One Pill, Two Pill, Red Pill, Blue Pill
In the U.S. and most of Europe, drug companies follow a simple rule of thumb for pill color: red pills are for stimulative effects, blue pills are for calming effects. Except in Italy, where passions for the national football team, which wears blue and white, run so high that blue pills fail to sooth. Red stimulants and blue stimulants of exactly the same dose show different results.
Surgery as Therapeutic Ritual
With its pristine, tiled temples and learned men and women in uniform masks and robes, there are few medical procedures fraught with more ritual than surgery, but are there less invasive ways of achieving the same results using the placebo effect?
Bilateral internal mammary artery ligation (BIMAL) was an effective and widely used treatment for coronary artery disease in the 1950s and 1960s. In this procedure, the internal mammary artery was exposed using a surgical procedure, tied off, and then the patient was sewn up.
Observational studies showed this procedure increased function and decreased chest pain from coronary arterial disease, or angina, by 70–80%. However, in laboratory experiments with dogs, ligation of the mammary artery did not result in improved blood flow.
Two placebo-controlled trials in humans were conducted. In these cases, patients were randomized to either obtain the full procedure, in which the mammary artery was tied off, or to simply have the artery exposed during surgery without ligation followed by closure of the chest wall. In both studies, relief from angina was significant in 70–80% of the patients whether they had had the sham or real procedure.
Soon after these studies were performed, clinicians claimed that BIMAL was all placebo effect and the procedure was dropped from practice. It was around this time that coronary artery bypass surgery—the procedure of choice today for many with coronary artery disease—came into fashion. However, coronary artery bypass surgery has never been tested in a placebo-controlled trial and ironically its effectiveness in treating angina is approximately the same as was BIMAL: 70–80%. Bypass and similar approaches are in widespread use for angina despite the lack of placebo-controlled studies to determine the extent of placebo effects from the procedure.
Hyperbaric Oxygen Therapy for Traumatic Brain Injury
Each year, there are approximately 1.4 million new cases of traumatic brain injury (TBI) and 50,000 deaths due to TBI. Despite the prevalence of this problem, there is currently no universal standard treatment for a traumatic brain injury. Advocates for hyperbaric oxygen (HBO2) therapy have proposed that inhaling oxygen at higher concentrations and pressures can minimize brain damage, improve tissue healing, improve long-term outcomes and minimize brain swelling.
In 2015, Samueli Institute researchers set out to examine the efficacy of hyperbaric oxygen (HBO2) therapy for patients suffering from the consequences of TBI to better understand whether the current evidence supports the use of this therapy, and what next steps are needed for the research field.
This systematic review revealed that for patients suffering from persistent symptoms after mild TBI, HBO2 therapy is no better than sham treatment, if, in fact the “sham” treatment is a true sham, and hence not recommended as a therapy. In comparison to “standard care” there is not enough evidence to draw conclusions at this time.
However, the improvements in outcomes shown within groups for both HBO2 and sham treatment cannot be ignored. The ritual of the therapeutic encounter involved with both the HBO2 treatment and the sham treatment may have been of a therapeutic value to patients suffering traumatic brain injury when compared with the standard level of care given to patients suffering TBI.
In other words, both real and sham HBO2 groups got much better compared to standard therapy. The oxygen did not heal but the ritual did. Thus, it could be that what is helping the patients receiving HBO2 therapy was the increased ritualized encounters with a care giver during the visits produced the improvements.
Only additional investigation into the placebo effect can help settle the question.