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Mind Over Matter: Placebos and Expectancies. 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

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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: Doctors can lie to patients if it is in the patient’s best interest.

  • From Latin placere - “to please” or “I will please”
  • Placebo
    • “an innocuous substance without a specific physiological effect”
      • Clearly active and not innocuous;
      • has physiological effects
    • any treatment devoid of specific actions on the patient’s symptoms or diseases that, somehow, can cause an effect upon the patient.
      • Obviously have specific actions but true that we don’t know precisely how
the placebo effect
The Placebo Effect
  • Based on expectancies
    • "anticipation of a systematic if/then relationship between events and objects." (Tolman, 1932)
  • Afflictions that have strong psychological components (pain, anxiety, and depression) tend to show high rates of placebo effects
    • ~ 65% of patients in antidepressant trials get better with drug
    • ~ 35% of patients in antidepressant trials get better with placebo
    • Many times these rates don’t differ statistically (30% rule)
  • A meta-analysis showed that antidepressants relied on the placebo effect for 75% of their effectiveness
  • The remaining 25% “real” drug effect may be a disguised placebo effect
the placebo effect cont
The Placebo Effect (cont)
  • Blocked by real drugs, e.g., opioid antagonists
  • Placebos have side effects (nocebo)
  • Placebo effects can last for a long time: over 8 weeks for panic disorder, 6 months for angina pectoris, and 2.5 years for rheumatoid arthritis.
  • Depressed patients who respond to placebos differ biochemically from those who don’t
    • Short-term depression (< 3 months) more responsive
    • Long-term depression (> 1year) not responsive
placebo effect
Placebo Effect
  • If expectation of pain can increase pain intensity,
    • how might expectation of pain reduction influence perception?
      • Experimental results
        • 85% of Ss given placebo for relief of pain caused by Herpes (cold sores or genital sores) reported pain reduction
        • 56% of patients given sham treatment (small skin incision) for angina (heart pain) reported significant pain reduction
        • On average, 33% of Ss in placebo pain studies report pain reduction
are many drug effects simply placebo effects
Are many drug effects simply placebo effects?
  • Placebo effects were discovered in the 1950s
    • Administering a simple sugar pill or water alleviated symptoms or even cured some diseases
  • However, it’s a minority view that it’s all placebo
  • Nonetheless, some placebo effects may be present in all drug effects
    • How do you dissociate placebo from other effects?
nocebo i will harm walter kennedy 1961
Nocebo (“I will harm”)(Walter Kennedy, 1961)

A nocebo response occurs when a drug-trial's subject's symptoms are worsened by the administration of a placebo.

If the patient believes a substance is harmful it can cause negative effects.

the nocebo effect
The Nocebo Effect
  • Emotional state, depression, anxiety, anger, hopelessness
  • Negative health care provider
  • No love in the family
  • Cynicism, suspicion and pessimistic expectations
  • Medical students disease (hypochondriasis)
  • Cardiac neurosis is a nocebo – 75% of chest pain is due to anxiety.
nocebo effect
Nocebo Effect
  • Approximately ¼ of patients receiving a placebo voluntarily report adverse side effects
  • When prompted, between 27% and 71% report adverse side effects
  • Usually general complaints (difficulty concentrating, nausea, fatigue)
placebo nocebo evidence based medicine
Placebo/Nocebo Evidence Based Medicine
  • All drugs and procedures need to be tested against the placebo/nocebo effect, as high as 70% in most medications and operations.
  • Treatment benefit = therapeutic gain + natural history of illness + placebo effect-nocebo effect
Note that if the nocebo effect is greater than the therapeutic gain and the natural history of the disease, the treatment will make the patient worse.
  • The evil eye – voodoo – witchcraft
dealing with placebo and nocebo effects in experiments
Dealing with Placebo and Nocebo Effects in Experiments

Study Designs

(randomly assigned to experimental/placebo arms; passive vs active placebos)

  • Blinded Study- Participant doesn’t know if they are receiving treatment or placebo
  • Double-Blinded Study- Participant and Experimenter do not know if treatment or placebo is being given
  • Double-Blind, Crossover Study- Same as double-blinded, except participants get treatment and placebo in random order (controls for Ss variability)
ethics of clinical studies
Ethics of Clinical Studies
  • Is placebo ethical?
    • Is prescribing placebos deceitful or unethical?
  • Sometimes standard therapies are found to be dangerous
why the high responsiveness to expectation of pain relief
Why the high responsiveness to expectation of pain relief?
  • Evidence that expectation of pain relief activates mu-opioid neurotransmitter system (“endorphins”)

Red & orange indicate regions of heightened mu-opioid activity when P reports positive effect of placebo

Zubieta et al - Placebo Effects Mediated by Endogenous Opioid Activity on µ-Opioid Receptors (2005)

other factors involved in the placebo effect cont
Other factors involved in the placebo effect (cont)
  • Natural disease progression may be cyclical
    • gets worse then gets better
  • Enrolling in a clinical trial or seeing a doctor gives some individuals a greater sense of control over the illness
  • Feelings of concern and caring from nurses, doctors, and researchers
    • A healing environment
  • Difficult to measure some illnesses/diseases
    • Scales for measuring pain/anxiety/depression are not clear cut and tend to be somewhat labile
  • Poor patient selection (no test for susceptibility to placebo)
cognitive explanations schemata
Cognitive Explanations: Schemata
  • Organized representations of conceptually-related information that guide processing of new information
    • Facilitate memory and comprehension
    • Influence the speed of information processing and problem solving
    • Gather information into meaningful and more easily retrieved units
    • Enable the individual to fill in missing information
    • Provide greater confidence in prediction and decision making.
creating expectations alcohol
Creating Expectations: Alcohol
  • Identified in various age, drinker groups
  • Alcohol schemas in pre-schoolers
  • Related to drinking levels
  • Predicts future drinking levels
  • Change in parallel with drinking levels
  • Experimentally manipulable with corresponding effects on drinking
  • Consistent with behavior after drinking
  • Some relationship with family history
  • Change with age before drinking
alcohol expectancies cont
Alcohol Expectancies (cont)
  • With age and drinking, alcohol

expectancies have more to do

with arousal/sedation than whether alcohol is good or bad