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Placebo responseIts role in OA research and
clinical practice
Paul Dieppe
Professor of Health and Wellbeing, Exeter, UK
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I would like to acknowledge the financial
support of the University of Exeter Medical
School, the UK National Institute of Health
Research (UK NIHR) and The Institute for
Integrative Health (TIIH, Baltimore, USA)
I have no other declarations of interest and
will now stop using slides with logos
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Outline of Presentation
1. The placebo effect and response
2. The efficacy and effectiveness of
placebos in osteoarthritis
3. How it might help us understand OA
4. The nocebo effect
5. Theories on placebo and nocebo effects
6. Implications for clinical practice
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1) Placebo effect/response
The placebo response is an artificial construct
derived from clinical trial methodology
Size of
response
Treatment Sham/Dummy
control
Placebo response
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1) Placebo effect/response
The placebo effect is more interesting
Size of
response
Treatment Sham/Dummy No treatment
control control
Placebo effect
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1) Placebo effect/response
It is interesting that giving someone a
sham or dummy treatment, which ‘should’
have no effect, can be efficacious
Size of
response
Treatment Sham/Dummy No treatment
control control
Placebo effect
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Advertising slogan:
“Nothing works better than Annadin”
Response of someone who understands placebo:
“Then use nothing”
‘NOTHING’ IS A VERY EFFECTIVE THERAPY
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‘NOTHING’ IS A VERY EFFECTIVE
THERAPY
Although, of course, it is not really
‘nothing’
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Efficacy and effectiveness of
‘nothing’ in OA
Efficacy (effect in the artificial setting of a clinical
trial – ‘can it work?’) is known to be very high:
Effect size of about 0.5 for pain and
stiffness (Zhang et al 2008)
Effectiveness (what happens in normal practice)
is not known, but as both a clinician and ‘patient’
with knee OA I think it can have a HUGE EFFECT
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The ‘natural history’ of OA
In longitudinal studies of OA that I was involved
in many years ago we found that lots of people
got a lot better over time (Cushnaghan et al)
At the time we thought it was the natural history
of the condition, but I now think it might have
been the placebo effect
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Experience trumps evidence
An experience of the ‘placebo effect in OA
I have advanced radiographic OA of both
knees. One hurts sometimes, the other does
not. It was very bad a couple of years ago, and
I was seeing a surgeon about replacement
Instead I met a healer, who to my surprise, has
‘healed’ me of knee pain
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‘Healing’ does work
The latest of several positive systematic reviews
and meta-analyses of healing studies has just
been published (Roe et al Explore 2015)
It is probably mediated through the focussed
attention with good intention of sensitive
people (Warber and Dieppe, in Press)
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Maybe this is all it
takes to help
someone with OA:
Focussed attention
with good intention
And maybe this is
the basis of much of
the ‘placebo effect’
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3) How might this help us
understand OA?
HUGELY
It might help us sort out
the discordance between
pathology and symptoms,
and the relationship
between pathophysiology
and illness
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What happens when OA is ‘healed’? (i.e. following a positive placebo effect)
1. Which symptoms are better and which
are still there?
2. How long does it last?
3. Has the radiograph changed?
4. Can any metabolic changes be detected?
This is all so EXCITING! (Poster 584)
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4) Placebo’s ‘evil twin’ – the
nocebo effect
The work of my ex-PhD student Maddy
Greville-Harris
See “Bad is more powerful than good: the
nocebo effect in medical consultations”
Am J Med 2015; 128: 126-9
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Doing ‘nothing’ (with or without the use of
any specific intervention) can make patients
much worse
This is most likely to occur when one or both
people involved in a consultation are feeling
unsafe or anxious
Bad is more even powerful than good
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5) Theories on how it all works
Psychological theories:
• Expectation (+ve or –ve)
• Conditioning(+ve or –ve)
• Making meaning (Moerman)
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5) Theories on how it all works
Neurophysiological theories:
• Activation/inhibition of descending inhibitory
pathways of pain control
• Release/blockage of natural endorphins
• Others
Neurophysiological theories:
• Activation/inhibition of descending inhibitory
pathways of pain control
• Release/blockage of natural endorphins
• Others
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Is it really just about what is going on
in the brain of the patient?
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NO
I think this research (which I
have contributed to!) misses
the point!
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It is about the quality of interactions
between individuals
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And there are both psychological and
neurophysiological theories of this
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One psychological theory:
‘Validation and Invalidation’
A communication theory developed by Linehan et al
in the context of dialectical behavioural therapy
It goes beyond empathy and compassion. You can be
compassionate to another, but if they do not feel
‘validated’ you achieve nothing
Validation communicates acceptance and
understanding of another’s thoughts and behaviours,
invalidation communicates the opposite
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Validation and invalidation
depend on your behaviour as
well as on what you say
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Validation and invalidation
depend on your behaviour as
well as on what you say
It is easy to invalidate people
‘by mistake’
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An example from the research of
Maddy Greville-Harris
The patient complains of pain
The doctor, with the best of intention, says
something like – “I don’t think you need to worry, I
cannot find anything serious wrong with you”
The patient thinks “He does not even believe me,
he thinks I am not even in pain”
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One neurophysiological theory
Stephen Porges’ ‘polyvagal theory’ of social
interaction
We are hard wired for a nurturing response which is
the opposite of the fight or flight response, and which
is activated when we feel safe (rather than unsafe)
When the nurturing response is activated we
communicate better with other people
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6) Implications for clinical practice
What can I say?
The implications of how you behave when
with a patient are massive
Just be ‘present’ – be there for another
human in a non-judgemental way