西亚试剂：No pain, no gain?

Mogil's data also challenge one of the fundamental principles of placebo-controlled trials — that comparing a drug against placebo tells us how well a drug works. A basic principle of these trials is that drug and placebo effects are additive: our total response to any drug we take is equal to the placebo response plus the drug's biochemical effect. But Mogil found that although placebo responses have increased over time, drug responses haven't risen by the same amount.

That suggests placebo and drug responses may not always be strictly additive. This isn't entirely unexpected, Mogil argues, because both placebos and pharmaceutical painkillers tap into similar biological mechanisms — such as the release of endorphins in the brain. But if true, it suggests that growing placebo responses are masking real painkilling effects. “There are a lot of people in the pain field who believe the drugs that are failing clinical trials actually work, it’s just that the trials can’t show it," he says.

For companies trying to develop treatments, one remedy might be to compare new drugs against their best competitors instead of against placebo — or to go back to conducting smaller, shorter trials. Benedetti is not convinced, however. "I don’t think that controlling the placebo response will increase the number of successful trials," he says. "What drug companies have to do is to find more effective drugs."

Mogil suggests it is also worth investigating the elements that generate the more powerful placebo response in US trials, and then incorporating those elements (such as the relationship between patient and nurse) into patient care. Ted Kaptchuk, director of placebo research at Harvard Medical School in Boston, Massachusetts, agrees. "If the major component of a drug in any particular condition is its placebo component, we need to develop non-pharmacological interventions as a first-line response," he says.

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