Mind Over Matter: Placebos and Expectancies

2. Mind Over Matter: Placebos and Expectancies

3. 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. Quiz!

4. 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

5. 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

6. 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

7. 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

8. 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?

9. 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.

10. 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.

11. 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)

12. 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

13. 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

14. 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)

15. Ethics of Clinical Studies • Is placebo ethical? • Is prescribing placebos deceitful or unethical? • Sometimes standard therapies are found to be dangerous

18. Source of Placebo: Pavlovian Conditioning

19. 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)

21. 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)

22. 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.

24. 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

25. Development of Alcohol Expectancies

26. Alcohol Expectancies (cont) • With age and drinking, alcohol expectancies have more to do with arousal/sedation than whether alcohol is good or bad