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The 'Nocebo' Effect: Pessimism Can Hinder Treatment

LAURAN NEERGAARD   02/28/11 03:01 PM ET  AP

WASHINGTON — Spine surgeon Anders Cohen puts a lot of stock in patients' expectations of pain relief. He prefers to operate only on those who "grab you by the collar and say, `I can't take it anymore.'"

New brain research proves doctors like Cohen are onto something: Pessimism can override the effectiveness of even powerful treatments.

You've heard of the placebo effect, the healing power of positive belief. This is the "nocebo" effect, the flip side, almost its evil twin.

And while the self-fulfilling prophecy of negative thinking isn't nearly as well studied, some scientists say it's time for doctors to start paying a lot more attention to their patients' outlook.

"We all know that many treatments work for some people but not for others," says neuroscientist Dr. Randy Gollub of Massachusetts General Hospital. Instead of stressing only the percentages, "say, `I have every reason to believe that you could be one of the people who will respond.'"

Scientists already know the placebo effect is real. They can measure it in studies that compare real drugs to dummy pills, where those given the fakes have noticeable improvements to pain and other symptoms.

But could a gloomy outlook really harm? British and German researchers performed the most sophisticated study yet to tell. They strapped a heat-beaming device onto the legs of 22 healthy volunteers, zapping it until people rated their pain at nearly 70 on a scale of 1 to 100.

Then the researchers hooked up an IV to give them the powerful morphine-like painkiller remifentanil. Typically used for surgery patients, it works rapidly but also is metabolized rapidly, able to be switched on and off as researchers alternated between giving the drug or plain fluid.

The volunteers' brains were scanned as they described how much pain, and pain relief, they experienced at different times. When the researchers induced the burn and surreptitiously turned on the drug, the volunteers said their pain improved a fair amount. The painkiller was working, expectations aside.

Here's the mind over matter: The researchers next told the volunteers they were about to inject the painkiller even though they'd never turned it off. Those pain ratings dropped even more – meaning expectations of relief doubled the drug's painkilling benefit.

Finally, the researchers lied again, saying they were stopping the drug and that pain would probably increase. Sure enough, the volunteers' pain levels soared back up to almost their pre-treated level as grim expectations canceled out the effect of a proven and potent painkiller. Anxiety levels fluctuated similarly.

Why? The brain scans tell the tantalizing tale – showing changes in neural pain networks that prove the people really did experience the changes in pain that they reported.

Moreover, expecting more pain fired up sections of the brain that control mood and anxiety, the researchers recently reported in the journal Science Translational Medicine. In contrast, anticipating pain relief fired up different regions previously found active in people given placebos.

It's a small study, dealing just with pain. But the results may apply to a range of drug therapies, especially in chronic diseases because so many of those patients are conditioned by months or years or frustrating treatment failures, concluded lead researcher Dr. Ulrike Bingel of Hamburg's University Medical Center, who teamed with Oxford University researchers for the study.

Learning how anxiety influences pain is crucial to understanding this nocebo effect – how you get the pain you expect, said co-author and Oxford neuroscientist Irene Tracey, in a recent review of the science of expectations in the journal Nature Medicine.

It's by no means a novel concept. Previous research has found people given a dummy pill can experience the side effects of the medication they thought they were getting.

While there's a lot yet to learn, for now doctors should at least try building closer relationships with their patients to encourage trust in recommended treatments, said Mass General's Gollub.

"Building these strong, positive expectations for doing well are part of what comes from believing in your treater as someone who cares about you," she said.

Directly managing patients' expectations – spelling out exactly what will happen at different points to take away some of the fear – also can help, said Cohen, chief of spine surgery at Brooklyn Hospital Center in New York. He teaches new doctors not to promise surgery patients they'll wake up free from pain because – while the old back pain may be fading – they're going to hurt from the operation.

When someone says, "`Wow, it's just like he told it was going to be, this guy told me the truth,' now you've got this bond of confidence," Cohen said. "You're partnering with your patient."

___

EDITOR'S NOTE – Lauran Neergaard covers health and medical issues for The Associated Press in Washington.

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12:09 AM on 04/20/2011
Rhetoricians, oh no! We have politicians for that. The last few paragraphs blew it for me. Keep it real, don't be playing mind games. If the patient has a negative attitude you should be making referrals, or at least have Dr. Emoto's book in your waiting room.
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wakawaka09
Capitalism is a cult.
11:26 PM on 03/05/2011
what are they really selling here, that people don't need pain meds? Just smile and stay positive and pop your placebos. You'll do fine.
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09:15 PM on 03/04/2011
i file this under common sense.
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jettNY
11:32 AM on 03/01/2011
Lots of comments here basically against taking placebo/nocebo effects seriously....especially in non-pain-related issues...

But one of the most interesting articles I've ever read on the subject is about the pharmaceutical industry's take on it all.... I recommend reading it...

http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo_effect?currentPage=all
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redsquirell
red squire LL
09:55 AM on 03/01/2011
pain
Etymology: L, poena, punishment
an unpleasant sensation caused by noxious stimulation of the sensory nerve endings. It is a subjective feeling and an individual response to the cause. Pain is a cardinal symptom of inflammation and is valuable in the diagnosis of many disorders and conditions. It may be mild or severe, chronic or acute, lancinating, burning, dull or sharp, precisely or poorly localized, or referred. Experiencing pain is influenced by physical, mental, biochemical, psychologic, physiologic, social, cultural, and emotional factors. See also acute pain, chronic pain, referred pain.
Mosby's Medical Dictionary, 8th edition. © 2009, Elsevier.
And this is the most "sophisticated study" on such a complex and subjective experience as the effects of one's psychology on pain?
I don't think so. I hope not.
To make broad statements about pain based on heating up healthy people's legs is odd at best.
Do we want to help only those who beg for help "enough times"?
Strange article indeed.
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robert horwitz
08:47 AM on 03/01/2011
Wait a moment isn't this the new Homeland Security Public Warning System? No more color coding for us. Not only that what did you do if you were color blind. No this new system is much better. The higher the corners of the mouth the safer we are. The lower the corners on the mouth are look out!
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DeAnnaClaudette
12:19 AM on 03/01/2011
Maybe THIS is why my anti-depressants don't work.
barbra1971
Sherry Hunt my hero
10:22 PM on 03/01/2011
How are your vitamins and hormones levels?
11:17 PM on 02/28/2011
Awesome post.
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drjasonmd
Shalom, compa!
10:07 PM on 02/28/2011
A lot of research into this area is needed, but the first step should be to correct the vocabulary.

There is no placebo "effect." There is only a placebo "perception". Placebo has never been shown to change any objective endpoint. That is to say, nothing that can be objectively measured has ever been affected by placebo. People may perceive less pain, less nausea, less anything nobody can measure, but placebo has never increased range of motion, endurance, survival rate, or anything else that can be objectively measured by an outside observer.

It's not so mysterious. As they used to tell us in the Marines, "it's mind over matter. If you don't mind, it don't matter."
barbra1971
Sherry Hunt my hero
10:26 PM on 03/01/2011
Our brain is very capable of many things, people who survived in dire situations are proof.
Know you body, listen to it, it will learn how to communicate with you.
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drjasonmd
Shalom, compa!
10:47 PM on 03/01/2011
Do you have any data to support that flowery rhetoric? Otherwise, it's no different than claiming that holy water can cure disease.
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Kristin Talbott
One should always be a little improbable.
09:09 PM on 03/03/2011
In The Holographic Universe, Michael Talbot talks about a chemotherapy study in which 30% of the people in the control group who received the placebo lost their hair. I would say that that is a very measurable and observable effect, wouldn't you?
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drjasonmd
Shalom, compa!
10:40 PM on 03/03/2011
I hear about that study all the time. Trouble is, nobody can ever provide a reference to it. Like so many things Michael Talbot puts in print, I'm pretty sure it's bogus.
Genders
Love, Tolerance, Enlightenment
09:39 PM on 02/28/2011
Great article, but Duh.
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leazzel
08:41 PM on 02/28/2011
I think having a positive outlook can have a positive effect on pain. However, what i don't understand is that when given a painkiller intravenously, the effect is noticable instantly. The relaxed feeling, droopy eyes and to some, major itching. I think, i would totally know if, i was given a pain killer, or not.
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CabCurious
let's be honest
07:47 PM on 02/28/2011
This headline is horrible.

The study is far more fascinating that it indicates. :)
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Kristin Talbott
One should always be a little improbable.
09:26 PM on 03/03/2011
It is horrible, isn't it? Same for the graphic. Almost begs us not to take the article seriously.

I think it will be a sign we have truly evolved a bit if these kinds of studies start getting priority placement in newspapers/broadcasts and the latest celebrity "news" and reality TV developments are relegated to the bottom of the heap.
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badders
Bad taste creates many more millionaires than good
07:24 PM on 02/28/2011
If a person is naturally gifted in math and science they tend to stay the hell away from medical science.
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Uncle Bob
Darwin loves you.
07:46 PM on 02/28/2011
Yah, people that are good at math don't accept statistical averages.
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drjasonmd
Shalom, compa!
10:08 PM on 02/28/2011
I was singled out as naturally gifted in both.
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Henry Owen Creque V
07:23 PM on 02/28/2011
This just in, New healthcare bill passed Demanding everyone to be happy and optimistic about everything. In turn this will save the government billions and help get the defecit down.
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09:46 PM on 02/28/2011
Good one! SSRIs are not doing the trick.
06:51 PM on 02/28/2011
There's just one problem: There is no placebo effect.

Most studies on placebo have only looked at two groups: One that receives treatment and one that receives a placebo. There is a third option that needs to be studied: One that receives no treatment of any kind, not even placebo, but is only observed. Since the body has the ability to repair itself, you need to study what happens when the body just does what it does if you're going to show that a placebo has any effect.

Well, people have looked into it and found that there is no placebo effect. For those studies that actually did all three groups (treatment, placebo, and observation), those who took placebo had no difference from those who were merely observed other than a slightly reduced reporting of pain.

http://www.slate.com/id/2176465/

This makes sense: Pain is partly a mental phenomenon and thus playing with your brain can affect how you perceive pain. But there's no way to think yourself out of cancer, infection, or other biological effects. Before some of the bloggers on this site who shall not be named recognize this fact, let us repeat the mantra:

This is only about pain, not infection.
This is only about pain, not cancer.
This is only about pain, not disease.
07:38 PM on 02/28/2011
i thought the evil twin was going to be when people heal and believe it was due to a medication when if fact the "real" medication did nothing but people thought it did so they believe it helped. i think there's a lot of that going around too.
08:17 PM on 02/28/2011
That would be "placebo": You're given something that doesn't actually do anything but you get better. According to the study that looked at those who received nothing, not even placebo, there is no such thing as a "placebo effect." In fact, the original paper that was written that got everybody thinking there was such a thing was a horrible mess: The only results that were reported were positive ones: All results that showed worse results under placebo than treatment were ignored.

Note to those who must not be named and their supporters: I do understand that there is a connection between the brain and the rest of the body. Our bodies respond to hormones, including stress hormones, and our mental attitudes have an effect on what is coursing through our bloodstream. You can think yourself into certain stress-related ailments. But notice the caveat: Stress-related. I can think myself into nausea, but I can't think myself into H. pylori. Learning to handle my stress will mean I won't have stress-related pains in my stomach, but it won't actually cure the bacteria eating a hole in my gut and causing an ulcer.

It may be that some medications are affected by various hormones in the blood. Some of those effects might be indirect. But it is not woo that's doing it but actual biology.
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09:49 PM on 02/28/2011
Thank you. F/F