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 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

• 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 mu-opioid neurotransmitter system (“endorphins”)

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

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

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