Neurotransmitters

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Mind Over Matter:
Placebos and Expectancies
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: Doctors can lie to patients if it
is in the patient’s best interest.
Placebo
• 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
• 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)
• 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
• 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?
• 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)
A nocebo response
occurs when a drugtrial'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
• 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
• 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
• 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
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
• Is placebo ethical?
• Is prescribing placebos deceitful or unethical?
• Sometimes standard therapies are found to be
dangerous
Source of Placebo: Pavlovian
Conditioning
Why the high responsiveness to
expectation of pain relief?
• Evidence that expectation of pain relief activates muopioid neurotransmitter system (“endorphins”)
Red & orange
indicate regions of
heightened muopioid 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)
• 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
• 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
• 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
Development of Alcohol Expectancies
Alcohol Expectancies (cont)
• With age and drinking, alcohol
expectancies have more to do
with arousal/sedation than
whether alcohol is good or bad
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