Placebo

Richard Asher

'If you can believe fervently in your treatment, even though controlled studies show that it is quite useless, then your results are much better, your patients are much better, and your income is much better too. I believe this accounts for the remarkable success of some of the less gifted, but more credulous members of our profession, and for the violent dislike of statistics and controlled tests which fashionable and successful doctors are accustomed to display'

The Placebo Effect

'The nonspecific psychological or psycho-physiological therapeutic effect produced by a placebo...' (Shapiro, 1997) 'The psychological phenomenon that involves expectation and anticipation of clinical improvement' (Kirsch, 1999)

Theories of How Placebos work: 1. Classical Conditioning

(Stewart-Williams & Podd, 2004) -Constant pairings of therapy administration (the unconditioned stimulus) that has a reliable therapeutic effect (the unconditioned response) with the features of a treatment setting (e.g., giving an injection; the demeanour of the nurse/doctor) - results in these stimuli alone being able to elicit a placebo response - the 'ritual' -Placebo responses can be conditioned in animals (Herrnstein, 1962)

The Nocebo Effect

-'Nocebo': from Latin; 'I will harm' -Also known as placebo 'side effects' -Patient feels unwell/worse after talking a placebo -Negative expectancies -Not as widely talked about or researched as the placebo effect, but important

Frequency of Placebo effect

->HrØbjartsson (2006); HrØbjartsson & Gøtzsche (2001; 2004); looked at 156 clinical trials using placebo >Placebo effect is hugely overestimated; reports of effectiveness are inflated and sometimes false >Trials often didn't use three conditions: treatment, placebo, no treatment (i.e., 'gold standard' in RCTs) >'Placebo effects' may in fact be statistical artifact (e.g., regression to the mean, improvement simply due to an illness taking its course) -Wampold and colleages (2006) looked at data again -HrØbjartsson & Gøtzsche had looked at all conditions/illnesses together -When conditions/illnesses looked at separately - placebo effects 'robust' and 'approach[es] the treatment effect'

Ethical Solution?

->Some have suggested openly prescribing placebos - telling patients that they're actually being given a placebo -New study: 'Placebos without -Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome' (Kaptchuk et al, 2010) -Patients who were openly given placebo treatment fared better those given no treatment at all -Authors state that more research needed - cautious

Placebo as Psychological Agents

-Beecher soley credited often BUT: Stewart Wolf (wrote about suggestion, conditioning and placebo effects, 1950) -Louis Lasagna (collaborator with Beecher)

The myth of the placebo responder

-Beecher's original trial methodologically flawed -No consistent evidence for 'placebo personality' that's consistent across time - we can't predict who will be responsive -Placebo effects don't tend to have long-lasting benefits (six months or more) - as far as we know

Placebo Effect and Objective measures

-Do placebos cause actual physical changes in the body? -Most trials showing strong placebo effects - use subjective measures (people feel better, but are they physically better?) -Placebo effect often doesn't 'stand up' when objective measures are looked at (e.g., blood tests, looking at post-surgery healing)

3. Personality

-Early on in placebo research, the following traits were hypothesized to be linked with placebo effects: depression, proneness to hypochondriasis, schizoid personality, religiosity, neuroticism, etc. -Idea that a specific personality type is related to placebo responding was dismissed - unable to replicate findings of previous studies (Buckalew, Ross, and Starr; Taylor, 1999) -More recent research has emerged, looking at interaction of personality and environmental context (person/situation); (Geers et al, 2005; Geers et al, 2006) - better approach; more likely that a certain type of person will respond to placebos in specific situations, but not in every type of situation

Nonspecific Effects/Factors = the placebo

-Everything other than the actual therapy (therapeutic relationship) -The ritual, the environment -Strong in psychotherapy -Difficult to measure all effects

Only certain conditions seem to respond to placebos

-Pain -Depression -Asthma -Inflammation -Gastric Ulcers

Biological Mechanism-Inflammation (Evans 2005)

-Placebos only work for certain conditions (relating to inflammation) -Placebos work by promoting release of endorphins in brain, reducing pain etc.

What make placebo powerful

-Quantity: two placebo pills more effective than one -Medium of delivery: placebo injection (e.g., saline solution) more effective than a placebo pill -Branding: well-known brands seen as more effective than generic brands (even though the meds are the same! (Branthwaite & Cooper, 1981) -Physical appearance: blue coloured placebos more powerful as sedatives than red placebos (but only in Italy!) -Severity of condition: people with 'mild' symptoms less likely to respond

The placebo effect: Fake surgery

-Sham cardiac surgery in patients with angina - chest incision but no actual procedure (e.g., Cobb et al, 1959) -Sham knee surgery for pain - patients reported significant decreases in pain a few weeks after (Mosley, 1994) -Key point - no objective, physical changes (the knees and hearts were not 'repaired'), but people report feeling better; need to take less medication

You cant test it??

-Some claim that we can't test certain therapies/treatments >>We can test/design experiments or trials to test any treatment

Summary Read chapter 16

-The placebo effect remains a controversial topic -Can we harness the 'power of the placebo'? -Are placebos ethical in all contexts? -Psychological research on topic sluggish - more research needed!

The ideal environment for placebo effect

-desirable patient characteristics -excellent communication, concern, understanding and time from freindly health practitioner -strong personal investment (cog. dissonance) -plausible/credible treatment

Prescribing Placebos: use in medical settings

-issue of informed consent -German Medical Association (2011) has recommended that prescribing/using placebos is a positive thing; doctors don't have to 'come clean' about it to patients -British Medical Association - use of placebos in medical settings is 'unscientific'

Other Biological Mechanisms Fabrizio Benedetti

-studied placebo effects in brain -Placebo administration in the context of pain -Brain imaging research - can see pain activity reduce when placebo given (effect reversed when analgesia blocker given)

Henry Beecher

>Groundbreaking paper 'The Powerful Placebo' (1955) - published in the Journal of The American Medical Association >Approx one-third (or 35.2%, with a margin of error of 2.2%, to be precise) of the general population will respond to placebos (according to Beecher's own research) >Spoke of placebo 'reactors' and 'non-reactors' - a sort of personality trait/type

'Regular medicine will kill you'

>Mineke Kamper, Mayo-based homeopath >Paul Howie - 49 year old farmer; attended for elbow pain in 2002, developed neck lump >Told lump would be gone within fortnight >'A laboratory analysis of tablets provided by Ms Kamper for Mr Howie revealed that they contained no controlled drugs and had no detectable active ingredient' >Howie died in 2005 - complications, suffocation >Kemper didn't attend inquest; fined €6.35

Placebo origin-clinical drug trial

>Study of placebos - relatively new to psychology >Placebos originally used as a practical 'tool' in drug trials: something to assess the effectiveness of new medicines/therapies >Some patients in the trial given new drug; some given placebo - is drug more effective than a placebo? Beecher popularized the placebo-noticed it in treatment of injured WW2 soldiers

Ethical Guidlines for research: The declaration of Helsinki

>World Medical Association (WMA) in 2000 (most recent version: 2008) ->'Although the Declaration is addressed primarily to physicians, the WMA encourages other participants in medical research involving human subjects to adopt these principles.' ->'The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best current proven intervention, except in the following circumstances: ->The use of placebo, or no treatment, is acceptable in studies where no current proven intervention exists; or, ->Where for compelling and scientifically sound methodological reasons the use of placebo is necessary to determine the efficacy or safety of an intervention and the patients who receive placebo or no treatment will not be subject to any risk of serious or irreversible harm. Extreme care must be taken to avoid abuse of this option.'

Exploiting the placebo effect: The problem of alternative medicine

A proven/rigourously tested therapy is simply called 'medicine' - no longer alternative 2008 case against manufacturers of magnetic bracelets in US; convicted of fraud and fined $16,000,000 In his ruling, Judge Frank Easterbrook said: Since the placebo effect can be obtained from sugar pills, charging 200 for a device that is represented as a miracle cure but works no better than a dummy pill is a form of fraud.

Gaddum 1953

According to the Shorter Oxford Dictionary the word placebo has been used since 1811 to mean a medicine given more to please than to benefit the patient

Pacebo def

Any therapy prescribed...for its therapeutic effect on a symptom or disease, but which is actually [medicinally] ineffective or not specifically effective for the symptom or disorder being treated' (Shapiro, 1997) -E.g., the classic 'sugar pill' - no medicinal properties (but can also be active medicine) -Not always something you ingest

Placebo eg's in history

Blood letting, purging, leeches, tonics/lotions/potions

Genetic Theory of Placebos

Hall, Loscalzo, Kaptchuk, 2015

Ethical Concerns

If we: -don't know/can't predict who will respond to a placebo, -or the exact circumstances that might create the placebo effect -> is it ethical to knowingly give placebos to people in exchange for payment?

2. Expectancy

Kirsch -Also known in the literature as 'response expectancy' -Expectancies are non-volitional (involuntary) -Person's past experience of treatment is more powerful than contrived suggestion manipulations carried out in experiments (Montgomery & Kirsch, 1997) -People normally experience what they expect

Recent research into role of Personality

Peciña and colleagues (2012) -Induced pain in participants -PET scan - opioid receptor activity (i.e., pain relief targeted) -Some not given pain relief, some given placebo -High agreeableness AND low neuroticism (combination) - predictive of placebo response -Authors stress need for replication

Ethics of Placebos

Physician/researcher, Dr Thomas Freeman, who conducted placebo-controlled trials with fetal cell brain implants for Parkinson's Disease said, "Ultimately, I decided it's more ethical to put 12 patients through an imitation operation than have thousands go through operations, claimed to be efficacious, that actually kill more people than they help."

Streitberger needle 1998 test acupuncture

They placed a plastic cover over the area of skin targeted and either in placebo condition rested needle on skin or in verum condition performed acupuncture.