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Placebo and Nocebo Effects - Coggle Diagram
Placebo and Nocebo Effects
Placebo
What is a placebo?
An inert medication or procedure that has no therapeutic effect.
Placebo = from Latin “I will please”
Can be pills, capsules, tablets, creams, injections, inhalers, or surgery.
We take medications in context > in certain places, in certain forms, from certain people, with certain information
This context has an impact on how the chemical agents work
Adding a substance with no therapeutic effect to a specific context can cause it to have positive or negative effects.
Placebo effect:
improvement in health or recovery from illness brought about not by active components of a medical treatment, but by nonspecific effects produced by the treatment context.
As many as 90% of trial participants experience improvements after taking a placebo.
Up to 88% of the effect of antidepressants may be the placebo effect > placebo effect forms part of the outcome from every active medication
Hashish (1988)
Test if ultrasounds after wisdom tooth surgery help with swelling and pain.
Control, ultrasound, placebo ultrasound (machine not turned on).
Placebo reported lower swelling and pain post-surgery than ultrasound and control.
Impact on subjectively reported pain, but also objectively reported swelling
Placebo effect is usually larger in subjective sensations
What can placebos affect?
Pain, cough, headache, nausea, anxiety, heart rate, weight loss, hunger hormones, blood pressure, swelling, muscle tension, etc etc
Placebo origin
Medics treating wounded soldiers ran out of morphine > giving them saline and telling them it’s morphine to provide the soldiers comfort.
It worked > less pain, fewer people going into shock.
Happened before evidence-based medicine (checking if the medicine actually works).
Placebo controls were introduced into clinical trials in the 70s/80s.
How to check whether it works:
Three broad components of an active drug effect > natural course, placebo/nocebo effect, drug-specific effect.
The drug-specific effect needs to be more than the placebo effect.
natural course: changes that would have happened anyway – these can be seen in the ‘no treatment’ group
placebo effect: changes due to the treatment context - the act of taking a medicine (even though it is inert) – this can be seen in the ‘placebo’ group
drug-specific effect: changes that are caused by the active ingredient in the medication – these can be seen in the ‘active drug’ group
Placebos in surgery
Able to test new treatments against placebo
Demonstrate effectiveness above placebo effect.
In knee pain, some surgeries involve irrigating the cartilage area, and some involve trimming and irrigating the problem area.
Placebo surgeries are just as effective as these > non-significantly having the best initial results, but all end up with less pain than before, even after 2 years.
Expectations
A placebo produces an effect because the recipient expects it to
How do expectations produce placebo and nocebo effects?
Perceptual shifts: shifting of sensory information that is received and interpreted > gate control theory, etc.
Activation of brain regions associated with expected experience: can activate the brain regions responsible for a sensory experience without the actual sensation > can be positive or negative (removing/adding pain, etc).
Activation of physiological pathways and processes: consequence of the other two, a result of neuromodulation that occurs with shifts in anxiety > different changes in different parts of the brain.
How are placebo (and nocebo) effects caused?
Social observation
seeing someone else experience side effects
Demonstrator reports less pain in response to green squares compared to red squares.
People who were watching and then getting shocked report less pain when seeing green squares compared to red
Information provision
doctor or pharmacist, or other source telling you about the medication.
Give two groups specific information: red square has easy-to-understand information, but green square has more specific and hard to understand information.
Green square has less perceived pain.
Conditioning and social have more of a placebo effect.
Classical conditioning (direct experience)
Experiencing a direct side effect (positive or negative) from a medication > persists when removing the context
A learning process that occurs when two stimuli are repeatedly paired: a response that is first elicited by the second stimulus is eventually elicited by the first stimulus alone.
Conditioned analgesia
reduces the dose of an active drug by substituting part of it with a placebo through conditioning.
Conditioning the active dose + specific drink.
Take placebo + specific drink > does the same thing
Conditioning people to think a treatment is happening that reduces pain, and then during treatment when stimulis is presented in the same way/intensity, placebo effect shows them feeling better
Studying placebo effects
Usually placebo vs no placebo or active treatment vs placebo
Changing context > empathetic vs mean researcher for example
Information provision: expectations influence active treatments
opioid stimulus for pain relief under different expectations > no expectation, positive, and negative
No expectation (just saying that the medication is in their body) causes some effect in reducing pain (shown through brain activity)
Positive expectation (saying its really gonna help) doubles the effect of the opioid
Negative expectations (saying it could end up worse) abolishes the opioid effect.
Potentially shows that people who have a negative mindset about a chronic condition could have less of an effect from treatment.
open/hidden paradigm:
Open application > medication for pain relief is administered by a physician
Hidden application > medication for pain relief administered by a machine, unknown to the patient.
Open generates more, faster pain relief compared to a hidden infusion.
Also the same for benzodiazepines > only works with a placebo effect.
What else influences the
placebo effect?
Price information
Higher price causes a greater pain reduction compared to medication of a lower price.
Brand labelling
Brand names work better than generic medication
Placebo with brand name is very successful at pain relief, but generic label with placebo is not as effective.
Warmth and empathy
Depression, anxiety, and stress > tell patients that their depression, anxiety, and stress will decrease if using a specific medication (placebo)
If cold and unempathetic, the placebo effect is not present
If warm and empathetic, the depression, anxiety, and stress went down after 3 days of using the placebo.
Nocebo
The nocebo effect
“I shall harm”
The pill is not active, but the side effects are real
The experience of adverse events or unpleasant symptoms in the response to an inert medication or procedure
Affects as many as 75% of patients in clinical trials.
Negative expectations as the primary mechanisms (anxiety also)
Nocebo effects contribute to side effects from actual treatments.
Triggered by the active ingredient in the drug
Howard et al 2021
Fear of muscle pain from statins.
Year-long study where each month you could get a placebo, statin, or no treatment.
Warnings about side effects
Account for a lot of drug side effects, as nocebo effects are very very easy to trigger.
If people are not warned about mild side effects, they are about 3x less likely to experience them, and 6x less likely to withdraw from the study due to them
What else influences nocebo effects?
Choice of treatment
Does giving people some sense of control (even if it's a meaningless choice between treatments) change the nocebo effect?
No treatment control, no choice, choice (2).
The only difference is in the information given on the meds, but they have the same function. Identical side effect list, but main is ‘commonly causes drowsiness vs headache’.
Nocebo effect is most prominent in the no-choice group.
Adding more treatment choices:
More choice (10) has the same effect as no choice > just as problematic as having too little choice.
Could be because its overwhelming?
However maybe putting in the time and effort to learn about all choices could cause the effect to go back to two choices.
Media coverage
Eltroxin case study
Thyroid hormone replacement drug had formula changed, but active ingredient was identical. Drug looked different post-change.
General public was not informed about change.
Lack of choice in drug > only one funded by government
News stories created more fear by highlighting the negatives and misrepresenting information.
After media reports, there was a 100x increase in adverse reaction reports for the drug.
After an alternative drug was announced, side effect reporting dropped almost instantly, even though the drug wasn’t actually available yet > relief.
After switching to new drug, most went back to the old one.
describing/framing information
How a procedure is described > the more positively framed the procedure, the less pain a person feels afterwards (epidural for labour)
How side effects are framed > focusing on the negative rather than positive > 27/100 people experience drowsiness vs 73/100 people don’t experience drowsiness.
More people experience side effects from a nocebo when given negatively framed information, compared to positively framed information.