Why We Respond to Placebos:Psychological Mechanisms

of the Placebo Effect

Prof. Irving Kirsch

University of Hull

Hypotheses• Global mechanisms

– Anxiety reduction– Faith and hope– Positive emotion– Therapeutic relationship

• Local mechanisms– Classical conditioning– Response expectancy

Origins of the Global Hypothesis

Stress

Health

DepressionAnxiety

Inferences to Positive Emotions

Correlates of Positive Emotions

• Longevity– Healthy Adults– AIDS patients

• Immune function– Risk of cold– NK cell cytotoxicity

Inducing Positive Emotions

• Satisfaction with psychotherapy– Compassionate touch (Alagna et al., 1979)

• Recovery from surgery– A Room with a View (Ulrich, 1984)

• Cardiovascular recovery from stressor– Emotional content of film

(Fredrickson & Levenson, 1998)

Augmenting the Placebo Effect(Kaptchuk et al., 2008)

• Irritable Bowel Syndrome• Wait list• Placebo

– 10 minute neutral 1st session• Augmented Placebo

– 45 minute 1st session– Warmth and Empathy– Positive expectation

Symptom Severity

0

20

40

60

80

100

120

3 weeks 6 weeks

Improvement from baseline

Wait list

Placebo

Augmented placebo

Quality of Life

0

2

4

6

8

10

12

14

16

18

3 weeks 6 weeks

Improvement from baseline

Wait list

Placebo

Augmented placebo

Local Mechanisms

Simultaneous vs. Sequential AdministrationMontgomery & Kirsch (1996)

Effect blocked by naloxone(Benedetti et al., 1999)

Intensity Unpleasantness0.000.050.100.150.200.250.300.350.40

Placebo EffectMontgomery & Kirsch (1996)

Sequential Silmultaneous

SMD

• Global mechanisms– Anxiety reduction– Faith and hope– Positive emotion– Therapeutic relationship– Endorphin release

• Local mechanisms– Classical conditioning– Response expectancy

Local Mechanisms: Expectancy Conditioningvs.and

Conditioning Model of Placebo Effects

Active Treatment(US) Improvement

(UR)

(CR)Vehicle

(pill, capsule, etc.)(CS)

Conditioned Enhancement of Placebo Analgesia(Voudouris et al., 1985; 1989; 1990)

Placebo cream

LessPain

Pain stimulus Pain

Before conditioning

Conditioning Trials(Voudouris et al., 1985; 1989; 1990)

Placebo cream

Even less pain

Surreptitiouslyloweredstimulusintensity

Old Classical Conditioning Theory(The Stimulus Substitution Model)

Conditioning trials

Conditioned response

Rescorla, R. A. (1988). Pavlovian conditioning: It's not what you think it is. American Psychologist

Contemporary Conditioning Theory(Rescora, 1988)

Conditioning trials

Representationof US

(Expectancy)

Response

Other sources ofinformation

Blocking the Conditioned Augmentation Effect (Montgomery & Kirsch, 1997; also see Watson et al., 2007)

0

0.5

1

1.5

2

2.5

Pain Reduction

Control Surreptitiouspairing

Informed pairing

Conditioned enhancement of the placebo effect

(Montgomery & Kirsch, 1997)

00.5

11.5

22.5

33.5

44.5

Expected pain

reduction

Control SurreptitiousConditioning

InformedConditioning

Correlation between Expectancy and Pain:

r = .70

Pain Reduction with Expectancy Controlled(Montgomery & Kirsch, 1997)

Control Surreptitious Conditioning

Informed Conditioning

0

0.5

1

1.5

2

2.5

Pain RReduction

Why Placebo Analgesia Cannot be an Automatic Conditioning Effect

• Humans– Placebo effects mimic drug effects

• Placebo morphine lowers pain

• Laboratory animals– Morphine CR: increased pain– Chlorpromazine CR: increased activity

• Conditioned compensatory responses

(Siegel, 1983; Siegel et al., 2000)

A Two-Factor Theory of Placebo Effects

Therapeutic Relationship

OtherContextualFactors

Conditioning

Other information sources

Positive Emotion

Response Expectancy

PlaceboEffect

A Two-Factor Theory of Placebo Effects

Therapeutic Relationship

OtherContextualFactors

Conditioning

Other information sources

Positive Emotion - depression - anxiety

Response Expectancy

OtherPlaceboEffects - pain alertness

Antidepressants as Active Placebos

SSRI NDRI SSRE0%

10%

20%

30%

40%

50%

60%

70%

Response Rates

Individual Differences

The Search for the Placebo Responder

Ibuprofen and Trivaricaine

The pain stimulus

Session1

Second trial

First trial

Ibuprofen None

None Trivaricaine

Session 2 (exactly the same)

Second trial

First trial

Ibuprofen None

None Trivaricaine

Consistency of the Placebo Effect

Trivaricaine day 1 x day 2

Ibuprofen day 1 x day 2

Trivaricaine x Ibuprofen

.00

.10

.20

.30

.40

.50

.60

.70

.80

.90

.60

.77

.10

Whalley, Hyland, & Kirsch (2008)

r

Personality Correlates• Experimental settings

– Dispositional pessimism predicts the nocebo effect (Geers et al., 2004)

• Clinical settings– Responding to “enhanced” placebo

associated with • extraversion• low neuroticism • openness to experience

• (Kelley et al., under review)

A Two-Factor Theory of Placebo Effects

Therapeutic relationship

OtherContextualFactors

Conditioning

Other information sources

Positive Emotion

Response expectancy

PlaceboEffectPersonality?