Placebo analgesia – the real deal?

BY Charley Boleys

The word placebo often evokes connotations of unreliability and fallacy, seeming particularly out of place in the context of clinical use. Placebo is generally thought of as an elusive concept, just the impressive ‘power of the mind’ which produces results with no efficacious treatment.

However, placebo analgesia, or pain relief, differs from your average placebo effect as it is thought to induce analgesia through the release of endogenous opioids. It also can be reversed by the administration of naloxone, commonly known as the opioid overdose reversal drug. The neurobiological effect paired with conditioning and expectations of pain relief allow placebo analgesia to elicit powerful results. Conditioning occurs in the way Pavlov achieved with his dogs, with them automatically salivating at the sound of a bell after repeatedly receiving food when they heard the bell. In this case, the association of an active treatment with the way person receives the treatment, for example through a pill or injection, is enough to evoke a therapeutic effect.

The current standard of pain management in the UK is relatively limited. According to the NHS 43% of people suffer from chronic pain in the UK, yet a notable dearth of successful long-term pain relief persists. Though opioids are thought to be the gold standard in pain management, they are accompanied by numerous negative side effects that are relatively common, with one of the most notable downsides being the highly addictive nature of the drug. Placebo analgesia has been shown to induce results as strong as doses of morphine and other opioids in pain studies when the patient is under the illusion that they are taking an actual painkiller.

In terms of using placebo analgesia in a clinical setting, I know what you’re thinking: you can’t lie to patients, and how would you ever go about implementing a legitimate, above-board placebo prescription without the consent of the patient themselves? Well, in short, you can’t. Not only would this completely undermine the autonomy of the patient but also the legitimacy of the healthcare system. When you go to the doctor for a prescription, you expect the drug to at least have an active ingredient, right?

Recent studies amongst experts have revealed a very exciting new potential for placebo analgesia in which the patient actually isn’t lied to about what it is they’re taking. This ‘open-label placebo’ is a relatively recent phenomenon in which patients are informed that what they’re being administered has no active ingredient, and therefore may or may not reduce their pain. This was shown in one of the earlier studies of patients with IBS: of those who had received an open-label placebo, 60% reported ‘adequate relief’ of their symptoms compared to only 37% of the no-treatment control group.

Dr Ted Kaptchuk is a professor of medicine at Harvard who has spent years focusing on the placebo effect. Work into open-label placebo bypasses the ethical issues associated with deception and presents a new type of treatment for patients whose conditions are notoriously hard to treat, such as IBS, and for patients who are not receptive to current analgesic medications. In a study Kaptchuk and colleagues carried out in 83 people with chronic lower back pain, those who received open-label placebo plus the usual treatment had a 28% reduction in pain as opposed to those who just received the usual treatment, showing a 9% reduction. Additionally, in a study of cancer patient fatigue, Kaptchuk found that after three weeks, those randomised to receive open label placebo reported 29% improvement in fatigue compared with 10% for the usual treatment control. Kaptchuk asserts that clearly these placebo effects cannot cure someone’s cancer, or shrink tumours, but may be an avenue of treatment for cancer related symptoms with high placebo responses such as nausea, pain and fatigue. The current trials have all been relatively small in population size and of short time frames: replications of these trials with larger sample sizes and for longer duration would be necessary.

The underlying mechanisms, both psychological and neurobiological, are relatively unknown for open-placebo, so further investigation would definitely be needed. While the future for open-label placebo in clinical care is uncertain, in a world where pain relief is still not anywhere up to the standard it needs to be, this alternative cannot be ruled out. The acquirement of understanding of open-label placebo could pave the way for a new, less harmful and potentially successful treatment for pain.

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