
Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why (2009) - adammichaelc
http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo_effect?currentPage=all
======
giberson
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.

~~~
sp332
There's at least one study recently that shows this effect.
[http://www.guardian.co.uk/science/2010/dec/22/placebo-
effect...](http://www.guardian.co.uk/science/2010/dec/22/placebo-effect-
patients-sham-drug) Even if you tell the patients that it's a placebo, they
still get better.

~~~
pella
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...](http://blogs.plos.org/neurotribes/2010/12/22/meet-the-ethical-
placebo-a-story-that-heals/)

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." _

------
tokenadult
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-for-
pain/)

[http://www.sciencebasedmedicine.org/index.php/placebo-
effect...](http://www.sciencebasedmedicine.org/index.php/placebo-effects-
revisited/)

[http://www.sciencebasedmedicine.org/index.php/the-placebo-
ef...](http://www.sciencebasedmedicine.org/index.php/the-placebo-effect/)

[http://www.sciencebasedmedicine.org/index.php/placebo-
effect...](http://www.sciencebasedmedicine.org/index.php/placebo-effects-
without-deception-well-not-exactly/)

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'."

~~~
Alex3917
"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?

~~~
tokenadult
_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.

~~~
Alex3917
"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.

------
powertower
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.

~~~
0x12
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.

~~~
jambo
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.

------
pella
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...](http://www.theatlantic.com/life/archive/2011/09/the-dark-side-of-the-
placebo-effect-when-intense-belief-kills/245065/)

 _"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"_

------
6ren
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).

------
51Cards
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.

~~~
ceejayoz
> 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".

~~~
51Cards
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.

------
jurjenh
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...

------
yoblin
I found this to be a better article on the subject:

[http://www.newyorker.com/reporting/2010/12/13/101213fa_fact_...](http://www.newyorker.com/reporting/2010/12/13/101213fa_fact_lehrer?currentPage=1)

~~~
tokenadult
Response from a much better source:

[http://www.sciencebasedmedicine.org/index.php/the-decline-
ef...](http://www.sciencebasedmedicine.org/index.php/the-decline-effect-or-a-
exaggeration-of-the-messiness-of-science-and-science-based-medicine/)

------
joeybaker
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?

------
pella
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...](http://genes2brains2mind2me.com/2008/12/06/rs4570625-gg-makes-me-a-
believer/)

critics: _"Neuroskeptic savages the "placebo gene"_
[http://scienceblogs.com/geneticfuture/2008/12/neuroskeptic_s...](http://scienceblogs.com/geneticfuture/2008/12/neuroskeptic_savages_the_place.php)

################

23AndMe service data ( if you have ):
<https://www.23andme.com/you/explorer/snp/?snp_name=rs4570625>

------
Alex3917
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.)

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

~~~
Alex3917
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...](http://www.amazon.com/Health-Behavior-Change-Treatment-
Adherence/dp/0195380401/ref=sr_1_4?ie=UTF8&qid=1316476206&sr=8-4)

------
mchusma
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.

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

------
ericb
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?

~~~
fferen
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.

------
jisaacstone
"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 _cough_ homeopathy _/cough_

~~~
cwp
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.

~~~
daemin
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).

------
pella
Real vs Placebo Coffee

 _"Caffeine expectancies influence the subjective and behavioral effects of
caffeine."_ [http://neuroskeptic.blogspot.com/2009/11/real-vs-placebo-
cof...](http://neuroskeptic.blogspot.com/2009/11/real-vs-placebo-coffee.html)

------
adammichaelc
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.

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

------
spyder
I feel better even just reading about placebos.

------
marze
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.

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

~~~
keeptrying
Wow I got downvoted for this. Interesting.

------
michaelfeathers
Maybe the reason is: better advertising.

~~~
Anti-Ratfish
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 $

------
felipemnoa
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.

~~~
Anti-Ratfish
Re running old trials is mentioned in the article.

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

