Placebo Field

One of the most successful physicians I have ever known, has assured me, that he used more bread pills, drops of colored water, and powders of hickory ashes, than of all other medicines put together. It was certainly a pious fraud.

Thomas Jefferson to Caspar Wistar, June 21, 1807

«Henry Beecher was an anesthesiologist and pain therapist in Italy during World War II. On the battlefield he noted no correlation between the intensity of pain experienced by soldiers and the severity of the injuries. When Beecher returned to his practice in the United States after World War II, he compared the injuries of his patients with those of the soldiers, and found that the requirement for painkillers was substantially higher in civilian patients than in the soldiers on the battlefield, thus emphasizing the lack of relationship between the extension of the wounds and the perceived experience of pain. Beecher suggested that this discrepancy between soldiers and civilians could be attributable to the different meanings of the injuries. Whereas, the wound on the battlefield meant survival and returning home, the injured civilian was more concerned with diminishment of activities and loss of income. 

Beecher was one of the first clinician scientists who realized that the context around the patient makes the difference, and that the negative pain experience can turn into a positive experience. Thus, Beecher understood that the global pain experience is tightly linked to a variety of psychological factors associated to the injuries. For example, in soldiers, anxiety, emotional stress, grief from the loss of friends could be involved in different pain perceptions, as well as fear of losing the injured arm or being impotent because of injuries around the genitals.

It is within this context that Beecher's interest in the placebo effect emerged. In fact, Beecher often administered placebos to the soldiers, due to the lack of analgesics on the battlefield, along with verbal suggestions that they were powerful painkiller. Many of them responded to the placebo. In particular, he noted that an injection of saline solution had 90% of the effectiveness of morphine in relieving acute pain after injury, compared to civilian hospitals, where the placebo effect dropped to 70% of the effectiveness of morphine in pain after surgery. Therefore, Beecher concluded that the placebo effect is related to the context in which it is being investigated. 

In his 1955 seminal paper, he reviewed 15 controlled trials involving 1,082 patients and reported that placebos have an average significant effectiveness of 35.2 ± 2.2%. This average of one-third of patients responding to placebos has since permeated medical texts and teachings, although today this notion of one-third should be abandoned. In fact, the main criticism to Beecher's conclusion was that patients who received a placebo were not compared to those who received no treatment, thus making it impossible to rule out spontaneous remissions. Despite these limitations, Beecher's studies boosted the interest of the scientific community in the placebo effect.

In a study, Beecher compared different analgesics, like morphine, codeine, acetylsalicylic acid, and placebos, emphasizing the problem of the placebo effect and stressing the importance of placebo-controlled trials. He was particularly concerned with the problem of placebo reactors and non-reactors in clinical research in the design of clinical trials and their interpretation. Not only did he consider placebo responsiveness of pain, but also of surgery. In another seminal paper, he emphasized how placebo effects can be powerful in both pharmacological and non-pharmacological treatments.»

Historical evolution of the scientific investigation of the placebo analgesic effect - Fabrizio Benedetti

in Frontiers in Pain Research, Volume 3 | 10 August 2022