Sometime Decemberish (when I was distracted with term papers to write and holidays on the horizon) it seemed like every journal and blog I followed was filled with nothing but stories on placebos. I think it had something to do with this:

Kaptchuk, T.J. et al., 2010. Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome I. Boutron, ed. PLoS ONE, 5(12), p.e15591.

Despite having sort of vaguely skimmed the stories, they managed to work their way into my “So, I read somewhere recently – something along the lines of…” conversational repertoire. The “I just remember the gist of it” was fine for holiday small-talk but is far less than satisfying for Tuesday-evening-everyone’s-in-the-kitchen, spent-all-day-in-lectures/labs, in-the-mood-for-something-gritty-to-debate-and-put-off-more-work. (I live with another Arch/Anth and two Philosophy/Physics students. The kitchen-debates are not only lively but often recourse to the blackboard – and generally demand references displayed on laptops being juggled between the stove and sink. Said debates are often carried on through the shower door/hallway interface and in the extended-tea-break intervals. And, far too frequently for my liking, devolve into the Normative vs Descriptive semantic argument…)

So – I made soup tonight while exploring the paranormal/supernatural (pre)cognitive intuition/insight as extension of reprocessing subconscious observations/data – and ended up at – the Placebo effect(s). And how they’re apparently not only more complex than we thought, but perhaps more than psychological.

(Not that I remember conversational segue, if there was any transition. I was, after all, making soup at the time. And not that the line(s) between psychological and psychosomatic and neuro-immuno-endocrinological aren’t worthy of another very long, and better referenced, discussion.)

What makes a placebo?

The short-version, straight from Wikipedia:

In medical research, placebos depend on the use of controlled and measured deception. Common placebos are inert tablets, sham surgery, and other procedures based on false information. In one common placebo procedure, a patient is given an inert pill, told that it may improve his/her condition, but not told that it is in fact inert. Such an intervention may cause the patient to believe the treatment will change his/her condition; and this belief may produce a subjective perception of a therapeutic effect, causing the patient to feel their condition has improved.

and… placebos are getting stronger?

(To be fair, that’s not the issue at all – it’s just how a frustrating number of journalists chose to phrase it.)

Wired’s “Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why.” typifies the headlines dealing with the the revelation that many antidepressants, upon re-testing, showed a decreased efficacy relative to placebos.

Why are inert pills suddenly overwhelming promising new drugs and established medicines alike? The reasons are only just beginning to be understood. A network of independent researchers is doggedly uncovering the inner workings—and potential therapeutic applications—of the placebo effect. At the same time, drugmakers are realizing they need to fully understand the mechanisms behind it so they can design trials that differentiate more clearly between the beneficial effects of their products and the body’s innate ability to heal itself. A special task force of the Foundation for the National Institutes of Health is seeking to stem the crisis by quietly undertaking one of the most ambitious data-sharing efforts in the history of the drug industry. After decades in the jungles of fringe science, the placebo effect has become the elephant in the boardroom.

(See Greg Laden’s What is the Placebo Effect, and it it getting stronger? for a better anthropological treatment of the issue.)

…or …could the results have just been irreplicable?

Jonah Lehrer for the New Yorker: The Truth Wears Off: Is there something wrong with the scientific method?

But now all sorts of well-established, multiply confirmed findings have started to look increasingly uncertain. It’s as if our facts were losing their truth: claims that have been enshrined in textbooks are suddenly unprovable. This phenomenon doesn’t yet have an official name, but it’s occurring across a wide range of fields, from psychology to ecology. In the field of medicine, the phenomenon seems extremely widespread, affecting not only antipsychotics but also therapies ranging from cardiac stents to Vitamin E and antidepressants: Davis has a forthcoming analysis demonstrating that the efficacy of antidepressants has gone down as much as threefold in recent decades.

For many scientists, the effect is especially troubling because of what it exposes about the scientific process. If replication is what separates the rigor of science from the squishiness of pseudoscience, where do we put all these rigorously validated findings that can no longer be proved? Which results should we believe? Francis Bacon, the early-modern philosopher and pioneer of the scientific method, once declared that experiments were essential, because they allowed us to “put nature to the question.” But it appears that nature often gives us different answers.

There’s a large number of known problems with placebo testing

Starting with just what we put in those sugar pills – from actual sugar to olive oil to who-knows-what that may have as-of-yet-unknown-properties, the unregulated pharmacopoeia it confuses the comparison of different studies – not to mention, depending on the ailment and possible complications from otherwise harmless compounds, enabling the ugly possibility of fraud and sabotage.

Then, there’s the somewhat oxymoronic issue of “active placebos” – while the presentation of the expected side-effects in patients receiving the placebo is common, the longer the study, the less so. It’s the “no pain, no gain” logic in which the lack of side-effects decrease the patient’s faith in the placebo (and tipping off the doctor) so, to keep the double-blindfolds perfectly in place, another drug with similar side-effects is used as the “placebo”.

And then, there’s The Curse of the Nocebo Effect – aka, voodoo.

Most of the problems, though, not onlycan be but must be explained by the fact that we can’t explain the ailments they are being used to treat. (Example: Depression. Even better example – given complication after recent complication with our clinical definitions much less understandings of the underlying mechanisms: Schizophrenia.)

Sure, the placebo’s a complicated catch-all – one that we’ve been comfortable generalizing. At least, when it comes to curing the patient – or alleviating his symptoms – we just explain it away as a self-fulfilling prophecy inspired by from the deep abiding faith that our Western pill-popping culture has in the hallowed medical profession (with care to stress the value of patient care – after all, attention and empathy are as good as chicken soup).

When it comes to testing pharmaceuticals and our deep and abiding faith in the scientific method – everyone’s become just a little more concerned….

Staring at the sun – or, does a placebo by any other name… do… exactly… what… again?

(I think I was a little ambitious with the pithy sayings and confused myself – or maybe proved my point. I’m going to hope for the latter.)

But it’s a pretty serious question – there’s enough issues with placebo testing – what about testing placebos?

One method – just increase the number of testing groups (one group receiving the medication knowingly, one group receiving the placebo unknowingly; plus, one group receiving the medication under the impression its the placebo; plus, one group receiving a different and counter-effective medication under the impression its the medication and another receiving this anti-medication under the impression its the placebo and another receiving the medication under the impression its the anti-medication; plus, each of the above groups with the physician under various impressions…. and so on… until we run out of flow charts to follow the levels of deception (and it resembles a Shakespearian comedy) and attempt to disprove the efficacy of all pharmaceuticals given without notification… and run up against the limit to the power “expectation” syndrome on the human physiology (one word: roofies).

And if we’re looking for something a bit less binary and more subtle – say, perhaps, the degree to which the nature of expectation and presentation can effect the results. Or, the role of medical-treatment-as-ritual…?

No deception needed!

A critical question is establishing how physicians and other providers can take optimal advantage of placebo effects consistent with their responsibility to foster patient trust and obtain informed consent. Directly harnessing placebo effects in a clinical setting has been problematic because of a widespread belief that beneficial responses to placebo treatment require concealment or deception.

[…..]

Patients randomized to the open-label placebo group were given a typical prescription medicine bottle of placebo pills with a label clearly marked ‘‘placebo pills’’ ‘‘take 2 pills twice daily.’’

And then they proved that people didn’t even need to believe they were on the placebo to react positively from it.

Which is absolutely amazing….

… but kind of raises more questions than it answers.

Does it work for any other pathology? Or is IBS special? The researchers chose IBS because, while the symptoms are treatable, “few therapies have been shown to be effective and safe in relieving the global symptoms of IBS”. (Translation – good chance that there’s a strong psychosomatic element involved. Particularly given that its a condition characterized by chronic pain and depression.) Plus (and even more importantly), previous research on IBS has shown “substantial and clinically significant” placebo results and that “patients can tolerate a high degree of ambiguity and uncertainty about placebo”.

Is the ritual of pill-popping primarily medical – or otherwise personal? Does the faith we have in taking pills stem from faith in medicine – or from faith in ourselves – or from memory – or from pattern and habit? Is it the nature of taking something designed and prescribed? Or is there more to very act of getting up, walking to the cupboard, taking out the bottle, opening it, getting a glass of water, and swallowing? Is the re-enacting of the memory of medicating in itself meliorative? To what degree does the water – the remembering to eat before or after – play a role? What about the self-satisfaction for just remembering to take the pill. (Or maybe I’m the only forgetful one who gets a rush from that – the fact that I care about myself enough to stick on course. Taking my vitamins in the morning makes follow up with all sorts of healthy non-college-student-like-activities…)

What about the excitement and optimism from being part of a “cutting edge medical experiment”?

A further possible limitation is that our results are not generalizable because our trial may have selectively attracted IBS patients who were attracted by an advertisement for “a novel mind-body” intervention. Obviously, we cannot rule out this possibility. However, selective attraction to the advertised treatment is a possibility in virtually all clinical trials.

Who did they test against? They didn’t test placebos so much as tested a supportive-structured-intervention vs a supportive-structured-intervention-with-pills. People who came in didn’t do as well as those who came in for inert pills.

Which is, not to be entirely negative here, is pretty interesting.

Just slightly minimized by how they primed the patients…. by telling them that placebos work. Basically, telling them that it was a form of medication. Which just proves that we have faith in medication.

I’d keep criticizing the study but I’m hardly the first to deconstruct it.

 

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