Placebo

A placebo is a treatment designed to look real to the person receiving it, but it has no pharmaceutical effect. Common examples include inert pills (such as sugar pills), saline injections, sham surgery, and similar procedures. Placebos are primarily used in randomized clinical trials to assess how well medical treatments work. In a placebo-controlled trial, any change observed in the control group is called the placebo response, and the difference between that response and receiving no treatment at all is known as the placebo effect. Ideally, placebos in trials should be indistinguishable from the actual treatments being tested (called verum treatments), except for the latter's specific hypothesized medicinal effect. This helps keep participants—who have given consent—from knowing whether they are receiving the placebo or the real treatment, since the expectations of both patients and clinicians can influence results.

The concept of a "placebo effect" was discussed as early as the 18th century in psychology, but it became more prominent in the 20th century. Modern research shows that placebos can affect certain outcomes, such as pain and nausea, but generally do not have important clinical effects otherwise. Improvements patients experience after taking a placebo may also stem from unrelated factors, like regression to the mean—a statistical phenomenon where an unusually high or low measurement is likely to be followed by a less extreme one. Using placebos in clinical medicine raises ethical concerns, especially when they are disguised as active treatments, because this introduces dishonesty into the doctor-patient relationship and bypasses informed consent. Placebos remain popular because they can sometimes provide relief through psychological mechanisms, influencing how patients perceive their condition and encouraging the body's chemical processes for relieving pain and a few other symptoms, but they have no impact on the disease itself.

The Latin term *placebo* means "I shall be pleasing." The definition of placebo has been debated; one definition holds that a treatment process is a placebo when none of its characteristic factors are effective (either remedial or harmful) for a given disease in a patient. In a clinical trial, the placebo response is the measured response of subjects to a placebo, while the placebo effect is the difference between that response and no treatment. The placebo response can include improvements from natural healing, declines from natural disease progression, the tendency for people who were temporarily feeling better or worse than usual to return to their average state (regression toward the mean), and errors in trial records that make it appear a change occurred when none did. This response is also part of the recorded response to any active medical intervention. Measurable placebo effects can be objective (such as lowered blood pressure) or subjective (such as a reduced perception of pain).

The placebo effect is well-documented but remains widely misunderstood and surrounded by misconceptions. Several studies have questioned its clinical relevance, fueling ongoing debate about its actual effectiveness. A 2001 meta-analysis of the placebo effect examined trials across 40 medical conditions and concluded that the only condition where a significant effect was shown was pain. A 2010 Cochrane review suggested that placebo effects are only apparent in subjective, continuous measures and in the treatment of pain and related conditions. That review found that placebos do not appear to affect actual diseases or outcomes that do not depend on a patient's perception. The authors, Asbjørn Hróbjartsson and Peter C. Gøtzsche, concluded that their study "did not find that placebo interventions have important clinical effects in general," though this interpretation has been criticized over concerns about methodology. More recent research has linked placebo interventions to improved motor functions in patients with Parkinson's disease. Other objective outcomes affected by placebos include immune and endocrine parameters, end-organ functions regulated by the autonomic nervous system, and sport performance.

Measuring the extent of the placebo effect is difficult due to confounding factors. For instance, a patient may feel better after taking a placebo because of regression to the mean (natural recovery or symptom change), but this can be ruled out by comparing the placebo group with a no-treatment group, as all placebo research does. It is even harder to distinguish the placebo effect from response bias, observer bias, and other trial methodology flaws, since a trial comparing placebo treatment to no treatment is not a blinded experiment. In their 2010 meta-analysis, Hróbjartsson and Gøtzsche argued that "even if there were no true effect of placebo, one would expect to record differences between placebo and no-treatment groups due to bias associated with lack of blinding." One way to measure the magnitude of placebo analgesia is through "open/hidden" studies, where some patients receive an analgesic and are told they are receiving it (open), while others receive the same drug without their knowledge (hidden). Such studies have found that analgesics are considerably more effective when patients know they are receiving them.

A review published in *JAMA Psychiatry* found that, in trials of antipsychotic medications, the change in response to receiving a placebo increased significantly between 1960 and 2013. The review's authors identified several factors that could be responsible for this increase.