The fact that an increasing number of medications are unable to beat sugar pills has thrown the industry into crisis. The stakes could hardly be higher. In today’s economy, the fate of a long-established company can hang on the outcome of a handful of tests.
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Potter discovered, however, that geographic location alone could determine whether a drug bested placebo or crossed the futility boundary. By the late ’90s, for example, the classic antianxiety drug diazepam (also known as Valium) was still beating placebo in France and Belgium. But when the drug was tested in the US, it was likely to fail. Conversely, Prozac performed better in America than it did in western Europe and South Africa. It was an unsettling prospect: FDA approval could hinge on where the company chose to conduct a trial.
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In one study, Benedetti found that Alzheimer’s patients with impaired cognitive function get less pain relief from analgesic drugs than normal volunteers do. Using advanced methods of EEG analysis, he discovered that the connections between the patients’ prefrontal lobes and their opioid systems had been damaged. Healthy volunteers feel the benefit of medication plus a placebo boost. Patients who are unable to formulate ideas about the future because of cortical deficits, however, feel only the effect of the drug itself. The experiment suggests that because Alzheimer’s patients don’t get the benefits of anticipating the treatment, they require higher doses of painkillers to experience normal levels of relief.

Benedetti often uses the phrase “placebo response” instead of placebo effect. By definition, inert pills have no effect, but under the right conditions they can act as a catalyst for what he calls the body’s “endogenous health care system.” Like any other internal network, the placebo response has limits. It can ease the discomfort of chemotherapy, but it won’t stop the growth of tumors. It also works in reverse to produce the placebo’s evil twin, the nocebo effect. For example, men taking a commonly prescribed prostate drug who were informed that the medication may cause sexual dysfunction were twice as likely to become impotent.
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Moreover, a pill’s shape, size, branding, and price all influence its effects on the body. Soothing blue capsules make more effective tranquilizers than angry red ones, except among Italian men, for whom the color blue is associated with their national soccer team—Forza Azzurri!