

The Placebo Phenomenon - paulsutter
http://harvardmagazine.com/2013/01/the-placebo-phenomenon

======
tokenadult
From the article: "Kaptchuk . . . doesn’t argue that you can simply 'think
yourself better.' 'Sham treatment won’t shrink tumors or cure viruses,' he
says."

That's an honest statement and an important point, because many publications
with Kaptchuk's name on them are overinterpreted to reach the conclusion that
there is a "real" placebo effect that can actually cure disease. In fact,
there is no strong evidence of that at all.

This issue has come up often enough on Hacker News that I have gathered some
links that are helpful for understanding what placebo effects are all about.
Some of these online links cite quite a few useful scholarly publications.

[http://www.sciencebasedmedicine.org/index.php/michael-
specte...](http://www.sciencebasedmedicine.org/index.php/michael-specter-on-
the-placebo-effect/)

"In other words, the best research we have strongly suggests that placebo
effects are illusions, not real physiological effects. The possible exception
to this are the subjective symptoms of pain and nausea, where the placebo
effects are highly variable and may be due to subjective reporting."

Numerous press releases on the Web point to publications co-authored by Ted
Kaptchuk, the main person profiled in the article kindly submitted here.
Although Kaptchuk has the academic title of an associate professor of
medicine, he has no medical training or credentials or clinical experience in
independently verified patient care.

[http://www.sciencebasedmedicine.org/index.php/dummy-
medicine...](http://www.sciencebasedmedicine.org/index.php/dummy-medicine-
dummy-doctors-and-a-dummy-degree-part-2-0-harvard-medical-school-and-the-
curious-case-of-ted-kaptchuk-omd/)

[http://www.sciencebasedmedicine.org/index.php/dummy-
medicine...](http://www.sciencebasedmedicine.org/index.php/dummy-medicine-
dummy-doctors-and-a-dummy-degree-part-2-2-harvard-medical-school-and-the-
curious-case-of-ted-kaptchuk-omd-cont-again/)

The article submitted here today, as befits an article from Harvard Magazine,
is pretty good about giving the point of view of researchers who disagree with
Kaptchuk, and is good about giving his updated opinion on issues he has
changed his mind about. The statements found in some earlier articles posted
to Hacker News, such as "Recent research demonstrates that placebo effects are
genuine psychobiological phenomenon [sic] attributable to the overall
therapeutic context, and that placebo effects can be robust in both laboratory
and clinical settings" are untrue.

[http://theness.com/neurologicablog/index.php/the-rise-and-
fa...](http://theness.com/neurologicablog/index.php/the-rise-and-fall-of-
placebo-medicine/)

"Despite the spin of the authors – these results put placebo medicine into
crystal clear perspective, and I think they are generalizable and consistent
with other placebo studies. For objective physiological outcomes, there is no
significant placebo effect. Placebos are no better than no treatment at all."

<http://www.ncbi.nlm.nih.gov/pubmed/20091554>

"We did not find that placebo interventions have important clinical effects in
general. However, in certain settings placebo interventions can influence
patient-reported outcomes, especially pain and nausea, though it is difficult
to distinguish patient-reported effects of placebo from biased reporting. The
effect on pain varied, even among trials with low risk of bias, from
negligible to clinically important. Variations in the effect of placebo were
partly explained by variations in how trials were conducted and how patients
were informed."

Fabrizio Benedetti, a co-author of one of the most cited papers who is also a
medical doctor, sums up his view this way: "I am a doctor, it is true, but I
am mainly a neurophysiologist, so I use the placebo response as a model to
understand how our brain works. I am not sure that in the future it will have
a clinical application."

[http://www.brainsciencepodcast.com/storage/transcripts/year-...](http://www.brainsciencepodcast.com/storage/transcripts/year-5/77-brainscience-
Benedetti.pdf)

To sum up, despite claims to the contrary that are often covered by the lay
press, the best-considered view among medical practitioners with clinical
experience is that the placebo response has no ethical clinical application.

See also:

[http://www.sciencebasedmedicine.org/index.php/does-
thinking-...](http://www.sciencebasedmedicine.org/index.php/does-thinking-
make-it-so-cam-placebo-fantasy-versus-scientific-reality/)

<http://www.skepdic.com/placebo.html>

[http://www.sciencebasedmedicine.org/index.php/revisiting-
dan...](http://www.sciencebasedmedicine.org/index.php/revisiting-daniel-
moerman-and-placebo-effects/)

And of course see LISP hacker and Google director of research Peter Norvig's
article "Warning Signs in Experimental Design and Interpretation" on how to
interpret scientific research.

<http://norvig.com/experiment-design.html>

~~~
smegel
Isn't focusing on the placebo effect ignoring the broader and more important
question of the impact of state of mind on the body's ability to fight disease
and heal itself? Once that question is well understood I imagine the
understanding of notions like the placebo effect will simply fall out.

~~~
AhtiK
A rather deep research and clinical practice on working with the mind to cure
the body has been conducted by John E Sarno.

The Mindbody Prescription [1] and The Divided Mind [2] are two of his books.

My interest in this started with the motivation to get some relief for the
RSI-like symptoms and it's been part of my recovery for a few weeks together
with the improved ergonomics.

[1] [http://www.amazon.com/The-Mindbody-Prescription-Healing-
Body...](http://www.amazon.com/The-Mindbody-Prescription-Healing-
Body/dp/0446675156/ref=pd_bxgy_b_text_y)

[2] [http://www.amazon.com/The-Divided-Mind-Epidemic-
Disorders/dp...](http://www.amazon.com/The-Divided-Mind-Epidemic-
Disorders/dp/0061174300/ref=sr_1_1?ie=UTF8&qid=1356217049&sr=8-1)

------
revelation
I get very uneasy reading articles that start to pitch "value of caring" and
someone who "didn't doubt the value of acupuncture" against "western medicine"
and "western doctors" who are portrayed as stubborn and close-minded.

~~~
thirdtruck
Agreed. "Western medicine" only exists as half of a false dichotomy.

If the doctors so labeled really were stubborn and close-minded, then we would
still perform blood-lettings and chew tree mark (instead of just the active
ingredient). Instead, these doctors are _more_ open to new information;
they're just willing to also incorporate the evidence _against_ efficacy so
often ignored by "alternative medicine" practitioners.

~~~
wisty
That's not 100% true. It's only really the case in patent protected medicines.

New drugs undergo testing, to get FDA approval. New surgical treatments don't.
New (and old) surgical treatments and old drugs aren't lucrative enough to
warrant real testing. Surgeons will claim it's for ethical reasons, or because
they just know better, or that they are artists who can't be constrained by
the laws of statistics, but it's simply a lack of regulations and / or
incentives.

~~~
thirdtruck
_That's not_ 100% _true._

Correct. That's why I expressed it as a relative position instead of making
any such absolute claims.

------
6ren
My theory: many disorders are stress-related. Receiving care - even if it's a
sham - relieves stress.

Going deeper: we human animals have limited physiological resources. Are they
channelled into healing or surviving? If you are in a dangerous environment,
then it's survival first, healing second. Therefore, a _sense_ of safety will
promote healing.

A placebo provides just that.

------
gruseom
If the placebo effect is superstition, as most comments in this thread seem to
imply, how come pharmaceutical companies are finding it increasingly hard to
beat?

[http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo...](http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo_effect?currentPage=all)

~~~
thirdtruck
Basically, the "effect" is the margin of error under which variations in self-
healing, self-reporting, and researcher bias obscure actual effect.

As we address more and more of the "big" pharmaceutical effects, that only
leaves the very minor ones or big ones that only apply to increasingly thinner
edge cases.

If the human body was software, one might say that the pharmaceutical
companies have debugged it to the point that they have little left to find
other than kilobyte-sized memory leaks. Beyond that, the vast majority of the
blue-screening issues remain PEBKAC errors.

------
petercooper
On a tangent, I think some of these massive open online courses going around
nowadays might act as a form of what Rory Sutherland terms "placebo
education". Education where you don't necessarily learn things but that gives
you the impression that you did, resulting in extra confidence leading to
extra success later on ;-)

~~~
stephengillie
If you continue this line of thinking, putting items on todo lists and
checking them off is a "placebo completion". Getting a fancy title instead of
a promotion or raise is a "placebo advancement".

~~~
petercooper
A placebromotion, if you will.

~~~
thirdtruck
Not to be confused with the hypophone, _bromotion_ , wherein the new title is
accompanied by a round of high-fives and concludes with a keg stand.

------
aufreak3
> Companies spend millions of dollars and often decades testing drugs; every
> drug must outperform placebos if it is to be marketed. “If we can identify
> people who have a low predisposition for placebo response, drug companies
> can preselect for them,” says Winkler. “This could seriously reduce the
> size, cost, and duration of clinical trials…bringing cheaper drugs to the
> market years earlier than before.”

Wat? Is that a typo? Shouldn't it be "preselect against them"? .. or better
still, include predisposition to placebo response as a variable?

~~~
haxplorer
I think what he means to convey there is that a person with a low
predisposition would be affected by the actual content in the drug than just
taking any pill.

Including predisposition to placebo as a variable would just increase the
number of experiments needed. Instead, if you could eliminate a variable from
the system by preselecting for people for whom the variable doesn't apply, it
would reduce the time to experiment

~~~
aufreak3
> Instead, if you could eliminate a variable from the system by preselecting
> for people for whom the variable doesn't apply, it would reduce the time to
> experiment

... _if_ the goal is to reduce the time to prove that your drugs work. That
goal is different from making drugs that work.

For an analogy - in order to prove that I'm smart, I must compete with those
others who're known to be smart, not with those who've (by some agreed on
measure) demonstrated a lack of the required aptitude.

Even _this_ article keeps emphasizing throughout that Kaptchuk is at Harvard,
he got praise from scholars, etc.

So the real proof of a drug's worthiness ought probably to be that it works
_over and above_ the placebo effect shown for those who respond very well to
placebos. That would provide more data to help evaluate the risk of a drug to
a patient, given placebo predisposition can indeed be measured. That would be
important particularly if the drug has significant unwanted side effects.

edit: And fwiw, preselecting for those who would respond well to placebos
would _also_ reduce the time to experiment .. but, I think, it would do so in
the right way.

------
confluence
The placebo/nocebo effect appears to be simply an example of the confirmation
bias, a couple of other psychological biases and various other known
statistical effects.

 _> False impressions of placebo effects can be produced in various ways.
Spontaneous improvement, fluctuation of symptoms, regression to the mean,
additional treatment, conditional switching of placebo treatment, scaling
bias, irrelevant response variables, answers of politeness, experimental
subordination, conditioned answers, neurotic or psychotic misjudgment,
psychosomatic phenomena, misquotation, etc. These factors are still prevalent
in modern placebo literature. The placebo topic seems to invite sloppy
methodological thinking. Therefore awareness of Beecher's mistakes and
misinterpretations is essential for an appropriate interpretation of current
placebo literature.

Beecher retrospectively attributed the improvements in the placebo groups to
effects of the placebo administration. However, on the basis of the published
data, in all of these trials the reported outcome in the placebo groups can be
fully, plausibly, and easily explained withoutpresuming any therapeutic
placebo effect. The published data of these trials make it quite obvious that
there were a variety of reasons for the reported results, such as spontaneous
improvements, additional treatments, methodological artifacts, etc. In some of
the original trial publications even the authors themselves had explicitly
written that there were no placebo effects._

Source: The powerful placebo effect: fact or fiction?, GS Kienle, H Kiene,
Journal of clinical epidemiology, 1997
([http://ukpmc.ac.uk/abstract/MED/9449934/reload=0;jsessionid=...](http://ukpmc.ac.uk/abstract/MED/9449934/reload=0;jsessionid=X21nexJpR1ki4fO6WJNg.0))

 _Placebo interventions were again not found to have important clinical
effects in general but may influence patient-reported outcomes in some
situations_

Source: <http://en.wikipedia.org/wiki/Placebo#Clinical_utility>

The effect, apparently, doesn't exist.

~~~
bambax
> _Placebo interventions were again not found to have important clinical
> effects in general but may influence patient-reported outcomes in some
> situations_

But doesn't this matter?

As it says in the article of course, feeling better when you're not actually
better can be dangerous for potentially lethal ailments; but in diseases that
don't kill you, feeling better means a lot.

------
seiji
Placebo in a nutshell: inject someone in pain with morphine. do it repeatedly
over time. once, without telling them, inject them with saline instead. their
brain will respond as if it was morphine and continue to block the pain.

The whole "people believing X so X happens" is a perverse co-opting of the
placebo title.

And, just for fun, if you give a patient naloxone (opiate blocker) before
giving them the saline, their brains won't interpret it as morphine. naloxone
blocks placebo response. in case you missed that, read it again: naloxone
blocks placebo response. (and once more: placebo means a very narrow thing. it
means your body responds as if it biologically received the medicine it had
been receiving -- it does _not_ mean any new age "think your way to better
health" mumbo jumbo).

~~~
psykotic
> inject someone in pain with morphine. do it repeatedly over time. once,
> without telling them, inject them with saline instead. their brain will
> respond as if it was morphine and continue to block the pain.

I must admit I have a very hard time believing this exact claim as written. Do
you have any sources?

~~~
iskander
Some related studies:

'Partial antagonism of placebo analgesia by naloxone'
(<http://www.ncbi.nlm.nih.gov/pubmed/6308540>) -- no actual morphine was ever
adminstered, only a regimen of saline injections, whose placebo effect is
apparently achieved by the release of endogenous opioids.

'A comprehensive review of the placebo
effect'([http://pharmacology.ucsd.edu/graduate/courseinfo/placebartic...](http://pharmacology.ucsd.edu/graduate/courseinfo/placebarticle.pdf)):
"placebos have actual biological effects on the brain and body and are more
than response biases."

~~~
jrogers65
In case you missed it, endocannabinoids (CB1 agonism, in particular) appear to
account for the other half of placebo analgesia:

<http://www.nature.com/nm/journal/v17/n10/full/nm.2435.html>

