The Placebo Effect

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The Placebo Effect

• Michael Putman

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Quiz!

• T/F Placebos make patients feel better they
  dont 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 Doctors can lie to patients if it is in
  the patients best interest.

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Overview

• Introduction Placebos, Meaning, and
  Misconceptions
• Psychoneuroimmunology
• Placebos and Anti-depressants
• Placebos, Doctors, and Deliberate Deception
• Debate!
• Concluding Thoughts

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Introduction

• Documentary on the Placebo Surgeries
• 124 615

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I Definition

• The effect of a treatment that arises from a
  patients expectations and response to the
  treatment, excluding the treatments specific
  action
• In medicine, it typically refers to a response
  observed after inert or inactive treatments

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I Examples of Placebos

• Inert pills, drugs, or injections
• Sham surgeries
• Inactive medical devices
• Effective/non-effective acupuncture

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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

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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

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I Moerman on Placebos

• Placebos do not cause anything because theyre
  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

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II Psychoneuroimmunology
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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

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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

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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

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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

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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

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III Placebos and Depression

• Placebos for Depression
• 1520 - 1900
• 1900 - 2015

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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

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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

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III The Emperors 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
  SSRIs
• 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?

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III The Emperors 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

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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

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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

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III Side Effects of SSRIs

• 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)

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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?
• 1216 1330 1445?
• ABC News Story

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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

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IV Debate

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

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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

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The End

• Final thoughts
• 2015 2045