The word placebo was used in a medicinal context in the late 18th century to describe a "commonplace method or medicine" and in 1811 it was defined as "any medicine adapted more to please than to benefit the patient". Although this definition contained a derogatory implication, [1] it did not necessarily imply that the remedy had no effect. [2]
Placebos have featured in medical use until well into the twentieth century. [3] In 1955 Henry K. Beecher published an influential paper entitled The Powerful Placebo which proposed idea that placebo effects were clinically important. [4] Subsequent re-analysis of his materials, however, found in them no evidence of any "placebo effect". [5]
Placebo is the opening word of the antiphon of vespers in the Office of the Dead, used as a name for the service as a whole. The full sentence, from the Vulgate, is Placebo Domino in regione vivorum 'I will please the Lord in the land of the living', from Psalm 116:9. [6] [7] To sing placebo at a funeral came to mean to falsely claim a connection to the deceased to get a share of the funeral meal, and hence a flatterer, and so a deceptive act to please. [1]
In the practice of medicine it had been long understood that, as Ambroise Paré (1510–1590) had expressed it, the physician's duty was to "cure occasionally, relieve often, console always" ("Guérir quelquefois, soulager souvent, consoler toujours"). Accordingly, placebos were widespread in medicine until the 20th century, and were often endorsed as necessary deceptions. [3]
According to Nicholas Jewson, eighteenth century English medicine was gradually moving away from a model in which the patient had considerable interaction with the physician – and, through this consultative relationship, had an equal influence on the physician's therapeutic approach. It was moving towards a paradigm in which the patient became the recipient of a more standardized form of intervention that was determined by the prevailing opinions of the medical profession of the day. [8]
Jewson characterized this as parallel to the changes that were taking place in the manner in which medical knowledge was being produced; namely, a transition from "bedside medicine", through to "hospital medicine", and finally to "laboratory medicine". [9]
The last vestiges of the "consoling" approach to treatment were the prescription of morale-boosting and pleasing remedies, such as the "sugar pill", electuary or pharmaceutical syrup; all of which had no known pharmacodynamic action, even at the time. Those doctors who provided their patients with these sorts of morale-boosting therapies (which, while having no pharmacologically active ingredients, provided reassurance and comfort) did so either to reassure their patients while the Vis medicatrix naturae (i.e., "the healing power of nature") performed its normalizing task of restoring them to health, or to gratify their patients' need for an active treatment.[ citation needed ]
In 1811, Hooper's Quincy's Lexicon–Medicum defined placebo as "an epithet given to any medicine adapted more to please than benefit the patient".
Early implementations of placebo controls date back to 16th-century Europe with Catholic efforts to discredit exorcisms. Individuals who claimed to be possessed by demonic forces were given false holy objects. If the person reacted with violent contortions, it was concluded that the possession was purely imagination. [10]
Use of the placebo effect as a medical treatment has been controversial throughout history, and was common until the mid twentieth century. [3] In 1903 Richard Cabot concluded that it should be avoided because it is deceptive. Newman points out the "placebo paradox" – it may be unethical to use a placebo, but also unethical "not to use something that heals". He suggests to solve this dilemma by appropriating the meaning response in medicine, that is make use of the placebo effect, as long as the "one administering... is honest, open, and believes in its potential healing power". [11]
John Haygarth was the first to investigate the efficacy of the placebo effect in the 18th century. [12] He tested a popular medical treatment of his time, called "Perkins tractors", and concluded that the remedy was ineffectual by demonstrating that the results from a dummy remedy were just as useful as from the alleged "active" remedy. [13]
Émile Coué, a French pharmacist, working as an apothecary at Troyes between 1882 and 1910, also advocated the effectiveness of the "Placebo Effect". He became known for reassuring his clients by praising each remedy's efficiency and leaving a small positive notice with each given medication. His book Self-Mastery Through Conscious Autosuggestion was published in England (1920) and in the United States (1922).
Placebos remained widespread in medicine until the 20th century, and they were sometimes endorsed as necessary deceptions. [3] In 1903, Richard Cabot said that he was brought up to use placebos, [3] but he ultimately concluded by saying that "I have not yet found any case in which a lie does not do more harm than good". [11]
T. C. Graves first defined the "placebo effect" in a published paper in The Lancet in 1920.[ original research? ] [14] He spoke of "the placebo effects of drugs" being manifested in those cases where "a real psychotherapeutic effect appears to have been produced". [15]
The placebo effect of new drugs was known anecdotally in the 18th century, as demonstrated by Michel-Philippe Bouvart's 1780s quip to a patient that she should "take [a remedy] ... and hurry up while it [still] cures." [16] A similar sentiment was expressed by William Heberden in 1803 [17] and Armand Trousseau in 1833. [18] It is often attributed to William Osler (1901) but without a precise source, and it does not appear in his publications. [19] [20]
The first to recognize and demonstrate the placebo effect was English physician John Haygarth in 1799. [21] He tested a popular medical treatment of his time, called "Perkins tractors", which were metal pointers supposedly able to 'draw out' disease. They were sold at the extremely high price of five guineas, and Haygarth set out to show that the high cost was unnecessary. He did this by comparing the results from dummy wooden tractors with a set of allegedly "active" metal tractors, and published his findings in a book On the Imagination as a Cause & as a Cure of Disorders of the Body. [22]
The wooden pointers were just as useful as the expensive metal ones, showing "to a degree which has never been suspected, what powerful influence upon diseases is produced by mere imagination". [23] While the word placebo had been used since 1772, this is the first real demonstration of the placebo effect.[ citation needed ]
In modern times the first to define and discuss the "placebo effect" was T.C. Graves, in a 1920 paper in The Lancet . [24] He spoke of "the placebo effects of drugs" being manifested in those cases where "a real psychotherapeutic effect appears to have been produced". [25]
At the Royal London Hospital in 1933, William Evans and Clifford Hoyle experimented with 90 subjects and published studies which compared the outcomes from the administration of an active drug and a dummy simulator ("placebo") in the same trial. The experiment displayed no significant difference between drug treatment and placebo treatment, leading the researchers to conclude that the drug exerted no specific effects in relation to the conditions being treated. [26] A similar experiment was carried out by Harry Gold, Nathaniel Kwit and Harold Otto in 1937, with the use of 700 subjects. [27]
In 1946, the Yale biostatistician and physiologist E. Morton Jellinek described the "placebo reaction" or "response". He probably used the terms "placebo response" and "placebo reaction" as interchangeable. [28] Henry K. Beecher's 1955 paper The Powerful Placebo was the first to use the term "placebo effect", which he contrasts with drug effects. [29] Beecher suggested placebo effects occurred in about 35% of people. However, this paper has been criticized for failing to distinguish the placebo effect from other factors, and for thereby encouraging an inflated notion of the placebo effect, [30] and a 1997 re-analysis failed to support Beecher's conclusions. [5]
In 1955, Henry K. Beecher published a paper entitled The Powerful Placebo. Since that time, 40 years ago, the placebo effect has been considered a scientific fact. Beecher was the first scientist to quantify the placebo effect. [...] This publication is still the most frequently cited placebo reference. Recently Beecher’s article was reanalyzed with surprising results: In contrast to his claim, no evidence was found of any placebo effect in any of the studies cited by him.
— Kienle & Kiene, The Powerful Placebo Effect: Fact or Fiction? [5]
In 1961 Henry K. Beecher concluded [31] that surgeons he categorized as enthusiasts relieved their patients' chest pain and heart problems more than skeptic surgeons. [11]
In 1961 Walter Kennedy introduced the word nocebo to refer to a neutral substance that creates harmful effects in a patient who takes it. [3] [32]
Beginning in the 1960s, the placebo effect became widely recognized and placebo-controlled trials became the norm in the approval of new medications. [33]
Dylan Evans argues that placebos are linked with activation of the acute-phase response so will work only on subjective conditions such as pain, swelling, stomach ulcers, depression, and anxiety that are linked to this. [34]
A 2001 systematic review of clinical trials concluded that there was no evidence of clinically important effects, except perhaps in the treatment of pain and continuous subjective outcomes. [4] The authors later published a Cochrane review with similar conclusions (updated as of 2010 [update] ). [35] Most studies have attributed the difference from baseline until the end of the trial to a placebo effect, but the reviewers examined studies which had both placebo and untreated groups in order to distinguish the placebo effect from the natural progression of the disease. [4]
Placebo observations differ between individuals. [36] [37] In the 1950s, there was considerable research to find whether there was a specific personality to those that responded to placebos. The findings could not be replicated [38] and it is now thought to have no effect. [39]
The word obecalp, "placebo" spelled backwards, was coined by an Australian doctor in 1998 when he recognised the need for a freely available placebo. [40] The word is sometimes used to make the use or prescription of fake medicine less obvious to the patient. [41]
It has been suggested that a distinction exists between the placebo effect (which applies to a group) and the placebo response (which is individual). [42]
Alternative medicine is any practice that aims to achieve the healing effects of medicine despite lacking biological plausibility, testability, repeatability or evidence of effectiveness. Unlike modern medicine, which employs the scientific method to test plausible therapies by way of responsible and ethical clinical trials, producing repeatable evidence of either effect or of no effect, alternative therapies reside outside of mainstream medicine and do not originate from using the scientific method, but instead rely on testimonials, anecdotes, religion, tradition, superstition, belief in supernatural "energies", pseudoscience, errors in reasoning, propaganda, fraud, or other unscientific sources. Frequently used terms for relevant practices are New Age medicine, pseudo-medicine, unorthodox medicine, holistic medicine, fringe medicine, and unconventional medicine, with little distinction from quackery.
Homeopathy or homoeopathy is a pseudoscientific system of alternative medicine. It was conceived in 1796 by the German physician Samuel Hahnemann. Its practitioners, called homeopaths or homeopathic physicians, believe that a substance that causes symptoms of a disease in healthy people can cure similar symptoms in sick people; this doctrine is called similia similibus curentur, or "like cures like". Homeopathic preparations are termed remedies and are made using homeopathic dilution. In this process, the selected substance is repeatedly diluted until the final product is chemically indistinguishable from the diluent. Often not even a single molecule of the original substance can be expected to remain in the product. Between each dilution homeopaths may hit and/or shake the product, claiming this makes the diluent "remember" the original substance after its removal. Practitioners claim that such preparations, upon oral intake, can treat or cure disease.
A placebo is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets, inert injections, sham surgery, and other procedures.
A randomized controlled trial is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical techniques, medical devices, diagnostic procedures, diets or other medical treatments.
In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from a participants' expectations, observer's effect on the participants, observer bias, confirmation bias, and other sources. A blind can be imposed on any participant of an experiment, including subjects, researchers, technicians, data analysts, and evaluators. In some cases, while blinding would be useful, it is impossible or unethical. For example, it is not possible to blind a patient to their treatment in a physical therapy intervention. A good clinical protocol ensures that blinding is as effective as possible within ethical and practical constraints.
Duloxetine, sold under the brand name Cymbalta among others, is a medication used to treat major depressive disorder, generalized anxiety disorder, obsessive-compulsive disorder, fibromyalgia, neuropathic pain and central sensitization. It is taken by mouth.
Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat major depressive disorder, a variety of pain syndromes such as neuropathic pain, fibromyalgia, migraine and tension headaches. Due to the frequency and prominence of side effects, amitriptyline is generally considered a second-line therapy for these indications.
Atorvastatin is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment. It is taken by mouth.
A nocebo effect is said to occur when negative expectations of the patient regarding a treatment cause the treatment to have a more negative effect than it otherwise would have. For example, when a patient anticipates a side effect of a medication, they can experience that effect even if the "medication" is actually an inert substance. The complementary concept, the placebo effect, is said to occur when positive expectations improve an outcome. The nocebo effect is also said to occur in someone who falls ill owing to the erroneous belief that they were exposed to a toxin, e.g. a physical phenomenon they believe is harmful, such as EM radiation.
An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complication is similar to adverse effect, but the latter is typically used in pharmacological contexts, or when the negative effect is expected or common. If the negative effect results from an unsuitable or incorrect dosage or procedure, this is called a medical error and not an adverse effect. Adverse effects are sometimes referred to as "iatrogenic" because they are generated by a physician/treatment. Some adverse effects occur only when starting, increasing or discontinuing a treatment. Using a drug or other medical intervention which is contraindicated may increase the risk of adverse effects. Adverse effects may cause complications of a disease or procedure and negatively affect its prognosis. They may also lead to non-compliance with a treatment regimen. Adverse effects of medical treatment resulted in 142,000 deaths in 2013 up from 94,000 deaths in 1990 globally.
Nabiximols is a specific Cannabis extract that was approved in 2010 as a botanical drug in the United Kingdom. Nabiximols is sold as a mouth spray intended to alleviate neuropathic pain, spasticity, overactive bladder, and other symptoms of multiple sclerosis; it was developed by the UK company GW Pharmaceuticals. In 2019, it was proposed that following application of the spray, nabiximols is washed away from the oral mucosa by the saliva flow and ingested into the stomach, with subsequent absorption from the gastro-intestinal tract. Nabiximols is a combination drug standardized in composition, formulation, and dose. Its principal active components are the cannabinoids: tetrahydrocannabinol (THC) and cannabidiol (CBD). Each spray delivers a dose of 2.7 mg THC and 2.5 mg CBD.
Agomelatine, sold under the brand names Valdoxan and Thymanax, among others, is an atypical antidepressant most commonly used to treat major depressive disorder and generalized anxiety disorder. One review found that it is as effective as other antidepressants with similar discontinuation rates overall but fewer discontinuations due to side effects. Another review also found it was similarly effective to many other antidepressants.
Henry Knowles Beecher was a pioneering American anesthesiologist, medical ethicist, and investigator of the placebo effect at Harvard Medical School.
Perindopril is a medication used to treat high blood pressure, heart failure, or stable coronary artery disease.
Therapeutic ultrasound refers generally to any type of ultrasonic procedure that uses ultrasound for therapeutic benefit. Physiotherapeutic ultrasound was introduced into clinical practice in the 1950s, with lithotripsy introduced in the 1980s. Others are at various stages in transitioning from research to clinical use: HIFU, targeted ultrasound drug delivery, trans-dermal ultrasound drug delivery, ultrasound hemostasis, cancer therapy, and ultrasound assisted thrombolysis It may use focused ultrasound or unfocused ultrasound.
Ted Jack Kaptchuk is an American medical researcher who holds professorships in medicine and in global health and social medicine at Harvard Medical School. He researches the placebo effect within the field of placebo studies.
Peter Christian Gøtzsche is a Danish physician, medical researcher, and former leader of the Nordic Cochrane Center at Rigshospitalet in Copenhagen, Denmark. He is a co-founder of the Cochrane Collaboration and has written numerous reviews for the organization. His membership in Cochrane was terminated by its Governing Board of Trustees on 25 September 2018. During the COVID-19 pandemic, Gøtzsche was criticised for spreading disinformation about COVID-19 vaccines.
Placebo-controlled studies are a way of testing a medical therapy in which, in addition to a group of subjects that receives the treatment to be evaluated, a separate control group receives a sham "placebo" treatment which is specifically designed to have no real effect. Placebos are most commonly used in blinded trials, where subjects do not know whether they are receiving real or placebo treatment. Often, there is also a further "natural history" group that does not receive any treatment at all.
Jeremy Howick is a Canadian-born, British residing clinical epidemiologist and philosopher of science. He researches evidence-based medicine, clinical empathy and the philosophy of medicine, including the use of placebos in clinical practice and clinical trials. He is the author of over 100 peer-reviewed papers, as well as two books, The Philosophy of Evidence-Based Medicine in 2011, and Doctor You in 2017. In 2016, he received the Dawkins & Strutt grant from the British Medical Association to study pain treatment. He publishes in Philosophy of Medicine and medical journals. He is a member of the Sigma Xi research honours society.
The infinitesimally low concentration of homeopathic preparations, which often lack even a single molecule of the diluted substance, has been the basis of questions about the effects of the preparations since the 19th century. Modern advocates of homeopathy have proposed a concept of "water memory", according to which water "remembers" the substances mixed in it, and transmits the effect of those substances when consumed. This concept is inconsistent with the current understanding of matter, and water memory has never been demonstrated to exist, in terms of any detectable effect, biological or otherwise.