Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why (2009) | Hacker News Reader

Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why (2009)

wired.com

141 pointsadammichaelc60 comments

The reason is placebos are receiving meta enhancement!

At first the placebo effect only had working for it the patients hope that they might be receiving the treatment pill and might get better. Alternatively, working against it was the concern they were getting the placebo and likelihood of getting worse. (Ie 1/2 odds at recovering)

But, as studies showed that even those receiving placebos were getting better patients came to realize that even if they were getting the placebo treatment they could still get better. So now, the placebo has working for it the patients hope of getting the treatment and getting better plus the hope that in the case they get the placebo they experience the placebo effect and get better anyways. Alternatively, placebo effect now only has working against it the "off chance" that if the patient gets the placebo he also does not experience the placebo effect. (Ie 2/3 odds at recovering)

Now, start with press releases like this and start stating that the placebo is so powerful, it always works--so much so we aren't going to bother giving the real drug to trial patients any more and just give them all sugar pills.. Then you'll get to watch placebo patients start consistently out performing trial drug patients at health recovery that eventually the above statement will be true.

And while I wrote this comment in good humor, I do think it's a valid argument that circular logic explains that the placebo effect is getting stronger because of the placebo effect (people believing in it). In fact, it may be the only valid and legitimate use case of circular logic.

There's at least one study recently that shows this effect. http://www.guardian.co.uk/science/2010/dec/22/placebo-effect... Even if you tell the patients that it's a placebo, they still get better.

Maybe it's an example of the Hawthorne Effect:

http://en.wikipedia.org/wiki/Hawthorne_effect

Unfortunately, there probably isn't an ethical way to subject people to medical testing without their knowledge.

other article by Steve Silberman ( December 22, 2010 )

"Meet the Ethical Placebo: A Story that Heals" http://blogs.plos.org/neurotribes/2010/12/22/meet-the-ethica...

about IBS placebo study: "Silberman: One interesting aspect of this study is that it suggests that are two layers of belief in the brain — one that knows there’s nothing in this pill, and another that knows that a placebo can be an effective treatment. It’s as if the brain can entertain two different notions of the effectiveness of a pill at once.

Kirsch: Yes, but they’re not contradictory notions. I believe in both. I know that this pill does not contain a physically active ingredient, and I also understand the conditioning process. I know that the placebo effect is real, so I understand that this inert pill might help trigger that healing response within me. We need to recognize and understand that patients are active agents in their treatment, not passive. The placebo effect does not come from the pill. It comes from the patient."

This is a very interesting observation.
I know a few registered nurses who had to study the placebo effect to earn their degree and I recall that placebos are only effective if the patient has a belief that the treatment would work (and then they are only about 30% effective).
following that logic it could be possible that placebo treatments become more effective as more of the population _believes_ that they are effective.
You just have to hope that no one pops the placebo-belief bubble for a particular treatment, or people might see that the emperor has no clothes ;)

Has it been at all shown that the placebo effect is at all correlated with any psychological frame or disposition whatsoever?

That doesn't explain why traditional medicines are stacking up shorter against placebos. If there was an increased belief amongst study participants that they would get better regardless of what they were given, the placebo effect would be just as strong for those who got the real medication. That is, if the medication is 50% effective and the placebo is 30% effective, then those who got the real medication would obtain some benefit both from the medication itself, as well as from the belief that they would gain some benefit from the placebo (which they don't know they didn't get).

The article isn't keeping up with the best research. (I'm glad that the submission title notes that the article was published in 2009.) In actual practice, placebos only look effective when the statistical tests in a study are poor, and most especially when the symptoms are self-reported by patients. Placebos are NOT effective in treating actual disease states or improving "hard endpoints" such as reduction of all-cause mortality or major morbidity from specific diseases with verifiable physiological signs. See
http://www.sciencebasedmedicine.org/index.php/placebo-effect...
http://www.sciencebasedmedicine.org/index.php/placebo-effect...
http://www.sciencebasedmedicine.org/index.php/the-placebo-ef...
http://www.sciencebasedmedicine.org/index.php/placebo-effect...
Placebo effects are strongest for patient self-reported subjective symptoms (classically, pain) and weakest for objective clinical signs measured by experienced observers.
Previous submission of same article as that opening this thread, 622 days ago:
http://news.ycombinator.com/item?id=1032149
An earlier comment there
http://news.ycombinator.com/item?id=1032710
had it just right: "As I've said before, this article is incredibly wrong and quite misleading. If you ever wanted evidence that most Americans do not understand how medicines are developed or what the Placebo Effect is, this article (and the responses here) serve as ample evidence. For a more rigorous refutation by a trained professional, please read:
http://www.sciencebasedmedicine.org/?p=1248
I'll pull the zinger quote from the article above for you:
>No, it’s not like that at all. Perhaps the studies are just that well done, or maybe the drugs being developed suck, or maybe companies are studying more candidate drugs and screening for efficacy. Just about any explanation that doesn’t involve aliens is better than 'placebo is getting stronger'."

Your point is very valid. The Wired article seems to suggest that placebos are genuinely effective. We shouldn't consider the medical researchers studying the placebo effect to be idiots however. Unfortunately, focusing only on hard clinical endpoints is not a luxury medical research has, and would involve excluding most psychiatric research, most palliative care research, quality of life analyses in cancer patients etc etc, in other words, lots of important stuff.
So if you still want to try and make people feel better, the placebo effect has to be dealt with.
I do agree with you though this being a poor article. Some additional points:
1. Placebos can have adverse effects. For example, it is quite common for patients to experience nausea and even vomiting when taking a dummy pill in a clinical trial. So they aren't universal panaceas.
2. Sometimes placebos can be the intervention arm, not the control arm:
http://www.thelancet.com/journals/lancet/article/PIIS0140-67...
This study compared simply administering air versus oxygen to patients with a terminal illness who were short of breath. Giving air was as effective as oxygen for relieving shortness of breath. This isn't the placebo effect getting stronger, this is just realising that doing less but doing something works perfectly well.

"Placebos are NOT effective in treating actual disease states or improving "hard endpoints" such as reduction of all-cause mortality"
Then how do you explain the metastudy that I linked to below in this thread that found that adherence to placebos reduced mortality as much as actual medications across a variety of diseases?

Then how do you explain the metastudy that I linked to below
I read the fine abstract of the article you kindly posted in your comment, where it says, "Moreover, the observed association between good adherence to placebo and mortality supports the existence of the 'healthy adherer' effect, whereby adherence to drug therapy may be a surrogate marker for overall healthy behaviour."
This finding (for which I would expect a lot more replication across independent data sets before relying on it too much for my own health) says that patients who make efforts to take care of themselves generally fare better than patients who are so careless that they don't even take physician-prescribed medicines according to the prescription schedule. If, once that difference in patient behavior is taken into account, some patients gain little additional benefit from a particular prescribed drug over the bare lifestyle difference benefit shown by patients taking only placebos, that suggests that the prescribed drugs can be improved (or that physician practice in choosing and dosing the prescribed drugs can be improved) but it doesn't suggest at all that placebos themselves are doing anything beneficial for patients.

"it doesn't suggest at all that placebos themselves are doing anything beneficial for patients."
Fair enough. But those patients who don't take their medicine as prescribed are ~25% of all U.S. patients. So in fact adherence studies are a much better measure of the efficacy of medicine than clinical trials, which means that just because a drug has been shown to have clinical efficacy doesn't mean that it actually at all effective in the real world.

>"....how medicines are developed "
"Mainstream medicine has tended to dismiss or ignore the placebo effect. Drug companies try to minimize it when conducting clinical trials." http://www.forbes.com/forbes/2010/0329/opinions-placebo-harv...
+
Biological, clinical, and ethical advances of placebo effects [ Lancet 2010; 375: 686–95 ] PDF : http://www.bioethics.nih.gov/departmentpubs/Miller%202010%20...
"For many years, placebos have been deffined by their inert content and their use as controls in clinical trials and treatments in clinical practice. Recent research shows that placebo effects are genuine psychobiological events attributable to the overall therapeutic context, and that these effects can be robust in both laboratory and clinical settings. There is also evidence that placebo effects can exist in clinical practice, even if no placebo is given. Further promotion and integration of laboratory and clinical research will allow advances in the ethical use of placebo mechanisms that are inherent in routine clinical care, and encourage the use of treatments that stimulate placebo effects." ..

I'd imagine placebos are getting more effective due to more people having purely headspace/mindset (or even imaginative) illnesses/causes due to stress factors.
The more it's in your head, the more likely you can cure it with another imaginative treatment... As long as you believe in it.
It's the only reasonable explanation.
Aside from that, the power of belief can also be a reasonably powerful treatment with a positive response on the body/mind.

Not sure why you got downvoted, it's not my cup of tea but it is as good an explanation as any other until the cause is known.

I downvoted the parent post because before the post was edited, the OP stated he didn't even read the article. If you come here to comment on an article, you should at least try to read it.

The poster edited their comment. It originally started something like "tl;dr no really I didn't read the article" and proceeded with the speculation (and hubris that it's the "only reasonable explanation") that remains at the time of this writing.
I downmodded the comment because it's the type of quick, non-substantial response that actually detracts from conversation among those who took the time to read the article and want a real discussion.

> I'd imagine placebos are getting more effective due to more people having purely headspace/mindset (or even imaginative) illnesses/causes due to stress factors
Here's a list of medical conditions studied by placebo treatements: http://en.wikipedia.org/wiki/Placebo#List_of_medical_conditi... Many of them had significant positive results for the placebo.
You could argue that many of those ailments could be due to mental/stress issues, and that it makes sense that calming the mind and believing in a treatment would work, but for some of them (Parkinson's, Herpes, food allergy), it's pretty amazing at how individuals are affected. Maybe we're under-crediting the brain's ability to control the body.

I'm reading Robert Sapolsky's Why Don't Zebras Get Ulcers right now (very interesting on subject of stress) and given what I've read, I would not be greatly shocked to learn that Parkinson's, herpes, or food allergies are affected by stress and the remediation of it.
It's impressive how integral stress hormones are to metabolism and disease. You wouldn't expect the psychogenic effects of a placebo to cure these diseases, but it makes sense that a placebo, or some factor tied to them that helps to lessen stress, could alleviate the intensity of outbreaks or symptoms.

I agree. WebMD has probably been a boom for drug companies as hypochondriacs (and wannabe hypochondriacs) research new ways for drug companies to take their money. I've met sane people who are positive they've got the latest bug or some rare disease.
The commercials you see on TV probably doesn't help too much either.

> wannabe hypochondriacs
so meta...

My biggest problem with WebMD and other sites like it is that they often give me the following kind of result using their diagnoser: "it's flu, allergies, or a rare and deadly cancer, see a doctor".

"Aside from that, the power of belief can also be a reasonably powerful treatment with a positive response on the body/mind."
No it can't. Your mind cannot heal anything. You can change your perception of symptoms but not heal. This is how placebo works. It only changes perception.
I strongly recommend listing to episode 5 of Mark Crislip's QuackCast podcast:
http://www.pusware.com/quackcast/quackcast5.mp3
It covers placebo very well including info about studies done on it.

if by "your mind cannot heal anything" means "everything dies eventually" then i agree wholeheartedly. but that's probably not what you meant. considering that many of a maladies today stem from chemical imbalances controlled by the brain, or by the second brain http://www.scientificamerican.com/article.cfm?id=gut-second-... your argument seems over the top. in fact, since it's hard to know what you know and impossible to know what you do not, how can any thinking being ever say anything cannot do anything. have you surveyed the depths of every human mind, animal mind, extraterrestrial mind to achieve such certainty? if so, what am i thinking right now (you should probably be able to guess because i'm lobbing it right down the middle).
the more one learns, the less one knows. of this, i am less certain every day.

Your mind cannot heal anything.
As some of the other posts have pointed out, the many real, observable actions of stress-response hormones complicate this statement considerably.

Nocebo effect:
"The Dark Side of the Placebo Effect: When Intense Belief Kills" ( SEP 14 2011, ) http://www.theatlantic.com/life/archive/2011/09/the-dark-sid...
"If you're still unsure that the nocebo effect could actually lead to premature death, Adler cites one stunning example of the effect from China. A team of researchers found that Chinese Americans die younger than expected "if they have a combination of disease and birth year which Chinese astrology and medicine considers ill-fated." That is to say, if they were born in a year that was astrologically linked to poor lung health, they would die an average of five years earlier from lung-related disease than someone born in some other year with the same disease. Similar effects were not found in the white populations around them. And how much sooner you died depended on the people's "strength of commitment to traditional Chinese culture."
Think about that for a minute. If you were born under a bad sign, you died five years younger from the same diseases as people born under good signs. But only if you believed in Chinese astrology"

Martin Seligman (of both "learned optimism" and "learned helplessness" fame) showed that rats' immune systems are influenced by their psychological state, specifically, the extent of control they had over unpleasant stimuli. This included tumour reduction.
In the light of this, the placebo effect does not seem so far-fetched.
My personal theory is that when an animal feels safe and secure in a non-threatening environment, the immune system is stimulated, because the immune system requires resources, and the body can spare these when it is safe. When volunteers are given placebos, in a controlled and professional setting, it is clearly a safe and stress-free environment. (This could be tested by putting the subjects in the same safe setting, but not giving them the placebo).

This is a wild speculation on my part but it just popped to mind. Perhaps the reason faux drugs are more and more useful is because we're using them to treat a rising number of faux illnesses. Maybe some of the cases where placebos are working more and more are illnesses we have dreamt up in a feel good society. Restless leg syndrome for example. I know because I get this from time to time but I don't think its an illness to be medicated... Usually I've just not been active enough or eaten too much dietary sugar before bed. We seem to be finding a condition to explain every little discomfort so perhaps, while some of the conditions may be real for some people, the more vague the symptoms become, the higher the odds someone in the study groups only thinks they have it, and the higher the placebo effect. Imaginary drugs for vague imaginary conditions. Anyhow, just a loose theory that just popped into my head completely unsubstantiated by any research. My legs are itchy, going for a walk.

> Restless leg syndrome for example. I know because I get this from time to time but I don't think its an illness to be medicated...
That's like saying because you have a mole that you know skin cancer is made up.
My wife has, at times, been up from 10pm to 6am, sobbing because she's exhausted yet can't sit still for longer than a few seconds. It's sure as hell not a "little discomfort". It's not "my legs are itchy", it's "I cannot stop moving my legs at all without experiencing extreme discomfort".

Agreed, which was why I included: "...while some of the conditions may be real for some people". I'm not disputing real conditions like your wife's, I'm saying some medical conditions these days have symptoms so loosely interpretable by the general public that anyone with achy legs may think they have it, and thus possibly try to medicate it. Perhaps this leads to a greater number of these people in study groups.... and perhaps that leads a measurable rise in placebo effectiveness. Anyhow, just an idle theory.

One thing that I didn't read in the article, and haven't heard about is whether the placebo effect continues on after the testing phase.
One thing that I could see affecting results is that people are selected for a trial, which may well influence their mindset ("OOh, I'm taking this incredible new drug in a special trial. It is soo much more effective than anything else on the market!") In other words, being part of the experimental group is more important than the placebo or actual drug being tested.
If these drugs are then available via normal channels, I imagine the placebo drug is not distributed, and the results may also not be monitored anymore.
Is there any indication whether this happens? In that packet of anti-depressants, half are placebo and there is no way to tell which is which? Could be cheaper to manufacture and unlikely to be detected. Not too sure of the legalities either...

I found this to be a better article on the subject:
http://www.newyorker.com/reporting/2010/12/13/101213fa_fact_...

Response from a much better source:
http://www.sciencebasedmedicine.org/index.php/the-decline-ef...

It raises the question: if humans are so prone to the placebo effect, how is your business affected? Or, is this a phenomenon that's regulated to medicine?

Placebo/Nocebo Genes ?
################
for example: http://www.snpedia.com/index.php/Rs4570625
- placebo side: "rs4570625(G;G) homozygosity was a significant predictor of clinical placebo response, being associated with greater improvement in anxiety symptoms." [PMID 19052197]
- Nocebo side: "rs4570625 may have a gender-dependent effect on susceptibility to Panic Disorder." [PMID 19132526]
################
"rs4570625 GG makes me a believer ?" http://genes2brains2mind2me.com/2008/12/06/rs4570625-gg-make...
critics: "Neuroskeptic savages the "placebo gene" http://scienceblogs.com/geneticfuture/2008/12/neuroskeptic_s...
################
23AndMe service data ( if you have ): https://www.23andme.com/you/explorer/snp/?snp_name=rs4570625

Apparently placebos are now as good as 'real' medications at preventing death across all diseases:
http://www.bmj.com/content/333/7557/15.full
(Or at least all diseases that have had adherence research studying the mortality risk with both drug and placebo therapy.)

"...adherence to drug therapy may be a surrogate marker for overall healthy behaviour."

Which suggests that non-drug interventions are generally better than drug interventions, at least when people actually do them. (Obviously people are much more likely to take a pill than to change their diet, which is part of what makes the research so interesting.)
Not surprisingly, many of the diseases with the lowest adherence are the ones where people would benefit the most. Type 2 diabetes is literally a disease of non-adherence, with 98% of patients not following their doctor's recommendations.
I've learned a ton from reading through the major adherence research findings over the last couple months, and I think there are a ton of ideas that can be applied to entrepreneurship and web startups especially. DiMatteo actually has a brand new book out on this so you don't even really need to read through all the original journal articles anymore to get the main ideas:
http://www.amazon.com/Health-Behavior-Change-Treatment-Adher...

This article reminds me of the Decline Effect, a BS way to describe experimental error. Experiments are prone to biases and problems than are worked out over time by a lot of good science.

Drug makers are just having trouble coming up with new drugs and making up asinine excuses. Placebos are still placebos.

If the mind is behind the placebo effect, can we cut out the middle man with a treatment of "deciding you are going to get better." If we remove the lie behind the placebo, and it still works--is this then a power we all possess, and have been accessing all along, but didn't understand or acknowledge?

Yes, this is what I was thinking. Could we teach people mental techniques to "delude" themselves into getting better? Kinda reminds me of doublethink from 1984.

"The fact that taking a faux drug can powerfully improve some people's health—the so-called placebo effect—has long been considered an embarrassment to the serious practice of pharmacology."
Not sure what is embarrassing, unless your treatments are effective only because of this coughhomeopathy/cough

Really? It's a multibillion dollar industry that can't outperform a sugar pill. That's pretty embarrassing.

Actually, I've come around to the idea that homeopathy is a brilliant piece of social engineering. The theory of homeopathy is simple, internally consistent and not obviously false, which makes it a good way to harness the placebo effect without lying to the patient. The whole idea that diluting medecine makes it more effective has a number of benefits as well:
Concentration/dilution is a simple, objective, physical property that can be measured for any medicine. It's much easier to think and talk about than wishy-washy concepts like "effectiveness in clinical trials."
Diluting medicines down to really low concentrations take sophisticated equipment, so it's legitimate to charge more for those medicines. By agreeing to pay more for less, patients can strengthen their belief and actually increase the effectiveness of the placebo.
The preoccupation with dilution also makes homeopathy safer. At the extreme, patients are being prescribed purified water. No side effects!
Dilution also mitigates any other harmful effects that the homeopathic industry might have on the world. A few leaves of St. John's Wart go a loooong way when they're diluted down to 1 part per million. Out-of-control homeopathy won't lead to, say, increased poaching of bears and tigers for their internal organs.
The whole thing is brilliant.

Internally consistent? How do they explain why drinking diluting sewage (say, bottled water) doesn't make me a greek god?

It only makes it safe to people that are not phyiscally sick (by physically I mean something that wouldn't be cured by using a placebo effect).

Real vs Placebo Coffee
"Caffeine expectancies influence the subjective and behavioral effects of caffeine." http://neuroskeptic.blogspot.com/2009/11/real-vs-placebo-cof...

An oldie but a goodie (it's been posted before). I think this phenomenon is so interesting I was hoping for a fresh discussion on what may cause this.

I'd bet visiting the sick is more effective than the placebo effect.

I feel better even just reading about placebos.

All of the medical industry propaganda airing on network TV (House, Grey's Anatomy, etc.) is really selling the idea that drugs work.
Shouldn't be surprising the placebo response is improving.

Does anyone know if any of these shows are funded by the pharama companies? Would be interesting to know?

Wow I got downvoted for this. Interesting.

"Drugs" in the general case do work. Empirically so.

Maybe the reason is: better advertising.

I could be mistaken, but I remember reading that USA and New Zealand are the only 2 countries that allow direct to the consumer advertising of prescription drugs. This causes all sorts of crappy pressures on prescribers and wastes ole try of $

They say placebos are getting more Effective. That seems a euphemism for "new drugs work just as good as placebos", which is to say, not at all.

Re running old trials is mentioned in the article.

And has medicine ever actually healed anyone but, rather, each person healing himself?

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