The Placebo Effect

1. The Placebo Effect Michael Putman

2. Quiz! • 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: Doctor’s can lie to patients if it is in the patient’s best interest.

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

4. Introduction Documentary on the Placebo Surgeries 1:24 – 6:15

5. I: Definition • The effect of a treatment that arises from a patient’s expectations and response to the treatment, excluding the treatment’s specific action • In medicine, it typically refers to a response observed after inert or inactive treatments

6. I: Examples of Placebos • Inert pills, drugs, or injections • Sham surgeries • Inactive medical devices • Effective/non-effective acupuncture

7. 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

8. 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

9. I: Moerman on Placebos • Placebos do not cause anything because they’re inert • It is the psychological/emotional meaningthat 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

10. II: Psychoneuroimmunology

11. 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

12. 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

13. 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

14. 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

15. 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

16. III: Placebos and Depression Placebos for Depression 15:20 - 19:00 19:00 - 20:15

17. 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

18. 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

19. III: The Emperor’s 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 SSRI’s • 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?

20. III: The Emperor’s 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

21. 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

22. 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

23. III: Side Effects of SSRI’s • 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)

24. 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? 12:16 – 13:30… 14:45? ABC News Story

25. 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

26. IV: Debate This house believes that doctors should aggressively prescribe placebos if proven treatments do not exist.

27. 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”

28. The End Final thoughts 20:15 – 20:45