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Could expecting symptoms be causing you symptoms?



Most of us have heard of the placebo effect – when someone takes a ‘fake’ medication, and we see improvements in their health even though the medication has no active ingredient. If you expect a pill to do something, the body responds with effects similar to what the medication might have done – the mind and body are very closely linked and has the capacity to produce these effects.


The power of the placebo can be used to our advantage for symptoms such as pain, insomnia and side effects like headache and nausea. Evidence shows that pain relief can be harnessed from the placebo effect [1]. A group of study participants had an inactive cream applied to their arms, but half of them were told that this may be a local anaesthetic cream and the other half were told it was inactive. Laser pain was then delivered to all of their arms (nothing crazy of course!) In the group who were told the cream was potentially a local anaesthetic, there was a significant reduction in pain symptoms compared to the group who were told the cream was inactive. Even without 100% certainty, just the idea that the cream might be a local anaesthetic was enough to produce a pain-relief effect. The expectation that the cream could reduce the pain was sufficient to make the experience of pain less severe - essentially what the placebo effect seems to be doing is tricking your brain into producing a pain-relief response.


Whilst the placebo effect might sound great, there’s also the negative counterpart that you may not have heard of… the nocebo effect. The nocebo effect is the experience of adverse symptoms in response to a medicine or treatment due to negative expectations [2]. Being in a state of expecting common symptoms like drowsiness, headache and nausea increases the likelihood that you’ll experience them, even if it’s not a direct consequence of the medication. Research estimates that up to 97% of reported side effects are not caused by the drug itself but by the nocebo effect and the misattribution of symptoms [3].


Think back to when the doctor has told you that taking a particular medication you’ve been prescribed comes with a list of side effects. Chances are you may have started to experience these unpleasant side-effects after and were more hypervigilant towards how you felt. Had the doctor not told you about them, do you think you would have noticed these symptoms or even had them in the first place? The expectation of symptoms has the power to produce actual physiological changes in the body, showing exactly how strong the mind-body link can be.


To use a recent example, clinical trials have explored the symptom reports of people receiving the COVID-19 vaccine versus a sham vaccine [4]. Overall, 35.2% of people receiving the first vaccine reported experiencing common symptoms such as headache and fatigue and in a similar group who in fact received a ‘fake’ vaccine, 31.8% reported the same symptoms despite no presence of an active dose. It is now believed that up to 76% of all common symptoms (i.e. headache, nausea, fatigue, arm pain) following the first covid vaccine can be accounted for by the nocebo effect and 52% of symptoms following the second dose. Whilst the symptoms experienced are very real and unpleasant, some of these symptoms are not down to the contents of the jab but our expectations and feelings of anxiety.


Due to legal obligations, clinicians are required to inform patients about every risk that may arise from treatment. Although it is important to be aware of side effects, are we doing more harm than good by telling people about potential symptoms? It’s likely that we’d be less bothered by these common symptoms if we weren’t aware of them but there is an ethical debate around this topic; should we tell people about all of the symptoms they’re likely to experience from taking a medication or is it fair to withhold information for the benefit of reducing the likelihood they experience unpleasant side-effects?


References


[1] Power, A., Brown, C. A., Sivan, M., Lenton, A., Rainey, T., El-Deredy, W., ... & Watson, A. (2020). Individuals with chronic pain have the same response to placebo analgesia as healthy controls in terms of magnitude and reproducibility. Pain, 161(12), 2720-2730.


[2] Schedlowski, M., Enck, P., Rief, W., & Bingel, U. (2015). Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice. Pharmacological Reviews, 67(3), 697-730. doi: 10.1124/pr.114.009423


[3] Faasse, K., Helfer, S. G., Barnes, K., Colagiuri, B., & Geers, A. L. (2019). Experimental assessment of nocebo effects and nocebo side effects: definitions, study design, and implications for psychiatry and beyond. Frontiers in psychiatry, 10, 396.


[4] Haas, J. W., Bender, F. L., Ballou, S., Kelley, J. M., Wilhelm, M., Miller, F. G., ... & Kaptchuk, T. J. (2022). Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials: A Systematic Review and Meta-analysis. JAMA network open, 5(1), e2143955-e2143955.

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