Optimising Placebos And Minimising Nocebos
The placebo effect was first established when Henry Beecher, a World War II doctor, ran out of morphine, and decided to give his patients a salt-water injection instead. He was surprised to learn that many of his patients (around a third) responded as though they had actually received morphine.
Since then, the benefits of placebo have been observed in treatments for illnesses as disparate as depression and Parkinson’s disease. One study even found that sham shoulder surgeries were as effective at improving symptoms as the real surgery itself (Schroder et al., 2017).
Whilst initially these benefits were thought of as ‘fake’, and those who experienced placebo effects were deemed suggestible, growing evidence suggests that there are real neurobiological mechanisms underpinning placebo effects. Supporting this is the mounting evidence fromopen-label placebo studies, where improvement has still been observed even when patients know they are receiving a placebo (BMJ, 2018), suggesting that conditioning alone can bring about the placebo effect. What’s more, personality factors are shown to be less important in determining response to placebo than factors determined by the broader context, like expectancy effects and the quality of the doctor-patient relationship.
The understanding that the context is crucial in eliciting the placebo response lends itself to the use of behavioural nudges to optimise the placebo response. Doctors already routinely prescribe placebos in their practices (Howick et al., 2013). Understanding how to best optimise the placebo response is important for medicine generally, as the success of conventional treatments is also bolstered via the placebo effect.
How Can We Optimise the Placebo Effect?
1. Priming: Placebos need to look legitimate, with branding and pricing being especially important. One study found higher-priced painkillers to be more effective than discounted painkillers (Waber et al., 2008); higher prices anchor expectations upwards. The colour of pills is important too, with learned associations having an impact on how we respond to drugs. We associated blue pills with sedation, yellow pills with mood enhancement and white pills with pain relief (Cohen, 2014). Setting the scene with good branding, thoughtful design and realisticpricing is key.
2. Affect: Creating a positive therapeutic relationship between patient and doctor is vital in eliciting the placebo response; our expectations about the efficacy of the medication are largely set in this interaction. The placebo effect is enhanced when doctors are more empathetic, have a warmer approach and spend longer with their patients (Benedetti, 2013). An initial positive interaction can improve the expectation that treatment is going to work and helps to ease anxiety.
Sometimes thought of as the ‘evil twin’ of the placebo effect is the nocebo effect, referring to the development of side-effects following exposure to a sham substance. Evidence for the nocebo effect also abounds, with sham medication leading to increased side-effect reporting for conditions including hypertension and cancer (Enck et al., 2013). Systematic reviews find that around half of placebo groups in clinical trials experience adverse effects that are attributed to the drug (Howick et al. 2018).
The nocebo effect is often observed during public health outbreaks, putting huge pressure onto health providers. For example, in 1985 ‘radioactive caesium 137’ was scavenged from a disused hospital site in Goiânia, Brazil. 120,000 people subsequently sought screening for radioactive contamination at health facilities, however of the first 60,000 people screened, only 5,000 were symptomatic. This begs the question; why do people sometimes think they are unwell when they haven’t been exposed to anything harmful?
People sometimes believe they are unwell because they re-interpret pre-existing common symptoms in light of information about the health outbreak, like fatigue or headaches. Anxiety about a health outbreak can also be sufficient in and of itself to also generate physical symptoms.
Aside from these influences, the nocebo effect can also have a very real influence on generating harmful side-effects, in the same way that placebo effects can have a tangible positive influence on the body. Expectancy, rather than conditioning, is the crucial mechanism underpinning the nocebo effect. One study found that verbal suggestion alone was sufficient to make low-level electric shocks be experienced as highly painful (Colloca, Sigaudo & Benedetti, 2008).
How Can We Minimise the Nocebo Effect?
1. Positive Framing: At present, we are often all too aware of the possible side-effects that may come about as a result of trying a new medication. Even mere mentions of such side-effects can be sufficient to generate expectations of such symptoms (Colloca, Sigaudo & Benedetti, 2008). These potential negative outcomes can weigh more heavily in our minds than the possible benefits.
Changing the conversation to make it more positive may subsequently lessen the experience of side-effects, with patients having greater expectancy that the treatment will be effective. Positive framing is needed in the doctor-patient interaction, but also on information leaflets and drug packaging, which at present tend to focus on the riskiness of medication, rather than the benefits.
2. Reducing Salience of Side-Effect Information: Research suggests that a particularly effective strategy to ward against nocebo effects is to omit information about side-effects altogether (Webster & Rubin, 2019), which poses something of an ethical dilemma. However, given that we know that people can experience side-effects just because they expect to experience them, it makes sense to be reporting on the potential for adverse experiences in a responsible way.
One example of this going wrong comes from press coverage over side-effects associated with statins. In 2013; it was estimated that 200,000 people in the UK stopped taking statins as a result. Expectancy of side-effects seemed to be sufficient for many people to change their perception of their experience of taking statins. As a result, it is predicted that the incidence of cardiovascular disease will rise by an additional 2000 cases over the next decade (Horton, 2016).
Tackling medical consent therefore poses something of a thorny issue: how do we adequately warn people of possible risks without inadvertently creating negative outcomes? There has been discussion over the idea of contextualised consent: where adverse effects are presented as more of a ‘grey area’, instead of a definite likelihood, and where doctors can withhold certain pieces of information in the best interest of the patient (Chamsi-Pasha, Albar & Chamsi-Pasha, 2017).
The use of placebos provides a cost-effective way to create tangible improvements in patients’ lives. Behavioural science is key to maximising the benefits from placebos, in part through limiting the likelihood of developing side-effects from taking them.
This was originally published on O Behave here.