THE PLACEBO EFFECT

Michael Putman

Quiz!

1. T/F: Placebos make patients feel better; they don’t actually get better

2. T/F: There are no negative effects of placebos

3. T/F: Placebos can reduce asthma and make wounds heal faster

4. T/F: Placebo therapy could be the end of biomedicine as we know it

5. 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

Debate!

V. Concluding Thoughts

Documentary on the Placebo Surgeries

1:24 – 6:15

Introduction

I: Definition

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

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)

Type of procedures Surgery is better than injection; injection is better

than pill Previous experience

Codeine cough syrup works really well the second time

Presentation 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…

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

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) 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

Ader and Cohen suspect that immunosupression can be behaviorally induced Investigate in rat paradigm CS: saccharin US: immunosuppressant

Discovered suppression of immune system by nothing more than taste

II: Kiecolt Glaser (1999): Immune Function

Stress dysregulates NK cell activity and decreases g-interferon (IFN-g) 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

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 Healing takes

significantly longer in controls Differences in

peripheral blood leukocytes

Placebos for Depression15:20 - 19:00 19:00 - 20:15

III: Placebos and Depression

III: Antidepressants: Brief Reminder

Serotonin system influences mood, sleep, arousal, etc. 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 Depression costs $44

billion per year to US economy

Global sales in 2005 of $16.2 billion US is 66% of the market

Most commonly written script as of 2005 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 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

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 Previous results

called into question 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?

File Drawer Effect Journals tend to publish

findings Unblinding of Raters

Side effects often reveal treatment group

FDA Standards Must show “safety and

efficacy” 2 placebo-controlled

trials required with positive results

III: Prozac and Suicide

Increased risk of suicide with Prozac

Oct 2004: FDA instructs SSRI makers to include black box warning Doubled risk of

suicide in adolescents July 2005: FDA issues

public health warning

III: Side Effects of SSRI’s

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)

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: Physicians and the Placebo

IV: Do Doctors Prescribe Placebos? 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 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

This house believes that doctors should aggressively prescribe placebos if proven treatments do not exist.

IV: Debate

V: Concluding Remarks

Placebos are much more than pills They have the potential to bring about real

physiological changes Placebos are tied to meaning

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

The Problem with Placebos They only work because “real drugs” “work”

THE END Final thoughts20:15 – 20:45