Tuesday, August 8, 2017

Strong Placebos


Where placebos are concerned, I’m something of a believer. In this post I examine the placebo effect itself; non-deceptive (aka “open label”) placebos; non-ingested placebos; machine-oriented placebos; nocebos; and what I’ll call the “hypothetical reverse-placebo” effect.

What I believe about placebos

I believe that a placebo—that is, a non-drug substance like a sugar pill being used in place of real medicine—can sometimes work if the person taking it has any faith whatsoever that it will. When I say “sometimes” I don’t mean “it’ll work some of the time,” but rather that certain maladies, or at least the perception of them, can be treated with hope alone (in the guise of medicine). There is evidence that this is the case, and I’ll get to that. But first, I have a few examples of my firsthand empirical success with placebos.

The first is Airborne, the so-called immune system supplement. I would never have tried this product on my own. My wife bought it once, and I humphed and hawed and studied the packaging with extreme skepticism. Well, it has Echinacea, I reasoned, which pregnant women aren’t supposed to take, and use of Echinacea for immune system support has at least some research behind it, such as this.  On that basis I tried out the Airborne, and found it fizzy and kind of yummy, and insofar as I didn’t get sick afterward, I decided maybe its benefit is real.

On that basis, my “evidence” wasn’t much better than that joke about the guy on the bus holding an imaginary box, from which he pinches an imaginary powder that he then flings around in the air, and then a fellow passenger says, “What are you doing?” and he says, “It’s to keep away lions!” To which the fellow passenger says, “There are no lions on this bus!” and the guy says, “See? It’s working!”

But there’s possibly more to this Airborne thing. Often I think I’m getting sick, and I figure it couldn’t hurt to take some Airborne. And on several occasions when I was sure I was getting sick, I took it and then rallied. But couldn’t I have been wrong about starting to get sick in the first place? Yeah, sure. But it’s such a relief to keep a virus at bay, I’m willing to ingest a fizzy drink that purports to help, just in case it somehow does. Meanwhile, I’ve sometimes had a virus last for days and days when I didn’t take Airborne, and other times my cold seemed to go away faster after I took it. I haven’t kept great notes or anything—this is all anecdotal—and yet I feel there’s a correlation, or at least there could be.

Sure, Airborne has a silly story (“Invented by a teacher!” as if teachers knew anything about pharmacology) and sure, the Airborne company was sued for false advertising … I don’t really care. If they called themselves medicine they’d be hucksters, but what they’re really purveying is hope.

(Does the house-brand of Airborne work? Too early to tell … my wife bought some recently and I’ve just getting into my one-subject clinical trials. In general I trust generic drugs so I’m optimistic. And really, if you have optimism about a placebo, what more do you need?)

Moving along, I have good results with the Camelbak Elixir tablets.  This product claims to be an electrolyte source, which automatically aroused my suspicion when I first heard of it. Energy drinks claim to be a source of electrolytes, but generally have only a tiny amount of sodium and even less potassium. A gallon of Gatorade has only 6% of your daily requirement of potassium. (You can get that much potassium from four ounces of orange juice.) The other common electrolytes—magnesium, chloride, calcium, phosphate, and bicarbonate—aren’t even listed on the label.

All that being said, a pal recommended the Camelbak tablets for recovery after bike rides, and I was just desperate enough to try them.  Desperate?  Yep.  I have this problem of totally sucking on the second day when I ride two days in a row. It’s particularly bad on the second stage of the Everest Challenge bike race—to the point that on one occasion I actually got dizzy and thought I made have to abandon. So finally, the last time I did this race, I gave the Camelbak tablets a try, and—Eureka!—finally had a good second stage.

You might be wondering how I could believe in this product, given what I said about its mere trace amount of electrolytes. In fact, the Camelbak Elixir has just 2.3% of the US recommended daily allowance for potassium and 3% for magnesium.  That said, it does have some manganese, which could be useful. Wikipedia says, “Manganese is an important element for human health, essential for development, metabolism, and the antioxidant system.” But I learned that after the fact. My belief in the product comes simply from its having seemed to work.  (Full disclosure—Camelbak used to sponsor my bike team, and gave us free product.)

Because I’m not convinced that Airborne and the Camelbak tablets are based on real science, I refer to both as “placebo.”  Like, I’ll ask my wife, “Hey, do we have any of those placebos?” and she’ll know I’m talking about Airborne. Or on my recent Tahoe cycling weekend I told my pals, “Hey, I brought a tube of those Camelback placebo tablets.” My pals happily partook, without challenging my “placebo” label.

Look, I’m not an idiot. (Or at least, my position on placebos doesn’t by itself prove that I’m an idiot.) I rightly hold that homeopathic medicine is a total crock, and I believe that declining to immunize one’s child is tantamount to reckless endangerment. (If a person wants to try out questionable quasi-medicine on himself, that’s one thing—but putting one’s child at risk based on wacky beliefs is totally different.)

I believe in real medicine. But I also acknowledge that some things work without anybody understanding exactly why. As mentioned here, a chemist won the Nobel Prize for figuring out how aspirin works, like 90 years after it was discovered, and scientists still don’t think they understand aspirin completely. So if there’s some reason—any reason—to believe that something could work, I’ll might try it, so long as it’s not standing in for a proven medicine that I ought to be using instead.  And I limit my placebo use to scenarios involving a subjective experience of suffering.

Non-deceptive placebos

Some time ago I stumbled across an article about how patients being given a placebo found it effective even when they were told that it was only a placebo. I’ve just corroborated this with a little research, turning up multiple articles, eight of which read all the way through.  In case you are curious, here are links to them:  1   2   3   4   5   6   7   8

That first link is to the original research, published in December of 2010, concerning irritable bowel syndrome. It’s a good start, though the study had had only 80 subjects. The researchers “tested whether open-label placebo (non-deceptive and non-concealed administration) is superior to a no-treatment control with matched patient-provider interactions” and found that 60% of patients receiving an open-label placebo reported relief from symptoms, vs. 35% who received nothing. That’s right, 6 out of 10 patients got good results from knowingly taking mere placebos.

That’s the good news about non-deceptive placebos. The bad news is that articles 2 thru 7 are all based on the same original study, so they don’t support it so much as reiterate it. Moreover, articles 4 thru 6 were published in 2016, and article 7 came out this year … which suggests no other studies on this subject have been done since the first one, almost seven years ago. I’d have more faith in this study if it had been replicated by somebody else. (This begs an interesting question: if I persist in believing in a study’s findings, even if they’ve not been substantiated, does that make the study itself an intellectual placebo?)

Article number 8, by the way, is a wacky “n=1” study (that’s right, just one subject) about a guy who takes placebo pills to alleviate writer’s block. As somebody who doesn’t have time for writer’s block, I’m going to lump that one in with homeopathic medicine.

Non-ingested placebos

Placebos aren’t limited to what you can swallow. This landmark study in The New England Journal of Medicine found that patients who underwent arthroscopic knee surgery fared no better than a placebo group, whose knees had incisions made but nothing else done to them (just instruments being handed around and saline “splashed to simulate the sounds of lavage”). This and other studies are described in this New York Times article, and the results were later replicated, as described here. The conclusions are twofold: 1) arthroscopic knee surgery isn’t very effective; 2) the very idea of knee surgery does provide some relief.

Fortunately, I can’t comment personally on the sham knee surgery thing; my closest experience with knee pain is the kind you can treat with ice. But I do have a ton of experience with a putatively pressure-point-based hiccups cure (click here for details) that might be more of a placebo thing. I’ve had excellent results with this cure for almost three decades, and I’m tempted to believe that it’s grounded in something physiological. 

But I’m not convinced, because the mere idea of this remedy is enough to cure my brother Geoff’s hiccups. We rented an apartment together in the late ‘80s, and worked together too, so I was always around when he got the hiccups, which was frequently. Knowing that this cure worked for him, I’d command him to stop hiccupping whenever he started up. The command alone was enough—he never even needed to apply the pressure to his finger! In fact, he eventually got kind of pissed off, because he wanted to have a sustained case of the hiccups from time to time, just to remember what it was like—but I’d never let him. Either this hiccups cure has a placebo component, or my authoritative command to stop was scary enough to cure his hiccups. (That was a joke, BTW.)

Machine-oriented placebos

Can a placebo work on a machine? Not exactly, but a human can enjoy a placebo effect from changes to a machine. I’m talking here about changes to our vehicles, primarily. This has come up a few times around bicycle wheels. Sure, if you put lighter wheels on a bike, it will take measurably less energy to accelerate it or propel the bike up a hill. That’s not a placebo. But not all technological changes have such a straightforward, undeniable benefit.  If we decide to believe a manufacturer’s claims, and then can “feel” the difference, but the improvement is really just hype, than we are enjoying a placebo effect, without having done anything to ourselves or ingested anything.

Case in point: my friend John bought some fancy new wheels for his racing bike recently, and explained their features and benefits thus:  
The bike shop owner described in detail the spoke lacing and why it had more “lateral stiffness blah blah when out of the saddle, but had more [unintelligible] when in the saddle.” I was all, “Really?  Cool….” The rear rim is “asymmetrical” in profile. Something about making it so spoke tensions are equal on drive side and non-drive side. Anyway, the result is new wheels on my bike, and… they feel great!  I kept trying to figure out what I was really feeling and what I was trying to convince myself of because I’d just spent a bunch of money.  I have to say they feel way smoother in multiple ways.  The most noticeable is that little bumps and cracks in the road are now less jarring, probably due mostly to the much wider rim.  I feel like they roll better too, but I could be making that up.
I myself am a believer in these wider rims, though I have to take it on faith that they really improve the ride. I went with these fat rims purely on the recommendation of ten or so bike pals who recommended them (details here.) Right away I could feel the difference … but was I perceiving anything real?  I told my dad, a former rocket scientist and engineer, about these fat rims and how the change they make to the tire profile makes the ride better (etc.), and my dad said (in a calm but authoritative voice, as if holding back exasperation), “I don’t see why they would.” More recently I put the question to a friend who’s a professor of mechanical engineering, and he also seemed puzzled at how a wider rim would improve the ride. I still do feel better on these wheels, but I don’t know enough to say where the design basis for this improvement lies along the spectrum between snake oil and aspirin.


In describing nocebos, Wikipedia is insistent on this point:  “We can never speak in terms of simulator-centered ‘nocebo effects,’ but only in terms of subject-centered ‘nocebo responses.’” Whatever, dudes. The point is, just as you can have a presumably unwarranted positive response to a non-drug, you can similarly unwarranted negative side effects from the same non-drug, or outsized side effects from a real drug. Prior to embarking upon this post, I’d never heard of this, but I guess it makes sense. This Times article nicely fleshes out the topic. For example, it describes how patients warned of erectile dysfunction as a side effect of a specific drug were three times as likely to suffer it.

In fact, I have firsthand experience of the nocebo effect—er, response—as well. The other night, I was suffering from some pretty bad hayfever, and I decided that my normal placebo—generic Zyrtec—wouldn’t be enough. (Even though Zyrtec has a bona fide active ingredient, it seems to make so little difference in my symptoms, I’ve decided it’s more of a placebo than anything. If this seems silly to you, consider this Times article about how hard the Claritin manufacturer had to work to get FDA approval, because the FDA medical officer declared it was “not very different than placebo clinically.”) Wanting real relief, I brought out the big guns: generic Benadryl. This drug has always worked wonders on my allergies, though its principal side effect—the near inability to wake up the next morning—is a beast.

Well, the drug did its job: my allergy symptoms were completely wiped out, though I had a really hard time getting up the next morning. My head was all muddy and I was stumbling around in the bathroom for quite a while trying to get my deodorant applied and my contact lenses put in. And then I spied something that kind of amazed me: the little pink generic Benadryl tablet, sitting there on our little bathroom shelf, uneaten.

I have no doubt this was the very tablet I thought I’d consumed, as it had been the last one in the package. So the antihistamine benefit, along with my Benadryl hangover, were both based on belief alone … a placebo paired with a nocebo.

Reverse-placebo effect?

This begs an interesting question: could the benefit of a drug be retroactively hampered by the suggestion that it was only a placebo? For example, if you suffered from appendicitis and had your appendix removed, and then were told later the surgery had been a sham … could your pain come back? In other words, is there any such thing as a reverse-placebo effect? Could you ruin the effect of a legitimate drug, or the results of an actual surgery, by telling the patient he hadn’t actually received it?

I don’t see any practical value in such a thing, but it would be an interesting thing to study.  Perhaps some silver-tongued professor or researcher is able to drum up some research funding. For what it’s worth, my recent experience with the generic Benadryl suggests that the placebo effect, along with the nocebo response, were unaffected by lifting the veil. I put the unconsumed tablet back in the package, shrugged, and continued to enjoy an allergy-free but decidedly hungover morning. But then, as I said, I’m a placebo believer.

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