The Placebo Effect: a psychological effect in which a treatment which contains no active medical substance causes an improvement in symptoms. For example, a participant in a trial takes a sugar pill believing it could be real medication and find their back pain goes away.
This effect has been well documented and is relatively well known (for more information read my blog post here). But what about the Nocebo effect? In this instance, the opposite happens. A participant in a trial takes a sugar pill, or receives a fake injection, and start to feel negative side effects of the medication. How is this possible when no active medication was received?
To begin to explain how this effect occurs, I’ll start by telling you a bit about how clinical trials are conducted. Before a participant consents to take part in the study, they have to read a participant information sheet which explains all the details of a trial and what will happen. In a drug trial, such as one testing a new medication to help persistent back pain, participants will also have to read a list of potential side effects, much like those you find on the leaflet that comes in the box with medication. When participants sign up, they are told that they might receive the real medication, or they might receive a sugar pill. Having the control group of those who receive fake medication is important in clinical trials, as it allows you to show that any improvement is due to the medication being tested and not other factors such as symptoms improving over time. The reason control groups are given fake medication instead of having no medication at all allows for researchers to see how much of the improvement of the real medication is due to it’s active ingredients, and to show that participants haven’t just got better because of the placebo effect.
Even though participants have received the placebo medication they can still believe it is the real one – a placebo should be administered in exactly the same way as the real medication to be a true control. Therefore, it is this belief that they have taken the real drugs that can lead them to report side effects from it. One review of the evidence shows that around a quarter of participants taking a placebo drug experience adverse side effects from it, and that this can be higher than the participants taking the real medication! (Barksy et al, 2002). Visual cues can also induce nocebo effects: one study tested how participants rated the effectiveness and side effects of either branded or unbranded drugs (both in fact were placebos). Perhaps unsurprisingly, participants rated the branded drugs as more effective, and thought the unbranded drugs caused more side effects (Faasse et al 2013).
Several explanations have been put forward to explain the nocebo effect, including conditioned responses or participant’s expectations. For example, a doctor giving you an injection warns you that it might hurt, so you feel subjectively more pain than if they had been reassuring. Some studies investigating the neural basis of the nocebo effect in pain have hypothesised that the effect is caused by increased activity in certain areas of the brain such as the hippocampal network (which is involved in pain modulation) (Ploghaus et al, 2001). This activity is in turn caused by increased anxiety, brought on by the expectation of pain.
This brings a certain ethical dilemma for healthcare professionals and those running clinical trials. It is important the the patient or participant is given all of the information, in order to give informed consent. However, if giving someone more information would cause them to feel more pain, what would you do?
Barsky, A.J., Saintfort, R., Rogers, M.P. and Borus, J.F., 2002. Nonspecific medication side effects and the nocebo phenomenon. Jama, 287(5), pp.622-627.
Faasse, K., Cundy, T., Gamble, G. and Petrie, K.J., 2013. The effect of an apparent change to a branded or generic medication on drug effectiveness and side effects. Psychosomatic medicine, 75(1), pp.90-96.
Ploghaus, A., Narain, C., Beckmann, C.F., Clare, S., Bantick, S., Wise, R., Matthews, P.M., Rawlins, J.N.P. and Tracey, I., 2001. Exacerbation of pain by anxiety is associated with activity in a hippocampal network. Journal of Neuroscience, 21(24), pp.9896-9903.