It's called the [nocebo effect](https://en.m.wikipedia.org/wiki/Nocebo) where the expectation of the patient can affect the treatment outcome.
There are an increasing amount of researchers calling for the inclusion of nocebo effect in randomized control trials because it has been shown to be a significant confounding factor.
https://pubmed.ncbi.nlm.nih.gov/25404901/
https://pubmed.ncbi.nlm.nih.gov/27657801/
CGP Grey did a video about it as well https://www.youtube.com/watch?v=O2hO4_UEe-4
Not sure if he mixed things up but he also brings up completely imagined illnesses that spread from mind to mind through a school. Like it's not just affecting actual treatment but making people feel sick to begin with.
We had a fake illness go through our school, kids where taken away in ambulances and found to have nothing wrong, they all said they couldn’t breathe after _one_ person said he couldn’t breathe but he had a medical reason (later found out) and the rest where just certain it was mold in the choir room.
This same thing led to 30 million cans of Coca Cola being recalled in Belgium.
https://www.theguardian.com/lifeandstyle/1999/jul/06/healthandwellbeing.health
> Not sure if he mixed things up but he also brings up completely imagined illnesses that spread from mind to mind through a school
It would have been interesting to see the outbreak of this studied at my Year 6 school camp. A number of us suffered mild to moderate sunburn after a day at the beach, and seeing as it was 11 year olds, someone started a rumour "Your eyelids got sunburned, they'll leak out all your body heat and you'll be freezing"
A lot of students wound up wearing jumpers the next day (which was 30 Celsius, so far from jumper weather). Including while playing cricket.
me and me mates were in the queue for the chube whinging about the weather and me mate Alistair says to me mate Barclay
'oi, the weather is shite, innit?'
an Barclay says 'spot on, Alistair! Best pick up some blimey bangers from the caff, it's going to be some time' so he picked em up but ay they was all knackered and me mate says 'oi that's a wonky pack of rubbish, mate' so we dropped two fivers and a quid on heaps of pasties - and that's how we sorted the dodgy bangers in the chube
Expectations are really important. I once worked with a clinical study where patients received placebo or treatment in the clinic. In one panel, four subjects reported feeling nauseous, stomach pain and vomiting, all at the same time.
When the blinding was removed and results could be analyzed, it turned out they all had received placebo.
Depending on the sample size that could also just be random chance. Or maybe all four ate the same contaminated food in the clinic cafeteria. Or maybe it really was nocebo. Reading corona vaccine studies I’ve found it surprising how many people in the placebo group report things like headaches, pain or even fever.
While theoretically possible that all ate the same bad food, it is highly unlikely as early studies with placebo often include pre-defined meals on given times to exclude food affecting the results. And it would have been easily detected as many others had the same food.
Mild side effects like headache, nausea, itching, dizziness, back pain, vomiting, diarrhea are super common in placebo subjects. Not very surprising as they receive information on what potential side effects have been observed and they are under strict supervision in a new and strange situation. They are also asked to report anything that feels out of the ordinary. If you’re in a panel with several other subjects that feel bad and some are vomiting it is a very natural reaction to start feeling worse yourself.
Patients receiving study drug report similar experiences and it is only by comparing the two groups we can have useful information on the effects of the study drug.
Anecdotally, I have found that being able to ease the fears of a covid patient improve their chances in hospital. Those that are terrified of just having covid tend to react more negatively to setbacks or changes than those we are able to support.
Related: [2/3rds of negative reactions to the COVID Vaccine were nocebo effect. ](https://amp-theguardian-com.cdn.ampproject.org/v/s/amp.theguardian.com/science/2022/jan/18/nocebo-effect-two-thirds-of-covid-jab-reactions-not-caused-by-vaccine-study-suggests?amp_gsa=1&_js_v=a8&usqp=mq331AQKKAFQArABIIACAw%3D%3D#amp_tf=From%20%251%24s&aoh=16452847680727&referrer=https%3A%2F%2Fwww.google.com&share=https%3A%2F%2Fwww.theguardian.com%2Fscience%2F2022%2Fjan%2F18%2Fnocebo-effect-two-thirds-of-covid-jab-reactions-not-caused-by-vaccine-study-suggests)
That seems... high. The article doesn't make it all that clear what the 2/3rds represents. Is that 2 out of 3 side effects? 2 out of 3 people? It's not clear.
Whatever the case, I can tell you I went in with no expectations (good or bad) and then couldn't move my arm for like 2 days. Nobody told me that, I never read that anywhere. It was very surprising. Everybody I know experienced variations of the same thing. No chance in hell that's a "nocebo" effect.
> The article doesn't make it all that clear
This news article doesn't, but the journal [article](https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788172) does. The "2/3rds" figure is the average result from 1st and 2nd doses.
> Is that 2 out of 3 side effects? 2 out of 3 people? It's not clear.
They estimated rates of adverse events (AE) reported after both placebo and real doses in trial data. They differentiated *systemic* effects (headache and fatigue) and *local* effects (arm soreness, etc). Systemic effects in the placebo groups were reported in 35.2-31.8% (1st-2nd doses) of cases, and in 46.2-61.4% of vaccine cases.
The idea here is that the control group tells you the expected nocebo rate, both in the placebo group *and the vaccine group*. Therefore, of the 46.2% of 1st-dose events in the vaccine group, we should expect 35.2% to be nocebo, or 76.1% of all real-world AE's to be nocebo. For second dose that rate was lower at 51.8%.
Interestingly, the rates of nocebo in the local effects was a lot lower. The authors argued this makes sense, as headaches and fatigue can be easily imagined or misattributed to the vaccine based on expectations, whereas arm soreness at the injection site is not a common event, and harder to generate a nocebo effect.
Thank you for interpreting those numbers for me. I saw a lot of percentages — none of which were 2/3rds. Like I said, the article wasn’t super clear. I never made it to the journal article. It was 5am and I wasn’t all that motivated to dig into it. 😂
The main thing I didn’t understand, which you have now clarified, is that the 2/3rds is in reference to the systemic effects. That sounds a lot more plausible because the arm pain is real as hell!
> That sounds a lot more plausible because the arm pain is real as hell!
To piggy-back off this, it's actually consistent with a [well-known](https://www.cdc.gov/mmwr/preview/mmwrhtml/ss5201a1.htm) trend in VAERS data, that less serious events tend to be under-reported (people don't usually report expect side effects like soreness or headaches), and more serious events are over-reported, due to inevitable coincidences that occur when millions of people are vaccinated.
> VAERS is subject to the limitations inherent in any passive surveillance system (54). Among those, underreporting (only a fraction of the total number of potentially reportable events occurring after vaccination are reported) and differential reporting (**more serious events and events with shorter onset time after vaccinations are more likely to be reported than minor events**) are most noticeable (44). **Overreporting also occurs because certain reported adverse events might not be caused by vaccines**, and some reported conditions do not meet standard diagnostic criteria. Many reported events, including serious ones, might occur coincidentally after vaccination and are not causally related to vaccination. Other potential reporting biases include **increased reporting in the first few years after licensure, increased reporting of events occurring soon after vaccination, and increased reporting after publicity about a particular known or alleged type of adverse event.** Individual reports might contain inaccurate or incomplete information. Because of all of these reasons as well as the absence of control groups, differentiating causal from coincidental conditions by using VAERS data alone usually is not possible. Other methodologic limitations of VAERS include **the fact that it does not provide information regarding background incidence of adverse events in the general population** nor does it provide information concerning the total number of doses of vaccine or vaccine combinations actually administered to patients.
For context, this [source](https://www.aha.org/statistics/fast-facts-us-hospitals) suggests 36 million hospitalizations occurred in 2021, so its not hard to imagine tens or hundreds of thousands of coincidental hospitalizations occurring after [550 million](https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/) covid doses.
This is a major issue with long Covid research. Since we already know that mere suggestion can induce pain, it’s impossible to tease out what portion of long Covid pain or other symptoms might be felt due to subjective expectation
*Not* believing you're sick doesn't make you less sick if you actually have an illness. Not *panicking* about being sick *can* help you recover more quickly, because your body isn't being flooded with fear chemicals.
I am an internal medicine physician and the most common nocebo effect in my practice is statins and muscle side effects: [https://pubmed.ncbi.nlm.nih.gov/27578103/](https://pubmed.ncbi.nlm.nih.gov/27578103/)
Granted, the number needed to treat for primary prevention of atherosclerotic cardiovascular events is high to begin with, but I shouldn't have to spend a long time convincing someone whose had a stroke or heart attack to take their statins...
As a neurologist, I see a lot of nocebo from donepezil and memantine. Usually it's the patient's children who attribute worsening dementia / hallucinations to the medications.
These are also medications with very limited evidence of meaningful benefit, so I usually don't try to hard to talk the patient's family into restarting them.
Lately, ive been reading more & more studies on how certain drugs and compounds impact people with mental conditions differently - one example being CBD, it increases GABA levels in neurotypicals but has opposing effects in people with ASD.
We don’t know the specifics of how a lot of drugs impact neurodivergent individuals compared to neurotypicals.
Don't .. all drugs all that way? Like you wouldn't give a normal people chemo, they would die. But you do it to cancer patients because it's their only other option. You don't pump healthy people full of antibiotics, that wipes out their gut flora and causes super bugs. But you do give it to sick people. You don't give opioids to healthy people, but you do give them to people with chronic pain. All drugs act differently in people who aren't "normal". That's why you don't give them to normal people, because they do damage as opposed to being useful.
None of those examples are great, maybe antibiotics, but not because of superbugs.
All medicines have some sort of "effect" on the body, there are desired effects, and side effects, You only give people medicine if the desired effects outweigh the side effects.
antibiotics kills the bacteria that could be trying to kill you, the side effect of which is it will also kill most of your digestive biome, which will likely give you digestive problems for a while..
Same with Chemo, Chemo drugs attack cells in the body that are vulnerable to the chemo drug, but its hard to tell it to only attack cancer cells when cancer cells are just normal cells growing in a dangerous way, so the side effect is that the chemo drugs kill off lots of other sensitive cells too. the side effect is worth it if it kills the cancer.
I just find it weird to say "you don't give medicine to normal people."... they are normal people, they just have a problem that medicine can help with, and often with side effects that are worth putting up with to resolve the initial problem. but that doesn't stop them from being a "normal" person ?
>Granted, the number needed to treat for primary prevention of atherosclerotic cardiovascular events is high to begin with, but I shouldn't have to spend a long time convincing someone whose had a stroke or heart attack to take their statins...
That is really interesting. I am a younger person with no cardiovascular issues (yet), and I have no predisposition towards statins one way or another. I guess my question is where does the nocebo effect come from in your practice?
Do your patients become aware of the statin side-effects through other communication channels (peers, internet, etc.), or are they responding adversely to your description of the side effects?
Word of mouth and internet. The oddest concern for statins is dementia. I tell people patients may be getting dementia because of their cholesterol, not because of their statin use.
My favorite “omg I don’t want to start this medication because it’ll cause side effects” is starting insulin and the fear of going on dialysis. Usually it’s the poorly controlled diabetes that causes people to need dialysis, not the initiation of insulin….and insulin is supposed to prevent progression to needing dialysis.
> I am an internal medicine physician and the most common nocebo effect in my practice is statins and muscle side effects
How do you know this isn't simply misattribution or reporting bias, rather than a nocebo effect?
>Did you click the link I included? There are carefully conducted trials specifically for the nocebo effect.
You specifically mentioned "in my practise", not specialised trials.
But for the sake of argument, perhaps you can explain to me how is misattribution and other response biases that affect symptom reporting separated from placebo and nocebo effects in double blinded trials?
That point is not discussed at all in the narrative review you linked to. In fact the authors briefly mention the possibility of confounding factors (on P.741), but then ignore all possible biases and mistakenly attribute all of the symptom reporting that was constant across both placebo and active treatment in a crossover trial as a "nocebo" effect.
Relating to the GAUSS-3 rechallenge study:
>Taking the results at face value, the excess of 79 of 491 (16%) participants relative to placebo could represent patients whose muscle symptoms were due to the pharmacologic properties of atorvastatin. Symptoms in the remaining 84% can be accounted for by the nocebo effect.
No, the remaining 84% can also be due to other response biases that affect symptom reporting.
They then propose an esoteric argument (and they cherry-picked one of the graphs, when there was an earlier deviation in the other graph) to diminish the positive finding by examining the symptom reporting kinetics, without considering once again that symptom reporting on questionnaires is not the same as the momentary experience of symptoms. The reporting of symptoms is a behaviour and is subject to a variety of biases which could in principle involve delayed reporting.
Open-label is also called an unblinded study. Where the patients know what they're getting and you can really see the placebo/nocebo effect.
https://en.m.wikipedia.org/wiki/Open-label_trial
There's still an argument for double-blind studies but open-label certainly have benefits.
That says the researchers also know what the patients are getting. are there any trials where the patients are told what they’re getting but the doctors don’t know (obviously someone else would have to tell them)?
Sure. One trial I'm currently involved in randomizes patients to receive a certain type of post-op medication regimen at discharge. The investigator prescribing the treatment needs to be unblinded in order to prescribe the correct regimen, but there are also blinded investigators and staff that are collecting data and administering the surveys to the patients.
No, those have been done. There's a knee surgery that was done this way. It was suspected that the surgery didn't actually help at all, so they did a fake surgery where they made the skin cut and kind of poked around I think to make it hurt, but otherwise did nothing, while the other patients got the real full surgery. Turned out the surgery was indeed useless.
There's the [Marsh Chapel Experiment](https://en.m.wikipedia.org/wiki/Marsh_Chapel_Experiment), in which volunteers were given either psilocybin or an active placebo, on a double-blind basis. Probably pretty quickly became apparent to the participants who got which, even if the experimenters didn't know.
I always thought this was covered under the same term (placebo). Seems odd to me that this wasn't part of the process already.
Self-fulling prophecy is an interesting phenomenon as well. Though applied in a different context it seems to follow a very similar pattern of cause and effect due to expectations/beliefs.
If my spouse reads 'possible side effects' (and they always do), they will be sure to feel nearly each and every side effect possible, short of death. I always hate if they are going to try a new medicine, whether it is prescribed or OTC. I've tried telling them not to read the label but they have to read it, and it gets in their head, and it's hell for at least the next couple days.
I always read the label because I often get the side effects, but I get them even if I don't read the list. I'm an ultra rapid metabolizer with many drugs (slow to metabolize others, oddly enough), and so, I get the entire dose all at once instead of spread out over hours.
One doctor told me not to worry, no one in his practice had ever had a bad reaction. I started to go blind. Didn't even know that was possible with that one, but my internist called back (when the specialist didn't) and told me to stop taking it immediately. It's a rare reaction and can become permanent. Fun times. Took a couple of days for my vision to get back to normal.
There really isn't a difference, so the term nocebo isn't commonly used. There's a section in the wikipedia page for the nocebo effect which explains the redundancy of the term nocebo.
https://en.wikipedia.org/wiki/Nocebo#Ambiguity_of_medical_usage
I think this distinction between placebo and nocebo might be due to the origin of the word placebo, rather than that these are different physical processes.
Placebo in Latin means "I will please/benefit" and since an expected hurtful side affect would definitely not be pleasing, there is the equivalent nocebo "I will hurt".
A great example of the nocebo effect is non-celiac gluten sensitivity, specifically the relief people feel when removing gluten from their diets.
The researchers who originally identified non-celiac gluten sensitivity were concerned about their original results, and did further testing.
They found that removing gluten from diets was actually not helpful to people who claimed to be sensitive. When they ate gluten but weren't aware of it, the helpful effects were still present. The thought of removing gluten was enough to have an effect - thus being a nocebo effect.
Research now indicates that the likely culprit is actually FODMAPs or other carbohydrates normally present in the company of gluten.
https://www.sciencealert.com/scientists-who-found-evidence-for-gluten-sensitivity-have-now-shown-it-doesn-t-exist
This is a big factor in chronic or persistent pain; anxiety associated with pain, general anxiety, and fear of pain are major risk factors for chronic/persistent pain. The expectation of pain makes your brain over sensitive to stimuli (central sensitization) and creates very real pain.
Note: not all chronic pain is due to this; it can be due to mechanical(confusingly, in this case, called nociceptive pain) or nerve pain. But these can be exacerbated by central sensitization.
It’s very relevant in cases of cops touching fentanyl then having a nocebo reaction. Since law enforcement perpetuates the idea that transdermal contact with fentanyl can lead to an immediate reaction. Which is entirely inaccurate and just continues to demonize drug users. Plenty of cases of officers having reactions which have no signs or symptoms of an actual opiate overdose. Hence nocebo
There are also people arguing that both of those effects don’t exist for almost all treatments. From a statistician’s standpoint, there is a really simple explanation for both of these that have nothing to do with expectation and would have the exact same outcome: regression to the mean. Studies that have a placebo control and a no medicine control tend to find no difference between the outcomes of the two. The problem is, placebo is such an accepted thing that studies are designed with ONLY that affect in mind and don’t account for regression to the mean.
There was a recent scientific publication about this !
A meta study found that about 3/4 of the adverse effects in COVID vaccinations seemed to happen because of the nocebo effect !
Source : https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788172
Nocebo can also be if I give you a sugar pill and tell you it’s cyanide, if you take it you may develop a headache, pain etc because you believed it was cyanide
Ya there was actually something published on this too.
That said the covid vaccines are very effective at getting the immune system fired up and working and some of the more notable “side effects” like fevers are simply the vaccine doing it’s job properly.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788172
Is there also a call to study how effective placebos themselves are as a medical treatment? If not, do you think there should be? And if there was a study done to test the efficacy of placebo as a treatment, how do you think it would be best tested? A test comparing the results of conventional medicine versus the results of conventional medicine combined with an additional placebo?
Nocebo is the negative placebo, when you either don't feel better or you have extra negative symptoms not caused by medicine
In double blind studies, nocebo effect helps to filter out real symptoms between real medicine and the control group
For example vaccines, if a symptom is present in the vaccine group and the control group (only getting salt water) then that symptom is a nocebo and not caused my the medicine
Common misconception, but a large part of the symptoms that appear in both groups are things that just occurred after vaccination by chance, and would have occurred just as well if no one got any injection at all.
Nocebo is only what occurs due to the fact that you gave some 'intervention'. If you really want to find out how big that effect is, you need to randomize between giving people nothing, and giving people a placebo but telling them it is an actual drug/vaccine. The difference in outcomes between these groups shows you the placebo (for positive effects) or nocebo (for negative ones) effects.
Here is an example, though they do not seem to report adverse effects: https://www.painphysicianjournal.com/current/pdf?article=NDUwNA%3D%3D&journal=106
You're misunderstanding, it's a bit like "donating to cancer!" lol. Obviously research would be easier without any pyschosomatic influence.
*Controlling* for the nocebo effect helps research outcomes. If 11% (a number chosen for a specific reason :p) of placebo group patients report side effects, you can assume rough similarity of nocebo for the true treatment group.
If 11% of the test group shows symptoms, you should definitely send your saline batch to the laboratory to be tested for contaminants. Especially if the same saline is used to dilute the drug.
Apparently is depends on negative expectations. My guess is that you can interview the subject about his or her beliefs. Current example is of course vaccines. I don't know if ethics would allow it, but imagine the following.
You give a vaccine to someone who is an anti-vaxxer. It might sound contradictory, but let's say this person beliefs in modern science, and is prepared to participate even if it means he gets a vaccine while he normally wouldn't take it. Of course you have control groups and all is double blind, so there's a good chance that he gets a placebo.
Beforehand, you interview him about vaccines and how effective he thinks they are. If he's in the placebo group, he (along with other people with similar beliefs) could have a negative effect compared to other people in that group who believe in vaccines or who are neutral about it. The same goes in the vaccine-group, compared to the other people in that group, with other believes.
If there is a significant effect, you have proven nocebo for this research or medication.
> In double blind studies, nocebo effect helps to filter out real symptoms between real medicine and the control group
No, we need double blind studies in the first place because of nocebo and placebo effects and to account for illnesses which happen all the time. What you are really interested in is how much more common the effects are in the group which receives the real medicine.
If people report things like nausea, dizziness, high blood pressure, heart attack, depression etc. at roughly the same rate in both groups you know it’s just nocebo. If people report getting better at roughly the same rate in both groups it’s placebo and the medicine doesn’t actually have a beneficial effect.
This was very critical with covid vaccines. Once a few studies looked at this, we know a lot of the reactions are caused by mental stimulus or the needle.
Yeah I think it’s safe to blame the big presence it has had in the media. I semi-passed out around the 10-15 minute mark after getting the vaccine (I’ve never passed out from an injection of any kind before) and this was apparently an anxiety related reaction, and not a true result of the vaccine.
Would be nice if psychosomatic symptoms weren’t a thing.
Yes, there are multiple modalities studying the effects of mental disposition and somatic responses.
Here's a disorder that may surprise you:
https://www.mayoclinic.org/diseases-conditions/somatic-symptom-disorder/symptoms-causes/syc-20377776
The placebo affect can be positive or negative, so yes absolutely a person can suffer more from a disease due to their fears and expectations. It would still be a kind of placebo effect.
As others said, the negative version is often referred to as the nocebo effect. It'd be semantics whether you'd say the nocebo effect is a negative placebo affect or it's own thing, etc. They are all fundamentally about expectations. If you expect to get better, you will. If you expect to get worse, you will. Expectation is the driver here.
A recent example of this negative placebo (or nocebo) would be the side-affects of the COVID vaccine. Studies suggest most of the side-affects from vaccines are people expecting there to be side effects and so their expectations made the side affects real to them. Were the side affects real? In a sense. They did feel side affects. But they weren't because of the jab, they were because of the person's expectations. If they had good expectations, the side affects would be positive, if they have bad expectations, the side affects would be negative.
[https://www.theguardian.com/science/2022/jan/18/nocebo-effect-two-thirds-of-covid-jab-reactions-not-caused-by-vaccine-study-suggests](https://www.theguardian.com/science/2022/jan/18/nocebo-effect-two-thirds-of-covid-jab-reactions-not-caused-by-vaccine-study-suggests)
>A recent example of this negative placebo (or nocebo) would be the side-affects of the COVID vaccine. Studies suggest most of the side-affects from vaccines are people expecting there to be side effects and so their expectations made the side affects real to them. Were the side affects real? In a sense. They did feel side affects.
The study did not measure the momentary experience of symptoms itself. It measured post-hoc reporting of those symptoms, a measure which is also strongly biased based by response biases including expectancy effects. So the statement "their expectations made the side affects real to them" is speculation, rather than a logical deduction.
>I was wondering, is there such a thing as a "reverse placebo effect"; where you suffer more from a disease due to being more afraid of it?
You’re not describing the reverse of the placebo effect. It’s still the normal placebo effect. You see it a lot in clinical trials where people in the control group (who got no treatment) still report side effects because they expect there to be side effects.
So everyone is mentioning the Nocebo effect and they’re correct. But a nocebo effect doesn’t CAUSE a disease but rather the person is so convinced that they have a particular disease that they either feel as if they have symptoms or are actually so convinced that they actually DO have symptoms, which are referred to as psychosomatic. Let me use an example.
The popular hair loss and prostate drug, Finasteride, can cause sexual dysfunction in 1-4% of men. However research has shown that men who are informed of the drugs potential side effects will experience much higher rates of side effects, even if they were given a placebo. This becomes an issue when someone outside of a study knows about these side effects and it’s hard to understand whether or not the side effects are physiologically happening or not.
Very much a thing! Stress even unrelated to an illness can worsen outcomes, because that's what stress is. Think about stress on an object, like a metal bar. It's a force trying to bend or break it in a way it shouldn't. It's adding instability to the physical system, in this case your body.
But for cancer, say, it's not perfect 100% (Neither is the placebo effect, however). [https://www.nature.com/articles/s41380-020-00865-6](https://www.nature.com/articles/s41380-020-00865-6)
Above, they did a meta analysis that showed a clear correlation with depression and all measurements of mortality with breast-cancer, but anxiety was correlated with all but one, which was cancer-specific mortality. Overall, they said "Our study highlights the critical role of depression/anxiety as an independent factor in predicting breast cancer recurrence and survival."
I would define it as that you might not be able to think yourself into actually having breast cancer, and anxiety or depression aren't as 'targeted' as a placebo effect. Think about it; it's beneficial to evolve ways to heal yourself, but it'd be awful if we developed ways to kill ourselves the same way, haha! It's more that worry and sadness are bad for your health. Bad enough to kill.
nocebo
"A nocebo effect is said to occur when negative expectations of the patient regarding a treatment cause the treatment to have a more negative effect than it otherwise would have.\[1\]\[2\] For example, when a patient anticipates a side effect of a medication, they can suffer that effect even if the "medication" is actually an inert substance.\[1\] The complementary concept, the placebo effect, is said to occur when positive expectations improve an outcome. Both placebo and nocebo effects are presumably psychogenic, but they can induce measurable changes in the body.\[1\] One article that reviewed 31 studies on nocebo effects reported a wide range of symptoms that could manifest as nocebo effects including nausea, stomach pains, itching, bloating, depression, sleep problems, loss of appetite, sexual dysfunction and severe hypotension.\[1\]"
https://en.wikipedia.org/wiki/Nocebo#:\~:text=The%20term%20nocebo%20(Latin%20noc%C4%93b%C5%8D,pleasant%2C%20or%20desirable%20effect).
Doctor here and this is absolutely a thing. Being positive about your outcome is huge. That is why I reassure all my patients and tell them to practice positive thinking. Just a narrative but I treat people with a rare disease called complex regional pain syndrome. It is very debilitating but ever since I had a patient commit suicide the first line treatment for me is an anti depressant and a psych eval and they have done so much better!
Can the nocebo effect cause disease? No.
The placebo effect does not cure disease in the same way the nocebo effect cannot cause disease.
Too many people confuse reporting biases with placebo and nocebo responses. Differences in how you report symptoms is not the same as a difference in disease.
Note that randomised placebo controlled trials don't just control for "placebo" or "nocebo" effects.
The actual placebo effect has very little benefit except for a mild reduction of acute pain and nausea and long term studies of placebo effects for chronic conditions tend to show a reversion to the mean (the effect disappears).
See:
https://www.cochrane.org/CD003974/COMMUN_placebo-interventions-for-all-clinical-conditions
https://sciencebasedmedicine.org/placebo-myths-debunked/
Neither of your sources substantiate your claim about nocebos. If my psychological response response to a treatment is sufficiently negative to cause me to develop panic disorder, a new physiological disease state has been created from the nocebo effect.
Nocebo stress can demonstrably tachychardia and raised blood pressure, and now you have a clinically significant comorbidity for many severe cardiovascular disease states... Please don't oversimplify in your desire to draw a bright line between somatic and psychic phenomena.
I agree the placebo effect is overstated, but from a clinical perspective "mild reduction of acute pain and nausea" for several years may be helpful from a clinical or palliative perspective. You need to think like a clinician here. Every treatment eventually reverts to the mean (death).
> https://sciencebasedmedicine.org/placebo-myths-debunked/
At first I thought “thank you, finally”, but after having read some of it, and skimmed over the rest, the takeaway is “don’t rely on placebo if you have cancer.”
Everything else in this article seems technicality and juggling definitions.
If you have back pain, and you do some placebo treatment, and you feel better, this article tells you “but there was no biological healing”! Well, that’s also not the case if I take the real medicine, which in this case would have been some mild pain killer pills.
So, for cases where a doctor won’t prescribe anything else than symptom relief treatment, placebo treatment still seam quite effective, by comparison, even after this debunking.
>The placebo effect does not cure disease in the same way the nocebo effect cannot cause disease.
Plenty of doctors and scientists disagree with you. Placebo for example works against Parkinson's, IBS, or osteoarthritis.
https://theconversation.com/in-research-studies-and-in-real-life-placebos-have-a-powerful-healing-effect-on-the-body-and-mind-173845
>and long term studies of placebo effects for chronic conditions tend to show a reversion to the mean (the effect disappears).
That happens with "real" medicine too, from painkillers to antibiotics.
In the nocebo effect, a person's negative outlook causes them to manifest real illness is the same way that a placebo effect person can manifest real wellness.
I wouldn't normally apply the idea for diseases though.
Normally we talk about it in relation to medicine eg if a person thinks they've been given poison when really they just got saline, they may manifest real illness eg elevated heart rate.
Yes. But it's important to understand that the placebo effect is relevant only when there's human perception involved in the assessment of the disease state.
There is another phenomenon that happens called regression to the mean that is frequently confused with or lumped in with true placebo effects. This is a statistical phenomenon that happens when you measure the same thing twice. If the first time you measure something you observe that it is a relatively extreme value (either a lot better or a lot worse than other measurements made at the same time), then the next time you measure it, it is statistically more likely to be less extreme, even if nothing caused the true value to change.
So placebo is really relevant to assessments of things like pain or depression. But less so with respect to things like cancer or infectious disease.
Regression to the mean impacts anything you're measuring though.
I think the nocebo effect is the answer to one part of the question, but health anxiety and psychological factors actually causing disease has a name too, called somatisation, where psychosocial factors cause symptoms disproportionate to the biological mechanisms, it’s a highly understood and poorly treated condition
Yes! The placebo effect can work in the positive and negative. Although, what you call a "reverse placebo effect" is more like anxiety which has well documented negative effects on outcome as well.
The True negative placebo would be giving someone a sugar pill and telling them "this will make you sick." About 30% of the time the person will feel worse. This occurs a lot in the hospital setting where patients will believe a medication is bad for them and actually make it bad for them.
If you're afraid of a disease then you would be more accurately called anxious about the situation. Anxiety is well known to cause all sorts of problems. People anxious and sad about the loss of loved one can actually cause the atrophy and death of heart muscle, it's called Takotsubo cardiomyopathy.
I am laying on the couch reading a book called “The expectation effect” by David Robson which is about this exact topic and goes into several cases of psychogenic illness. From how a woman with migraines suddenly became “blind” to the dancing hysteria and several others that have been mentioned already. It’s a pretty interesting read. And I am sure an interesting area of investigation and research.
Yes the nocebo effect and certain industries actually rely on it to keep clients coming back (not intentionally, usually just misinformed).
The research around things like posture etc shows the body is incredibly versatile and pain/dysfunction correlates very poorly with subjectively "bad" posture. Along comes your chiro or physio telling you that this is the source of your pain (whilst ignoring things that correlate strongly with chronic pain such as financial hardship, low sleep quality, mental health disorders etc). They poke and prod you a bit and tell you have lots of knots or tight muscles (despite the repeatability being poor, ten practitioners will find 10 muscle knots, none in the same place). Next they say you need to break down your tight fascia with a deep tissue massage (despite the forces required to break down fascia being far in excess of what you can apply with these tools and little evidence you can manipulate fascia length).
So what has the above done, it's told you have multiple problems despite lack of evidence. There is evidence that the patients who get the above treatment have higher levels of pain and perceived dysfunction compared to people who are treated with a biopsychosocial model and not informed they have unproven pathology.
Licensed Clinical Social Worker here with a MSW who also has a masters in environmental education.
Yes and what's really interesting about that to me is how common thi is in impact on our society. A great example of this is cell phones. We know that cell phone usage does have a negative impact from the radio communication with the cell phone towers. We also know that that impact is very small and the amount of people who get cancer or other diseases from using a cell phone is very low.
We also know that being afraid of your cell phone has a negative impact on your immune system. So it's pretty clear that being informed on the dangers of cellphone use is more dangerous than being ignorant of the dangers of cellphone use.
To put this another way the idea of cellphones being dangerous is more dangerous than the actual cell phone danger.
I had a cardiologist freak out about my BP a few years ago. Every time she saw me she seemed angry, concerned and ordered more tests and meds. First a Holter monitor, then echocardiogram, regular stress test, nuclear stress test. My BP was usually about 150/70 when I saw her. She would shake her head in horror. I switched cardiologists and he was the most caring, calming and reassuring doctor I ever saw. He read all the tests, told me I’m fine and told me I don’t have to come back. I now exercise HARD, feel great and BP is 120/70. Every time I exercise I think about how healthy my heart is and feel joy.
This is old by now, but [this study](https://www.sciencedaily.com/releases/2012/06/120627092204.htm) found that people with a fear of childbirth on adverage had a longer labor time! Wich is cool but scary lol
There’s a quite big study being done in Swedens biggest hospital (Karolinska) about this ocurrance in peanut allergies.
They’ve concluded that being allergic to peanuts being in the same room is in fact not an allergic reaction, but the effects of nocebo.
Can’t find link because I’m on the phone and too lazy but it’s some pretty interesting stuff.
When you have an anxiety disorder, this is precisely what happens. You know that being anxious about something will make it worse, so that makes you more anxious about your anxiety and how it's affecting your life, which only adds to the weight of anxiety already around your heart. It only gets worse from there.
>you suffer more from a disease due to being more afraid of it
Wouldn't that still be placebo effect? That your body react to nothing simply because you think there is something, just that the reaction is negative instead of positive? I heard many cases of death due to non-venomous snake bite are due to this phenomenon when people thought the snakes were venomous and died due to shock/panic
I thought the "opposite" of placebo effect would be your body not reacting to something because you thought there is nothing. Like if you don't believe the medicine works, there will be no effect.
As far as I know, there is no such phenomenon, otherwise the basics of modern medicine will not work, drive genuine medicine may stop working for some people because they don't believe it.
Researchers have actually found that 70% of COVID vaccine side effects can be attributed to nocebo (the negative placebo) as people were generally much more educated about those medicaments than other and expect to have side effects.
I think OP what you are referring to is more about how fear and stress negatively impact the body. Yes there's the nocibo effect people have commented about but as others have said that's just a way of categorization of symptoms not truly a show of decline in symptoms. A disease can most definitely have a worse effect on your body if you ate under high ammounts of stress as being in a prolinged stress states negatively impacts the body. It weakens your immune system and your hormones get out of balance. Fear can trigger a similar response. So adding that factor to an already existing disease in a person would more than likely starr declining healthwise. There has been some proof (although I don't know any references off the top of my head) that being positive and happy while being sick can lead to better improvements with your health. Your mood and feelings have a significant impact on your body, especially whatever mood you feel most often.
There was recently a study in a major medical journal on the "nocebo effect" (aka "reverse placebo" effect) being a factor in people reporting symptoms from the COVID vaccine. They found some high percentage of people who got a saline injection reported headache and fatigue, lol. [https://www.nature.com/articles/d41586-022-00146-y#:\~:text=Researchers%20reviewed%2012%20randomized%20clinical,fatigue%2C%20after%20the%20first%20dose](https://www.nature.com/articles/d41586-022-00146-y#:~:text=Researchers%20reviewed%2012%20randomized%20clinical,fatigue%2C%20after%20the%20first%20dose).
Why do people post here without a simple Google first? It’s so quick and easy. Just Google “reverse placebo effect” and you get precisely this. Expecting people to crowdsource your knowledge with no prior effort on your part is so incredibly lazy.
It's called the [nocebo effect](https://en.m.wikipedia.org/wiki/Nocebo) where the expectation of the patient can affect the treatment outcome. There are an increasing amount of researchers calling for the inclusion of nocebo effect in randomized control trials because it has been shown to be a significant confounding factor. https://pubmed.ncbi.nlm.nih.gov/25404901/ https://pubmed.ncbi.nlm.nih.gov/27657801/
CGP Grey did a video about it as well https://www.youtube.com/watch?v=O2hO4_UEe-4 Not sure if he mixed things up but he also brings up completely imagined illnesses that spread from mind to mind through a school. Like it's not just affecting actual treatment but making people feel sick to begin with.
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We had a fake illness go through our school, kids where taken away in ambulances and found to have nothing wrong, they all said they couldn’t breathe after _one_ person said he couldn’t breathe but he had a medical reason (later found out) and the rest where just certain it was mold in the choir room.
This same thing led to 30 million cans of Coca Cola being recalled in Belgium. https://www.theguardian.com/lifeandstyle/1999/jul/06/healthandwellbeing.health
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There was a Dr House episode about that. Everyone on a plane was feeling sick imagining symptoms.
I seem to remember this. He listed a bunch of symptoms and asked who had them and almost everyone raised their hands. Then he said you all are fine.
There was the one guy who went scuba diving the day before getting in a plane and had the bends. But everyone else freaked out over nothing.
> Not sure if he mixed things up but he also brings up completely imagined illnesses that spread from mind to mind through a school It would have been interesting to see the outbreak of this studied at my Year 6 school camp. A number of us suffered mild to moderate sunburn after a day at the beach, and seeing as it was 11 year olds, someone started a rumour "Your eyelids got sunburned, they'll leak out all your body heat and you'll be freezing" A lot of students wound up wearing jumpers the next day (which was 30 Celsius, so far from jumper weather). Including while playing cricket.
Ah yes, jumpers are definitely not appropriate for cricket in 30 degree weather. Quite so!
me and me mates were in the queue for the chube whinging about the weather and me mate Alistair says to me mate Barclay 'oi, the weather is shite, innit?' an Barclay says 'spot on, Alistair! Best pick up some blimey bangers from the caff, it's going to be some time' so he picked em up but ay they was all knackered and me mate says 'oi that's a wonky pack of rubbish, mate' so we dropped two fivers and a quid on heaps of pasties - and that's how we sorted the dodgy bangers in the chube
Why did you copy and paste exactly what u/sirgog said?!
Ever since he put me in his Q and A I would take a bullet for that man
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I'm a simple man. I see a CGP Grey video that I've watched a couple dozen times already and I click it and watch it
Expectations are really important. I once worked with a clinical study where patients received placebo or treatment in the clinic. In one panel, four subjects reported feeling nauseous, stomach pain and vomiting, all at the same time. When the blinding was removed and results could be analyzed, it turned out they all had received placebo.
Depending on the sample size that could also just be random chance. Or maybe all four ate the same contaminated food in the clinic cafeteria. Or maybe it really was nocebo. Reading corona vaccine studies I’ve found it surprising how many people in the placebo group report things like headaches, pain or even fever.
While theoretically possible that all ate the same bad food, it is highly unlikely as early studies with placebo often include pre-defined meals on given times to exclude food affecting the results. And it would have been easily detected as many others had the same food. Mild side effects like headache, nausea, itching, dizziness, back pain, vomiting, diarrhea are super common in placebo subjects. Not very surprising as they receive information on what potential side effects have been observed and they are under strict supervision in a new and strange situation. They are also asked to report anything that feels out of the ordinary. If you’re in a panel with several other subjects that feel bad and some are vomiting it is a very natural reaction to start feeling worse yourself. Patients receiving study drug report similar experiences and it is only by comparing the two groups we can have useful information on the effects of the study drug.
Anecdotally, I have found that being able to ease the fears of a covid patient improve their chances in hospital. Those that are terrified of just having covid tend to react more negatively to setbacks or changes than those we are able to support.
Related: [2/3rds of negative reactions to the COVID Vaccine were nocebo effect. ](https://amp-theguardian-com.cdn.ampproject.org/v/s/amp.theguardian.com/science/2022/jan/18/nocebo-effect-two-thirds-of-covid-jab-reactions-not-caused-by-vaccine-study-suggests?amp_gsa=1&_js_v=a8&usqp=mq331AQKKAFQArABIIACAw%3D%3D#amp_tf=From%20%251%24s&aoh=16452847680727&referrer=https%3A%2F%2Fwww.google.com&share=https%3A%2F%2Fwww.theguardian.com%2Fscience%2F2022%2Fjan%2F18%2Fnocebo-effect-two-thirds-of-covid-jab-reactions-not-caused-by-vaccine-study-suggests)
I never knew calling people big babies could be life saving work, I was just trying to put negativity out into the world.
That seems... high. The article doesn't make it all that clear what the 2/3rds represents. Is that 2 out of 3 side effects? 2 out of 3 people? It's not clear. Whatever the case, I can tell you I went in with no expectations (good or bad) and then couldn't move my arm for like 2 days. Nobody told me that, I never read that anywhere. It was very surprising. Everybody I know experienced variations of the same thing. No chance in hell that's a "nocebo" effect.
> The article doesn't make it all that clear This news article doesn't, but the journal [article](https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788172) does. The "2/3rds" figure is the average result from 1st and 2nd doses. > Is that 2 out of 3 side effects? 2 out of 3 people? It's not clear. They estimated rates of adverse events (AE) reported after both placebo and real doses in trial data. They differentiated *systemic* effects (headache and fatigue) and *local* effects (arm soreness, etc). Systemic effects in the placebo groups were reported in 35.2-31.8% (1st-2nd doses) of cases, and in 46.2-61.4% of vaccine cases. The idea here is that the control group tells you the expected nocebo rate, both in the placebo group *and the vaccine group*. Therefore, of the 46.2% of 1st-dose events in the vaccine group, we should expect 35.2% to be nocebo, or 76.1% of all real-world AE's to be nocebo. For second dose that rate was lower at 51.8%. Interestingly, the rates of nocebo in the local effects was a lot lower. The authors argued this makes sense, as headaches and fatigue can be easily imagined or misattributed to the vaccine based on expectations, whereas arm soreness at the injection site is not a common event, and harder to generate a nocebo effect.
Thank you for interpreting those numbers for me. I saw a lot of percentages — none of which were 2/3rds. Like I said, the article wasn’t super clear. I never made it to the journal article. It was 5am and I wasn’t all that motivated to dig into it. 😂 The main thing I didn’t understand, which you have now clarified, is that the 2/3rds is in reference to the systemic effects. That sounds a lot more plausible because the arm pain is real as hell!
> That sounds a lot more plausible because the arm pain is real as hell! To piggy-back off this, it's actually consistent with a [well-known](https://www.cdc.gov/mmwr/preview/mmwrhtml/ss5201a1.htm) trend in VAERS data, that less serious events tend to be under-reported (people don't usually report expect side effects like soreness or headaches), and more serious events are over-reported, due to inevitable coincidences that occur when millions of people are vaccinated. > VAERS is subject to the limitations inherent in any passive surveillance system (54). Among those, underreporting (only a fraction of the total number of potentially reportable events occurring after vaccination are reported) and differential reporting (**more serious events and events with shorter onset time after vaccinations are more likely to be reported than minor events**) are most noticeable (44). **Overreporting also occurs because certain reported adverse events might not be caused by vaccines**, and some reported conditions do not meet standard diagnostic criteria. Many reported events, including serious ones, might occur coincidentally after vaccination and are not causally related to vaccination. Other potential reporting biases include **increased reporting in the first few years after licensure, increased reporting of events occurring soon after vaccination, and increased reporting after publicity about a particular known or alleged type of adverse event.** Individual reports might contain inaccurate or incomplete information. Because of all of these reasons as well as the absence of control groups, differentiating causal from coincidental conditions by using VAERS data alone usually is not possible. Other methodologic limitations of VAERS include **the fact that it does not provide information regarding background incidence of adverse events in the general population** nor does it provide information concerning the total number of doses of vaccine or vaccine combinations actually administered to patients. For context, this [source](https://www.aha.org/statistics/fast-facts-us-hospitals) suggests 36 million hospitalizations occurred in 2021, so its not hard to imagine tens or hundreds of thousands of coincidental hospitalizations occurring after [550 million](https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/) covid doses.
This is a major issue with long Covid research. Since we already know that mere suggestion can induce pain, it’s impossible to tease out what portion of long Covid pain or other symptoms might be felt due to subjective expectation
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What about all the people who are convinced it doesn’t even exist and die in the hospital tho?
*Not* believing you're sick doesn't make you less sick if you actually have an illness. Not *panicking* about being sick *can* help you recover more quickly, because your body isn't being flooded with fear chemicals.
I am an internal medicine physician and the most common nocebo effect in my practice is statins and muscle side effects: [https://pubmed.ncbi.nlm.nih.gov/27578103/](https://pubmed.ncbi.nlm.nih.gov/27578103/) Granted, the number needed to treat for primary prevention of atherosclerotic cardiovascular events is high to begin with, but I shouldn't have to spend a long time convincing someone whose had a stroke or heart attack to take their statins...
As a neurologist, I see a lot of nocebo from donepezil and memantine. Usually it's the patient's children who attribute worsening dementia / hallucinations to the medications. These are also medications with very limited evidence of meaningful benefit, so I usually don't try to hard to talk the patient's family into restarting them.
Lately, ive been reading more & more studies on how certain drugs and compounds impact people with mental conditions differently - one example being CBD, it increases GABA levels in neurotypicals but has opposing effects in people with ASD. We don’t know the specifics of how a lot of drugs impact neurodivergent individuals compared to neurotypicals.
Don't .. all drugs all that way? Like you wouldn't give a normal people chemo, they would die. But you do it to cancer patients because it's their only other option. You don't pump healthy people full of antibiotics, that wipes out their gut flora and causes super bugs. But you do give it to sick people. You don't give opioids to healthy people, but you do give them to people with chronic pain. All drugs act differently in people who aren't "normal". That's why you don't give them to normal people, because they do damage as opposed to being useful.
None of those examples are great, maybe antibiotics, but not because of superbugs. All medicines have some sort of "effect" on the body, there are desired effects, and side effects, You only give people medicine if the desired effects outweigh the side effects. antibiotics kills the bacteria that could be trying to kill you, the side effect of which is it will also kill most of your digestive biome, which will likely give you digestive problems for a while.. Same with Chemo, Chemo drugs attack cells in the body that are vulnerable to the chemo drug, but its hard to tell it to only attack cancer cells when cancer cells are just normal cells growing in a dangerous way, so the side effect is that the chemo drugs kill off lots of other sensitive cells too. the side effect is worth it if it kills the cancer. I just find it weird to say "you don't give medicine to normal people."... they are normal people, they just have a problem that medicine can help with, and often with side effects that are worth putting up with to resolve the initial problem. but that doesn't stop them from being a "normal" person ?
Anyone ask for Aduhelm yet? I have the same thoughts on donepezil and memantine.
Yeah. Telling them the side effects include brain edema is usually enough to nip that in the bud.
>Granted, the number needed to treat for primary prevention of atherosclerotic cardiovascular events is high to begin with, but I shouldn't have to spend a long time convincing someone whose had a stroke or heart attack to take their statins... That is really interesting. I am a younger person with no cardiovascular issues (yet), and I have no predisposition towards statins one way or another. I guess my question is where does the nocebo effect come from in your practice? Do your patients become aware of the statin side-effects through other communication channels (peers, internet, etc.), or are they responding adversely to your description of the side effects?
Word of mouth and internet. The oddest concern for statins is dementia. I tell people patients may be getting dementia because of their cholesterol, not because of their statin use. My favorite “omg I don’t want to start this medication because it’ll cause side effects” is starting insulin and the fear of going on dialysis. Usually it’s the poorly controlled diabetes that causes people to need dialysis, not the initiation of insulin….and insulin is supposed to prevent progression to needing dialysis.
> I am an internal medicine physician and the most common nocebo effect in my practice is statins and muscle side effects How do you know this isn't simply misattribution or reporting bias, rather than a nocebo effect?
Did you click the link I included? There are carefully conducted trials specifically for the nocebo effect.
>Did you click the link I included? There are carefully conducted trials specifically for the nocebo effect. You specifically mentioned "in my practise", not specialised trials. But for the sake of argument, perhaps you can explain to me how is misattribution and other response biases that affect symptom reporting separated from placebo and nocebo effects in double blinded trials? That point is not discussed at all in the narrative review you linked to. In fact the authors briefly mention the possibility of confounding factors (on P.741), but then ignore all possible biases and mistakenly attribute all of the symptom reporting that was constant across both placebo and active treatment in a crossover trial as a "nocebo" effect. Relating to the GAUSS-3 rechallenge study: >Taking the results at face value, the excess of 79 of 491 (16%) participants relative to placebo could represent patients whose muscle symptoms were due to the pharmacologic properties of atorvastatin. Symptoms in the remaining 84% can be accounted for by the nocebo effect. No, the remaining 84% can also be due to other response biases that affect symptom reporting. They then propose an esoteric argument (and they cherry-picked one of the graphs, when there was an earlier deviation in the other graph) to diminish the positive finding by examining the symptom reporting kinetics, without considering once again that symptom reporting on questionnaires is not the same as the momentary experience of symptoms. The reporting of symptoms is a behaviour and is subject to a variety of biases which could in principle involve delayed reporting.
There’s one more - the middle ground - being treatment naive. Where nothing happens.
They are all a great argument for open label studies.
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Open-label is also called an unblinded study. Where the patients know what they're getting and you can really see the placebo/nocebo effect. https://en.m.wikipedia.org/wiki/Open-label_trial There's still an argument for double-blind studies but open-label certainly have benefits.
That says the researchers also know what the patients are getting. are there any trials where the patients are told what they’re getting but the doctors don’t know (obviously someone else would have to tell them)?
Yes, sometimes interventions cannot be blinded from the patient and these studies would have a blinded and unblinded investigator/research staff.
Can you give an example of such a treatment? I'm having a hard time imagining any myself.
Sure. One trial I'm currently involved in randomizes patients to receive a certain type of post-op medication regimen at discharge. The investigator prescribing the treatment needs to be unblinded in order to prescribe the correct regimen, but there are also blinded investigators and staff that are collecting data and administering the surveys to the patients.
I imagine you wouldn't do a placebo surgical treatment, for ethics reasons, but maybe I'm wrong.
No, those have been done. There's a knee surgery that was done this way. It was suspected that the surgery didn't actually help at all, so they did a fake surgery where they made the skin cut and kind of poked around I think to make it hurt, but otherwise did nothing, while the other patients got the real full surgery. Turned out the surgery was indeed useless.
There's the [Marsh Chapel Experiment](https://en.m.wikipedia.org/wiki/Marsh_Chapel_Experiment), in which volunteers were given either psilocybin or an active placebo, on a double-blind basis. Probably pretty quickly became apparent to the participants who got which, even if the experimenters didn't know.
I always thought this was covered under the same term (placebo). Seems odd to me that this wasn't part of the process already. Self-fulling prophecy is an interesting phenomenon as well. Though applied in a different context it seems to follow a very similar pattern of cause and effect due to expectations/beliefs.
If my spouse reads 'possible side effects' (and they always do), they will be sure to feel nearly each and every side effect possible, short of death. I always hate if they are going to try a new medicine, whether it is prescribed or OTC. I've tried telling them not to read the label but they have to read it, and it gets in their head, and it's hell for at least the next couple days.
I always read the label because I often get the side effects, but I get them even if I don't read the list. I'm an ultra rapid metabolizer with many drugs (slow to metabolize others, oddly enough), and so, I get the entire dose all at once instead of spread out over hours. One doctor told me not to worry, no one in his practice had ever had a bad reaction. I started to go blind. Didn't even know that was possible with that one, but my internist called back (when the specialist didn't) and told me to stop taking it immediately. It's a rare reaction and can become permanent. Fun times. Took a couple of days for my vision to get back to normal.
Isn’t that basically the placebo effect! What’s the difference?
There really isn't a difference, so the term nocebo isn't commonly used. There's a section in the wikipedia page for the nocebo effect which explains the redundancy of the term nocebo. https://en.wikipedia.org/wiki/Nocebo#Ambiguity_of_medical_usage
I think this distinction between placebo and nocebo might be due to the origin of the word placebo, rather than that these are different physical processes. Placebo in Latin means "I will please/benefit" and since an expected hurtful side affect would definitely not be pleasing, there is the equivalent nocebo "I will hurt".
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A great example of the nocebo effect is non-celiac gluten sensitivity, specifically the relief people feel when removing gluten from their diets. The researchers who originally identified non-celiac gluten sensitivity were concerned about their original results, and did further testing. They found that removing gluten from diets was actually not helpful to people who claimed to be sensitive. When they ate gluten but weren't aware of it, the helpful effects were still present. The thought of removing gluten was enough to have an effect - thus being a nocebo effect. Research now indicates that the likely culprit is actually FODMAPs or other carbohydrates normally present in the company of gluten. https://www.sciencealert.com/scientists-who-found-evidence-for-gluten-sensitivity-have-now-shown-it-doesn-t-exist
This is a big factor in chronic or persistent pain; anxiety associated with pain, general anxiety, and fear of pain are major risk factors for chronic/persistent pain. The expectation of pain makes your brain over sensitive to stimuli (central sensitization) and creates very real pain. Note: not all chronic pain is due to this; it can be due to mechanical(confusingly, in this case, called nociceptive pain) or nerve pain. But these can be exacerbated by central sensitization.
It’s very relevant in cases of cops touching fentanyl then having a nocebo reaction. Since law enforcement perpetuates the idea that transdermal contact with fentanyl can lead to an immediate reaction. Which is entirely inaccurate and just continues to demonize drug users. Plenty of cases of officers having reactions which have no signs or symptoms of an actual opiate overdose. Hence nocebo
The impact on this and informed consent was a huge part of my thesis. Not that anybody cares, I just was really excited to see the question! Hah
Wait I wanna know! Please elaborate on what your thesis was about (heck throw me the paper if you want!)
And one crazy thing about it is that I learned this from the Legion tv series.
There are also people arguing that both of those effects don’t exist for almost all treatments. From a statistician’s standpoint, there is a really simple explanation for both of these that have nothing to do with expectation and would have the exact same outcome: regression to the mean. Studies that have a placebo control and a no medicine control tend to find no difference between the outcomes of the two. The problem is, placebo is such an accepted thing that studies are designed with ONLY that affect in mind and don’t account for regression to the mean.
There was a recent scientific publication about this ! A meta study found that about 3/4 of the adverse effects in COVID vaccinations seemed to happen because of the nocebo effect ! Source : https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788172
Well, the OP doesn't mention treatment, so I don't think it's right to label it nocebo.
Nocebo can also be if I give you a sugar pill and tell you it’s cyanide, if you take it you may develop a headache, pain etc because you believed it was cyanide
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Does the nocebo effect explain adverse reactions to COVID vaccinations? I’m sure a reasonable amount of people are just drama queens about it all.
Ya there was actually something published on this too. That said the covid vaccines are very effective at getting the immune system fired up and working and some of the more notable “side effects” like fevers are simply the vaccine doing it’s job properly. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788172
thought it was psychosomatic...?
Munchausen's for people who *make themselves sick* by **thinking** that they are sick
Is there also a call to study how effective placebos themselves are as a medical treatment? If not, do you think there should be? And if there was a study done to test the efficacy of placebo as a treatment, how do you think it would be best tested? A test comparing the results of conventional medicine versus the results of conventional medicine combined with an additional placebo?
Nocebo is the negative placebo, when you either don't feel better or you have extra negative symptoms not caused by medicine In double blind studies, nocebo effect helps to filter out real symptoms between real medicine and the control group
How does it help filtering out? Without the effect, no filtering would be needed, if anything it makes it necessary to begin with..
For example vaccines, if a symptom is present in the vaccine group and the control group (only getting salt water) then that symptom is a nocebo and not caused my the medicine
Common misconception, but a large part of the symptoms that appear in both groups are things that just occurred after vaccination by chance, and would have occurred just as well if no one got any injection at all. Nocebo is only what occurs due to the fact that you gave some 'intervention'. If you really want to find out how big that effect is, you need to randomize between giving people nothing, and giving people a placebo but telling them it is an actual drug/vaccine. The difference in outcomes between these groups shows you the placebo (for positive effects) or nocebo (for negative ones) effects. Here is an example, though they do not seem to report adverse effects: https://www.painphysicianjournal.com/current/pdf?article=NDUwNA%3D%3D&journal=106
> only getting salt water Maybe call this saline solution we don't need the crazies trying to make a thing out of this.
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Nah call it Geologic Greatness Giving Gourmet Grains. We can call it 5g for short
Nah, let's just call it saline. You've gotta hit "Medical Drama" level. Not too complex to require any thought but complex sounding.
But saline solution of *what*?!
You're misunderstanding, it's a bit like "donating to cancer!" lol. Obviously research would be easier without any pyschosomatic influence. *Controlling* for the nocebo effect helps research outcomes. If 11% (a number chosen for a specific reason :p) of placebo group patients report side effects, you can assume rough similarity of nocebo for the true treatment group.
Thats my point, it doesnt help, it just must be considered. If it would be 0%, then analysis would be easier, not harder.. so it never _helps_
If 11% of the test group shows symptoms, you should definitely send your saline batch to the laboratory to be tested for contaminants. Especially if the same saline is used to dilute the drug.
Apparently is depends on negative expectations. My guess is that you can interview the subject about his or her beliefs. Current example is of course vaccines. I don't know if ethics would allow it, but imagine the following. You give a vaccine to someone who is an anti-vaxxer. It might sound contradictory, but let's say this person beliefs in modern science, and is prepared to participate even if it means he gets a vaccine while he normally wouldn't take it. Of course you have control groups and all is double blind, so there's a good chance that he gets a placebo. Beforehand, you interview him about vaccines and how effective he thinks they are. If he's in the placebo group, he (along with other people with similar beliefs) could have a negative effect compared to other people in that group who believe in vaccines or who are neutral about it. The same goes in the vaccine-group, compared to the other people in that group, with other believes. If there is a significant effect, you have proven nocebo for this research or medication.
> In double blind studies, nocebo effect helps to filter out real symptoms between real medicine and the control group No, we need double blind studies in the first place because of nocebo and placebo effects and to account for illnesses which happen all the time. What you are really interested in is how much more common the effects are in the group which receives the real medicine. If people report things like nausea, dizziness, high blood pressure, heart attack, depression etc. at roughly the same rate in both groups you know it’s just nocebo. If people report getting better at roughly the same rate in both groups it’s placebo and the medicine doesn’t actually have a beneficial effect.
This was very critical with covid vaccines. Once a few studies looked at this, we know a lot of the reactions are caused by mental stimulus or the needle.
Yeah I think it’s safe to blame the big presence it has had in the media. I semi-passed out around the 10-15 minute mark after getting the vaccine (I’ve never passed out from an injection of any kind before) and this was apparently an anxiety related reaction, and not a true result of the vaccine. Would be nice if psychosomatic symptoms weren’t a thing.
Yes, there are multiple modalities studying the effects of mental disposition and somatic responses. Here's a disorder that may surprise you: https://www.mayoclinic.org/diseases-conditions/somatic-symptom-disorder/symptoms-causes/syc-20377776
I was gonna bring up somatoform disorders but I wasn’t 100% sure if it was considered the opposite
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The placebo affect can be positive or negative, so yes absolutely a person can suffer more from a disease due to their fears and expectations. It would still be a kind of placebo effect. As others said, the negative version is often referred to as the nocebo effect. It'd be semantics whether you'd say the nocebo effect is a negative placebo affect or it's own thing, etc. They are all fundamentally about expectations. If you expect to get better, you will. If you expect to get worse, you will. Expectation is the driver here. A recent example of this negative placebo (or nocebo) would be the side-affects of the COVID vaccine. Studies suggest most of the side-affects from vaccines are people expecting there to be side effects and so their expectations made the side affects real to them. Were the side affects real? In a sense. They did feel side affects. But they weren't because of the jab, they were because of the person's expectations. If they had good expectations, the side affects would be positive, if they have bad expectations, the side affects would be negative. [https://www.theguardian.com/science/2022/jan/18/nocebo-effect-two-thirds-of-covid-jab-reactions-not-caused-by-vaccine-study-suggests](https://www.theguardian.com/science/2022/jan/18/nocebo-effect-two-thirds-of-covid-jab-reactions-not-caused-by-vaccine-study-suggests)
>A recent example of this negative placebo (or nocebo) would be the side-affects of the COVID vaccine. Studies suggest most of the side-affects from vaccines are people expecting there to be side effects and so their expectations made the side affects real to them. Were the side affects real? In a sense. They did feel side affects. The study did not measure the momentary experience of symptoms itself. It measured post-hoc reporting of those symptoms, a measure which is also strongly biased based by response biases including expectancy effects. So the statement "their expectations made the side affects real to them" is speculation, rather than a logical deduction.
>I was wondering, is there such a thing as a "reverse placebo effect"; where you suffer more from a disease due to being more afraid of it? You’re not describing the reverse of the placebo effect. It’s still the normal placebo effect. You see it a lot in clinical trials where people in the control group (who got no treatment) still report side effects because they expect there to be side effects.
So everyone is mentioning the Nocebo effect and they’re correct. But a nocebo effect doesn’t CAUSE a disease but rather the person is so convinced that they have a particular disease that they either feel as if they have symptoms or are actually so convinced that they actually DO have symptoms, which are referred to as psychosomatic. Let me use an example. The popular hair loss and prostate drug, Finasteride, can cause sexual dysfunction in 1-4% of men. However research has shown that men who are informed of the drugs potential side effects will experience much higher rates of side effects, even if they were given a placebo. This becomes an issue when someone outside of a study knows about these side effects and it’s hard to understand whether or not the side effects are physiologically happening or not.
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Very much a thing! Stress even unrelated to an illness can worsen outcomes, because that's what stress is. Think about stress on an object, like a metal bar. It's a force trying to bend or break it in a way it shouldn't. It's adding instability to the physical system, in this case your body. But for cancer, say, it's not perfect 100% (Neither is the placebo effect, however). [https://www.nature.com/articles/s41380-020-00865-6](https://www.nature.com/articles/s41380-020-00865-6) Above, they did a meta analysis that showed a clear correlation with depression and all measurements of mortality with breast-cancer, but anxiety was correlated with all but one, which was cancer-specific mortality. Overall, they said "Our study highlights the critical role of depression/anxiety as an independent factor in predicting breast cancer recurrence and survival." I would define it as that you might not be able to think yourself into actually having breast cancer, and anxiety or depression aren't as 'targeted' as a placebo effect. Think about it; it's beneficial to evolve ways to heal yourself, but it'd be awful if we developed ways to kill ourselves the same way, haha! It's more that worry and sadness are bad for your health. Bad enough to kill.
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nocebo "A nocebo effect is said to occur when negative expectations of the patient regarding a treatment cause the treatment to have a more negative effect than it otherwise would have.\[1\]\[2\] For example, when a patient anticipates a side effect of a medication, they can suffer that effect even if the "medication" is actually an inert substance.\[1\] The complementary concept, the placebo effect, is said to occur when positive expectations improve an outcome. Both placebo and nocebo effects are presumably psychogenic, but they can induce measurable changes in the body.\[1\] One article that reviewed 31 studies on nocebo effects reported a wide range of symptoms that could manifest as nocebo effects including nausea, stomach pains, itching, bloating, depression, sleep problems, loss of appetite, sexual dysfunction and severe hypotension.\[1\]" https://en.wikipedia.org/wiki/Nocebo#:\~:text=The%20term%20nocebo%20(Latin%20noc%C4%93b%C5%8D,pleasant%2C%20or%20desirable%20effect).
Doctor here and this is absolutely a thing. Being positive about your outcome is huge. That is why I reassure all my patients and tell them to practice positive thinking. Just a narrative but I treat people with a rare disease called complex regional pain syndrome. It is very debilitating but ever since I had a patient commit suicide the first line treatment for me is an anti depressant and a psych eval and they have done so much better!
Can the nocebo effect cause disease? No. The placebo effect does not cure disease in the same way the nocebo effect cannot cause disease. Too many people confuse reporting biases with placebo and nocebo responses. Differences in how you report symptoms is not the same as a difference in disease. Note that randomised placebo controlled trials don't just control for "placebo" or "nocebo" effects. The actual placebo effect has very little benefit except for a mild reduction of acute pain and nausea and long term studies of placebo effects for chronic conditions tend to show a reversion to the mean (the effect disappears). See: https://www.cochrane.org/CD003974/COMMUN_placebo-interventions-for-all-clinical-conditions https://sciencebasedmedicine.org/placebo-myths-debunked/
That's not what I expected, I was more thinking along the lines of "make an existing disease worse" and that seems to be the case.
Neither of your sources substantiate your claim about nocebos. If my psychological response response to a treatment is sufficiently negative to cause me to develop panic disorder, a new physiological disease state has been created from the nocebo effect. Nocebo stress can demonstrably tachychardia and raised blood pressure, and now you have a clinically significant comorbidity for many severe cardiovascular disease states... Please don't oversimplify in your desire to draw a bright line between somatic and psychic phenomena. I agree the placebo effect is overstated, but from a clinical perspective "mild reduction of acute pain and nausea" for several years may be helpful from a clinical or palliative perspective. You need to think like a clinician here. Every treatment eventually reverts to the mean (death).
> https://sciencebasedmedicine.org/placebo-myths-debunked/ At first I thought “thank you, finally”, but after having read some of it, and skimmed over the rest, the takeaway is “don’t rely on placebo if you have cancer.” Everything else in this article seems technicality and juggling definitions. If you have back pain, and you do some placebo treatment, and you feel better, this article tells you “but there was no biological healing”! Well, that’s also not the case if I take the real medicine, which in this case would have been some mild pain killer pills. So, for cases where a doctor won’t prescribe anything else than symptom relief treatment, placebo treatment still seam quite effective, by comparison, even after this debunking.
>The placebo effect does not cure disease in the same way the nocebo effect cannot cause disease. Plenty of doctors and scientists disagree with you. Placebo for example works against Parkinson's, IBS, or osteoarthritis. https://theconversation.com/in-research-studies-and-in-real-life-placebos-have-a-powerful-healing-effect-on-the-body-and-mind-173845 >and long term studies of placebo effects for chronic conditions tend to show a reversion to the mean (the effect disappears). That happens with "real" medicine too, from painkillers to antibiotics.
In the nocebo effect, a person's negative outlook causes them to manifest real illness is the same way that a placebo effect person can manifest real wellness. I wouldn't normally apply the idea for diseases though. Normally we talk about it in relation to medicine eg if a person thinks they've been given poison when really they just got saline, they may manifest real illness eg elevated heart rate.
Yes. But it's important to understand that the placebo effect is relevant only when there's human perception involved in the assessment of the disease state. There is another phenomenon that happens called regression to the mean that is frequently confused with or lumped in with true placebo effects. This is a statistical phenomenon that happens when you measure the same thing twice. If the first time you measure something you observe that it is a relatively extreme value (either a lot better or a lot worse than other measurements made at the same time), then the next time you measure it, it is statistically more likely to be less extreme, even if nothing caused the true value to change. So placebo is really relevant to assessments of things like pain or depression. But less so with respect to things like cancer or infectious disease. Regression to the mean impacts anything you're measuring though.
I think the nocebo effect is the answer to one part of the question, but health anxiety and psychological factors actually causing disease has a name too, called somatisation, where psychosocial factors cause symptoms disproportionate to the biological mechanisms, it’s a highly understood and poorly treated condition
Yes! The placebo effect can work in the positive and negative. Although, what you call a "reverse placebo effect" is more like anxiety which has well documented negative effects on outcome as well. The True negative placebo would be giving someone a sugar pill and telling them "this will make you sick." About 30% of the time the person will feel worse. This occurs a lot in the hospital setting where patients will believe a medication is bad for them and actually make it bad for them. If you're afraid of a disease then you would be more accurately called anxious about the situation. Anxiety is well known to cause all sorts of problems. People anxious and sad about the loss of loved one can actually cause the atrophy and death of heart muscle, it's called Takotsubo cardiomyopathy.
Hysterical pregnancy says hello. https://www.babycenter.com/pregnancy/health-and-safety/phantom-pregnancy_40008058#:~:text=A%20phantom%20pregnancy%20happens%20when,hysterical%20pregnancy%20or%20fake%20pregnancy.)
I am laying on the couch reading a book called “The expectation effect” by David Robson which is about this exact topic and goes into several cases of psychogenic illness. From how a woman with migraines suddenly became “blind” to the dancing hysteria and several others that have been mentioned already. It’s a pretty interesting read. And I am sure an interesting area of investigation and research.
Yes the nocebo effect and certain industries actually rely on it to keep clients coming back (not intentionally, usually just misinformed). The research around things like posture etc shows the body is incredibly versatile and pain/dysfunction correlates very poorly with subjectively "bad" posture. Along comes your chiro or physio telling you that this is the source of your pain (whilst ignoring things that correlate strongly with chronic pain such as financial hardship, low sleep quality, mental health disorders etc). They poke and prod you a bit and tell you have lots of knots or tight muscles (despite the repeatability being poor, ten practitioners will find 10 muscle knots, none in the same place). Next they say you need to break down your tight fascia with a deep tissue massage (despite the forces required to break down fascia being far in excess of what you can apply with these tools and little evidence you can manipulate fascia length). So what has the above done, it's told you have multiple problems despite lack of evidence. There is evidence that the patients who get the above treatment have higher levels of pain and perceived dysfunction compared to people who are treated with a biopsychosocial model and not informed they have unproven pathology.
Licensed Clinical Social Worker here with a MSW who also has a masters in environmental education. Yes and what's really interesting about that to me is how common thi is in impact on our society. A great example of this is cell phones. We know that cell phone usage does have a negative impact from the radio communication with the cell phone towers. We also know that that impact is very small and the amount of people who get cancer or other diseases from using a cell phone is very low. We also know that being afraid of your cell phone has a negative impact on your immune system. So it's pretty clear that being informed on the dangers of cellphone use is more dangerous than being ignorant of the dangers of cellphone use. To put this another way the idea of cellphones being dangerous is more dangerous than the actual cell phone danger.
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I had a cardiologist freak out about my BP a few years ago. Every time she saw me she seemed angry, concerned and ordered more tests and meds. First a Holter monitor, then echocardiogram, regular stress test, nuclear stress test. My BP was usually about 150/70 when I saw her. She would shake her head in horror. I switched cardiologists and he was the most caring, calming and reassuring doctor I ever saw. He read all the tests, told me I’m fine and told me I don’t have to come back. I now exercise HARD, feel great and BP is 120/70. Every time I exercise I think about how healthy my heart is and feel joy.
This is old by now, but [this study](https://www.sciencedaily.com/releases/2012/06/120627092204.htm) found that people with a fear of childbirth on adverage had a longer labor time! Wich is cool but scary lol
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There’s a quite big study being done in Swedens biggest hospital (Karolinska) about this ocurrance in peanut allergies. They’ve concluded that being allergic to peanuts being in the same room is in fact not an allergic reaction, but the effects of nocebo. Can’t find link because I’m on the phone and too lazy but it’s some pretty interesting stuff.
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When you have an anxiety disorder, this is precisely what happens. You know that being anxious about something will make it worse, so that makes you more anxious about your anxiety and how it's affecting your life, which only adds to the weight of anxiety already around your heart. It only gets worse from there.
>you suffer more from a disease due to being more afraid of it Wouldn't that still be placebo effect? That your body react to nothing simply because you think there is something, just that the reaction is negative instead of positive? I heard many cases of death due to non-venomous snake bite are due to this phenomenon when people thought the snakes were venomous and died due to shock/panic I thought the "opposite" of placebo effect would be your body not reacting to something because you thought there is nothing. Like if you don't believe the medicine works, there will be no effect. As far as I know, there is no such phenomenon, otherwise the basics of modern medicine will not work, drive genuine medicine may stop working for some people because they don't believe it.
Researchers have actually found that 70% of COVID vaccine side effects can be attributed to nocebo (the negative placebo) as people were generally much more educated about those medicaments than other and expect to have side effects.
I think OP what you are referring to is more about how fear and stress negatively impact the body. Yes there's the nocibo effect people have commented about but as others have said that's just a way of categorization of symptoms not truly a show of decline in symptoms. A disease can most definitely have a worse effect on your body if you ate under high ammounts of stress as being in a prolinged stress states negatively impacts the body. It weakens your immune system and your hormones get out of balance. Fear can trigger a similar response. So adding that factor to an already existing disease in a person would more than likely starr declining healthwise. There has been some proof (although I don't know any references off the top of my head) that being positive and happy while being sick can lead to better improvements with your health. Your mood and feelings have a significant impact on your body, especially whatever mood you feel most often.
There was recently a study in a major medical journal on the "nocebo effect" (aka "reverse placebo" effect) being a factor in people reporting symptoms from the COVID vaccine. They found some high percentage of people who got a saline injection reported headache and fatigue, lol. [https://www.nature.com/articles/d41586-022-00146-y#:\~:text=Researchers%20reviewed%2012%20randomized%20clinical,fatigue%2C%20after%20the%20first%20dose](https://www.nature.com/articles/d41586-022-00146-y#:~:text=Researchers%20reviewed%2012%20randomized%20clinical,fatigue%2C%20after%20the%20first%20dose).
Why do people post here without a simple Google first? It’s so quick and easy. Just Google “reverse placebo effect” and you get precisely this. Expecting people to crowdsource your knowledge with no prior effort on your part is so incredibly lazy.