Endob Medyr2: Preventing Illness and Patient-Professional Encounters - Placebos (PDF)

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn ENDOB MEDYR2: Preventing illness and the patient- professional encounter - Placebos Placebos Enter subtitle here (24pt, Arial Regular) Enter date: 25.06.13 Class MED Year 2 - BAHRAIN 2023/2024...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn ENDOB MEDYR2: Preventing illness and the patient- professional encounter - Placebos Placebos Enter subtitle here (24pt, Arial Regular) Enter date: 25.06.13 Class MED Year 2 - BAHRAIN 2023/2024 Module ENDOB Lecturer Ms. Luma Bashmi Date 30th January 2024  Learning Outcomes ▪ Define placebo and describe how definitions have changed over time ▪ Describe a randomised, double-blind placebo controlled trial ▪ Outline the different theories of how the placebo works, giving examples for each ▪ Define and describe a nocebo ▪ Outline clinical and ethical implications of placebo use/abuse Learning Outcomes Define placebo and describe how definitions have changed over time Describe a randomised, double-blind placebo controlled trial  Placebos – Evolving definitions ….a pharmacologically inert substance which is given to benefit or ‘please’ a patient ….any component of therapy that is without specific (biological) activity for the condition being treated or evaluated ….the effects of a treatment that are not attributable to the mechanics of the treatment itself but rather to the circumstances surrounding it Randomised double-blind placebo controlled trial Randomised controlled trial (RCT) – An experiment in which two or more interventions are compared by being randomly allocated to participants Randomised placebo controlled trial – An inactive substance or procedure administered to a participant. Placebos are used in clinical trials to blind people to their treatment allocation. Placebos should be indistinguishable from the active intervention to ensure adequate blinding Randomised double blind placebo controlled trial – Blinding is the process of preventing those involved in a trial from knowing to which comparison group a particular participant belongs. Double blind - both clinician and participant are prevented from knowing Source: http://www.cochrane.org/glossary Placebo – contemporary views Modern scientific medicine constructed on the notion of the randomized, double-blind, placebo-controlled trial where drugs have to perform better than a dummy pill or inert saline injection Now things are not so clear Gap in research that needs to be addressed Placebo Effect: Typical Example (Houde et al., 1990) Placebo Effect Evidence in both routine practice & experimental studies Shown to exhibit changes in: Physiological status Behavioural responses Subjective experiences Can mimic most drug groups Habituation (tendency to increase dose over time) Withdrawal symptoms Dependency Strength of Placebo Effect Placebo response rates 30-50%, sometimes reported as approx. half strength of active drug. Wide variation in who responds to placebos WHO : estimates 35% of patients will respond to placebos History and Significance Placebos carry the stigma of "some unspoken and unacknowledged conspiracy between caregiver and patient, one pretending to help, the other pretending to get better." "There is a presumption that the psychological is not quite real, that that which emerges from suggestion is just made up.” Robert M. Rose, Director of Mental Health, John D. and Catherine T. MacArthur Foundation. Learning Outcomes Outline the different theories of how the placebo works, giving examples for each  How does Placebo work? Non-interactive theories Interactive theories Treatment Experimenter bias characteristics Reporting error Patient characteristics Learning theory Characteristics of Anxiety reduction health professionals theory Physiological theories Patient expectations Non-Interactive Theories: Patient Characteristics Placebo personality traits? – Emotional dependency; extraversion; neurosis; high suggestibility have all been examined – No personal characteristics will predict whether or not a patient will respond positively to a placebo Non-Interactive Theories: Treatment Characteristics The more serious the perception of the treatment, the larger the placebo effect – Sham surgery – Injection – Pills More pills better than fewer (same total dosage) Large pills better than small pills Colour of pills important depending on condition Brand names more effective than generic “New” drugs more effective than “old” ones  People assume expensive drugs work better Copyright ©2008 BMJ Publishing Group Ltd. BMJ 2008;336:582-583 Non-Interactive Theories: Characteristics of the Health Professional The higher the professional status of the health care provider, the greater the placebo effect. The more enthusiasm for the treatment by the medical professional, and the greater the status of the treatment in their opinion, the greater the placebo effect Kelley et al 2009 – Warm, empathic manner of practitioner a key variable Non-Interactive Theories: Problems Examine only the patient, treatment, or professional, and ignores interactions Assumes these factors exist in isolation and can be examined independently of each other Interactive Theories: Experimenter Bias Experimenter bias: – the impact that the experimenter’s expectations have on the outcome of the study – Gracely et al. (1985) : Study of doctor expectations – Patients who were given treatment by doctors who believed the patient had a chance of receiving analgesic (but unknowingly gave a placebo) showed decrease in pain Interactive Theories: Reporting Error Confabulations: symptoms remain the same, but patient reports getting better Biased perceptions of patients and doctors - misattribute spontaneous improvements in symptoms as treatment (placebo) Problems with this theory: not all symptom changes are positive. Are the effects really there? Wechsler et al. BMJ 2011;343:bmj.d4562 Interactive Theories: Learning Theory Patients associate certain factors with recovery and improvement in symptoms Based on classical conditioning http://encarta.msn.com/media Interactive Theories: Learning Theory Unconditioned stimulus (treatment) associated with unconditioned response (recovery) Unconditioned stimulus (treatment) paired with conditioned stimulus (e.g., Hospital / white coat) - conditioned stimulus alone could elicit a conditioned response (recovery) Interactive Theories: Anxiety Reduction Receiving any treatment can reduce one’s anxiety Placebo may decrease anxiety by encouraging patient to feel they are in control of their pain Relaxation can close the pain gate and reduce pain Challenge: Placebos show an effect on more than pain  Physiological Theories Placebos activate the body’s natural pain-killing system (opiate release) which decreases pain Placebos can create dependence, withdrawal, tolerance Placebo effect can be blocked by naloxone, an opiate antagonist Physiological theory: Study of endorphin release Levine, Gordon, Fields (1978): Medication given to patients after oral surgery to remove wisdom teeth Patients divided into 4 groups: Group 1: Morphine Group 2: Naloxone (opiate antagonist) Group 3a: Placebo + placebo one hour later Group 3b: Placebo + naloxone one hour later Summary of Results: Endorphin Study Placebo responders: – 39% reported a reduction in pain on first placebo but reported increased pain when naloxone given later Conclusion: – Endorphin release must have occurred with the placebo  Patient Expectation: Expectation Theory Patient believes that a change will occur Motivation (the desire to experience a change) also plays a role e.g. Wilson, 1982 - the effects of expectations of alcohol intoxication The patient’s expectation of getting better may be the central psychological component of placebo efficacy – Expectation should produce: Less anxiety Experimenter bias Reporting error Treatment characteristics – Learning might produce the expectation which may trigger the physiological effect Central Role of Patient Expectations Conditioning Physiological theory Experimenter bias Patient Expectations Reporting error Anxiety reduction Patient Expectations: Study of Beta-blockers vs. Placebo Two groups of men (age 30-69) All had survived an acute heart attack: Group 1: received a beta-blocker (n=1082) Group 2: received a placebo (n=1094) Measures: psychosocial factors (eg, stress, smoking), adherence, clinical characteristics measured Mortality measured after 12 months Horwitz et al., 1990 Study of Beta-blockers vs.Placebo: Results Mortality highest among those with a history of heart congestion, who were not married; who were more socially isolated and had higher life stress Poor adherers twice as likely to have died The adherence effect was true for the beta-blocker and the placebo groups! Horwitz et al., 1990 Study of Beta-blockers vs. Placebo: Results Study of Beta-blockers vs. Placebo: Conclusions Authors conclusions: “ Perhaps the most provocative explanation for the good effect of good adherence on health is the one most perplexing to clinicians: the role of patient expectancies or self efficacy” Reflects the complex interrelationship between beliefs, behaviour & health Patient Expectations: Open-Hidden Study of Morphine Benedetti et al (2003): Study of pain relief Group 1: analgesics given by physician Group 2: analgesics given via intravenous line (hidden to patients) Open-Hidden Study of Morphine: Results Those given analgesics visibly (Group 1) reported more pain relief = placebo effect Those “deceived” (Group 2) got less benefit (Amanzio, Pollo, Maggi & Benedetti, 2001) Open-Hidden Study of Morphine: Conclusions Evidence of the importance of context in the outcome of treatment Expectations are mechanism of placebo effect (possibly activate the opioid system) Illustrates the problem with the definition of placebo - no “placebo” was given By increasing expectations in clinical practice, may be possible to further enhance the efficacy of effective analgesic Summary of placebo effect theories No single patient characteristic accounts for it Type of treatment and health professionals manner can enhance it Expectation of experimenter can impact outcome & learning theory can explain ‘white coat’ effect Doing anything can reduce anxiety – can in turn activate body’s natural pain killing system? Central psychological component underlying all of these is the expectations of the patient 42 Learning Outcomes Define and describe a nocebo Outline clinical and ethical implications of placebo use/abuse “Placebo Effect” Misnamed? Outcome is assortment of many factors “[It is a] fallacy to label the therapeutic consequences of being in a control group as the ‘placebo effect’” Effects of “the consequences of the meaning of the medication or procedure, the construction of understandings shared between doctor, patient, community...” I call the ‘meaning response’ (Moerman, 2002) Benevolent deception? Placebo use in Contemporary Medicine? Nitzan & Lichtenberg: BMJ Oct. 2004 Survey of Placebo use by Israeli doctors – N=89 hospital doctors, senior nurses, community clinic doctors – Results: 60% prescribed placebos in last year 62% of prescribers used them monthly or more frequently 68% did not tell patient it was a placebo 28% used them as a diagnostic tool Placebo use in UK Primary Care (2013) UK doctors who used pure placebos at least once in their career = 12% UK doctors who used impure placebos at least once in their career = 97% UK doctors who used impure placebos at least once per week = 77% Most (66% for pure, 84% for impure) respondents stated placebos were ethical in some circumstances Professional Opinions: American Medical Association A placebo must not be given merely to mollify a difficult patient, because doing so serves the convenience of the physician more than it promotes the patient’s welfare. Physicians can avoid using a placebo, yet produce a placebo-like effect through the skillful use of reassurance and encouragement. In this way, the physician builds respect and trust, promotes the patient-physician relationship, and improves health outcomes (I, II, VIII). Issued June 2007 based on the report "Placebo Use in Clinical Practice,"adopted November 2006. Source: http://www.ama-assn.org/ama/pub/physician-resources/medical-ethics/code- medical-ethics/opinion8083.page 48 Nocebo Effects Nocebo: negative effects “I will harm” If patient is told about “possible” side- effects, more likely to report “side- effects” than those not told Nocebo Effects Usually more generalised and diffuse: – Drowsiness, nausea, fatigue, insomnia More common in women More likely if patients have previous experience of negative effects More likely if patients expect negative effects Dilemma: patient information v nocebo Required Reading: Alder B., et al. Psychology and Sociology applied to Medicine. > Placebo pp90-91 Koshi & Short, (2007). Placebo theory and its implications for research and clinical practice: A review of the recent literature. Pain Practice, 7(1):4-20. Recommended Reading: Ogden, Ch. 13, pp. 307-326.