Lecture 7: Placebo & Nocebo Effects

What is a placebo?

inert medication or procedure - a substance has no therapeutic effect. Comes from the Latin word - ‘i will please’ - can be creams, injections, pills, even surgery.

What is the 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.

How widespread is the placebo effect?

As many as 90% of trial participants experience improvements after taking a placebo
Up to 88% of the effect of antidepressants may be placebo effect (Hengartner et al., 2018)
An important part of active treatments too.

Explain the placebo ultrasound study?

In wisdom tooth surgery, patients were given ultrasound or a placebo ultrasound, or a control and then ranked their swelling and pain.
This shows that decreases in pain was more due to a placebo effect instead of an effect.

What can placebo affect?

Pain • Cough • Headache • Nausea • Anxiety • Heart rate • Weight loss • Hunger hormones • Blood pressure • Swelling • Muscle tension
Note that placebo effects generally impact subjective perceptions more.

Where did the placebo effect originate from?

During WW2, nurses gave injured soldiers saline, rather than morphine, due to shortages. Actually decreased pain and changed outcomes.
Modern medicine actually started placebo controls in 1970-80s due to the discovery of placebo effects.

How to check if a medication works?

We will compare no treatment, placebo and active drug groups, however, we will test in each category, natural course, placebo effect and the drug specific effects.

What is a natural course?

changes that would have happened anyway – these can be seen in the ‘no treatment’ group.

What is a 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.

What are drug-specific effects?

changes that are caused by the active ingredient in the medication – these can be seen in the ‘active drug’ group .

Describe placebos in surgery?

Able to test new treatments against placebo, demonstrates effectiveness above placebo effect
Experiment on placebo knee surgery finds that even just the support provided from surgery allows for long term improvement in health and wellbeing. (even increased initial improvements)

How do expectations produce placebo and nocebo effects?

Perceptual shifts
Activation of brain regions associated with expected experiences
Activation of physiological pathways and processes.

How are placebo (nocebo) effects caused?

Classical conditioning – wherein direct experience (either a benefit or a side effect) causes you to continue to have the same effect despite the active ingredient
Social observation – seeing other people having the same effect may cause you to have the same expectation leading to an placebo or nocebo effects
Information provisions - basically having the expectations of a medicine working will make the medicine work.

Note about expectations

Looks like placebo effects occurs as a result of conscious expectations
But the effect can exist without conscious expectation .

Explain the conditioned analgesia example?

wherein a medication was paired with a strongly flavored drink over time. The person's medication was reduced, but the person began to drink the strongly flavored drink. Found that the physiological response to the drug was the same.
Note that the person did know that they were being conditioned with a placebo.

Explain colloca and benedetti study?

Red is associated with higher pain and green is associated with lower pain in the conditioning phrase.
In the testing phrase, a placebo effect was generated.
Note that if you tell participants about the conditioning before the test phrase, a placebo effect will not occur, but it will occur even if you tell the participants during the test phrase.

Explain the social learning of pain relief?

States that vicarious learning of pain, will also induce placebo effects. In the study an experience acted out the pain associated with each type of shock.

What to note about information for pain relief?

it tends to have less of a placebo effect compared to social learning or classical conditioning.

What are some common ways to study placebo effects?

Placebo or no placebo, or active treatment vs. placebo, nice researcher vs. neutral researcher.

Describe the information provision study in the context of opioids?

Positive expectation - doubled placebo effects
No expectation - acted as a baseline
Negative expectation - nocebo effect
Psychology matters more than pharmacology.

Explain the open/hidden paradigm?

In which researchers administered treatment based on hidden application vs. open application of medication.
In the hidden application, people don’t even know that the machine gives them pain relief, compared to an open application wherein a doctor sets up positive expectations for pain relief. Obvi, the open application had larger impacts compared to the hidden application.
Note that diazepam only works with a placebo effect.

What else influences the placebo effect?

Warmth and empathy
Price information
Brand labelling.

What is the effect of warmth and empathy on the placebo effect?

Warmth and empathy triggers a much larger placebo effect compared to cold approaches.
Note that those who did not experience a warm experimenter, also had nocebo effects.

What is the effect of an expensive vs. a brand name pill?

Note that a more expensive placebo did a much better job than a cheap one.
Note that brand name pain relief created a higher placebo effect as compared to a generic label.

What are nocebo effects?

“I shall harm”
“The pill may be inactive, but the side effects are real”
The experience of adverse events or unpleasant symptoms in response to an inert medication or procedure (Barsky et al., 2002) • As many as 75% of patients in clinical trials

What can influence nocebo effects?

Nocebo effects contribute to side effects from active treatment

Describe nocebo effect paradigms?

What did the meta-analysis of the effect of active vs. placebo drugs find?

Found that active vs. placebo drugs basically match effectiveness.
More recent study on statin drugs, looked at the nocebo drugs effects,
Found that negative expectation of muscle pain contributed to a clear nocebo effect – 45% of the side effects are attributed to the nocebo effect, rather than anything else.

Should we be warning people about side-effects?

Study looking at the effect of aspirin, company did not properly warn people of possible GI side-effects on some forms compared to others.
Found that those for those who have not been warmed, tended to report 3 x less side effects compared to those who weren’t.

What else might influence the nocebo effect?

Describing/framing information
Choice of treatment - allows people to stick for treatment for
Media coverage .

Describe the bee sting procedure?

Pregnant women are told differently about the effect of the epidural injection.
Two framing -
‘ We are going to give you a local anesthetic that will numb the area and you will be comfortable during the procedure ‘
‘ You are going to feel a big bee sting this is the worst part of the procedure. ‘
I found that the 1st option is the best way to help people to handle pain – FOCUS ON THE POSITIVE EFFECTS OF THE TREATMENT.

What is the effect of information framing?

aka 27 out of 100 will experience drowsiness vs. 73 of 100 people will NOT experience drowsiness.
The delivery of numerically equivalent information in different ways will change symptom scores.
The positively framed information group tend to report less side-effects.

What is the effect of choice of treatment?

Found that participants who had no choice, had higher warning symptom scores than those with choice across symptom scores.

What to note about the effect of choice when choices increase?

When there are too many choices, the effect of more choices is not better in reducing nocebo choices.

Describe the Eltroxin story?

Thyroid hormone replacement drug, publicly announced a formulation change, however, the active ingredient was identical. Note that Eltroxin’s tablet’s changed colour.
Example of a real-life large scale nocebo effect that occurred in a group of patients in New Zealand.
After TV news reporting, the amount of side effects increased significantly.
Once TV news coverage reported that a different drug’s funding was increasing and therefore people had another drug, with symptoms decreasing immediately.