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| Archive : Summer
2006 |
YOU, A RESEARCH SUBJECT:
Take the pill the pleasant doctor gives you // Feel better, just as you thought you would // Suffer the side effects she warned you about // Confuse trial results because your sugar pill works just as well as the genuine article.
The Placebo Problem [page 3]
 By
Rachael Moeller Gorman // Illustrations by Leigh Wells
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Other studies have delved deeper into the expectation aspect of the placebo response. In the 1980s and 1990s, researchers at the University of California at San Francisco and at the University of Torino Medical School, in Italy, studied post-operative patients hooked up to intravenous lines. Either a doctor openly injected a painkiller or a computer fed it into the line without the patient’s knowledge. Remarkably, a hidden injection of morphine worked no better than an open injection of saline that the patients thought was morphine. What’s more, in another study, an open injection of a painkiller called buprenorphine worked immediately, whereas a hidden one lagged by nearly two hours. In other words, much of the drug’s effectiveness derived from a patient’s expectation.
Brain-imaging studies have identified a sort of “expectation” pathway in the brain that might help explain some of these intriguing results. In 2004, a team led by Tor Wager, a cognitive neuroscientist at Columbia University, scanned subjects with functional magnetic resonance imaging (fMRI), which shows small changes in blood flow to precise areas of the brain, an indicator of neuronal activity. As subjects watched a computer screen, Wager flashed a cue indicating that pain would follow shortly, and a few seconds later he shocked their wrists. Next Wager rubbed placebo pain-relief cream on the wrists of some subjects, and repeated the cue and shock. On the fMRI scans, brain areas associated with pain—including the thalamus, insula and anterior cingulate cortex—lit up with the shock but then dimmed in patients rubbed with the sham cream.
Wager’s study also looked at another part of the brain, the prefrontal cortex, which seems to be associated with generating expectations of pain and pain relief. That region showed increased activity on the scans when patients expected the placebo to reduce the pain they felt. Says Wager, “We think the prefrontal cortex participates in decision-making about how much pain you should feel and how you should respond.” Patients whose prefrontal cortex lit up in anticipation of pain relief also showed less activity in the pain-processing regions of the brain, and reported less pain.
Though much of the research into the placebo effect has involved pain relief, other studies have examined depression, Alzheimer’s disease and immune suppression. Scientists have even found a “nocebo” effect, the side effects of taking a placebo, including the dry mouth and fatigue patients in Kaptchuk’s trial experienced. In a study published this past January, Arthur Barsky, a Harvard Medical School psychiatrist, looked at the side effects experienced by the placebo group in RCTs of cholesterol-lowering statins. As many as one in four subjects (the percentage was quite variable) dropped out because of “perceived side effects.” Barsky thinks this is because doctors—who don’t know which patients are on the real drug and which ones are on the placebo—must tell all patients about the potential side effects of the real drug. Subjects then may be more focused on that area of the body and redefine pre-existing sensations as the suggested side effects.
Though the placebo effect is proving to be far more complex, variable and powerful than scientists had long believed, most researchers don’t see fundamental flaws in the basic design of RCTs, which still provide vital information on whether a new drug works better than a placebo. Yet many also agree that the standard trial regimen needs an update to improve the information it provides, and that more placebo research (which is still in its infancy) is needed. |
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Illustrations by Leigh Wells
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