L26 - PLACEBO & NOCEBO EFFECTS

Question 1

Definition of placebo effect:
- old
- new
- description of placebo & nocebo

Answer 1

Definition – old
- Placebo = as sham / fake treatment which is not able to determine effect

Definition – new
= effects of psychosocial / ritual context around therapy

Different context lead to different clinical outcomes
- Positive context = placebo effects => easing pain
- Negative context = nocebo effects => worsening pain

Question 2

Psychobiology: different theories proposed

Answer 2

Expectations
Learning
Psychological
Mindset
Genetics
Health subjects vs patients

Question 3

Expectation theory: description

Answer 3

Expectation: power of words
= belief or anticipation that treatment lead to specific outcomes, which can trigger real physiological & psychological responses based on beliefs

“This therapy will help you”:
> satisfaction
> compliance
< pain

“I don’t know if this therapy will help you”
< satisfaction
< compliance
> pain

Question 4

Learning theory: description

Answer 4

Learning: typology
Classical conditioning: neutral stimulus associated with natural response

Observational learning: learning occurs through observation & imitation of others

Associative learning: power of previous experience
If previous negative experience with specific / same technique:
< satisfaction
< compliance
> pain

Social learning: power of social contagion / influence
Patient shares experiences in common spaces & clinician assess & manage +/- social contagion:
< satisfaction
< compliance
> pain

Question 5

Expectation vs learning

Answer 5

Expectation vs learning: 2 sides of same coin
Previous experiences / learning has greater weight in chronic pain compared to patient’s expectation

Question 6

Mindset theory: description

Answer 6

Mindset: power of perception of side-effects

If clinician said: “little bit of pain after exercise is ok, positive sign”
> satisfaction
> compliance
< pain

If clinician said: “little bit of pain after exercise is not ok, negative, adverse effects”
< satisfaction
< compliance
> pain

Question 7

Psychological features:
- optimist
- pessimism

Answer 7

Psychological feature: situational, unstable, changeable traits

Power of yellow flags
Optimist:
- Goal seeking
- Self-efficacy
- Locus of control
- Suggestibility
- Fun seeking
- Sensation seeking
- Neuroticism
 Placebo responders

Pessimism:
- Anxiety sensitivity & suggestibility
- Social desirability
- Neuroticism
- Pain catastrophizing
- Blunting behavior
- Frail & submissive personality
- Hypervigilance & fear
- Somatization & amplification
 Nocebo responders

Question 8

Genetic theory

Answer 8

Genetics: polymorphisms
Specific genes influence response to placebo or nocebo effects

Question 9

Health subject’s vs patients

Answer 9

Health subject’s vs patients: response to context is same
Both patients & health individuals respond similarly to placebo treatments, highlighting importance of context in driving placebo effects

Question 10

Key points of determinants

Answer 10

Key points
- Different psycho-biological determinants have been proposed
- Expectations & learning processes (associative & social) are main determinants
- Genetic, mindset & psychological traits recently proposed as additional determinants

Question 11

Mechanisms:
- name
- description with + & - context
- key points

Answer 11

Neurophysiology
Positive & negative contexts determine release of neurotransmitters
Implicated network: DLPC, ACC, PAG, Spine (major areas)

IMAGE

Key points
- Opioids system, endocannabinoid, dopamine, oxytocin / vasopressin implicated in placebo /
positive context
- Cholecystokinin, dopamine / opioid deactivation, cyclooxygenase-prostaglandins implicated in nocebo/negative context
- Despite different areas implicated in placebo / nocebo effects, key regions are: DLPF, ACC,
PAG and dorsal horn

Question 12

Confounders:
- definition
- other sources of recovery or aggravation
- key points

Answer 12

Confounders = variable influencing relationship between independent variable & dependent variable, leading to misleading conclusions
- Not all patient’s clinical changes due to placebo/nocebo effects

Other sources of recovery or aggravation
- Natural history of disease
- Regression to mean
- Biases by clinicians & patients
- Unidentified co-interventions
- Adverse side-effects in placebo group in RCT

Key points
- Not all clinical improvements / worsening depends on placebo & nocebo effects
- Natural history, regression to mean, co-interventions, prejudices o patient & clinician,
represent cofounders

Question 13

Contextual factors: outcomes:
- definition
- therapeutic outcomes: 5 domain & description
- clinical relevance

Answer 13

Definition
= context represents whole atmosphere around therapy

Therapeutic outcome – 5 domains
a) Physiotherapist’s features
- Professionalism
- Mindset
- Appearance
- Beliefs & behavior

b) Patient’s features
- Expectation
- Preferences
- Previous experience
- MSK conditions
- Gender
- Age

c) Patient-physiotherapist relationship
- Verbal communication
- Non-verbal communication

d) Treatment features
- Therapeutic touch
- Modality
- Posology
- Marketing
- Clear diagnosis
- Overt therapy
- Observational learning
- Patient-centered approach
- Global process of care

e) Healthcare setting features
- Positive distractors
- Supportive indications
- Environment: Comfort element
- Architecture interior design: Decorations & ornaments

Clinical relevance
Therapeutic outcome = specific treatment (active & biological) + psychosocial context
Greater effect on illness component (subjective outcomes)
Minor effect on disease component (objective outcomes)
Illness: person’s subjective experience of symptoms. What patient brings to
doctor
Disease: underlying pathology, biologically defined, practitioner’s perspective.
Illness seen in terms of theory of disorder

Sickness: social & cultural conceptions of condition: cultural beliefs & reactions such as fear or rejection, these affect how patient reacts. Also covers what is considered disorders suitable for medical
treatment
30% of outcome it has historically been associated with context
Contextual effect varies from large to small due to characteristics of patient, practitioner, condition,
intervention & metric used
Prefrontal lobe injury  Alzheimer’s disease

Question 14

Key points on outcomes

Answer 14

Key points
- Context influences all clinical conditions with different weight
- In “non-lifesaving” pathologies greater effect, while in “Lifesaving” pathologies a limited effect
- Subjective outcomes more influenced by context compared to objective outcomes

Question 15

Contextual factors: clinical reasoning:
- patient’s role: description, different needs

Answer 15

Is a non-linear adaptative complex system
Creates perceptions of symptoms through context
Has perceptions +/- based on congruence / incongruence of context
- Previous + patient’s expectations
- Interaction with positive context
- Positive final healthcare experience
> Congruence = placebo effects

• Previous + patient’s expectation
• Integration with negative context
• Negative final healthcare experience
  < Congruence = nocebo effects

Seeks answers to cognitive & emotional needs in physiotherapy

TABLE

Question 16

Contextual factors: clinical reasoning:
- clinician’s role: patient improvement, aggravation, Dunning-Kruger effect & description of situations

Answer 16

Clinician’s role
Should be aware of personal biases, “limits of profession”
Patient’s improvement depends on:
- Skills as clinicians
- Training course carried out
- Specificity of therapy
- New machine purchased

Patient’s aggravation depends on:
- Discrepancy of eligibility for practice
- Presence of psychological problem
- Delivery of non-specific technique
- Lack of commitment to follow directions

Dunning-Kruger effect
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Modifies incongruence of context to influence patient’s perceptions

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Keeps “gaze” turned to patients, putting himself in their shoes
Thins in parallel about “what” to ho & “how” to do it
Can’t afford to lose patient for using negative contexts

Question 17

Contextual factors: clinical reasoning: role of context

Answer 17

Always interacts with patients, when seeking care

Receiving therapy & meeting therapist are
contextual factors

Acts with different weights
Can change trajectory of physiotherapy intervention
Offers meaning, triggering psycho-neuro-immuno-endocrine effects

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Question 18

Contextual factors: clinical reasoning: role of treatments

Answer 18

Represent modulatory inputs
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Are strongly influenced by context (manual therapy, needles & modalities, therapeutic exercise, pharmacological treatment, psychotherapy, surgery)

Is changed during COVID-19 pandemic
- Telerehabilitation
- Personal protective equipment

Question 19

Contextual factors: clinical reasoning: role of researcher

Answer 19

Should challenge creation of placebo-control RCT in MSK care
- Placebo treatments do not exist: complex multi-sensory intervention & impossibility to
differentiate specific component from contextual one

Applied same technique, enriched therapeutic context VS neutral or poor therapeutic context

Question 20

Key points of clinical reasoning

Answer 20

Key points
- Patient is a complex system influenced by context
- As clinicians we can manage context aimed to triggers placebo effects & to avoid nocebo
effects
- Using context patient can predict healthcare outcome
- Physiotherapy treatment (manual therapy, exercise…) represent input able to modulate
system

Question 21

Contextual factors: tip & tricks: patient / clinician relationship
- element
- Clinician’s dynamic elements
- Problems of poor communication with patients
- what happens in practice
- reciprocity of language
- touch
- management of unexpected

Answer 21

Patient – clinician relationship
Elements
- Verbal content
- Tone of voice
- Body language

Clinician’s dynamic elements
Evolutionary function: happiness, confusion, sadness, surprise, anger, excitement

Problems of poor communication with patients
- Conduct shorter interviews
- Make fewer statements for managing course of interviews
- Make fewer statement encouraging patients to elaborate on thoughts or offer opinions
- Make fewer statements to ensure patients understand what is said
- Less humor & laughter during interviews
 70-80% of legal procedures

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What happens in clinical practice
- Average first interruption after 22 sec
- Patient’s memory of first visit highly variable (17-60% after visit & 12% after month)
- Clinician speaks 2 times more than patient
- Technical content superior to emotional one
Relation styles: communication depends on patient’s needs:
- Patient: cognitive needs => Clinician: competence
- Patient: emotional needs => Clinician: humanity

Reciprocity of language
If use medical language, add explanation (from nocebo to placebo)
Use images & metaphors (placebo)

Touch
Different types but the more occurrence is assistive touch

Management of unexpected: rupture & repair
- Disagreement on goals
- Disagreement on tasks
- Empathic failure within emotional bond

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Question 22

Contextual factors: tip & tricks: patient / clinician features

Answer 22

Concept of professionalism = multi-dimensional
Only have first chance to make good first impression
Direct impact on patients’ outcomes
Private settings:
> professional
< professional & favorite
As number of visits increases, habitus has lower weight
Clinician’s way of thinking impacts patient’s outcome

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Question 23

Contextual factors: tip & tricks: patient / patient’s features:
- pre treatment screening
- Strategies for managing patient’s point of view

Answer 23

Investigate patients’ point of view & align with them

Pre-treatment screening
Internal model:
Prior high precision
- Strong expectations
- Strong priors
Prior low precision
- Weak expectations
- Weak priors
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Strategies for managing patient’s point of view
Pre-treatment – Cognition → post-treatment
Pre-treatment – Disconfirmation / exposure → post-treatment
Pain → No pain
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Question 24

Contextual factors: tip & tricks: features of treatment

Answer 24

Features of treatment
History taking, physical examination = therapy themselves
Open administration is better than covert
Different treatments have different rituality
Rituality: emphasizing it during therapy administration = key
Interaction among patients on common areas:
- Be aware of possible interactions among patients
- In waiting room or in gym room

Question 25

Contextual factors: tip & tricks: features of healthcare setting:
- description
- symbols of care
- personal elements

Answer 25

Feature of healthcare setting
Adequate health setting influences recovery in operated patients
- Examples of healthcare settings: number of days of hospitalization, number of doses of
treatment, view from room stay

Adequate health setting influences patients’ outcome
< pain
> quality of sleep
< stress, anxiety, fear & depression
< days of hospitalization, perception of privacy
> spatial orientation
> communication, social support
> satisfaction

Symbols of care: useful to define status of professional
- Diploma, certificate
- Posters
- Skeleton
- Instruments
- Books…

Personal elements: useful to define person behind professional
- Images of trips
- Design
- Clock
- Books
- Aquarium …

Elements not always changeable, but to be considered for clinical impact

Risk of extreme (nocebo effect):
- Effect excessively cold & detached
- Unprofessional & irrelevant

Finding balance guarantees (placebo effect):
- More adequate health setting
- Equilibrium between professionalism & humanity

Question 26

Contextual factors: ethics: deontology principles
- description
- principle of ethics
- key points

Answer 26

Deontological principles
Managing patient’s perspective, we need to respect bioethical principles
Principles of ethics:
- Autonomy
- Justice
- Beneficence
- Nonmaleficence
Placebo / nocebo effects & context follow evidence-based practice
TABLE

Use of context factors = opportunity to enrich EBM therapies
TABLE

Key points
- Placebo, nocebo & contextual factors should not justify pseudo-science
- As healthcare providers, we need to base practice on ethical & deontological principles
- There is need to balance external evidence with patients’ expectation, considering clinical
expertise

Question 27

Conclusion: clinical consideration & resume of lesson

Answer 27

Clinical consideration
Don’t focus on finger, look at moon
- Confounders (natural history of disease, regression towards mean)
- Contextual factors (clinical ritual, expectations, language…)
- Specificity of treatment

Resume of lesson
- Therapeutic result more than sum of individual parts
- Placebo & nocebo effects affect physiotherapy outcomes
- Moving beyond technique broadens perspective
- Challenging preconceptions is tiring, but necessary to grow
- Stimulating placebo effect is good, but avoiding nocebo effect is key
- In practice, think about what to do but also on how to do it