In the medical world, a clinical research trial or clinicalresearch study is usually done to prove whether a new medicationor therapy is effective, before it becomes an approved and widelyused treatment. Patients with the target disease are often askedto take part in clinical research trials. To show that the newtreatment is truly effective, it is often compared to a placebo.
Placebos are usually thought of as "sugar pills." They are important"sham" or phony treatments that are used to keep doctors andpatients honest in testing new drugs or procedures. To provethat a drug works, it is generally tested against a placebo:a "dummy" medication that should have no effect on the condition.
Placebos are not only drugs. Sometimes patients get sham orphony surgery, sham radiation, or some other "pretend" treatment.Many patients and many doctors are unaware of the strength of"mind over matter." I often tell my patients about a personwho was in a study where the drug did not work. He insistedthat the drug did work, and that he should be given the drugafter the study ended. It turned out that he was not receivingthe drug and that he wanted more of the placebo!
Doctors and patients both want to see benefit from a new treatment.To prove that a therapy "really" works, some of the patientsare given the sugar pill, and some get the drug. Who receivesactive drug and who receives placebo is often decided by a "cointoss" or a process called randomization. This process makessure that patients are fairly divided between the two treatments.The change with the real drug is compared to the change withthe placebo. The patient and doctors are not told until afterthe study is over who got the active drug and who got the placebo.
Some people wonder whether it is fair or ethical to give a placebotreatment to a patient with a disease and not tell the patient.Many research studies are designed so that all patients eventuallyare able to use the study medication, even if they do not receiveit at first. Studies are carefully reviewed to be sure thatuse of a placebo treatment does not create a dangerous situationfor a patient. In the end, all patients benefit from studiesthat are carefully done using a placebo, so that the true effectof the treatment can be fully understood.
How placebos work is still a mystery. It is important to understandthat not all placebo effects are good. Just as some patientsimprove with the power of positive thinking, some get worseand drop out of research studies because of the side effectscaused by the placebo. In a recent, well-publicized and fascinatingstudy of Parkinson disease (PD), it was discovered that thepatients who improved with placebo had changes in their brainthat were identical to the changes caused by the actual medication(called levodopa).1 Levodopa causes an increase in brain dopamine,and the placebo should not. However, the patients who got betterwith placebo had a similar increase in dopamine, identical towhat happened in those who were given the drug. Talk about mindover matter! That is like convincing yourself you can run a40-yard dash in 4 seconds and then doing it. Similar effectsof changes in brain chemistry have been found in studies ofpain and of depression. However, this does not work in secret.When patients in a study of treatment for pain were given painmedications without their knowledge, the benefit was far lessthan when they were given placebo and they were able to expecta benefit.
WHAT DID THE AUTHORS OF THIS STUDY DISCOVER ABOUT PLACEBOS?
Diederich and Goetz2 brought together some placebo studies inthe areas of PD, depression, and pain, and they tried to developa theory as to why the placebo effect is so large, and how itoccurs. They reviewed studies designed to investigate how aplacebo produces benefit. The patients with PD who thought thatthey were receiving the real treatment but who really receiveda placebo had the same changes in their brains on PET scansas those who received the medication. It was the expectationof the benefit that led to the same chemical response in theplacebo group. Similar chemical changes on brain imaging testswere seen with placebo in studies of pain and in studies ofdepression. In the studies of PD and of pain, the more severethe disease symptoms and the more dramatic the treatment (surgery,injection that the patient can see rather than by a pump), themore likely the subjects were to experience benefit with placebotreatment.
Why should brain chemistry change when patients are convincedthey are receiving a treatment and their physicians expect themto improve? It seems that the expectation of benefit activatesthe same natural pathways in the brain as medications. If wecould harness these same mechanisms in the clinic, patientscould help themselves without the side effects of medications.
WHY ARE THESE STUDIES IMPORTANT? WHAT DOES THE FUTURE HOLD?
The authors point out that placebo effects make the study ofnew treatments very difficult. This is because the effect ofa new treatment has to be much greater than the placebo effect,which can be quite large.
If the placebo effect is strong, it is harder to prove thata drug or treatment is effective. This means that most researchtrials have to use many more people than they would if the placeboeffect was very small or did not exist at all. This makes thestudies cost more and take longer to accomplish. Better understandingof the placebo effect will help us to design faster, more effectivestudies to better combat disease. Perhaps one day we will alsolearn how to better harness the positive parts of the placeboeffect to use as part of medical therapy.
de la Fuente-Fernandez R, Ruth TJ, Sossi V, et al. Expectation and dopamine release: mechanism of the placebo effect in Parkinson's disease. Science 2001;293:1164–1166.[Abstract/Free Full Text]
Diederich NJ, Goetz CG. The placebo treatments in neurosciences: new insights from clinical and neuroimaging studies. Neurology 2008;71:677–684.[Abstract/Free Full Text]
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WHAT IS A CLINICAL...
WHAT IS A PLACEBO?
