Placebo Effect


Article Author:
Swapna Munnangi


Article Editor:
Lambros Angus


Editors In Chief:
Sisira Reddy
Joseph Nahas


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
3/23/2019 1:42:12 AM

Introduction

Placebos have been in use since antiquity and may have been significant in improving health and quality of life when little was known about the etiology of most illnesses. In fact, most outcomes were likely due to a placebo effect since the available treatments were unproven. For example, the use of snake oil and bloodletting was a common practice of the past. However, those that responded positively to those treatments likely did so because of a placebo effect. The emergence of placebo-controlled clinical trials in the 1940s reintroduced the placebo effect to the modern day. The classic article “The Powerful Placebo” by Henry Beecher highlighted the placebo effect and emphasized a need to account for it to evaluate the efficacy of a treatment modality properly. Both research and clinical settings utilize the placebo effect [1],[2][1].

The placebo effect is a fascinating phenomenon that occurs when a sham medical intervention causes improvement in a patient's condition because of the factors associated with the patient’s perception of the intervention. Examples of placebo interventions include sugar pills, saline injections, and therapeutic rituals. Placebo effects are not limited to inert interventions. Proven effective treatments can also generate a placebo effect. Traditionally, the placebo effect was considered a nuisance variable to be controlled for; however, in light of some remarkable research demonstrating its potential to modulate treatment outcomes in recent decades, there has been a spiked interest in studying this phenomenon[3].

The placebo effect can be verbally induced or result from conditioning and prior experiences that shape patient expectations. The role of the placebo effect as a powerful determinant of health in certain disease conditions has been demonstrated in several research studies. Migraines, joint pain, arthritis, asthma, high blood pressure, and depression are some disease conditions that are more sensitive to the placebo effect. It is a complex phenomenon with several underlying psychological and neurobiological mechanisms. These underlying mechanisms that mediate placebo responses differ based on the medical condition and the investigated outcomes. Not all results of a placebo are beneficial, and as such, placebos can also result in undesirable outcomes. Indeed, the term "nocebo effect," derived from the Latin nocere meaning “harm,” is commonly used when a placebo causes an unfavorable outcome. Both placebo and nocebo effects have the same mechanisms which presumably are psychogenic, but they can induce measurable changes in the body[4].

Mechanisms of Placebo Effect

Despite dramatic advances in scientific knowledge surrounding the placebo effect, efforts to characterize this phenomenon are in primitive stages. The complex nature of mind-body interactions, supplemented by the negative connotations associated with placebo effects in the past, have hampered understanding of it. However, researchers are beginning to unravel the neurobiological basis of placebo effects. Classical conditioning and expectancy are two hypothesized psychological mechanisms known to mediate the placebo effect. Classical conditioning is a form of learning where an association is formed between a stimulus and a response. The association is then remembered, affecting future experiences. Through this process of association, patients may acquire a behavior. For example, a patient may report a decrease in pain after receiving a placebo pill that looks similar to pain medication that was previously effective in easing the pain. Whenever the same stimulus is encountered in the future, the patient conditions himself by shaping expectations and shows a response that was previously imprinted in his memory. Learning and adaptation, therefore, drive a conditioned response[5].

Expectations of the patient also play a vital role in mediating a placebo effect. Expectations can impact the course of treatment by affecting the psychological and physiological responses to that treatment. Along with classic conditioning, expectations can be induced by verbal instructions or social learning. For example, a research subject treated for pain with placebo in the context of a verbal cue that the placebo is in an effective analgesic may shape his expectations and elicit an analgesic response. Conditioning and expectancy are often entangled mechanisms mediating placebo responses. Neurobiological mechanisms underlying the placebo effect are best characterized in placebo analgesia. In addition to these mechanisms, several other influential elements are at work during the placebo effect. These include the patient-physician relationship, patient’s psychological state and personality, the severity of the medical condition, and environmental circumstances. The patient's genetics may also influence the degree of placebo effect. Researchers are studying how genes can influence the placebo effect in various pathways, including the dopamine, opioid, serotonin, and endocannabinoid systems. Evidence also indicates that the therapeutic benefits of the placebo effect may not impact the pathophysiology of the underlying disease being studied, but rather address the subjective self-appraised symptoms of the disease. Elucidating the underlying mechanisms that mediate the placebo effect may prove beneficial to clinical practice and drug development[1].

Function

Placebo effects play a vital role in several areas. Primarily, placebo interventions serve as control treatments in experimental studies, enabling researchers to determine the specific effects of a particular treatment. Clinical investigators use randomized, double-blind placebo-controlled trials as a gold standard to validate treatments. Non-blinded trials may result in a disproportionately large placebo effect. In placebo-controlled trials, the placebo effect observed may be greater for psychological and self-rated measures relative to other more objective measures that are objective. Using a placebo in psychological and medical studies is advantageous as it helps minimize the influence of patient expectations on the outcome. Additionally, studying placebo effect at its core can help clinicians and researchers understand the context of how beliefs can shape various sensory and emotional perceptions. Identifying a physiological basis for the placebo effect may open doors to modulating processes that can improve mental and physical health. A clear understanding of the underlying mechanisms of placebo response with scientific work may enable clinicians to harness the placebo effect and improve the care provided to the patients.

Issues of Concern

It is challenging for medical professionals to sidestep the placebo effect and only measure the intrinsic activity of the treatment that they are testing. Therefore, therapeutic evaluations become difficult in medical conditions that are sensitive to the placebo effect. Interindividual differences also complicate the studies of the placebo effect. It is important that physicians separate the placebo effect from the treatment. Placebo research is challenging because of a certain degree of deception.

Clinical Significance

Understanding how placebo responses form is vital for clinical practice as it can play a crucial role in determining the therapeutic outcome of the patient. Although placebo effects frequently occur in clinical practice, they often go underrecognized. The therapeutic rituals and the psychosocial context surrounding the patient can mediate a placebo effect. The placebo effect is considered a melting pot of ideas in neuroscience. Translating the knowledge of the placebo effect to benefit the patient requires a thorough evaluation of the clinical effectiveness of the intended effect. Therefore, attempts to generate beneficial placebo responses should be done only under strict professional, legal, and ethical norms after obtaining appropriate informed consent[6].

Other Issues

Placebo effects have been a subject of ethical concern in clinical practice as well. Additionally, the ethical dimensions of placebo-controlled trials such as the use of sham invasive procedures, withholding potential proven treatments, or deception are issues of concern in studying the placebo effect.

Enhancing Healthcare Team Outcomes

An understanding of the placebo effect and a coordinated team effort must be made by nurses, pharmacists, and prescribers to ethical treat patients particularly in the performance of placebo-controlled trials.


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Placebo Effect - Questions

Take a quiz of the questions on this article.

Take Quiz
Which of the following is true of a positive response to a placebo?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the response to placebo for migraines at 2 hours in randomized clinical trials?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is the beneficial effect observed during an ineffectual medical treatment?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient was given a sugar pill for a mild headache and reports that it was very effective. Which of the following may be a reason for this outcome?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the phenomenon observed when an inert medical intervention causes improvement in a patient's condition because of the factors associated with the patient’s perception of the intervention?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Placebo Effect - References

References

Placebo and the new physiology of the doctor-patient relationship., Benedetti F,, Physiological reviews, 2013 Jul     [PubMed]
The placebo effect: From concepts to genes., Colagiuri B,Schenk LA,Kessler MD,Dorsey SG,Colloca L,, Neuroscience, 2015 Oct 29     [PubMed]
A Review of the Theoretical and Biological Understanding of the Nocebo and Placebo Phenomena., Dodd S,Dean OM,Vian J,Berk M,, Clinical therapeutics, 2017 Mar     [PubMed]
The placebo-nocebo response: controversies and challenges from clinical and research perspective., Jakovljevic M,, European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2014 Mar     [PubMed]
Introduction to placebo effects in medicine: mechanisms and clinical implications., Meissner K,Kohls N,Colloca L,, Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2011 Jun 27     [PubMed]
The powerful placebo., BEECHER HK,, Journal of the American Medical Association, 1955 Dec 24     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Rheumatology. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Rheumatology, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Rheumatology, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Rheumatology. When it is time for the Rheumatology board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Rheumatology.