Chronic pain can take a toll on a person's morale. As a result, individuals with chronic pain often lose confidence in the effectiveness of physical, psychological, and medicinal treatments. Unfortunately, this loss of faith, or worse, the development of negative expectations, can have a dramatic impact on the healing process. Pain levels can rise, and new problems may emerge. Fortunately, there are ways to neutralize this nocebo effect. But first, let's delve into what the nocebo actually is and why it poses a problem.
What Is the Nocebo Effect?
To introduce the concept of the nocebo effect, let me share a true story (Reeves, Ladner, and Burke, 2007). It's about a nurse who worked in the emergency room of a hospital and witnessed a situation she'll never forget.
She recalls it was a day like any other. Towards the end of her shift, around 9:00 pm, a man stumbled in, shouting, "Help me! I've taken all my pills!" This 26-year-old man then collapsed. An empty pill bottle slipped from one of his hands. Kim immediately checked the man's vital signs. His heart was racing, and his blood pressure was dangerously low. He was pale and sweaty, and he soon lost consciousness. Luckily, before he did, he managed to tell the nurses that he had taken all 31 of his antidepressant pills following an argument with his girlfriend. He wanted to end his life but quickly regretted it.
Immediately, the nurse administered a saline infusion to normalize his blood pressure and heart rate; however, this would take some time. Meanwhile, colleagues examined the man's pill bottle. They discovered that the man had taken the medications as part of an experimental study for a new antidepressant. They called the scientists responsible for the study, and the lead researcher quickly came to the hospital. The nurse couldn't believe what she heard next. The scientist told the man that he had received a placebo, not an active antidepressant. He had ingested sugar pills. Within 15 minutes, the man's heart rate and blood pressure returned to normal. He was fully conscious and overwhelmed with relief.
So, what happened here? The nurse witnessed the nocebo effect. Just as the placebo effect creates a positive response or a healing effect from an inert treatment, the nocebo effect is the adverse response to a harmless treatment. In the case of the man, his beliefs and expectations of intoxication acted as a self-fulfilling prophecy. These expectations triggered a bodily response that mimicked actual intoxication. His blood pressure and heart rate shot up, and he lost consciousness, which was not without danger.
Nocebo Side Effects
The previous case demonstrated that patients can create side effects themselves, which were clearly visible when monitoring the man's vital signs. These findings are replicated in scientific studies. Here, both groups received two different placebo treatments to treat arm pain. However, the goal was to investigate the nocebo effect. A few patients from the group receiving placebo pills reported being so tired that they couldn't get out of bed. Meanwhile, the group receiving sham acupuncture reported swelling, redness, and intense pain. Interestingly, these are precisely the side effects they were told they might experience (Kaptchuk, et al., 2006).
Approximately 20% of patients taking a sugar pill report uncomfortable side effects (Flaten, Simonsen, and Olsen, 1999). For example, if you tell a patient being treated with a placebo that they might feel nauseous, there's a good chance they'll feel nauseous. Suggest that they might get a headache, and it might happen. Patients who believed they were receiving chemotherapy but were actually injected with saline actually vomited, and some even lost their hair (Brazil, 2018).
This clearly shows that the nocebo effect is real and deserving of attention. In every placebo-controlled study, there are side effects, and patients drop out due to unbearable discomfort (Hansen & Zech, 2019). Besides hindering scientific progress, the nocebo effect also occurs in medicine. Studies show that a significant portion of medication side effects can be attributed to the nocebo effect (Petrie and Rief, 2019). So, to put it plainly, these side effects occur because patients read or hear about them rather than the actual ingredients harming their bodies.
Nocebo and the Media
We now know that the nocebo effect can be responsible for unwanted side effects. Since patients discontinue treatment due to these side effects, the nocebo effect hampers clinical research and drug therapies. Unfortunately, there's more. Research shows that the nocebo effect can also influence the effectiveness of pain medications. It turns out that belief in a medication's effectiveness is also crucial.
A well-known example came from New Zealand in 2017. A subsidized brand of venlafaxine changed the appearance of its tablets. They shifted from a commercial brand with a logo and glossy packaging to a more generic look. However, they still contained the same active ingredients, sourced from the same place. Initially, there was no significant increase in reported side effects. However, after media reports in 2018 that the newly subsidized brand wasn't as effective, complaints skyrocketed (Mackrill et al., 2019).
This example illustrates two things. Firstly, appearances matter, even for medications. This finding in New Zealand is replicated in a study. For pain relief, painkillers with a fancy appearance, special labeling, and advertising were compared to plain packaging, despite containing the same active ingredients. Fancy packaging led to greater analgesia (Faasse & Martin, 2018). Secondly, it shows that the nocebo effect can also be triggered by media reporting. Before it was in the news, there were hardly any complaints. This once again demonstrates that awareness plays a significant role in amplifying the nocebo effect. This is supported by several studies showing how the media can trigger symptoms (Faasse, Cundy, & Petrie, 2009).
Pain-Boosting Chemicals
We've seen previously that it's crucial to manage expectations. For instance, by changing the appearance of a medication to look cheaper, its effectiveness decreases, especially when extensively discussed in the media. So now the question arises: what causes this deterioration in outcomes?
It appears that cholecystokinins play a significant role. This is a natural chemical produced by our brains for digestion and appetite. However, there's also evidence that cholecystokinin plays a role in anxiety and panic. In our case, it's possible that due to a lack of trust in pain medication, the person fears that the pain will persist or worsen. This fear triggers the release of cholecystokinin, which, in turn, facilitates pain transmission. This reaction sets off a vicious cycle of anxiety and pain, which can explain the nocebo effect (Colloca & Benedetti, 2007; Benedetti, et al., 2006).
So, just as positive expectations of pain medication can activate the production of natural painkillers like endorphins, negative expectations activate pain-boosting chemicals like cholecystokinin. The same researchers also studied what happens in the brain after having negative expectations. They found that negative expectations also activated the so-called pain blueprint in the brain. Essentially, this puts the pain control center in your brain into overdrive, increasing the volume of pain (Colloca & Benedetti, 2007).
In short, negative thoughts don't just affect your mood. They can change your biology, upgrading your pain-producing machinery with the production of pain-enhancing chemicals. This is clearly an upgrade we'd rather not have. Fortunately, thoughts can be changed. We can transform harmful thoughts into positive expectations.
The Ethical Dilemma
As we review the literature, it's clear that providing information about possible side effects can backfire. Often, awareness triggers the nocebo effect. But keeping patients completely in the dark is also unethical. Instead, we need to find a way to communicate the risk while emphasizing the positive outcomes. In the Netherlands, the government has already experimented with redesigning prescriptions. They reduce the list of side effects and make them less prominent while highlighting how the medication helps.
How Does Pain-Changer Address the Nocebo Effect?
Improving your pain medication can be done in two ways. Firstly, we can enhance the placebo effect, flooding your body with natural painkillers. Secondly, we can reduce adverse forces by addressing the nocebo effect. We do this by providing our clients with stories that demonstrate the power of the nocebo effect. Simply being aware of the nocebo effect can significantly minimize its consequences. Additionally, we educate our clients on how it works, work on reframing thoughts and expectations, and design our products to minimize the nocebo effect.
Curious about how we exactly approach this? Get in touch or sign up for one of our services to experience it for yourself. Ultimately, we aim to reduce pain levels for all patients with chronic pain by eliminating any nocebo effect present in their lives.
If you've benefited from this content in any way, please share it with your network and help us spread the message. Let's upgrade our pain medication so we need less of it.
References
Benedetti, F., Amanzio, M., Vighetti, S., & Asteggiano, G. (2006). The biochemical and neuroendocrine bases of the hyperalgesic nocebo effect. Journal of Neuroscience, 26(46), 12014-12022.
Brazil, R. (2018). Nocebo: the evil twin of the placebo effect. The Pharmaceutical Journal, 300(05).
Colloca, L., & Benedetti, F. (2007). Nocebo hyperalgesia: how anxiety is turned into pain. Current Opinion in Anesthesiology, 20(5), 435-439.
Hansen, E., & Zech, N. (2019). Nocebo effects and negative suggestions in daily clinical practice–forms, impact, and approaches to avoid them. Frontiers in Pharmacology, 77.
Faasse, K., Cundy, T., & Petrie, K. J. (2009). Thyroxine: anatomy of a health scare. Bmj, 339.
Faasse, K., & Martin, L. R. (2018). The power of labeling in nocebo effects. International review of neurobiology, 139, 379-406.
Flaten, M. A., Simonsen, T., & Olsen, H. (1999). Drug-related information generates placebo and nocebo responses that modify the drug response. Psychosomatic medicine, 61(2), 250-255.
Kaptchuk, T. J., Stason, W. B., Davis, R. B., Legedza, A. R., Schnyer, R. N., Kerr, C. E., ... & Goldman, R. H. (2006). Sham device v inert pill: randomised controlled trial of two placebo treatments. Bmj, 332(7538), 391-397.
MacKrill, K., Gamble, G. D., Bean, D. J., Cundy, T., & Petrie, K. J. (2019). Evidence of a media-induced nocebo response following a nationwide antidepressant drug switch. Clinical Psychology in Europe, 1(1), 1-12.
Petrie, K. J., & Rief, W. (2019). Psychobiological mechanisms of placebo and nocebo effects: pathways to improve treatments and reduce side effects. Annual Review of Psychology, 70, 599-625.
Reeves, R. R., Ladner, M. E., Hart, R. H., & Burke, R. S. (2007). Nocebo effects with antidepressant clinical drug trial placebos. General hospital psychiatry, 29(3), 275-277.
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