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Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why. (wired.com)
113 points by mcantelon 2140 days ago | 69 comments



My take away from this is that, in addition to checklists, one low-cost intervention to improve healthcare would be to have the doctor spend a few minutes chatting the patient up and expressing cheery optimism about their prognosis. If the doctor's time is too valuable, find some unemployed psych grad with good people skills and put him in a lab coat.

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Occam's razor suggests that Wired's explanation is complete bullshit. Let me give a far simpler explanation that would explain all the phenomena mentioned in the article:

We are seeing a rise in physical health problems due to increasing social isolation and other mental health risk factors.

As we replace the community barbeques with family grills we're losing more than a fun weekend activity, we're losing something that's evolved over hundreds of thousands of years to keep us mentally healthy. And more and more, scientists are learning that mental health is one of the greatest predictors (if not the greatest) of physical well being.

Why do you think ~50% of college students experience clinical depression? I'm sure that stress, poor diet, lack of sleep, and excessive alcohol consumption are all contributing factors, but at the end of the day these poor lifestyle "choices" aren't really choices at all; rather, they're triggered by specific design decisions made at the institutional and societal level.

Placebos aren't working better because people have more faith in medicine, they're working better because of the Hawthorne effect; people feel like they have someone who cares about them. That's why the effectiveness is radically different across populations, depending on the social environment, even though we're all exposed to the same media.

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To be blunt: citations needed.

The article not only talks about conditions that are clearly mental (depression) and ones that are arguably mentally related (IBS), but also ones that you'd have a hard time attributing to "lifestyle 'choices' that aren't really choices at all" (Parkinson's).

> Placebos aren't working better because people have more faith in medicine, they're working better because of the Hawthorne effect

The article talks about both effects and more (placebos working less well for conditions that are locally under-diagnosed, for example). The article presents a rich collection of causes for the rise of the placebo effect instead of a single cause. And I think Occam, who could appreciate the complexity of the brain and see that they've got data, would agree that it couldn't be as simple as you suggest.

(Also, across populations we don't all get exposed to the same media. Something tells me that there aren't constant erectile dysfunction commercials in Bangalore.)

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The book Emotional Intelligence references a bunch of scientific studies about both the effect of mental health on physical health, and also about the placebo effect. The opening of Gladwell's new book is also about the effect of mental health on physical health.

There have been many studies done that show clear health benefits to joining civic organizations or participating in church. As the opportunities for civic participation decline, participating in medical studies may increasingly make people feel like they are giving back to society, which causes a change in brain chemistry that ameliorates the underlying physical symptoms.

Clearly both of my (related) hypotheses need testing, but at least they are falsifiable, unlike some of the dubious theories posed by the original article.

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From your first post (and my real contention):

> Placebos aren't working better because people have more faith in medicine, they're working better because of the Hawthorne effect; people feel like they have someone who cares about them.

The problem isn't that placebos are working better, the problem is that they're working better relative to medications. If it was merely an issue of "someone who cares about [the patients]" then we'd expect that the actual drugs would benefit from the same effect too. As it stands, the problem is that placebos have been working better, while the same drugs have been basically steady. If Prozac couldn't beat placebos now, it tells us something, but doesn't tell us anything about how much better things were back in the old days when when we were participating more in civic organizations and church.

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If Prozac couldn't beat placebos now

If I understand recent findings correctly, it's not that Prozac can't beat placebos now; it never beat placebos and the studies showing this were simply suppressed. (I just posted about this: http://news.ycombinator.com/item?id=784271).

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>If it was merely an issue of "someone who cares about [the patients]" then we'd expect that the actual drugs would benefit from the same effect too.

Great point, this could completely sink my theory. Two arguments though:

1) If the placebo was less effective than the drug and they both gained the same amount of efficacy, then mathematically the placebo is now more effective relative to the medication.

2) It doesn't seem possible to really debunk my theory without taking a look at how patients are recruited for experimental drug studies, as I can imagine the standard procedure being such that my theory would still hold. but I don't know enough about this to say much offhand.

Anyway I'm not going for a Nobel prize in science, but if I were then this is still what I'd bet on.

edit: I wonder if watching funny movies has become more effective over time. This would be an interesting preliminary test.

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I'm curious what "dubious theories" you're referring to.

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Drug companies have always favored trials that show positive results. Maybe they've refined their ability to construct favorable trials to the point where they're exaggerating the placebo effect. Maybe there's an optimum level of distortion that maximizes the difference between a mildly effective drug and a placebo, and they've gone past that point.

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That's an interesting idea. And, noting particularly your last sentence, it is one that is testable. Now if only someone would test it ....

(On a completely unrelated note, isn't Google's logo today lovely? I mean the "Galileo's telescope" logo, shown on 25 Aug 2009.)

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You perceive that people are increasingly socially isolated, but this is not necessarily the case.

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But keep it super hush hush. If the populace grows uncertainty about whether it's getting the drug, the placebo effect may turn against the patient.

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Theory: there isn't anything really all that wrong with most people; it's all in their minds, so the placebo works.

Watch the evening news on a network and count the number of advertisements you see for prescription drugs. I did this a couple of weeks ago watching the CBS Evening news, a half-hour program, and about 65 percent of the commercials were for pills of some sort: migraine pills, anti-depression pills, pills for seniors, etc.

The prescription drug industry in the US has got a slimy underbelly; it goes out of its way to convince people that there's something "wrong" with them, and then falls all over itself attempting to pat itself on the back for "curing" them.

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"Theory: there isn't anything really all that wrong with most people; it's all in their minds, so the placebo works."

Nope. Placebos can really and truly cure things. And not just things that are in the mind.

For example the immune system is under brain control, and placebos can affect it. Allergies can be cured by placebo, ref: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=27...

Lots of things that you would not expect can be cured by placebo.

Read some drug trials (or those inserts in drug packages) and notice how in pretty much all cases the placebo group improved relative to the starting point.

As I said in a different comment in this thread: most people refuse to believe placebos can work, and say things like what you did "it's all in their head", "there was nothing actually wrong with them". But they really do work.

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Especially in the case of pain this makes total sense to me. Pain is just a signal that something is wrong with you. If you believe in some deep way that the problem has been fixed, then there's no reason for your body to keep making you feel pain.

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For example the immune system is under brain control, and placebos can affect it.

Then it would be the act of taking the placebo that cures, not the actual placebo itself. My theory was simply that by taking something with the expectation of a cure, many people can already be on their way to wellness because, as you mentioned, a lot of healing begins within the brain.

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Pharma advertising is something that always strikes me when I watch US TV feeds. Here in Canada, pharma advertising is very heavily regulated by the Federal government.

It can come in essentially two forms. One is the "for sale" form, in which case the ad is limited to the drug name, the amount, and the price - no description of what it's for, or any other information. The other is the "informational" form, in which case the ad can talk about a symptom, like "acid reflux is dangerous - here are some signs", but it can't mention the name of the drug or pharmaceutical company producing it, and it has to talk about alternative non-drug remedies.

The net result is that there are very few pharmaceutical ads on TV here, since they have so little value in what they're allowed to say.

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> Here in Canada, pharma advertising is very heavily regulated by the Federal government

"The United States is one of only two developed countries that allows direct-to-consumer advertising (DTCA) of prescription drugs. (The other country is New Zealand)."

http://www.sourcewatch.org/index.php?title=Direct-to-consume...

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I read this as only 2 countries in the world trust their citizens enough to make their own drug choices.

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Except it's regulations on PRESCRIPTION drugs, so it's still up to the doctors.

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I wish. Then it wouldn't mean spending ~$160 to visit the doctor and get a prescription if I wanted to try a different medication to treat the same problem.

I do not favor direct-to-consumer advertising of this kind; for one thing it might well create a reverse placebo effect where people believe there's something wrong with them because they're bombarded with lists of symptoms, for another you can't actually buy these medications yourself, as above; for a third, most people don't have the inclination (and maybe not the education either) to read all the small print.

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Here in Canada, pharma advertising is very heavily regulated by the Federal government.

While I think these regulations are very useful in general, they sometimes break horribly. I've found that sometimes the only way to get information about medicine I am currently taking is to click "I am a medical professional" on the manufacturer's website -- because drug companies have been told that web sites count as "advertising", and that they are consequently not allowed to put information online for public consumption.

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About the Canadian drug ads, I wonder—can a company buy two ad spots, one for the problem information (w/o drug) and one for the drug (w/o information), and then run them one after the other? Might help people make the connection; I've never been able to understand the drug-name-and-that's-it spots.

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I don't think there's an explicit prohibition against it, but I imagine Health Canada would probably lay the smack down pretty hard on both the network and the company for trying to skirt the rules - seeing as HC owns the game, it's probably not worth it for them to try.

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Ironically, there is an argument in the article that the Parmaceutical ads on TV enhance the placebo effect, and are therefore helping those people who see the ads and then take the drug more than those who don't see the Ad.

Better health through advertising.

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I'm rather amused by the women beaming with confidence as they proclaim "I'm on Alesse"... took me awhile to figure out it was birth control

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I'm always put off by folks (on television) telling me about their E.D. meds. I don't know why anyone would tell the whole world about that.

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> I'm always put off by folks (on television) telling me about their E.D. meds.

Are you talking about commercials or something else?

If commercials, how do you propose that folks who have those problems become aware that it's okay to get help? Or do you think that they should just give up on sex?

Remember - you asserted the reasonable proposition that it's reasonably normal to be embarrassed about such problems.

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I noticed this when I was in SF recently. In Australia we have next to no pill commercials (just the ocassional government awareness of a new vaccine or vitamin ads).

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Ghod knows that folks who have problems always talk to doctors about said problems....

> it goes out of its way to convince people that there's something "wrong" with them

I don't see that. I see "hey, if you can't make it through a round of golf without needing to urinate, you've got a problem and you should go to the doctor and get our drug".

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If your theory were correct, there should be a correlation between placebo effectiveness and exposure to the "perils" of modern western thinking.

There isn't.

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I have a theory as to why Placebos are getting _more_ effective; which is the real curiosity of this article.

Television. If as a child, you watch 10,000 hours of commercials telling you how effective drugs are. Is it any wonder that you are convinced enough that your body actually makes it true, even if you got the Obecal P instead of the real deal.

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http://www.slash7.com/articles/2009/8/25/oh-yeah-there-s-a-s...

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It's been shown that antidepressants are no better clinically than placebos. The drug companies simply suppressed the trials that didn't yield the results they wanted and cherry-picked the ones that did in order to get FDA approval. This all came out a couple of years ago when a long-running Freedom of Information Act suit forced them to release all the trials.

http://www.guardian.co.uk/society/2008/feb/26/mentalhealth.m...

Edit: I just remembered that I posted about this to HN back when the study came out: http://news.ycombinator.com/item?id=123575. A commenter pointed out that the study was limited to SSRIs, the most widely used antidepressants.

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I've always thought you could make a killing on the late night infomercial market, selling "Placebo" to people.

Think of all the research out there on the well-documented Placebo Effect. Now you can benefit from this safe, effective, miracle cure. Order now and we'll throw in a second bottle of Placebo free of charge!

Considering the things that stupid people fall for, this would seem guaranteed to work.

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They already do that, it's called a q-ray bracelet I think.

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The book predictably irrational discusses the placebo effect on surgery. http://www.predictablyirrational.com/pdfs/Placebo1.pdf Very interesting results.

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The unsung hero in all this is the analytics data they used to debunk widely held assumptions about the placebo effect in clinical trials. Nothing like cold, hard data to inflict some cognitive dissonance on some "experts".

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This is an incredibly interesting article - one of the more effective ways of healing the body is to engage the brain to heal it for you. Placebo Effects, in many cases, are as powerful as the effects of the drug. Previously, the Pharma industry took this as in indication their drug's weren't effective. The central thesis of this article isn't that the drugs are ineffective, it's that the Placebo effect is a real, and sometimes _very_ effective mechanism for healing people.

From the article:

"one way that placebo aids recovery is by hacking the mind's ability to predict the future. We are constantly parsing the reactions of those around us—such as the tone a doctor uses to deliver a diagnosis—to generate more-accurate estimations of our fate. One of the most powerful placebogenic triggers is watching someone else experience the benefits of an alleged drug. Researchers call these social aspects of medicine the therapeutic ritual."

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If placebo works by helping the brain decide that we should get better, causing it to release its own defensive chemicals then it stands to reason that other actions might also be able to induce the same response. The mechanisms involved pre-exist the entire concept of "drugs". Maybe the old-time "placebo" was going to the local healer who jumped up and down and proclaimed that you will get better.

Derren Brown's videos come to mind, especially his bit on the subway where he convincingly causes a man to become incapable of recalling where he is going, simply by commanding him to not remember.

If other people can cause such powerful changes in our brain function, then there should be ways to do it yourself.

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I wouldn't put it past Derren Brown to have represented that situation on the subway somewhat differently than it actually happened - he is an entertainer after all (his program about faith healing and religious beliefs was amusing). Your point about influence still stands of course.

I found 'Meaning, Medicine and the Placebo Effect' to be rather good: http://cambridge.org/catalogue/catalogue.asp?isbn=0521000874

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My question: why do the pharms think this is bad news for them?

The placebo effect requires belief that the placebo is fixing the problem. Studies are double-blind so that the patient does have that belief. Without the expectation of being cured, there is no improvement.

For the placebo effect to be a significant influence in general health, the public needs to be convinced that it is receiving a legitimate fix. The best way to show people it's a real cure? Give them a real cure, and tell them all about how it works. The need for chemical compounds that change some aspect of body chemistry will not decrease because of the placebo effect; instead, these compounds become the placebo. It's another, more effective layer of manipulation.

But despite my wording, I see no problem with it. It might technically be a giant fraud, if the power of healing lies with the buyer all along. But if it happened in finance, who would complain? "Company convinces clients they have more money; buying power mysteriously increases" doesn't sound all that fraudulent to me.

Essentially, it's business as usual for pharms. Develop compounds that may or may not work, tell everyone they work, sell them, produce actual results. What's all the fuss about?

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IMO it's quite a simple explanation. You only have to watch 5 minutes of US advertising (I'm from the UK and living in Canada) to think you should have something wrong with you. If you think you should have something wrong with you for long enough, you will, it's called hypochondria and there's long been the suggestion of prescribing placebos to them until they're capable of getting access to a psychologist or psychiatrist.

You get the problem that when pills cure everything and you're sick and not on a pill, you worry. This makes you feel worse, which makes you sicker. The sugar pill not only has a placebo effect, but it also stops you worrying so really its having two effects opposed to the usual one we've classically seen.

When stress is the leading form of disease in the western world, you're going to have to remove stressed people from the drug tests to get impartial results. It just happens to suck that most sick people are stressed out. I guess they'll have to give a placebo to the test and control group to relieve stress and then give a second to the control group pretending its actual medicine.

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The problem is the depression (clinical depression) is one of the most horrifyingly over-diagnosed diseases on the face of the planet.

EVERYONE gets depressed. If people didn't, we'd be living in Utopia. When you hand some person who is having a crappy day a pill and say something like "this is full of magic chemicals that are going to make you feel better", their outlook on life improves, and they aren't depressed anymore!

Clinical depression is different. Clinical depression is as much a real disease as anything else, and it cannot be treated with a placebo any more than a broken leg can. Real depression is not a psychological problem, it is a neurochemical one...

Clinical depression does not even always manifest itself as feeling sad or anxious. It can present itself as bad memory, poor focus, decreased creativity...These things, while psychologicacl problems, have neurological causes.

Yes, being sad does as well, but being sad is as easy to "cure" as being hungry.

This is why the placebo worked.

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That's what the drug companies want people to think. But it's not actually true.

Even the type of depression you are talking about responds to placebos. And it responds very well to therapy, but barely at all to drugs - except that the drugs work well as placebos.

It is a real condition - don't get me wrong, I'm not saying it isn't. It's just that the drugs don't do as much as people think they do.

Most people when they first hear about placebos flatly refuse to believe they work as well as they do. But they do.

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I'm sorry, but no. If you're depressed, a placebo may improve your outlook and this improved outlook may present itself as a decrease in symptoms which, like I said, manifest psycologically, but unless you've got something to increase the amount of seratonin in your brain (which is used as a neurotransmitter...this is why depression can present as poor short-term memory, and poor focus) then you're fixing a physical problem with a psychological solution.

If this makes somebody feel better, then fantastic for them! I'm sorry for being a bit combative about this...sever mania and depression is something that runs in my family, and debilitating depression and anxiety are something I've dealt with my entire life. Believe me, if there was a placebo-based solution to this, I would be the first person in line to get it...

I don't mean to take offense, I know you don't mean any, but saying what you're saying is a bit akin to telling a cancer patient that they need to just get over it.

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> Believe me, if there was a placebo-based solution to this, I would be the first person in line to get it...

If you are taking drugs for this, then you are in line already. Every one I have read about has studies showing it is only slightly more effective than placebos.

I really am not trying to say the problem is not real. I'm only saying that placebos are far more effective than you realize.

For example some quotes from wikipedia:

"Notably, however, a recent Cochrane review of the efficacy of the SSRIs concluded that they were only slightly more effective than placebo for the treatment of people with depression."

"A widely-reported meta-analysis combined 35 clinical trials submitted to the U.S. Food and Drug Administration (FDA) before licensing of four newer antidepressants (including the SSRIs paroxetine and fluoxetine, and two non-SSRI antidepressants nefazodone and venlafaxine). The authors found that although the antidepressants were statistically superior to placebo they did not exceed the NICE criteria for a 'clinically significant' effect. In particular they found that the effect size was very small for moderate depression but increased with severity reaching 'clinical significance' for very severe depression. The relationship between severity and efficacy was attributed to a reduction of the placebo effect in severely depressed patients, rather than an increase in the effect of the medication."

(Especially note the last sentence.)

Please don't understand this in reverse and assume people should/can do nothing. My point is placebos work, and people should make more use of them.

Another thing: just because something is all in your head does not mean it's not real. People often assume that "since a placebo fixed it, it was not real to begin with". NO! That's is NOT the case. The problem was REAL, and the placebo fixed it.

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I don't mean to take offense, I know you don't mean any, but saying what you're saying is a bit akin to telling a cancer patient that they need to just get over it.

I hear what you are saying, but I do not think he is being that harsh. The harshest part of his post is this:

And it responds very well to therapy, but barely at all to drugs.

It might be an overexageration, but the points he makes about the effectiveness of therapy and placebo are good ones. You of course are correct too; chemical imbalance is a valid factor to consider, and something that is correctable via drugs. I don't think you two are on opposite ends of a spectrum here. There is a wide range of possible solutions to depression. :-)

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You're missing the point. Placebos produce real physical effects, as real as those produced by non-placebos.

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Guys, let's not down vote someone below 1 who is trusting enough to share some personal detail for the benefit of discussion. I think it's the right thing to do, regardless of correctness or lack of correctness.

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You seem to believe placebos do not affect actual medical problems. It's interesting in this regard that in placebo trials vs a gastric acid reducer (to treat ulcers), 48% of those taking a placebo improved, while 76% of those taking the real drug improved. The interesting part is that it's now known that ulcers are not caused by gastric acid, but by bacteria, so even the "real" drug here worked via placebo effect, but it did work for most patients.

Edit: source: http://en.wikipedia.org/wiki/Placebo#Gastric_and_duodenal_ul...

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That's probably due to the "leaky placebo" effect: if the placebo does something to you (e.g., gives you a headache, or other side effect), it makes you think it is really working.

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bad memory, poor focus, decreased creativity...

Oh No! I'm depressed. Help!

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Fascinating article. But they didn't mention the obvious economic reason why placebo effects have been shunned or suppressed: placebos are free.

If the pharmaceutical industry gets clever about finding ways to make money off the placebo effect, as opposed to getting more devious about pushing drugs into people, that seems to me a good thing.

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Homeopathy anyone?

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They should just sell the placebo. No FDA issues, and if it does what tests show it does can you imagine the profit margin!

On a serious note, I'm enjoying keeping an eye on the US Health Care debate from afar (Australia, to be precise). Anybody think it will result in sustainable change for the better?

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Anybody think it will result in sustainable change for the better?

As someone who is keeping an eye from up-close, hahahahahaha! Sustainable change for the better. Good one. Let me sum up American politics for you: we have the best PR in the world. This means that with enough money, you can convince people that your brand will cure them even if you're selling sugar pills. That's why American pharmaceuticals spend more on marketing than R&D. It also means you can convince people to hate socialized medicine, even if they're recipients of medicare/medicaid.

Hence, in America, the only time something gets done is when a group with lots of money/power gets even more money/power out of it. The good news is that there are a lot of conflicting powerful interests. Car manufacturers and many banks, for example, have a lot to gain from a public option for healthcare - the former hopes to lower expenses for their retirees (huge expense for them). The latter hopes to stop mortgage foreclosures tied to medical expenses. The bad news is that often, the way to optimizing for powerful interests isn't very close to optimizing for the interests of the public at large.

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They do. It's called homeopathy or gingko balboa or any other number of items that can be found in natural foods stores and the like. It doesn't matter if they work or not, what matters is people think they work.

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Well they do work - that's the point.

True it's not because of what they are made off, but it doesn't matter. What matters is they work.

That's why so many people take them (they work), and why they always fail when tested against placebos - it's because they basically ARE placebos. And very effective ones too.

The typical response when hearing that is: get rid of them, they do nothing. But the correct response is use them, because placebos are very effective.

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Which will ultimately lead to a Homeopathic Accident & Emergency department:

http://www.youtube.com/watch?v=bgxzSUxxRzE

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As a matter of fact however, there is a commercially available placebo. It's for kids and is called Obecalp:

http://www.nytimes.com/2008/05/27/health/27plac.html

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Coca cola.

Coke was initially sold as a medication.

In the 80's, blind trials showed that people preferred the taste of Pepsi - but when they knew the brand, they preferred Coke. Coca cola executives were so worried by this that they launched "New Coke" which was more like Pepsi, and people preferred it in blind tests. But it failed utterly, and the original Coke itself continued to be popular, as it has been to this day.

See the "Rx for Success" side bar on page 2. The last two items are branding and clever names.

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Also, what tastes good in a single sip for a blind taste-test can be different from what tastes good when you drink a glass of it. I think Malcolm Gladwell talked about this in Blink.

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> They should just sell the placebo.

Behold... Placebocin!

http://groups.google.com/group/sci.chem/msg/d0e62fe17efdc0d0...

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It's probably directly related to the number of people regularly taking medication for other conditions. More people have more faith in magic pills to solve all their problems. We have become a heavily medicated society.

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Well, the US govt took the prohibitions off drug advertising in the mid-90s and now it's a >6 billion-a-year industry. Just the ads and promotions, that is.

All those ads say that pills work for all range of problems (even imaginary ones that the drug makers made up to sell more pills - such as pre-menstrual dysphoric disorder, to sell renamed Prozac and renew their patent).

Those ads weren't there before. The ads still aren't shown in Europe, where the real drugs are beating the placebo effect (the article mentions trials in France and Italy where diazepam wins; in the US, diazepam fails against the placebo).

Drug advertising is simply not legal in most parts of the EU.

They don't think that has something to do with it? Ads affect belief - maybe nobody says "Oh, well now I believe xyz will cure me," because they pretend to be immune to advertising, but if you're surrounding by messaging that pill = cure, you are going to eventually believe it as it is absorbed as cultural knowledge. Just like low-fat = healthy has become a "fact" that "everyone knows."

I was shocked that the article barely even made a nod to this, and didn't follow it to the its conclusion.

I think it's hilarious that the drug co's went along thinking that they won big with that repeal of consumer protection laws, and that their own exploitation of known human weakness is causing their drugs to be less effective than sugar pills.

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A person is responsible for their own mental condition. Period.

That is what this placebo situation demonstrates, more than anything. YOU are responsible for YOUR condition.

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I'll be sure to tell that to the homeless dude who digs through my garbage every night and has heated arguments with the fire hydrant..

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Tell him. If he doesn't /take/ responsibility, it doesn't change the fact that his life is his own and whatever he is experiencing, belongs to him alone.

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