine, although long-term studies and studies comparing acupuncture with other treatment options are still required. The current NICE guidance (clinical guideline CG150) is that a course of up to 10 sessions of acupuncture over 5–8 weeks is recommended for tension-type headache and migraine [12].
Perusing these lists of systematic reviews, I am…underwhelmed. The Cochrane review, for instance, showed an effect of acupuncture versus sham that was small and of questionable clinical significance. The last reference (50) was from a Chinese study at very high risk of bias. Steve Novella has discussed how acupuncture advocates like to spin negative studies of acupuncture for migraine as positive, and I’m getting the feeling that the authors bought into the hype a bit too much.
Chronic low back and/or neck pain
Regarding acupuncture for back pain, the authors again note that there are insufficient high quality clinical trials:
Evidence suggests that there are insufficient high-quality RCTs to judge the efficacy of acupuncture for low back pain. In 2009, NICE published guidance for the management of non-specific low back pain that recommended a course of acupuncture as part of first line treatment [10]. This guidance produced much debate. Subsequently, NICE have updated guidance for the management of low back pain and sciatica in people over 16 (NG59) and currently recommend in Section 1.2.8 “Do not offer acupuncture for managing low back pain with or without sciatica”, even though the evidence had not significantly changed [9].
This tends to be the most common indication used to justify acupuncture, mainly because chronic low back pain is such a common complaint. Of course, as I can’t help but note that twirling toothpicks against the skin works just as well for back pain as “true” acupuncture.
Myofascial pain syndromes
The mantra stays the same, a vague possibility of improvement plus a comment that there is insufficient evidence:
In 2017, Espejo-Antúnez et al. published a SR that evaluated the clinical efficacy of dry needling to alleviate pain associated with myofascial trigger points (15 RCTs [106]) and found a possible short-term benefit following dry needling. In 2017, SRs have found tentative evidence that acupuncture alone or combined with other therapies improved outcomes associated with myofascial pain syndrome (10 RCTs [108]; 33 RCTs [107]), although substantial heterogeneity and a high risk of bias, including inadequate sample sizes in the primary RCTs, undermined confidence in the findings.
Evidence from SRs suggests that dry needling acupuncture might be effective in alleviating pain associated with myofascial trigger points, at least in the short-term, although there are insufficient high-quality RCTs to judge the efficacy with any degree of certainty. There is no guidance from NICE on the management of myofascial pain syndrome.
I note that reference 107 is another review from China at a very high risk of bias. Remember, the Chinese rarely, if ever, publish negative studies of acupuncture.
Cancer pain
This is getting repetitive, but repetition is worthwhile when it serves a purpose:
Evidence from the SRs suggests that there are insufficient high-quality RCTs to judge the efficacy of acupuncture for cancer-related pain and more high-quality, appropriately designed and adequately powered studies are needed. The most recent guidance from NICE (CSG4) recognises that patients who are receiving palliative care often seek complementary therapies, but it does not specifically recommend acupuncture. It recognises that “Many studies have a considerable number of methodological limitations, making it difficult to draw definitive conclusions” (Section 11.27) [199].
And, again, more than one of the systematic reviews are from China. Speaking of acupuncture for cancer pain, there is a recent systematic review in JAMA Oncology of acupuncture for cancer pain. Edzard Ernst let me know about it and thinks it’s so bad that it should be investigated for consideration of retraction. Why? It suffers from many of the problems we see in such systematic reviews of acupuncture. For example, roughly half the studies included were Chinese, including ones written in Chinese, and, as Edzard Ernst, Steve Novella, and I have repeatedly emphasized, virtually 100% of acupuncture studies that come out of China, particularly those published in Chinese, are positive. Also, as Prof. Ernst notes, one study is a doctoral thesis, which is usually not peer-reviewed, and the quality of the studies included is generally extremely poor, with one study entitled “Clinical observation on 30 cases of moderate and severe cancer pain of bone metastasis treated by auricular acupressure” appearing to be a case series rather than a randomized clinical trial. He also notes:
The authors state that they included only clinical trials that compared acupuncture and acupressure with a sham control, analgesic therapy, or usual care. However, this is evidently not true; many of the studies had the infamous A+B versus B design comparing acupuncture plus a conventional therapy against the conventional therapy. As we have discussed ad nauseam on this blog, such trials cannot produce a negative finding even if ‘A’ is a placebo.
“Methodological limitations,” indeed. I saw most, but not all, of the limitations that Prof. Ernst enumerated, probably because I didn’t delve as deeply into the list of publications as he did. In any event, this meta-analysis was even worse than I thought it was. Disappointingly, one of the authors of this systematic review and meta-analysis is Dr. Jun Mao, chief of the integrative medicine service at Memorial Sloan-Kettering Cancer Center. I have to wonder if that had anything to do with how such a shoddy paper was accepted for publication by such a high impact journal.
And all the rest
As I said before, this review got very repetitive to read very quickly; so I’ll summarize the conclusions for the remaining conditions, which include fibromyalgia, pelvic pain, inflammatory arthritis, neuropathic pain, and other pain conditions: Evidence from the systematic reviews suggests that there are insufficient high-quality RCTs to judge the efficacy of acupuncture for any of these conditions. Of course, I would spin it a bit differently. If there are hundreds of studies for an intervention for a variety of indications, and we still can’t conclude confidently that it’s effective for any of them, then it’s almost certainly ineffective and the “positive” studies are nothing more than random statistical noise that will produce a few seemingly “positive” studies by random chance alone, more if bias is present. Add to the mix the observation that there is no physiologically plausible mechanism for acupuncture to “work”, and the most reasonable conclusion is that acupuncture is nothing more than an elaborate theatrical placebo with no specific effects on pain.
In their discussion, the authors bring up three main challenges of acupuncture research: inadequate sample size, of appropriate controls, and of adequacy of dose. The first part, about using an adequate sample size, is a no-brainer, but, as the authors note, bigger trials cost more money to carry out, making them more difficult, particularly for an intervention like acupuncture. Low sample sizes are associated with overestimation of treatment effect size. These are all reasonable observations, but then the authors go off the deep end about how to deal with them:
Often, pain data used as the primary outcome within RCTs is a continuous variable, such as pain intensity measured on a visual analogue scale (VAS) and expressed as an average. Averages of pain intensity data from VAS can be misleading because averages may obscure good and poor responders to acupuncture [206,207]. There is a likelihood that scores of pain intensity produce U-shaped rather than bell-shaped distributions, with some participants experiencing large reductions in pain and others not. Thus, pain intensity data from acupuncture responders may be diluted by data from non-responders [208]. For this reason, the Pain and Palliative Support and Care group of the Cochrane collaboration recommends the use of primary outcome responder rates of participants reporting relief of 30% or greater (i.e., at least moderate pain relief) or 50% or greater (i.e., significant pain relief) expressed as frequency (dichotomous) data.
There are a lot of assumptions here, particularly the assumption that designing acupuncture studies this way would actually result in finding an effect that’s currently obscured.
The authors also discuss the role of proper sham acupuncture groups in clinical trials of acupuncture. They actually (surprisingly) do a pretty good job discussing why a sham acupuncture control is necessary and the argument that sham needling is not physiologically inert is not a reason not to use a sham control group in acupuncture trials. This discussion, however, included this rather curious passage:
Placebo controls are research tools that enable isolation of effects associated with the active ingredient(s) of the treatment. Thus, a comparison of effects during real needling versus sham needling, whereby needles touch but do not penetrate the skin, enable investigators to isolate the magnitude and incidence of effects associated with needles piercing the skin per se (i.e., the ‘acu’ and ‘puncture’). If puncturing the skin with needles produces equivalent benefits to touching without puncturing the skin, then it may be safer not to puncture the skin in clinical practice, providing that the sham needles do less harm. Interestingly, a system of evaluating the physiological effects of sham needling has been proposed to assist researchers [212].
If the needles don’t penetrate the skin, then it isn’t really acupuncture, is it? Similarly, if it doesn’t matter where you stick the needles, given that there is no reliably detectable difference in effect between sham and “real” acupuncture, then the entire edifice and rationale behind acupuncture, both from a traditional Chinese medicine standpoint (magical “life energy” qi) and the tortured “neurophysiological” basis of acupuncture made up by acupuncture apologists who want there to be a scientific basis to the practice, become meaningless.
Finally, the authors discuss “dose”, leading to my favorite quack gambit of all, an appeal to “individualization”, the idea that standardizing treatments for a randomized clinical trial guarantees that some patients are “underdosed” with acupuncture. Of course, the authors never seem to consider that some patients would be “overdosed” as well. In any event, they authors tout Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA), a set of standards for reporting the exact acupuncture interventions used in a clinical trial. I can only be reminded of what Harriet Hall likes to call “Tooth Fairy science“.
The authors conclude by arguing that a way to study acupuncture in a manner more likely to produce interpretable results is a different trial design:
It has been argued that enriched enrolment with randomised withdrawal (EERW) study designs are of value for treatments influencing symptoms but not necessarily the course of the underlying disease or pathology, as is the case for acupuncture in the management of chronic pain [224]. The potential for using such designs in the assessment of pharmacological agents has been recognised [225], although EERW designs are rarely used to assess non-pharmacological interventions. The EERW trials consist of (i) an observational ‘open-label’ phase with all participants receiving active treatment (acupuncture), during which treatment technique and dosage would be titrated and optimized, followed by (ii) a RCT phase, whereby participants who had potential for response were enrolled (i.e., an enriched sample) and randomised to receive either experimental (real needling) or control interventions (sham needling). Selection of participants for the enriched sample of the RCT is based on the findings from phase one and would exclude participants who did not wish to continue treatment or experienced non-manageable adverse events, although their data from phase one would be analysed. Trials with EERW designs increase sensitivity to detect treatment effects by enriching the sample of participants enrolling into the randomised controlled phase of the trial, thus reducing the need for large sample sizes [207].
So, basically, the authors propose to use the EERW design to enrich the subsequent randomized clinical trial with patients prone to experiencing more intense placebo effects than average. (Remember, acupuncture is just theatrical placebo; so “enriching” the study population for responders means enriching for those who experience more intense placebo effects.) Yeah, that’ll work: To pollute the literature with more “positive” acupuncture trials that really aren’t.
I might be a bit sarcastic about what the authors propose as a way forward to study acupuncture and also snark on them a bit because they did this review with an eye towards clinical trial designs more likely to find a significant treatment effect from acupuncture. However, don’t let that lead you to think that I don’t find this systematic review useful. For believers in acupuncture, the authors were surprisingly honest and blunt about how poor the evidence-base is for the practice. Acupuncture for chronic pain is, as it is for all conditions for which it’s currently used, theatrical placebo. This systematic review is more evidence supporting that conclusion.