When is a placebo not a placebo? It seems that placebos are no as ‘unreactive’ as the literature would suggest. Research hastened and made more urgent by the rushed efforts to develop a Covid-19 vaccine have revealed the need to create a standard for the actual content/ingredients of the placebo used in a given trial.
“Some researchers conducting clinical trials on a COVID-19 vaccine have not revealed to the public what the placebo contains, but they should. This is because the placebo ingredients influence how effective or harmful the active treatment, with which the placebo is compared, appears.”
Later, the article continues:
“Placebo controls are rightly the gold standard against which new treatments are measured. If a new treatment proves to be better than a placebo, it is taken to be effective. Otherwise, it isn’t. The problem is that until today, there has been no standard for placebos, which made estimates of side-effects confusing. Our new guideline fixes this problem by encouraging rigorous reporting of placebo ingredients.
We’ve known about the failure – and need – to report what’s in placebos for 15 years. By following the new guideline, we can get more accurate information about how beneficial and harmful treatments tested in placebo-controlled trials are.”
We all know about the ‘nocebo’ effect by now – the dark twin of the beneficial placebo effect. For example, a study showed that the pharmacological efficacy of remifentanil (a pain medication) was significantly decreased after patients were told the infusion was stopped during a heat-pain modulation test. Although the infusion had not actually been halted, participants experienced a significant exacerbation of pain even while still receiving remifentanil.
To counter undesirable ‘nocebo’ effects, this article suggests to health practitioners that ‘pragmatic strategies related to patient–practitioner interaction, clinical setting, and context may be implemented to help minimize and prevent the consolidation of negative expectations’.
There is some evidence – for example, in this study – that simply receiving the results of DNA tests can have a physical impact. Why? Well, once more the Placebo Effect is mentioned (as well as its dark twin, the Nocebo Effect, also covered on this website.
DNA tests are becoming quicker, cheaper and more reliable, so this is an issue we’ll hear more about.
We’ve posted elsewhere about the placebo’s dark twin, the nocebo, the phenomenon of the mind provoking negative and damaging effects through the same mechanism that accounts for the positive effects of a placebo.
This paper brings focus to ‘nocebo algesia and hyperalgesia (ie, the occurrence and worsening of nocebo-induced pain, respectively)’ and makes practical suggestions for reducing the incidence of this. As always, these relate to the patient-practitioner relationships and interactions, and strongly reinforce the ‘subjective’ and ‘negotiated’ nature of the experience of pain.
‘In general, the literature shows that uncaring interactions that convey a message of invalidation and lack of warmth may trigger nocebo effects. Avoiding negative communication and interactions with a patient may help to shape a safe and positive environment that not only promotes placebo effects but that also reduces nocebo effects.’
It is becoming increasingly clear that the placebo effect has a great influence on medical treatment. An international, interdisciplinary team of researchers led by Professor of Health Psychology Andrea Evers from Leiden University has now written a first set of guidelines on how to apply the placebo effect in clinical practice, published in Psychotherapy and Psychosomatics.
It was the result of the first official conference of the Society for Interdisciplinary Placebo Studies (SIPS), which was held in Leiden last year. During an interdisciplinary workshop led by Evers, a group of leading international researchers reached the consensus that knowledge about placebo and nocebo effects could lead to better treatment results with fewer side-effects. According to the researchers, it is crucial that patients receive more information about these effects, and that doctors receive training on the best doctor-patient communication to maximise placebo effects and minimise nocebo effects.
Several years ago, a published case study describes a 26-year-old man who was taken to the emergency room. After arguing with his ex-girlfriend, he attempted suicide by swallowing 29 capsules of an experimental drug that he obtained from a clinical trial that was testing a new antidepressant. When he arrived at the hospital, he was sluggish, shaking, and sweating and had rapid breathing. His blood pressure was extremely low at 80/40, and his pulse was 110.
Doctors were successful at raising his blood pressure. Over the course of four hours, they injected him with 6 liters of saline solution. His blood pressure increased to 100/62, which is at the lower end of the normal range, but his pulse remained high at 106.
What finally cured the patient wasn’t anything the emergency room staff did. Instead, a doctor from the clinical trial arrived at the hospital. He told the patient that those antidepressant pills weren’t antidepressants because he had been randomized into the control arm of the trial. Yes, that’s right: He overdosed on placebos.
Within 15 minutes, the patient’s blood pressure stabilized at 126/80, and his heart rate dropped to a perfectly normal 80 beats per minute.
Do males and females respond differently to the placebo effect? This review of 18 studies concludes that “1) males responded more strongly to placebo treatment, and females responded more strongly to nocebo treatment, and 2) males responded with larger placebo effects induced by verbal information, and females responded with larger nocebo effects induced by conditioning procedures.”
It seems “that … differences in the placebo and nocebo effects (are) probably caused by sex differences in stress, anxiety, and the endogenous opioid system.”