Placebos Work In the Absence of Deception

[zoobyshoe]

A sugar pill's magic lies in deception—the patient must believe she's getting the real thing. Right?

Wrong, according to a groundbreaking study published in PLoS One. Researchers asked patients suffering from irritable bowel syndrome (a common, hard-to-treat disorder with mostly subjective symptoms) to take placebo pills twice a day. They told participants that the pills had no active ingredients, but—this is key—they also explained that placebos can improve IBS symptoms "through mind-body self-healing processes."

By the end of the three-week trial, 59 percent of pill takers (vs. 35 percent of controls) reported adequate relief. The placebo also doubled the degree of symptom reduction and improvement in quality of life.

http://www.psychologytoday.com/collections/201201/the-placebo-effect/wising-dummy-pills

The actual study:
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015591

Methods
Two-group, randomized, controlled three week trial (August 2009-April 2010) conducted at a single academic center, involving 80 primarily female (70%) patients, mean age 47±18 with IBS diagnosed by Rome III criteria and with a score ≥150 on the IBS Symptom Severity Scale (IBS-SSS). Patients were randomized to either open-label placebo pills presented as “placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes” or no-treatment controls with the same quality of interaction with providers. The primary outcome was IBS Global Improvement Scale (IBS-GIS). Secondary measures were IBS Symptom Severity Scale (IBS-SSS), IBS Adequate Relief (IBS-AR) and IBS Quality of Life (IBS-QoL).

Findings
Open-label placebo produced significantly higher mean (±SD) global improvement scores (IBS-GIS) at both 11-day midpoint (5.2±1.0 vs. 4.0±1.1, p<.001) and at 21-day endpoint (5.0±1.5 vs. 3.9±1.3, p = .002). Significant results were also observed at both time points for reduced symptom severity (IBS-SSS, p = .008 and p = .03) and adequate relief (IBS-AR, p = .02 and p = .03); and a trend favoring open-label placebo was observed for quality of life (IBS-QoL) at the 21-day endpoint (p = .08).

Conclusion
Placebos administered without deception may be an effective treatment for IBS. Further research is warranted in IBS, and perhaps other conditions, to elucidate whether physicians can benefit patients using placebos consistent with informed consent.

 

[Curious3141]

http://www.psychologytoday.com/collections/201201/the-placebo-effect/wising-dummy-pills

The actual study:
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015591

You know, I didn't want to get embroiled in your "nice" discussion on how you thought modern psychiatry is pseudoscience, and where you defended (the rest of) Medicine as not being pseudoscience. I'm not going to mention anything more about psych here so as not to derail the thread (I just mentioned it to highlight your interesting stance), but I will say this: as a medical doctor, I think the rest of Medicine also has a lot of baggage that might be called pseudoscience.

The placebo (and nocebo) effect is chief among them. It's ill-defined - is deception crucial to the definition of a proper placebo? Does this have to be "active" deception, i.e. do you have to tell the patient this is a wonder drug? Or can it be a "passive" deception, which is the form used in controlled clinical trials, where the patient is told they will not know whether they are getting active compound or placebo. I don't think anyone has previously considered this sort of "no deception" placebo, which is why this study is useful, but again, the fact that almost no one has thought about this very clearly till now is a bit depressing (though there was a BMJ letter in 1994 that mentioned Shapiro's definition of the placebo and distinguished briefly between "intentional" and "inadvertent" placebos). And of course, the mechanism of action is not well-elucidated at all, with lots of handwaving about neural pathways. The plethora of different postulated mechanisms that seem curiously unfalsifiable does not make for a proper scientific theory.

 

[Pebble1]

Interesting definition of no deception. No one fully understands the placebo effect, the precise role of regression to the mean versus psychological priming to respond etc. So telling the patients to expect benefit by a particular mechanism is a form of deception. What the study does support is that the mechanism is related to psychological priming rather than regression to the mean.
The difficult bit is excluding a negative impact of "no treatment" - however the quality of interaction is controlled - this remains by definition an unblinded observation with a soft end point. The second issue is the patients were recruited for a study of placebo' so this may have attracted a biased study population.

 

[zoobyshoe]

...I think the rest of Medicine also has a lot of baggage that might be called pseudoscience.

The placebo (and nocebo) effect is chief among them.

I take this to mean that, since the placebo effect is not completely understood, you find it pseudoscientific that every drug is tested against a placebo?

 

[Number Nine]

they also explained that placebos can improve IBS symptoms "through mind-body self-healing processes."

So they told participants that taking placebos would make them feel better, and then the participants felt better? That seems like pretty standard placebo effect to me.

 

[zoobyshoe]

Interesting definition of no deception. No one fully understands the placebo effect, the precise role of regression to the mean versus psychological priming to respond etc. So telling the patients to expect benefit by a particular mechanism is a form of deception. What the study does support is that the mechanism is related to psychological priming rather than regression to the mean.

Yes, the "without deception" is deceptive. I'd be interested in seeing the participants interviewed and having them explain in detail what “placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes” means to them, what they heard by it. The psychological priming of "that have been shown in clinical studies to produce significant improvement" is almost certainly what they all found salient, and they rationalized the rest away if they had any doubts about it.

The difficult bit is excluding a negative impact of "no treatment" - however the quality of interaction is controlled - this remains by definition an unblinded observation with a soft end point.

Not sure what this means.

The second issue is the patients were recruited for a study of placebo' so this may have attracted a biased study population.

IBS patients, in particular, had already been shown to be 'placebo friendly':

Previous research has demonstrated that placebo responses in IBS are substantial and clinically significant. [14], [15] Furthermore, data from our previous qualitative study of IBS patients being treated single-blind with placebos indicated that patients can tolerate a high degree of ambiguity and uncertainty about placebo treatment and still benefit. [16] In view of these considerations, we selected IBS as a suitable condition to test the widespread belief that placebo responses are neutralized by awareness or knowledge that the treatment is a placebo.

 

[Evo]

My doctor told me that IBS cannot actually be diagnosed. When the patient has bowel problems and all tests come back negative, then they use the "IBS" label, meaning no cause found.

IBS can be due to anxiety or diet, in which case, a placebo could work because it's not a disease.

How is IBS diagnosed?
IBS is generally diagnosed on the basis of a complete medical history that includes a careful description of symptoms and a physical examination.

No specific test for IBS exists, although diagnostic tests may be performed to rule out other problems. These tests may include stool sample testing, blood tests, and x rays. Typically, a doctor will perform a sigmoidoscopy or colonoscopy, which allows the doctor to look inside the colon by inserting a small, flexible tube with a camera on the end of it through the anus. The camera then transfers the images of the colon onto a large screen for the doctor to see better.

If test results are negative, the doctor may diagnose IBS based on symptoms

http://digestive.niddk.nih.gov/ddiseases/pubs/ibs/#diagnostic

 

[Curious3141]

I take this to mean that, since the placebo effect is not completely understood, you find it pseudoscientific that every drug is tested against a placebo?

Not at all. The placebo effect is well-documented (even it it's not well-defined in most statements). Studies are meaningless without controls, so one needs to include a control group of some sort. In a double-blinded placebo-controlled trial, the control is the placebo, and it should be indistinguishable from the active study compound by both subject and researcher, and exactly the same instructions should be given to the subject no matter what they're on (which is easy when it's double-blind). I'm not disputing any of this. If this were not done, most prospective studies would be invalid, too.

What I *am* saying is that, to date, the placebo effect has been observed without a serious, concerted effort to elucidate its mechanisms. What really causes it? Do the instructions matter? How about "suggestibility" of the subject (which in itself needs to be better defined)? And are all placebos equal? Would a bitter-tasting placebo be more or less effective than a neutral or sweet tasting one? How about colours and textures of pills?

The problem is that the placebo effect has been entirely empirically studied to date, and even that has left something to be desired. Lots of the observations are subjective, in that they are reported by the patient, without a measurable correlate (e.g. pain scores, although certain measures like blood-pressure and heart rate can be objectively measured). There has been very little laid by way of biochemical or physiological foundation. This is, I believe, similar to the issue you had with psychiatry - where lots of things are empirically studied (and subjectively "measured") but there's been no convincing biochemical foundation. Although, personally, I'd say there's far more evidence for neurotransmitter involvement in psychiatric illness than there is for any brain chemistry change in the placebo effect. That makes a lot of psychiatry less "pseudoscientific" than the "placebo effect" (which is simply accepted in mainstream Medicine).

 

[Curious3141]

My doctor told me that IBS cannot actually be diagnosed. When the patient has bowel problems and all tests come back negative, then they use the "IBS" label, meaning no cause found.

IBS can be due to anxiety or diet, in which case, a placebo could work because it's not a disease.



http://digestive.niddk.nih.gov/ddiseases/pubs/ibs/#diagnostic

Placebos have been documented to produce effect in diseases with well-defined organic causes as well. So it's not quite right to state that something has to not be a(n organic) disease for placebo to work.

 

[Pythagorean]

There was actually a neuroscience paper a couple of years ago claiming to have "found" the placebo effect (neuroanatomically speaking) I made a thread about it here.

Will dig it, or the paper up once I get to a real keyboard (if someone doesn't beat me to it).

 

[Pythagorean]

thread:

https://www.physicsforums.com/showthread.php?t=346339

peer-reviewed journal:

http://www.sciencemag.org/content/326/5951/404.abstract

 

[Evo]

Placebos have been documented to produce effect in diseases with well-defined organic causes as well. So it's not quite right to state that something has to not be a(n organic) disease for placebo to work.

I was specifically addressing the use of placebos with "IBS", yeah, looking at my post, I can see how it could be taken to mean that it can't aleviate syptoms where disease is present.

I agree that placebos can influence how a patient feels and self reports perceived improvements. I was thinking more of actually eliminating symptoms of IBS since it's not disease based, AFAIK.

 

[Curious3141]

I was thinking more of actually eliminating symptoms of IBS since it's not disease based, AFAIK.

Although physiological mechanisms (pertaining to the "enteric nervous system") have been proposed and largely accepted, e.g. see: http://www.ncbi.nlm.nih.gov/pubmed/15798484

 

[zoobyshoe]

What I *am* saying is that, to date, the placebo effect has been observed without a serious, concerted effort to elucidate its mechanisms. What really causes it? Do the instructions matter? How about "suggestibility" of the subject (which in itself needs to be better defined)? And are all placebos equal? Would a bitter-tasting placebo be more or less effective than a neutral or sweet tasting one? How about colours and textures of pills?

The problem is that the placebo effect has been entirely empirically studied to date, and even that has left something to be desired. Lots of the observations are subjective, in that they are reported by the patient, without a measurable correlate (e.g. pain scores, although certain measures like blood-pressure and heart rate can be objectively measured). There has been very little laid by way of biochemical or physiological foundation.

I found this article while I was googling placebos, which reports they're getting a lot more serious attention than they used to:
http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo_effect?currentPage=all

This is, I believe, similar to the issue you had with psychiatry - where lots of things are empirically studied (and subjectively "measured") but there's been no convincing biochemical foundation. Although, personally, I'd say there's far more evidence for neurotransmitter involvement in psychiatric illness than there is for any brain chemistry change in the placebo effect. That makes a lot of psychiatry less "pseudoscientific" than the "placebo effect" (which is simply accepted in mainstream Medicine).

I'm tempted, but don't want to derail my own thread.

 

[zoobyshoe]

I agree that placebos can influence how a patient feels and self reports perceived improvements. I was thinking more of actually eliminating symptoms of IBS since it's not disease based, AFAIK.

I read over the whole page you linked to. It does make it look very psycho-somatic, but I wouldn't be surprised if it turned out to be a hypothalamus problem. A quick google tells me people are looking into this:

http://www.ncbi.nlm.nih.gov/pubmed/16472586

 

[Curious3141]

I found this article while I was googling placebos, which reports they're getting a lot more serious attention than they used to:
http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo_effect?currentPage=all

That was an excellent article, thank you. I had no idea there was a major placebo-related conference in 2000.

I'm tempted, but don't want to derail my own thread.

LOL.

 

[zoobyshoe]

That was an excellent article, thank you. I had no idea there was a major placebo-related conference in 2000.

Yes and there's this "secret" research underway, as well:

Under the auspices of the FNIH1, Potter and his colleagues are acquiring decades of trial data—including blood and DNA samples—to determine which variables are responsible for the apparent rise in the placebo effect. Merck, Lilly, Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi-Aventis, Johnson & Johnson, and other major firms are funding the study, and the process of scrubbing volunteers' names and other personal information from the database is about to begin.

In typically secretive industry fashion, the existence of the project itself is being kept under wraps. FNIH staffers2 are willing to talk about it only anonymously, concerned about offending the companies paying for it.

For Potter, who used to ride along with his father on house calls in Indiana, the significance of the survey goes beyond Big Pharma's finally admitting it has a placebo problem. It also marks the twilight of an era when the drug industry was confident that its products were strong enough to cure illness by themselves.

And a few of your questions were answered:

RX FOR SUCCESS
What turns a dummy pill into a catalyst for relieving pain, anxiety, depression, sexual dysfunction, or the tremors of Parkinson's disease? The brain's own healing mechanisms, unleashed by the belief that a phony medication is the real thing. The most important ingredient in any placebo is the doctor's bedside manner, but according to research, the color of a tablet can boost the effectiveness even of genuine meds—or help convince a patient that a placebo is a potent remedy.—Steve Silberman

Yellow pills
make the most effective antidepressants, like little doses of pharmaceutical sunshine.

Red pills
can give you a more stimulating kick. Wake up, Neo.


The color green
reduces anxiety, adding more chill to the pill.

White tablets—
particularly those labeled "antacid"—are superior for soothing ulcers, even when they contain nothing but lactose.


More is better,
scientists say. Placebos taken four times a day deliver greater relief than those taken twice daily.

Branding matters.
Placebos stamped or packaged with widely recognized trademarks are more effective than "generic" placebos.


Clever names
can add a placebo boost to the physiological punch in real drugs. Viagra implies both vitality and an unstoppable Niagara of sexy

 

[Antiphon]

Where can I buy placebos? Do they come in different doses? If they'll work on IBS without active ingredients I'll be they'll work on all kinds of ailments.

Actually, this might vindicate homeopathy where there's maybe 1 molecule of an active ingredient if you're lucky.

 

[zoobyshoe]

Where can I buy placebos? Do they come in different doses? If they'll work on IBS without active ingredients I'll be they'll work on all kinds of ailments.

Actually, this might vindicate homeopathy where there's maybe 1 molecule of an active ingredient if you're lucky.

This site sells "Universal Placebos". $20 a bottle:

http://www.placebo.com.au/

 

[zoobyshoe]

Interesting: I just discovered this same test of non-deceptive placebo administration was carried out on "neurotics" in the 1960's:

http://www.leecrandallparkmd.net/researchpages/placebo1.html

They seem to have done a more thorough job of telling the patients they would just be getting sugar pills, but the confident attitude of the doctors that the pills would work, and their inability to understand why they would be given inactive pills, lead some to conclude they were being deceived about them being sugar:

The patient reported there was clear evidence he was receiving a drug. Not only did he improve markedly more than on any other pill, but he noted side-reactions 30 minutes to one hour after each dose, consisting of dry mouth, along with butterflies in the abdominal area, lasting about one hour. He felt that perhaps the doctor had told him he was receiving placebo so that he would think that he was helping himself, when actually the drug was the factor.

At the return visit the patient entered the interview room saying, "They're not sugar pills." Upon questioning about this, she stated, "Because they worked." She also reported that this medicine was somewhat better than the other medicines she had received for emotional symptoms. When asked why the doctor would prescribe a drug and describe it as placebo, she stated, "Maybe he wanted to see how I reacted to it. I don't know about psychiatrists, I've never been around them. I've been around a lot of doctors, 22 in the last seven years, but not psychiatrists."

Other patients vascillated over whether they were getting placebos or not:

Although it was clearly explained that there was no medicine of any sort in the capsules, the patient's last question in the initial interview was whether the medication would make her too drowsy. At the time of her final appointment, the patient reported she was markedly improved, feeling better than she had in over 20 years. She stated that although she believed she had been receiving placebo, she had noted that the contents of the capsules tasted sweet. The contents were actually tasteless.

Initially, he reported that there was essentially no improvement, stating that only ineffectual "hypochondriacs" are influenced by such pills. When questioned about specific symptoms, he became aware that he was less irritable, with fewer temper outbursts; lie pointed out that improvement had actually started even before he came to see us. He subsequently thought of two further explanations for improvement during the treatment week. The first was that he had helped himself. Also, he stated the pills might well contain a "mild tranquilizer," commenting that the doctor could have told him that they were placebo simply to make sure that he would take them.

When placebo was introduced, she asked, "Why would it help, because for people, each time they take a pill, it's a symbol or something of someone caring about you, thinking about you three or four times a day?" When she returned for the second visit, the patient reported considerable improvement with regard to her anxious and apprehensive feelings, although she had been able to cut down only slightly on the smoking. She had noted considerable dry mouth during the treatment week, which she attributed to the pills. She felt the pills did not contain medicine in the usual sense, although they probably contained something "like a liniment." "I consider medicine something that will alleviate your symptoms, but this didn't alleviate the symptoms, just the desire to smoke." "Well, it's like these liniments that you rub on, the skin gets hot and makes the pain go." In further discussion, she indicated that the prescription by a psychiatrist of a pill containing nothing to help the anxiety symptoms brought to her awareness the thought that she could help herself. As a result of this, she made a number of changes in her environmental situation, which was quite at variance with her usual passive approach to problems.