The Placebo Question
People are often very curious about how acupuncture works. This is especially true if it’s their first appointment and they’re feeling some change about their health complaint after the first few needles are in. Explanations for what’s going on can be quite complicated. Acupuncture is looking at the body through an entirely different lens relative to conventional medicine and providing an understandable explanation requires a lot of tangential digression. The first conclusion many people jump to is: this must be placebo.
Honestly, it’s a fair initial thought. After all, acupuncture needles are solid, we aren’t introducing any substances into the body nor are we taking anything out. In a culture where medicine usually involves adding something to or removing something from the body, it can be very difficult to wrap one’s mind around affecting the system without doing either one of those things.
There are lots of claims that acupuncture is placebo. Usually these claims are made by people who’ve never studied, practiced, or even tried acupuncture. These claims are also typically made after looking at a handful of very old studies with poor methodology while disregarding new research and the entire body of evidence we’ve accumulated. Let’s examine the placebo effect and then see how it is applied to acupuncture.
For starters, every therapeutic intervention, whether alternative or conventional, has as part of its effect some aspect of placebo. It turns out that when a patient believes they’re being treated for a condition, there is usually some improvement in that condition, regardless of whether the treatment is “real”.
With a few exceptions, pharmaceutical trials use placebo control. They do this because they know placebo is potentially part of every treatment and they want to separate the effect of placebo from the effect of the drug being studied. The question isn’t, “Is this treatment placebo?” The question is, “How much better than placebo is this treatment?”
There are a couple of underlying assumptions here:
The placebo effect is embedded in treatment
The placebo effect is stable. In other words: if we figure out statistically how much of the treatment effect is due to placebo, that amount isn’t going to change substantially over time.
Are these assumptions true?
Well, not exactly. As the placebo question relates to acupuncture, it doesn’t look like placebo treatment is doing the same thing as actual treatment. This information comes from an fMRI pain study using “sham” acupuncture and real acupuncture. Both methods relieved pain but did so via different mechanisms [16, 21]. Sham acupuncture stimulated the release of endogenous opiate peptides (the body’s own pain relieving system) and had a very short duration of effect . Real acupuncture increased the number of opiate receptors in the brain, exerting a much longer lasting effect . Since the two treatments did different things, we are led to question whether or not placebo control is a valid way to examine acupuncture in the first place .
The stability of the placebo effect is also in question. In some studies, it seems the placebo effect, as a percentage of total drug effect, has increased over time . We also have conflicting studies as to what we should expect in terms of placebo as a percentage of the total treatment effect [14, 20].
Where are we if neither assumption is true? In a very complicated situation. Placebo control may not be what we think it is, work like we think it does, or be the proper way to study complex interventions like acupuncture or surgery.
Even from the physician perspective, placebo controlled trials aren’t all that useful. Doctors don’t make clinical decisions between treatment and placebo. They do make clinical decision between treatment A, treatment B and no treatment. From a safety perspective, placebo controlled trials have some value. It’s useful to understand the side-effect and adverse-event rate of a real drug relative to an inert substance. However, when choosing a treatment, physicians often need to know not only the side-effect/adverse-event profile, but how the treatment they’re considering stacks up against other options.
Why does acupuncture, in some studies, not show an effect beyond placebo? To answer this, we need to step back a little bit and first think about acupuncture on its own terms.
There are many different systems of acupuncture some of which utilize or emphasize different aspects of Chinese medical theory. For the most part, the classics of Chinese medicine talk about acupuncture from the perspective of the channels, yin-yang theory and wuxing theory. I’m not going to delve into yin-yang or wuxing here, but we do need to discuss the channels.
The channels represent spaces in the body. Generally, they can be thought of as the fascial planes between muscle groups . The Chinese had a name for this system: JingLuo (經絡) or channels and collaterals. Jing Mai (經脈) is the term for the 12 primary channels and Luo Mai (絡脈) is the name for the collateral network which connects the channels. These are not, strictly speaking, separate structures; there are a variety of complicated inter-relationships which are modelled in different ways – also a discussion for another time.
And here we hit a tangential digression. In order to understand what I’m about to say, it’s helpful to understand a little about the Chinese language, particularly the written language.
In English, written words are composed of letters. Each letter represents a sound, the sounds together create a word and that word stands for some idea; a person, place, thing, action, etc.
Written Chinese doesn’t work this way. The Chinese cut out the middle-man and each symbol directly represents an idea. In this way, the symbols are more akin to pictograms or hieroglyphs relative to a purely phonetic alphabet like most western languages.
Which brings us back to Jing Mai (經脈). What is that character showing us? Let’s just focus on the “jing” part (經). This character is composed of two parts and the first part of the character is derived from the symbol used to represent “silk” (絲) so there is a sense of warp and woof or weaving to this character . The first part of luo (絡) has the same derivation . In fact, the literal translation of luo is net or small net. The meaning, then, is more like a net or a weave, similar to fabric, as opposed to distinct lines with minimal interconnection.
If we think about a piece of woven fabric, there are no points which can be affected in insolation. If I pull on one part of the fabric, the entire piece responds – some areas more strongly than others. If we transpose this analogy to the human system it means that there is no place on the body a needle won’t exert some effect. There are some places on the body where a needle might exert a larger effect than others.
If we set aside all the studies and simply consider acupuncture on its own terms and in light of this linguistic information, what might we conjecture? Our hypothesis might look something like this: understanding that JingLuo represents an interconnected network, when applying true acupuncture, sham acupuncture and no treatment, we expect true acupuncture and sham acupuncture to both show a treatment effect. We expect true acupuncture will outperform sham acupuncture and both true and sham should outperform no treatment.
When we set up a study like this, what do we find? Usually we find that both true acupuncture and sham acupuncture constitute treatment. Most of the time we also find true acupuncture outperforms sham acupuncture and both true and sham outperform no treatment. In simplified form: true acupuncture > sham acupuncture > no treatment.
If this is true, then why did the idea that acupuncture is no better than placebo become so prevalent? Early on, the idea seems to have been that acupuncture studies needed to conform to the so-called “gold standard” randomized controlled trial (RCT). RCT studies generally use placebo controls and early attempts at placebo often amounted to inserting needles in places not on recognized channels or in places not thought to have an effect on the condition being studied. Remember, JingLuo represents an interconnected network. Needles anywhere can stimulate the network producing a result, with some locations producing a greater effect than others.
These early studies of acupuncture also often did not take a three-arm approach. They used only “true” acupuncture and “sham” acupuncture. Since our basic conjecture from acupuncture’s standpoint is that “true” acupuncture and “sham” acupuncture are both going to have some treatment effect, it makes sense that there was little difference between them and, statistically, no difference – particularly in low powered studies (more on this in a moment).
Current studies in the RCT model often use non-penetrating “sham”. Still problematic as there are a variety of systems of acupuncture, some of which use non-penetrating needles or other devices which do not break the skin. These systems achieve clinical results and are widely practiced. In short, anything interacting with the interconnected network is going to exert some treatment effect, some places will provide stronger results than others, but it’s all treatment.
There is another issue which may play a role and it has to do with study power. The power of a study is related to the number of study participants. When the difference in effect between the two modalities being studied is small, you need a high powered study to find it. In other words, to find small differences between treatments you need a lot of people to participate in your study.
How many participants is enough? Studies appear to be mixed, but it seems like, for acupuncture, the number is somewhere around 100 [23, 24] if we’re randomizing in to two arms (placebo and real acupuncture). Not every study has this number of participants, which means, if it was a sham controlled study, researchers may not have been able to tell the difference between true acupuncture and sham.
Since it can take a lot of people to find the difference between true acupuncture and sham [23, 24]. And we’re starting to see evidence that sham acupuncture is doing something very different from true acupuncture , what should we do?
It is clear acupuncture needs to subject itself to studies. We’re asking people to spend money on treatment. Insurance often doesn’t cover acupuncture and, even when it does, that’s simply cost shifting – the money still has to come from somewhere. Patients need to have some level of confidence that acupuncture treatment is going to provide a beneficial effect.
In my opinion, the best approach would be two-fold:
If the study is to compare sham acupuncture to true acupuncture, it must be sufficiently powered. That means at least 100 participants randomized in to two arms – true acupuncture and sham acupuncture.
We should focus on pragmatic studies.
Pragmatic studies are becoming more popular in conventional circles. Unlike a controlled trial, pragmatic studies often don’t have a placebo arm. Instead, they compare different treatments for a given condition or they compare treatment to no treatment/wait list. This is much more useful because it gives us some idea how treatment options compare. Pragmatic studies also produce results that are much more in line with the way clinical decisions are made.
Have we done pragmatic trials of acupuncture? Yes, there have been several and I see new pragmatic studies popping up all the time. When we look at acupuncture compared to, say, pharmaceuticals what do we find? I’m glad you asked, the outcomes can be quite interesting:
Acupuncture matches the performance of calcium channel blockers in hypertension .
Acupuncture matches the effect of SSRI in mild depression .
Acupuncture outperforms IV morphine in acute pain .
Acupuncture outperforms drugs in IBS .
Acupuncture matches the effect of sleep-aids in insomnia .
Acupuncture matches the effect of common allergy drugs in the treatment of allergic rhinitis .
Acupuncture matches steroid inhaler in COPD .
Acupuncture outperforms drugs in chronic prostatitis .
Acupuncture increases drug effectiveness in trigeminal neuralgia .
Acupuncture outperformed donepezil in Alzheimer’s .
Acupuncture plus fertility treatment outperforms fertility treatment alone .
Acupuncture with herbs outperforms hormone treatment in irregular menstruation .
Acupuncture outperforms drugs in the treatment of Bell’s Palsy .
Acupuncture outperforms alprazolam in anxiety .
Acupuncture outperforms lactulose in post-stroke constipation .
Acupuncture enhances drug regimen in the treatment of arrhythmia .
As we can see, when tested pragmatically, acupuncture is usually at least as good as a drug, a lot of the time it outperforms drugs and sometimes makes conventional therapy more effective while mitigating drug side-effects. Back to the core placebo question for a moment: since most of these drugs are tested against placebo controls, if acupuncture matches the performance of the drug then acupuncture must have some effect beyond placebo.
There are a couple other things to mention, since we’re having this discussion. First, acupuncture doesn’t have near the risk of side-effect, adverse-event or addiction as drugs.
Second, acupuncture treatments are not necessarily ongoing. In chronic conditions, when using pharmaceutical management, a patient is typically on that prescription for life. Not necessarily so with acupuncture. Generally, there is an acupuncture loading dose period of 8-10 treatments followed by a maintenance period. When a patient hits maintenance, they may require fewer treatments over the course of time to sustain the acupuncture effect. Some studies show that after a loading dose, the acupuncture effect can persist for as long as 12 months with little fall off . In the long run, even if someone is paying cash for acupuncture, it can be much cheaper relative to pharmaceuticals.
Is acupuncture placebo? No, it’s not. Study methods are adapting as we learn more about acupuncture and how it works. Most of the recent studies are sufficiently powered or pragmatic and clearly show effect beyond placebo. We’re also starting to get good systematic reviews and meta-analysis which provide large patient populations and show acupuncture has an effect beyond placebo.
Unfortunately, this information percolates out to providers and the general public very slowly.
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