Transcript The Placebo Effect - Vanderbilt University

THE PLACEBO EFFECT
Michael Putman
Quiz!
1.
2.
3.
4.
5.
T/F: Placebos make patients feel
better; they don’t actually get better
T/F: There are no negative effects of
placebos
T/F: Placebos can reduce asthma and
make wounds heal faster
T/F: Placebo therapy could be the end
of biomedicine as we know it
T/F: Doctor’s can lie to patients if it is in
the patient’s best interest.
Overview
I.
Introduction – Placebos, Meaning, and Misconceptions
II.
Psychoneuroimmunology
III.
Placebos and Anti-depressants
IV.
Placebos, Doctors, and Deliberate Deception

V.
Debate!
Concluding Thoughts
Introduction
Documentary on the Placebo Surgeries
1:24 – 6:15
I: Definition
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The effect of a treatment that arises from a
patient’s expectations and response to the
treatment, excluding the treatment’s specific action
In medicine, it typically refers to a response
observed after inert or inactive treatments
I: Examples of Placebos

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Inert pills, drugs, or
injections
Sham surgeries
Inactive medical
devices
Effective/non-effective
acupuncture
I: Changes in Efficacy

Specific aspects of placebo
Big branded pills in high quantity work better than smaller ones
in low quantity
 The color of pills also matters (red vs. blue)
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Type of procedures

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Previous experience

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Codeine cough syrup works really well the second time
Presentation

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Surgery is better than injection; injection is better than pill
How doctor presents it / advertising / etc.
All of these relate to the meaning imparted by the
treatment

The biggest factor is what the person believes about it
I: Placebos Can…
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Constrict the pupils, alter blood pressure, change
heart rate and respiration, influence gastrointestinal
secretions and peristalsis, change body temperature,
produce eosinophilia and leucocytosis, enhance
corticosteroid reactions, and change blood levels of
creatine and lipoproteins (Perry 1981)
Negatives: Cause dry mouth, nausea, heaviness,
headache, difficulty concentrating, drowsiness, sleep
disturbance
I: Moerman on Placebos
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Placebos do not cause anything because they’re inert
It is the psychological/emotional meaning that defines
the response
This response is elicited by far more than just inert
pills


Must think about active agents as well
The meaning response goes well beyond
psychological effects and results in physiological
changes as well
II: Psychoneuroimmunology
II: Psychoneuroimmunology (PNI)
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Hard evidence of the
placebo effect in
complex pathologies
Connections between
mind, brain, and
immune system
Strives to find tangible
linkage between
mind/body
II: PNI Foundations
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Ader and Cohen suspect
that immunosupression can
be behaviorally induced
Investigate in rat paradigm
 CS: saccharin
 US: immunosuppressant
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Discovered suppression of
immune system by nothing
more than taste
II: Kiecolt Glaser (1999): Immune Function

Stress dysregulates NK cell
activity and decreases ginterferon (IFN-g)
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Prospective study w/med
students
Stressed students have a
suppressed immune response
Prospective study found that
relaxation enhances NK
activity
II: Castes, Hagel (1999): Asthma

Prospective study of
children in Venezuela with
asthma
One group receives
psychosocialintervention
(PSI)
 Asthma attacks are
reduced

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PSI increases immune
function as well
Higher NK activity
 Higher T-cell activity
 Improved surface markers

II: Kiecolt-Glaser (1995): Wound Healing

Prospective study of
stress on wound healing
Caregivers vs. controls
 Both undergo biopsy
wound
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Healing takes
significantly longer in
controls

Differences in peripheral
blood leukocytes
III: Placebos and Depression
Placebos for Depression
15:20 - 19:00
19:00 - 20:15
III: Antidepressants: Brief Reminder
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Serotonin system influences mood,
sleep, arousal, etc.
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Other modulatory systems (DA, NE)
overlap in function
Selective Serotonin Reuptake Inhibitor
(SSRI)

Blocks clearing mechanism

Increases bioavailability of serotonin in
synaptic cleft
Treat depression, anxiety, and
personality disorders
Very complex process: at least 15
subtypes
III: Rise in Antidepressant Therapy
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Depression costs $44 billion
per year to US economy
Global sales in 2005 of
$16.2 billion

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Most commonly written
script as of 2005
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US is 66% of the market
More than drugs for high
blood pressure, high
cholesterol, or asthma
118 million scripts/year
Top two in 2005 were Paxil
and Lexapro
III: The Emperor’s New Clothes
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Kirsch et al. 2002

Meta-analysis (47 trials) of data
submitted to the FDA from 1987
to 1999 on the 6 most popular
SSRI’s
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Mean difference between
placebo and drug was ~2 points
out of 50 and 62 point scales

80% of the effect due to
placebo
Authors conclude that drug effect
was clinically negligible
 Breaking the blind?
III: The Emperor’s New Clothes 2.0
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Previous results called into
question
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Same studies as before
Included initial levels of
depression this time
Conclude that there is a
slight difference for
severely depressed
patients

This was due to a decrease in
placebo efficacy
III: How is this Possible?
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File Drawer Effect
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Unblinding of Raters
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Journals tend to publish
findings
Side effects often reveal
treatment group
FDA Standards
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Must show “safety and
efficacy”
2 placebo-controlled trials
required with positive results
III: Prozac and Suicide
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Increased risk of
suicide with Prozac
Oct 2004: FDA instructs
SSRI makers to include
black box warning
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Doubled risk of suicide
in adolescents
July 2005: FDA issues
public health warning
III: Side Effects of SSRI’s
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Anhedonia; apathy; nausea; drowsiness or somnolence;
headache; clenching of teeth; extremely vivid and strange
dreams; dizziness; changes in appetiteweight loss/gain; may
result in a double risk of bone fractures and injuries; changes
in sexual behaviour; increased feelings of depression and
anxiety (which may sometimes provoke panic attacks);
tremors; autonomic dysfunction including orthostatic
hypotension, increased or reduced sweating; akathisia; liver
or renal impairment; suicidal ideation (thoughts of suicide);
Photosensitivity (increased risk of sunburn)
IV: Physicians and the Placebo
Sir William Osler (1849-1919) – The “Father of Modern Medicine”
“We should use new remedies quickly, while they are still efficacious”
Doctors Prescribing Placebos?
12:16 – 13:30… 14:45?
ABC News Story
IV: Do Doctors Prescribe Placebos?
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NY Times: “Half of doctors routinely prescribe
placebos”
679 internists and rheumatologists from national list
 Everything from vitamins and headache pills to vitamins
antibiotics and sedatives
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Time Magazine: “Is your Doctor Prescribing
Placebos?”
466 faculty surveyed in Chicago medical schools
 45% have prescribed placebos in regular practice
 96% believe placebos can have “therapeutic effects”
 1/5 lied outright, claiming it was medication

IV: Debate
This house believes that doctors should
aggressively prescribe placebos if proven
treatments do not exist.
V: Concluding Remarks
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Placebos are much more than pills
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Placebos are tied to meaning
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They have the potential to bring about real physiological
changes
Surgery is very powerful; presentation, beliefs, etc. all
influence the power of individual placebos
The “Meaning Response” has real clinical application
The way doctors present things changes them
 Prescribing fake drugs may actually work
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The Problem with Placebos
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They only work because “real drugs” “work”
THE END
Final thoughts
20:15 – 20:45