August 13, 2013. The placebo response, in which patients’ symptoms improve following treatments that have no known effect on their condition, has been known for centuries. But the phenomenon is of great current interest because placebos are a cornerstone of randomized controlled clinical trials—the gold standard of drug development—which are so called because patients are randomly assigned to groups that receive either active drug compounds or a placebo, usually a sugar pill (the control group). To be considered useful, a drug not only has to be effective against symptoms, but it also has to be significantly more effective than the placebo.
For reasons that are not fully understood, the percentage of patients responding to placebo, especially in trials of psychiatric drugs, has been significantly increasing over the past few decades, and promising new compounds are failing in late-stage trials because placebo control groups of patients are showing only slightly less improvement nearly as much as than those receiving the actual test drug being tested.
In a new look at the problem, published in the American Journal of Psychiatry, Ofer Agid of the Centre for Addiction and Mental Health in Toronto, Canada, and a team of international colleagues examined 40 years’ worth of randomized controlled trials of drugs for schizophrenia, searching for aspects of trial design or characteristics of study populations that may have pushed up the placebo response. They found that studies that included younger patients or patients with more severe or short-lived illness were more vulnerable to strong placebo responses. In addition, the placebo response rose in tandem with the number of study sites participating in the trial, especially if these sites were not academic centers or affiliated with the Veterans Administration. The authors propose that the placebo response may be lowered if future investigators pay careful attention to these factors when designing new trials. (For more details, see the related news story.)—Pete Farley.