What Is the Placebo Effect and Why Is it Getting Stronger?

The placebo effect – and its critical importance in the testing of new drugs – emerges from a lie told by a nurse in a field hospital during World War II. The hospital had run out of morphine, and in an attempt to comfort a soldier who was in pain, the nurse gave him an injection of saline (salt water) and told him it was morphine. The soldier was instantly comforted, just as if he had been given a real injection of morphine.

Dr. Henry Beecher was an anesthetist witnessing this, and recognized what an important discovery it was. When he returned to the U.S., he became a leading advocate for revising the at-the-time shoddy practices related to the testing and release of new drugs. His advocacy led to the current standard that a new drug must pass to be deemed as effective – it must score better in treating the ailment it would be prescribed for than an inert sugar pill (a placebo) would be. This is the very reason that all modern Stage II drug trials (in which the drugs are first tested against a placebo) contain two groups, one receiving the real drug and one receiving the placebo, with the subjects (and sometimes the testers) not knowing which they’re receiving.

This sounds like a good methodology…what’s the problem with it?

The problem is that this procedure is now backfiring. In new drug trials, it is becoming increasingly difficult for manufacturers to prove that their drugs have any more effectiveness than placebos. When modern researchers go back to replicate tests done on drugs a few years ago, in which the results were near-conclusive, they have repeatedly been unable to do so because in the newer tests the placebo group reports nearly as many “cures” or positive benefits as the group receiving the actual drug. It’s not, researchers point out, that the drugs in question have gotten weaker; it’s that the placebo effect is getting stronger.

This situation has become the “elephant in the room,” and has thrown the pharmacology industry into a panic. Between 2001 and 2006, 20% more drugs were dropped by their manufacturers after their Phase II clinical trials, because they couldn’t beat the placebos. In Phase III trials that are even more extensive, failure rates during this period went up 11 percent. Despite historic levels of investment and development by drug companies during this period, the FDA approved a mere 19 first-of-their-type drugs in 2007 and just 24 in 2008.

What is causing the placebo effect to grow stronger?

No one knows for sure, and that is one of the things that worries scientists and pharmacy companies, both of which groups are scrambling to design new testing protocols that will overcome this problem and allow accurate results. The issue at heart seems to be that the very fact that a test subject with a certain condition has been recruited to participate in a drug study and is given a pill to take – often by a person wearing a white coat – is enough to trigger the body’s own immune system sufficiently to trigger the same sort of positive reactions that the drug is supposed to produce.

The problem is most acute in the testing of psychotropic drugs designed to give relief to those suffering from anxiety or depression. Doctors theorize that so many people have heard so many stories of people gaining relief from antidepressant and anti-anxiety medications that the mere fact that someone has given them a pill to take causes them to “feel better” – less anxious or less depressed. This is great for the subjects, whether they receive the real drug or the placebo, but terrible for the manufacturers of the real drug, who cannot achieve the test results necessary to have the FDA approve the drug for wide release. And the problem is retroactive; drugs like Prozac, which has been on the market for decades, are failing more recent tests.

In a fascinating turn of events, modern researchers are finding that the very color or shape of the pills – whether “real” or placebo – has a significant effect on how effective subjects find them to be. The geographic location in which the tests are conducted can also affect the results; a drug found to be “conclusively effective” in the U.S. can fail completely in India, or vice-versa.

So what does all of this mean? What is being done about this problem?

The fallout of this situation is twofold. First, researchers are scrambling to find new ways to administer drugs being tested so that the subjects don’t even know that they are receiving them, or even that they’re part of a drug study at all. Some of these approaches have worked, and others have not.

But the biggest possible benefit of learning that the placebo effect is growing more powerful is that a number of health-care researchers are looking more in depth into placebo as a treatment methodology in itself. If placebos work so well in many conditions, they think, why do we need “real” drugs? Researchers such as Fabrizio Benedetti at the University of Turin have been researching placebos and have identified several different types of placebo reaction. Opioids released by nothing more than a placebo not only relieve pain, they can modulate the patient’s heart and respiration rate. Placebos can also trigger an increased release of the neurotransmitter dopamine, which has been shown to improve motor function in Parkinson’s patients, even though they received no real Parkinson’s medication.

So although the increasing power of the placebo effect may be a problem – and a significant one – for the companies developing drug treatments for illness, in the long run this “problem” may turn out to be a benefit, a “nudge” in the direction of finding non-drug treatments that trigger the body’s own immune system to heal illnesses on its own.

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Juliette Siegfried, MPH

Juliette Siegfried, MPH, has been involved in health communications since 1991. Shortly after obtaining her Master of Public Health degree, she began her career at the National Institutes of Health in Bethesda, Maryland. Juliette now lives in Europe, where she launched ServingMed(.)com, a small medical writing and editing business for health professionals all over the world.

Juliette's resume, facebook: juliette.siegfriedmph, linkedin: juliettes, (+31) 683 673 767

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