The Nocebo effect, dramatically illustrated …
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.
Read the entire article here.
A recent ‘meta-study’ claims that placebo are NOT, in fact, on par with conventional antidepressant medications, as we have reported numerous times in this blog. It seems, however, that this study should be read with certain caveats, most particularly that “The review’s authors have acknowledged that almost 80% of the studies they analysed had been funded by the pharmaceuticals industry.” (Fawning Coverage of New Antidepressants Review Masks Key Caveats) Confirmation bias, anyone?
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.”
Download the study ‘A systematic review of sex differences in the placebo and the nocebo effect’
We know that communication matters – in regard to any human exchange and any human relationship. We can also consider the words we use, and the way we use them, in relation to their value as ‘placebo’. The effectiveness (or ineffectiveness) of communication can generate a placebo (or nocebo) effect, evidenced very clearly in the way that health practitioners interact with their clients, as illustrated in this article in the Irish Times, “Doctors Say One Thing. Patients Often Hear Something Else”.
“How patients frame questions and how doctors frame advice is an important element in successful health communication. Behavioural economists describe a phenomenon known as loss aversion: as humans, we are primed to feel losses nearly twice as heavily as we appreciate gains.
So for actions that we perceive as risky, a health message that presents the lack of action as an even greater risk is more effective. However, for actions that we don’t see as especially risky, presenting the action itself as beneficial has been shown to produce a better behavioural response.”
No, seriously, do they?
“Is the placebo effect biologically real? We’re not sure. But, if it is, then it is safe to say that it evolved over time, that it confers some survival advantage, and most importantly, it should also be able to be seen in other organisms. It has been reported in rats on occasion. But, what if we could study the placebo effect in lower organisms like fruit flies (Drosophila melanogaster) or worms (Caenorhabditis elegans)?
In the study of aging, these tiny, but powerful animals who age quickly, make it easier to do many experiments in a shorter period of time. Worms, in particular, are a fantastic model for the field of dietary restriction (DR), a programmed method of reducing calorie intake and the most scientifically sound method of extending lifespan. But in worms, the extended lifespan offered through DR is disrupted by the smell of food which tricks their bodies out of DR mode and stops the extension of life.”
Check out Simon C. Harvey, Chris J. Beedie, “Studying placebo effects in model organisms will help us understand them in humans” Biology Letters. 29 November 2017 or read the ACSH article here.
A recent ‘meta-analysis’ of the placebo effect on the use of anti-depressants in children and adolescents (shudder …), based on data from trials involving more than 6,500 children and adolescents up to the age of 18, has been published by the University of Basel and Harvard Medical School and published in the journal ‘JAMA Psychiatry’.
The most common mental disorders in children and adolescents include anxiety disorders, depressive disorders, obsessive-compulsive disorder, and post-traumatic stress disorder.
“The results of the meta-analysis show that, although antidepressants work significantly better than placebos across the range of disorders, the difference is small and varies according to the type of mental disorder. However, the results also showed that the placebo effect played a significant role in the efficacy of antidepressants. The study also found that patients treated with antidepressants complained of greater side effects than those who received a placebo. The side effects included everything from mild symptoms such as headaches to suicidal behavior.”
‘Suicidal behaviour’ as a ‘side effect’ … Really?
Consistent with other posts through this blog, the analysis also shows that the placebo effect is stronger in cases of depression.
The placebo effect is one of the most mystifying phenomena in medicine. When we expect a pill to make us feel better, it does. If we see others get better while using a medicine, we will too.
But the placebo effect has an evil twin: the nocebo. It can kick in when negative expectations steer our experience of symptoms and create side effects where none should occur.
This means, incredibly, that you can get side effects from a sugar pill. And sometimes these side effects are so severe that patients drop out of clinical trials. More info here.
Recent evidence suggests that the muscle aches might be a big nocebo.
Whether you know you’re taking a placebo pill or not, it will still have a beneficial effect, new research has revealed (Is the rationale more important than deception? A randomized controlled trial of open-label placebo analgesia.)
Scientists from Harvard University and the University of Basel prescribed a group of minor burn victims with a “treatment” cream, telling only some of them that it was a placebo.
After the cream was applied, both groups reported benefits, despite the placebo cream containing no medicine.
Read the full article here
On the subject of Open Label Placebos, here’s a link to research on their efficacy in chronic lower-back pain.
A new study finds that people who have a better handle on their negative emotions may be more likely to experience a stronger placebo effect. Researchers at the University of Luxembourg found that participants who were better at interpreting negative events in a positive light felt more relief from a placebo pain-relieving cream.
The placebo effect has traditionally been viewed in a negative light; however, within the last decade, researchers have investigated the placebo effect itself and found that placebos can trigger real biological changes in the body, including the brain.
In a related article:
“All participants reported less pain: the placebo effect was working. Interestingly, those with a higher capacity to control their negative feelings showed the largest responses to the placebo cream in the brain. Their activity in those brain regions that process pain was most reduced. This suggests that your ability to regulate emotions affects how strong your response to a placebo will be.”
“Branding acts like a placebo. It changes consumer perception and, in turn, those perceptions alter the nature of the product.”
Read the fascinating story of Lieutenant Colonel Beecher here (as well as a commentary on the placebo effect in marketing).
A recent example? The internet recently has been alive with stories about research into the placebo effect and our apprehension of the quality of wine – and, perhaps worryingly for some, the brain functions which govern our actual experience of its taste! (Hint: higher price = higher quality).
Here’s a sample article: Why expensive wine appears to taste better: It’s the price tag. The authros point out:
“Price labels influence our liking of wine: The same wine tastes better to participants when it is labeled with a higher price tag. Scientists have discovered that the decision-making and motivation center in the brain plays a pivotal role in such price biases to occur. The medial pre-frontal cortex and the ventral striatum are particularly involved in this.”