The Placebo effect

DISCLOSURE

- The clinical use of placebo treatment requires deceiving the patient - Disclosing to the patient that we are using placebo treatment eliminates this problem - Disclosing this to the patient would eliminate the positive effect of the placebo treatment

PLACEBO & CHRONIC PAIN

2.5-hour educational regimen largely eliminated pain pattern on fMRI

The Brigham Comparison

300 young adult Bostonians recruited who had been experience regional musculoskeletal disorders of the arm for ≥3 months Divided into two groups, each then randomized into a controlled trial for two months acupuncture v. sham acupuncture twice weekly with experienced acupuncturist applied sheathed needle to the skin repeatedly each session Amitriptyline v. placebo pill Everyone improved in both trials Sham acupuncture helped faster than placebo pill What's different? ritual body language explanations during treatment Requires optimistic expectations and confidence of the clinician

HOW DO PLACEBOS WORK?

Commonly associated with hypochondriasis Psychological benefit is well-accepted "All in your mind" v. "all in your brain" There is also a measurable, significant biological effect

FIRST, DO NO HARM "Primum non nocere"

Ethical principal of non-maleficence Must consider the possible harm from intervention Doing nothing may be safer than administering a chosen intervention

NOBEBO

Nocere - L. - to harm Nocebo - "I will harm you" Etymologically related to 'nociception'

PLACEBO WITHOUT DECEPTION

Perhaps the beliefs are so ingrained in the mind that placebo treatment still results in a net positive outcome

PLACEBO STRENGTH

Placebo strength differs for several unexpected, unusual reasons: • Perceived dosage • Ritual of administration • Color of pill • Shape of pill • Physical environment • Situational factors Large sugar pills are more effective than small sugar pills Two sugar pills are more effective than one sugar pill Two sugar pills QD are more effective than one sugar pill BID • A placebo capsule is stronger than a placebo pill • A placebo injection is stronger than a placebo capsule • Sham devices are more effective than placebo injections • "Brand name" sugar pills are more effective than "generics" • Discounting the price of placebo pills make them less effective • Plain packaging decreases the effectiveness of placebo pills The same placebo that has been shown to be half the strength of aspirin has also been shown to be half the strength of morphine

PLACEBO & SURGERY

Placebos can decrease the size of duodenal ulcers Knee arthroscopy for OA is no better than sham arthroscopy! Hypertrophic cardiomyopathy improves with placebo pacemaker implantation

PLACEBOS & CULTURE

Placebos have differing levels of effectiveness from culture to culture • In Europe, Germany ranks first in placebo effectiveness for GI ulcers • In Europe, Germany ranks last for placebo effectiveness in HTN • Stimulants in Italy are most effective when they are colored blue • Acupuncture is found to be most effective when performed by a Chinese acupuncturist on a Chinese patient in China

PLACEBO

Placere - L. - to please Placebo - "I will please you"

Placebo effect

Something with no known therapeutic value creates any kind of positive change: • subjective - patient's perception • objective - measurable findings • due to the patient's beliefs and expectations • Traditionally studied in pharmaceutical industry with "sugar pills" or some kind of iner t "filler" • Can also come in other forms: • injectable medication • modalities • traction • surgery • others

Recommended Online Videos

The Strange Powers of the Placebo Effect [no link] Ben Goldacre for the UK's NHS: https://www.youtube.com/watch?v=wsFTgirKXHk Ben Goldacre at Nerdstock [no link]

PLACEBO & RESEARCH

Use of placebos in research due to the long-standing acknowledgement that non-medical aspects of healthcare can impart significant benefits Discern the true effect of the drug itself

What medical treatment has been proven effective in more clinical trials than any other? Placebo

https://www.youtube.com/watch?v=yfRVCaA5o18

PLACEBO & ANTIDEPRESSANTS

• Antidepressants are largely placebo for those with mild depression, but seem to work well for severe depression

PARADIGM SHIFT

• Anyone who is conscious, has a culture, and has personal beliefs experiences the placebo effect • EVERYONE experiences the placebo effect - no one is immune • YOU are a placebo responder • The vast majority of people are very resistant to this idea • Most believe that, if it is true, it does not apply to them

PLACEBO PRESENTATION

• Beliefs of the clinician influences the strength of the placebo effect • Can foster a "self-fulfilling prophecy", positively or negatively • Similar to a parent-child relationship • Based on limited research, animals can be placebo responders

PLACEBO & CAFFEINE

• Caffeine results in a spike in alertness • Causes a decrease in ability to learn new material • Placebo caffeine pill resulted in improved learning • Caffeine results in decreased performance but increased opinion of performance • Taking a short nap results in the most positive benefit!

ARE PLACEBOS ETHICAL?

• Concealing information and deceiving research subjects during research may be a part of study design • Concealing information and deceiving patients infringes upon their autonomy • Non-maleficence v. beneficence • Medical paternalism

Drug- related information generates placebo and nocebo responses that modify the drug response (see table of results)

• Double-blind placebo study of 66 subjects divided into 6 groups of 11 subjects •Active group given a muscle relaxant (Soma [carisoprodol]) •Blink reflexes measured every 15 min for 2 hours • Blood drawn after 40, 80, and 125 min to correlate responses with serum blood levels of Soma • Oral meds take 25~30 min to show the first signs of increased serum blood levels • Conditions 2, 3, 5 & 6 showed blink reflexes responses at first measurement (20 min) • Significantly higher blood serum levels of Soma in group 6 v. group 5! • Information was able to alter absorption of the drug • Placebo AND nocebo responses were generated by information about the effects of the drug • The best minds in research don't fully understand how this occurs: • Sympathetic response decreases gastric acid production, leading to slower breakdown of medication • Sympathetic response decreases intestinal motility leading to slower absorption of medication

PROPOSED MECHANISMS

• Early example: Pavlov modified his famous salivation experiments • Administered morphine to dogs in a small experimental chamber • Dogs were conditioned to exhibit a morphine-like response when placed in the chamber (i.e. vomiting/defecation/sleep) • Similar response occurs in humans with chemotherapy

PLACEBO & TREATMENT

• Even manual therapy seems to have 20~30% placebo benefit • One of the known effects of manual therapy - "psychological effects - not the reason we manipulate, but it must be considered" • We suspect that it is extremely likely that it occurs in all other PT specialty areas as well • TherapeuticTouch is an integral part of physical therapy • Everything we do in healthcare can have a placebo effect • Everything we do in healthcare can have a nocebo effect • Things we do in our daily lives have a placebo/nocebo effect

SOCIAL CONSIDERATIONS

• If placebo treatment is reimbursable, this means that all of the insured are paying to cover these services • Should taxpayers have to fund Medicare reimbursement of placebo treatment? • Would a policy of reimbursing placebo treatment hinder us from finding more effective treatments? • What is the right thing to do?

APTA CODE OF ETHICS

• Involves 5 of the 8 principles of the APTA's Code of Ethics • Three of the APTA's core values: • integrity • compassion • social responsibility

ETHICAL CONSIDERATIONS

• Is it right to deny treatment to someone that is likely to help them? • What would good evidence-based practice guidelines dictate? • Does this consider the patient's values? • Does this allow the patient to make an Informed Choice? • Does this infringe upon the patient's autonomy? • Is there any scenario in which billing for placebo treatment can be justified??? • Where do we draw the line?

CULTURE & CHILDBIRTH

• Labor anesthesia rates range from 21.9% (NM) to 78.2% (KY) • 63.4% for obstetricians; 49.8% for midwives • White women are the most likely to receive an epidural • Many known complications of spinal epidurals • Bradley natural childbirth class participants: unmedicated for 85~90% of vaginal births • Due, in large part, to beliefs and expectations

ANIMALS CAN BE PLACEBO RESPONDERS

• Meta-analysis of the three known prospective, placebo-controlled canine epilepsy trials • Average reduction in seizures of 26% • 22 of 28 dogs (79%) demonstrated a decrease in seizure frequency • 8 of 29 dogs (29%) demonstrated a ≥50% decrease • A placebo will make subjects feel better if told that it will do so • The same placebo will make subjects feel worse if told that it will do so

THE PLURAL OF ANECDOTE IS NOT DATA

• Placebo responders gain conviction that treatment is effective • When the modality is labeled a placebo, the patient often feels the need to justify their improvement • Patient advocates for that placebo based on their experience • Clinicians advocate for treatments they experience as effective • Fields advocate for treatments their members declare effective • THE PLURAL OF ANECDOTE IS NOT DATA

PLACEBO & EXERCISE

• Placebo study on hotel housekeeping staff - long hours, physical labor • Harvard researchers measured body fat, waist-to-hip ratio, blood pressure, weight and BMI • 84 subjects divided into two groups: control and education group (information regarding calories burned and surgeon general's definition of an active lifestyle) • One month later, there was a decrease in the education group regarding: • systolic blood pressure • weight • waist-to-hip ratio

PLACEBO & DEPENDENCE

• Placebos can be addictive • Sudden cessation of long-term placebo therapy results in withdrawal symptoms in 40% of subjects • Good compliance with scheduled medications decreases mortality, even if all the medications are placebo

WHAT DO WE DO WITH THIS KNOWLEDGE?

• Present information more authoritatively? ("sage on the stage") • Ac-cent-uate the positive?/E- lim-in-ate the negative? • Create a more positive clinical environment? • Create an image of a facility where people get better 100% of the time? • EmphasizeTherapeutic Touch?

PLACEBOS & PERFORMANCE

• There is a movement in the sports world to ban placebos from competition • No ability to enforce this type of ban!

TREATMENT V.TREATMENT ACT

• Treatment: what is done to the patient • Treatment act: a therapeutic envelope in which the treatment is administered. Almost always includes human interaction. • With rare exception, all modalities that have been tested are no more effective than a sham alternative • Almost all modalities have been tested