bensing icch09 plenary powerpoint

The Silent Healer the Role of Communication

in Placebo Effects

Jozien BensingWilliam Verheul

2009 Bensing Ask for permission before adopting

Placebo

“I will please”


Structure of Presentation

A Bit of History

Current Knowledge

Looking Forward


Hooper’s Medical Dictionary (1811)

Placebo: an epithet given to any medicine adapted more to please than to benefit the patient


Hippocrates, 460 – 400 B.C.

“some patients, though conscious that their condition is perilous, recover their health simply through their contentment with the goodness of the physician”

precepts VI2009 Bensing Ask for permission before adopting

Around the midst of the 17th century, the times they were a’ changing ……..

Throughout history, physicians have always been well aware of the healing power of a comforting attitude

Jan Steen, 1650

Ack

no

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dgm

ent

: Han

ne

ke d

e H

aes

W. Chandler, 1785


René Descartes1596 - 1650

Cartesian dualism

Mind-body dichotomy

Body is a machine

Reductionistic approach

Strategic Decision!Mind: domain of church

Body: domain of physicians


Jozien

The Science of Medicine

The Art of Medicine

This could be a happy marriage

Unfortunately, there is a hierarchy


Henry Knowles Beecher1904 - 1976

"Three-quarters of badly wounded men, although they have received no morphine for hours... have so little pain that they do not want pain relief medication, even though the questions raised remind them that such is available for the asking.”

Pain in Men Wounded in Battle (1946)


Henry Knowles Beecher

1955

In the JAMA, Beecher announces – based on a review of 15 clinical studies - that on average 35 percent of a drug’s or a doctor’s succes is due to the patient’s expectation of a desired outcome, or the “placebo effect”:

“The powerful Placebo”


Beecher

Placebo research

Placebo-controlled clinical trials


placebo-effects in RCT’s

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control placebo intervention

In biomedical research only the therapeutical effect is considered

Therapeutical effect

control

placebo

intervention

Hrobjartsson et al, 2002 2009 Bensing Ask for permission before adopting

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Hrobjartsson et al, 2002

control

placebo

intervention

placebo-effects: noise or focus?

In biomedical research placebo-effects are often considered as noise or as a nuisance

However, these are a fascinating target for scientific inquiry

placebo effect


It is getting time to open the black box of the physician’s healing power

White, 1988

How can we learn to understand (and thus enhance) placebo-effects?



A bit of history

Current knowledge

Looking forward


How do patients recover?

Natural course

Biomedical treatment

Placebo (context) effects

Health outcome

Dutch Medical Schools (p/y):2000 clinical trials900 PhD theses7500 publications


Placebo: a relic from the past?

WIRED MAGAZINE: 17.09.2009

Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why.

Steve Silberman2009 Bensing Ask for permission before adopting

What do we mean with ‘placebo effects’? Placebo effects are the aspecific or nonspecific effects

of a medical treatment on patients’ health or wellbeing (Shapiro & Shapiro, 1997)

Placebo effects are the incidental factors of a treatment to be discerned from the characteristic factors of a treatment (Grünbaum, 1986; Hrobjartsson, 2002)

Placebo effects are the genuine psychological or physiological effects, which are attributable to receiving a substance or undergoing a procedure, but are not due to the inherent powers of that substance or procedure (Stewart-Williams et al. 2004)


The content of the placebo-concept is temporary

If we understand the mechanisms: it is no longer non-specific or a-specific we

learn to understand how it exactly works It is no longer incidental we can apply it in

a planned and systematic way We can make it an integrated part of medical

treatment and teaching medicine2009 Bensing Ask for permission before adopting

Non-specific or incidental factors can also have negative influences on patient outcomes

Nocebo effects


Are placebo effects real and robust?

NO Hrobjartsson, Nw Eng J Med, 2002

Hrobjartsson, J Int Med, 2004

Hrobjartsson, J Clin Epid, 2006

YES DiBlasi, Lancet, 2001 Vase, Pain, 2002 Guess, BMJ-books, 2002 Sauro, J Psychosom Res, 2003 Hyland, Clinical Medicine, 2003 Wager, Science, 2004 Stewart-Williams, Psych Bull, 2004 Collaca, Nature, 2005 Wampold, J Clin Psy, 2007 Price, Ann Psych Rev, 2008

Placebo-effects are always demonstrated in those studies where placebo-effects can be expected to exist


Where do we find placebo-effects? Asthma Bronchitis Common cold Coughing Heart failure Hypertension Herpes simplex Parkinson Rheumatoïd arthritis etcetera

Anxiety Depression Schizofrenia Psychoneuroses Stress disorders Psychosomatic

disorders Medically Unexplained

Symptoms Pain


What can cause placebo effects?Treatment characteristics

(e.g. colour, size, shape of drug)

Health care setting

(e.g. home, hospital, room layout)

Patient characteristics

(e.g. illness / treatment beliefs, anxiety, adherence)

Patient-practitioner relationship

(e.g. compassion, reassurance, suggestion)

Practitioners characteristics

(e.g. status, sex, illness and treatment beliefs)

DiBlasi et al, Lancet, 2001


Mechanisms behind placebo effects

Classic Conditioning

Positive or Negative Expectancies

Positive or Negative Affect

These mechanisms are interlinked in many ways

Van Dulmen & Bensing, 20012009 Bensing Ask for permission before adopting

Mechanism 1: conditioning

A therapy or therapeutic procedure can produce a context-effect on health outcome, when it is associated – consciously or unconsciously – with previous experiences

These experiences (and thus the health outcmes) can be either positive or negative


Mechanism 1: classic conditioning

The natural response of a dog on the infusion of adrenaline is: elevated blood pressure

Amaral & Sabbatini, 1999


The natural response of a dog on the infusion of acethylcholine is: lowered blood pressure

Mechanism 1: classic conditioning 2009 Bensing Ask for permission before adopting

Amaral & Sabbatini, 1999

Mechanism 1: classic conditioning 2009 Bensing Ask for permission before adopting

Review placebo effects based on conditioning

Conditioned placebo-responses have been demonstrated in human beings and in animals

The effects in humans include pain relief, immunosuppression (MS), the production of hormones (Parkinson) a.o.

Conditioning seems to be ‘hardwired’ in the brain Conditioning can take place unconsciously and

consciously CAVEAT! If consciously, it is related to expectancies

Stewart-Wiliams, 2004, Price, 2008


A medical treatment or procedure can produce a placebo-effect because the recipient expects it to.

Expectancies may be seen as: the patients’ beliefs about the efficacy of

treatment (outcome expectancies) and

the patients’ beliefs about their abilities to cope with the disease and its treatment (self-efficacy).

Mechanism 2: expectancies

Crow, 1999, Stewart-Williams, 20042009 Bensing Ask for permission before adopting

Pain reduction based on expectancies:open versus hidden treatment

With several types of painkillers, patients experience more pain relief if they know the painkiller is administrated

Price, 20082009 Bensing Ask for permission before adopting

Colloca & Benedetti, 2005

Hidden vs open paradigma


Review Open vs Hidden Treatment:

When manipulated experimentally, open treatment is more effective than hidden treatment

Expectations seem to play an important role in producing these context effects

These effects can be influenced both by previous experiences and/or verbal suggestion

Amanzio et al. 2001, Benedetti et al.2003, Colloca et al. 2004, Levine & Gordon 19842009 Bensing Ask for permission before adopting

Review: placebo effects based on expectancies

Many controlled studies show the influence of expectancies on health outcomes

There is a clear neurobiological substrate, meaning that these effects are genuine, not only response bias

CAVEAT! In most studies no distinction is being made between positive words (raising expectations) and positive affect (a warm and friendly doctor) 2009 Bensing Ask for permission before adopting

Mechanism 3: Affect A medical treatment or procedure can produce a

placebo-effect if it is administered in a warm and empathic way.

This may serve a number of functions:Stress reductionAnxiety reductionSocial support

Its influence on health outcome is sometimes direct (relaxation), but also via moderators like self disclosure, self care, adherence, etc.DiBlasi, 2001, Kelley,1997, Epstein, 2007, Price, 2008, Street,

2009


support for the role of affect in placebo effects

The placebo-response is stronger in stressed and/or anxious patients (Wasan, 2006)

The placebo-response is stronger in clinical pain than in experimental pain (Price, 1997, 2008)

‘desire for relief’ is an important factor apart from ‘expectancies’ (Harrington, 1997)

The processing of negative emotions shares neural networks with pain responses (Eisenberger, 2004)


studies on the effects of affect

Affective communication (warmth, empathy, nodding, eye contact) has shown to be related to several patient outcomes, including:satisfaction, adherence health outcomes (Hb1ac, blood pressure)

Stewart, 1995, DiBlasi et al, 2001, Beck et al, 2002, Griffin, 2004, Rao, 2007


Limitations in communication research

Much research is descriptive and correlational RCT’s are conducted, but communication is often used

as a container concept Rigorous experiments testing specified communication

elements are difficult to perform it is unethical to confront real patients in clinical

situations with negative affect (cold, impersonal communication)

Communication is per se interactive, thus difficult to standardize

Researchers are reluctant to adopt a reductionistic approach


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control

placebo

intervention

What do we know about placebo-effects?

Placebo-effects exist and are genuine

At least 3 mechanisms are responsible:ConditioningExpectanciesAffect

Communication seems to play an important role

But can we really prove how?

placebo effect



A Bit of History

Current Knowledge

Looking Forward (back to the future)


Medicine is a delicate balance between art, science and communication (Carole Guzman)


The Science of Medicine

The Art of Medicine

This could be a happy marriage

Unfortunately, there is a hierarchy

Art and science should be integrated


Neurocognitive sciences can help

By providing knowledge about mind-body interaction

By introducing new technologies

By inspiring new methodologies


New knowledge: Neurobiological substrates of placebo effects

Endogenuous opioids are found in placebo-responders (Benedetti, 1999)

Placebo-induced release of endogenous opioids has been obtained by using in vivo receptor binding with positron emission tomography (Zubieta, 2005)

Similar regions in the cerebral cortex and in the brainstem are affected by both a placebo and a painkiller (remifentanil) (Petrovic, 2002)

; 2009 Bensing Ask for permission before adopting

New technologies (neuro-imaging)

Collaca & Benedetti, 20052009 Bensing Ask for permission before adopting

New methodologies

Analogue patient paradigm Standardized medical visits are watched by

analogue patients The assumption is that watching a videotaped

consultation produces the same effects as participating in this consultation

Fogarty, 1999, Schmid Mast, 2005, 2007, 2008, Eide, 20082009 Bensing Ask for permission before adopting

Coherence of skin conductance(participating in versus watching a medical visit)


New methodologies

The human mirror system acts as the neurological hardware for analogue patients’ empathy for the patient

This methodology has shown to be able to evoke discriminating reactions in response to different communication-stimuli

Which opens the possibility of testing the effects of different communication elements on patient outcomes

Fogarty, 1999, Schmid Mast, 2005, 2007, 20082009 Bensing Ask for permission before adopting

Experimental conditions (2x2)Positive Affect Friendly and inviting

welcome Showing empathy Eye contact & body

posture

Negative Affect Formal and cold welcome No empathic statements Little eye contact and

diverted body posture

Positive Expectancies Positive about the type of

drugs Positive about expected

effect on pain

Negative Expectancies Drug is mentioned in a

neutral way Hesitation about

expected effect2009 Bensing Ask for permission before adopting

change in: "The treatment will help against the pain"

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AFF-/EXP- AFF-/EXP+ AFF+/EXP- AFF+/EXP+-3,5

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Participating in visit Watching visit


change in "the pain will continue for a long time"

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Change in state anxiety

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Experiences with methodologyIntervention check: positiveDoctors & patients judged the videos as

realisticThe women had no problems ‘playing their

role’ of a patient with severe period painMost women had no problems with

identifying themselves with the patient on video 2009 Bensing Ask for permission before adopting

Reflection on results

Raising expectations in itself is not sufficient to produce robust effects on patient outcomes

Showing positive affect in itself is not sufficient to produce robust effects on patient oucomes

It is the combination that works!Nocebo effects are evident as well


General conclusions Placebo effects exist and are genuine, no response

bias Three mechanisms (conditioning, expectancies and

showing affect) seem to be responsible All three mechanisms have shown a neurobiological

substrate, which takes placebo research out of the hazy area

Placebo effects are often interlinked but can be manipulated in experimental designs

Communication plays a major role2009 Bensing Ask for permission before adopting

General Conclusions II Much progress has been made in the study of

placebo effects in health care

Thanks to: Multi- and Interdisciplinary efforts New technologiesNew methodologies Rigorous experimental testing

But many new questions arise, eg. About the specific role of different communication elements

An exciting research domain is developing really fast


facilitating

Open – closed questions

EMPATHY Summarizing

Eye contact Nodding Tailoring

Interruptions Expectancies

Explicit vs implicit Information

Being Positive - Neutral

Experiences

Let us open the black box of the physician’s healing power !


For information:[email protected]@nivel.nl


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"The treatment will help against the pain"

pre post


bensing icch09 plenary powerpoint

Health & Medicine

clinical trials

domain of physicians

history current knowledge

domain of church body

clinical studies

physicians healing power

science of medicine

patients expectation