Placebos: Art and Science: Adam Goldstein, MD UNC Dept Family Medicine 10/16/00 Placebos: Art and Science


Placebos: History Range of Response Therapeutic Uses Ethical Concerns Show off... Placebos


Slide4: $200 $400 $600 $800 $1000 $200 $400 $600 $800 $1000 Placebos! $200 $400 $600 $800 $1000 $200 $400 $600 $800 $1000 $200 $400 $600 $800 $1000


All of these things have one thing in common.: Crocodile Dung Lizard’s blood Oil of earthworms Burning juice of Cassia The touch of a king All of these things have one thing in common.


Slide8: What were some of the earliest mentions of placebos? From 1500 B.C. to the early 17th century, many remedies were used as placebos


This type of placebo was very popular during the 19th century: This type of placebo was very popular during the 19th century


What are sugar pills?: What are sugar pills? 1900- Richard Cabot: “…using placebo, bread pills, water and other devices… I doubt if there is a physician in this room who has not used them (and) .. often.” Not believed to have negative consequences Not generally believed to be beneficial either


In 19__, the leading international medical journal ____ said that placebos “… reinforce patients’ confidence… when the diagnosis is undoubted and no more effective treatment is possible.”: In 19__, the leading international medical journal ____ said that placebos “… reinforce patients’ confidence… when the diagnosis is undoubted and no more effective treatment is possible.”


What is the Lancet? : a6a What is the Lancet? In 1954, published article on placebos.


This innovation reshaped the way modern medicine thinks about placebos: This innovation reshaped the way modern medicine thinks about placebos


What is the randomized controlled trial?: What is the randomized controlled trial? Beecher, JAMA, 1955, The Powerful Placebo 15 clinical trials aggregated, 1082 patients, 35% benefitted in placebo arm Effects were independent of intelligence The total effect of a drug = active + placebo


There are at least 3 problems with Beecher’s seminal work in JAMA: There are at least 3 problems with Beecher’s seminal work in JAMA


Slide16: a10a Are placebos uniform in their effect? Is the placebo effect confused with things such as regression to the mean, the natural history of the disease, etc? Can the placebo effect be harmful as well as beneficial? Can the placebo effect operate differentially in different arms of RCT? What about other aspects of placebos that relate to response such as relationships, physical setting, etc..?


Patients who are ill get better for at least three reasons: Patients who are ill get better for at least three reasons


Slide18: What is the: Natural history of disease? Specific therapy? Regression to the mean? vs “nonspecific” effects Yet, what are the limits of evidence-based medicine? Ill-defined conditions = “grey zomes”


Besides a pharmaceutical prescription, these things also strongly evoke a placebo response. (name three): Besides a pharmaceutical prescription, these things also strongly evoke a placebo response. (name three)


What are:: What are: Words Herbs Procedures Actions Balint said: “By far… the most frequently used drug … (is) the doctor.”


According to Sapirstein in the NEJM, the successful treatment of this condition is almost entirely due to the placebo response: According to Sapirstein in the NEJM, the successful treatment of this condition is almost entirely due to the placebo response


What is depression?: What is depression? NEJM 1998 Combined results from 39 studies of depression and medication Included meds like SSRI’s and TCA’s Placebo effects accounted for at 75% of the benefit and 50% of effect of drugs True drug effect only 25%


Classic internal mammary ligation for angina pectoris was an accepted treatment until this experiment was done.: Classic internal mammary ligation for angina pectoris was an accepted treatment until this experiment was done.


How did skin incision alone lead to equal improvement in symptoms compared to surgery?: How did skin incision alone lead to equal improvement in symptoms compared to surgery? 56% improvement in symptoms; 42% decrease in NTG use; 100% improvement in exercise tolerance Positive placebo effects seen in other objective condition such as ulcerative colitis, acne, HTN and BPH Lancet, 1997, 89 RCT’s Homeopathy-30-35% response Psoriasis- 25% placebo decrease in severity with accupuncture “The placebo effect of a thoracotomy should not be underestimated, particularly in patients for whom all therapeutic options have been exhausted and particularly when the procedure is combined with the use of a laser device.” (Quote from letter questioning value of laser surgery for inoperable CAD, NEJM, 1999)


Warning: The placebo side effects from this product (researched and reported on at UNC GI clinic) may cause gas and/or diarrhea: Warning: The placebo side effects from this product (researched and reported on at UNC GI clinic) may cause gas and/or diarrhea


What is Olestra?: What is Olestra? (Annals Int Med, 1999, Sandler) 6 week trial of olestra containing or regular chips People taking olestra and guessing that they were eating olestra- 45% GI symptoms People taking olestra and guessing that they were eating fat chips- 31% GI symptoms People taking fat chips who thought they were eating olestra- 44% GI symptoms People taking fat chips who thought they were eating fat chips- 29% GI symptoms


Specific aspects (name one) of the therapeutic relationship may be thought of as a placebo: Specific aspects (name one) of the therapeutic relationship may be thought of as a placebo


What are interpersonal skills?: What are interpersonal skills? Improved interpersonal skills are related to: improved compliance behavior change “PPD”- personality, presentation, demeanor Client’s desire to return to the therapist


This article by Herbert Adler in the JABFP in 1997 showed that by doing this when taking the history of the present illness on a patient, you will likely increase the placebo response.: This article by Herbert Adler in the JABFP in 1997 showed that by doing this when taking the history of the present illness on a patient, you will likely increase the placebo response.


What is summarizing the HPI?: What is summarizing the HPI? “Placebo response, sustained partnership, and emotional resilience in practice” Think of the HPI as a “large dose” of medication. Transform the database into a narrative


These patient-related factors (name 3) are likely to increase the placebo response.: These patient-related factors (name 3) are likely to increase the placebo response.


Slide32: Who are anxious patients When are patient expectations of treatment met? Do patients believe in the expertise of the provider? Do patients believe in the power of the treatment? Does the patient have social support


These provider-related factors (name 3) are likely to increase the placebo response.: These provider-related factors (name 3) are likely to increase the placebo response.


Slide34: Does the provider exhibit confidence, friendliness and a positive attitude? Does the provider give a mechanism of disease that fits with the patient’s belief system? Ddoes the provider give an explanation of why this disease at this time? Does the provider relate back a story that the patient believes is their strsry (HPI)? Does the provider form a therapeutic relationship in the encounter?


The acronym “SURE” is an easy way to remember the types of provider behaviors that are most likely to maximize placebo responses. Two of the letters in the acronym could stand for ___ and ____ and an example of each behavior would include ______________. : The acronym “SURE” is an easy way to remember the types of provider behaviors that are most likely to maximize placebo responses. Two of the letters in the acronym could stand for ___ and ____ and an example of each behavior would include ______________.


What are Support, Understanding, Respect and Empathy?: What are Support, Understanding, Respect and Empathy? Support: “I’ll do whatever it takes” “we will work together” Understanding: Think about facial and verbal expressions as well as posture Respect: Think about how well you listen and affirm the patient’s views “I respect…” Empathy: Think about how often and in what manner you touch patients, how often you you reflect back empathetic statements like “I know it must be difficult for you to …”


A medline search of this term retrieves the following: AIDS, HIV infections, Cardiovascular diseases, hepatocellular carcinoma, blindness, nurses, medical missions, emotions: d2 A medline search of this term retrieves the following: AIDS, HIV infections, Cardiovascular diseases, hepatocellular carcinoma, blindness, nurses, medical missions, emotions


What is hope?: What is hope? Traditional western medicine has frowned on the use of placebos. The use of alternative modalities has only recently gained more acceptance. The use of placebos is at the interface of alternative and complementary medicine. Placebo effect is seen in patients in interventions but no specific effect. Placebo effect also seen as explanation for positive effects of some alternative modalities.


The opposite of a placebo can sometimes be called this...: The opposite of a placebo can sometimes be called this...


What is a “nocebo”?: What is a “nocebo”? When the words we use or actions we do cause harm Howard Spiro- placebo as a "… stand-in for some alternative practices (which) can bring good or bad effects that depend in part on what patients expect.” (J Pain Symp Man, 1998, Staats) 36 subjects, randomized hand exposure to ice water Positive and negative placebo suggestions, control group Pain tolerance, pain threshold, and pain endurance Positive placebo > Control > Negative placebo Example: Eye doctor tells a patient with retinal vein occlusion that “there is nothing else we can do...”


Doubler: Doubler Make a Wager


Placebos, Ethics, and Women Entertainment Wire 1999 - VIBE Magazine, New York- In AIDS ravaged Africa, a controversial drug study is leaving pregnant women at risk and stirring outrage. As President Clinton publicly apologized to the survivors and families of the infamous Tuskegee syphilis study, in which the U.S. PHS withheld treatment form black males with syphilis (not to mention their wives) so that it could observe the disease's progression, it's happening again.What is it’s?: Placebos, Ethics, and Women Entertainment Wire 1999 - VIBE Magazine, New York- In AIDS ravaged Africa, a controversial drug study is leaving pregnant women at risk and stirring outrage. As President Clinton publicly apologized to the survivors and families of the infamous Tuskegee syphilis study, in which the U.S. PHS withheld treatment form black males with syphilis (not to mention their wives) so that it could observe the disease's progression, it's happening again. What is it’s?


Can the giving of a placebo in a research trial be unethical?: Can the giving of a placebo in a research trial be unethical? In AIDS trials in Africa, concerns raised about witholding known effective treatments...


Name one of your own ethical concerns about using placebos: Name one of your own ethical concerns about using placebos


?????????: ?????????


These medical practices may or may not be ethical (name 3): These medical practices may or may not be ethical (name 3)


What are:: What are: Giving antibiotics when the patient wants them but you think the cause is viral Giving a B-12 shot when the level is “borderline low” or to improve memory Telling a patient that they are unlikely to experience significant side-effects from a medication


Placebo responses are specific...: Placebo responses are specific...


Do placebo responses for one disease predict response to another?: Do placebo responses for one disease predict response to another? Placebo responses for one disease do not predict response to another It is important to individualize messages and approaches It is important to define patients’ expectations


A medline searches for these two similar categories highlight important differences between the two terms: 1) 19945 2) 529: A medline searches for these two similar categories highlight important differences between the two terms: 1) 19945 2) 529


What is the difference between placebo and placebo effect?: What is the difference between placebo and placebo effect? Placebos and placebo responses are quite different Placebo is any inert compound Placebo response is a system in action and may or may not include a compound


This family physician has written extensively on placebos: This family physician has written extensively on placebos


Who is Howard Brody?: Who is Howard Brody? Professor of FP at Mich State U. Placebos and the Philosophy of Medicine The Placebo Response


There are at least three purported mechanisms by which placebos may work (name 2): There are at least three purported mechanisms by which placebos may work (name 2)


What is: : What is: the endorphin pathway? the stress/relaxation pathway? the psychoneuroimmune pathway?


The derivation of the term “placebo” comes from this Latin or Roman Catholic custom: The derivation of the term “placebo” comes from this Latin or Roman Catholic custom


What is placare- “I shall please”?: What is placare- “I shall please”? A medication prescribed more for mental relief of the patient than for its actual effect on a disorder The Roman Catholic vespers for the dead whereby paid mourners prayed for a dead person These terms reflect a negative view towards placebos


Last Call: Last Call And the Last Call Category is: Make a Wager COLORS


Last Call Answer is:: Last Call Answer is: These colors are the most potent ones for sedating drugs as reported in a systematic review of controlled clinical trials.


Slide60: Most colors have universal meanings in a wide variety of cultures, red generally being considered strong and active, and blue and green associated with good. Studies on perceived action of coloured drugs showed that red, yellow, and orange are associated with a stimulant effect, while blue and green are related to a sedating effect (BMJ, 12/96). The perceived strength of coloured capsules: red and black are perceived as strong and white as weak. Capsules are perceived as stronger compared to tablets. What are blue and green?


Slide61: In a single blind experiment showing the effect of placebo 100 medical students participated in an experiment in which they received either a sedative or stimulant drug. All of the 56 students who volunteered in fact received either a blue or a pink placebo. Subjects taking the blue placebos felt less alert (66%) than those taking the pink (26%) and also more drowsy (72% v 37% respectively). (Lancet, 1972)


Slide62: Patients admitted for elective surgery were randomised to receive either a hypnotic agent or placebo on the first night. On the second night all patients received the other study drug, which was the same colour as that on the night before. Two colours were tested, blue and orange. Patients taking blue capsules reported falling asleep significantly more quickly than those taking the orange capsules, and those taking the blue capsules slept longer. (Euro J Clin Pharm 1978)