The placebo effect - what is it in simple words? Principle of action and types of drugs. From politics to evidence-based medicine

Placebo is a sham or other medically ineffective treatment for a disease or other medical condition intended to deceive the recipient. Sometimes patients who receive it experience a perceived or actual improvement in their medical condition, a phenomenon commonly called the placebo effect or placebo response. The placebo effect is made up of several different effects combined, and the route of administration can be as important as the administration itself.

IN medical research placebos are given as control treatments and they depend on the use of an estimated assumption. Common treatment dummies include inert tablets, solvent carriers, fictitious surgeries, and other procedures based on false information. However, it may have a positive effect on the subjective experience of a patient who knows that the treatment does not include an active drug, compared with a control group who does not knowingly receive a placebo. In addition, it has been demonstrated that the use of treatment methods that patients are not aware of is less effective than the use of those about which patients are informed.

Placebo effects are a subject scientific research, aimed at understanding the underlying neurobiological mechanisms of action in alleviating pain, immunosuppression, Parkinson's disease and depression. Brain imaging techniques by Emeran Mayer, Johanna Jarko and Matt Lieberman have shown that placebos can have real, measurable effects on physiological changes in the brain. Some objective physiological changes have been reported, ranging from changes in heart rate and blood pressure to chemical activity in the brain in cases associated with pain, depression, anxiety, fatigue and some symptoms of Parkinson's disease, but in other cases, such as asthma, the effect was purely subjective when the patient reports improvement, despite the absence of objective changes in the underlying condition.

Placebos are widely used in medical research and medicine, and their effect is common. Indeed, it is part of the response to any active medical intervention.

The placebo effect speaks to the importance of perception and the role of the brain in physical health. However, using a pacifier as a treatment method in clinical medicine(as opposed to laboratory research) is ethically problematic because it adds deception and dishonesty to the doctor-patient relationship.

Following the publication of The Powerful Placebo by Henry C. Beecher in 1955, the phenomenon was recognized as having clinically important effects. This view was particularly challenged when a systematic review of clinical trials in 2001 concluded that there was no evidence of clinically important effects, except perhaps for pain management and continuous subjective outcomes. The article received a barrage of criticism, but the authors later published a Cochrane review with similar conclusions (updated 2010). Most studies do not explain the difference from start to finish of the trial, but reviewers analyzed studies that had placebo and no-treatment groups to distinguish the placebo effect from the natural progression of the disease.

Definitions, effects and ethics

A placebo is defined as a substance or procedure that does not objectively have a definite effect on the condition being treated. By this definition, a wide variety of things can exhibit this effect. This effect may represent a component of pharmacological therapy: pain-relieving and anxiety-relieving drugs that are administered secretly without the patient's knowledge are less effective than when the patient knows he is receiving them. Likewise, the effects of stimulation from electrodes implanted in the brains of patients with Parkinson's disease are greater when the patients are aware of the stimulation. Sometimes the administration or prescription of a placebo is conflated with a counterfeit drug.

The placebo effect is sometimes defined as a physiological effect caused by a dummy drug, but Moerman and Jonas pointed out that this seems counterintuitive since it is essentially an inert substance that does not directly cause anything. Instead, they coined the term “meaningful response” for the concept that the brain associates with a placebo, resulting in a physiological effect from it. They suggested that placebos, which can be unethical, can be avoided entirely if doctors reassure their patients and encourage their health. Ernst and Resch also attempted to differentiate between the "true" and the "perceived" placebo effect, as they argued that some of the effects attributed to this effect may be due to other factors.

The placebo effect has been controversial throughout history. It was endorsed by prominent medical organizations, but in 1903 Richard Cabot concluded that it should be avoided because it was deceptive. Newman spoke of the “placebo paradox,” meaning that it may be unethical to use it, but it is also unethical not to use something that cures. His solution to this dilemma is to correlate significant reaction to a drug that takes advantage of the placebo effect as long as the person administering it is honest, open, and believes in its potentially healing power.

Video about placebo

Mechanism of the placebo effect

Given that the placebo response is simply a patient response that cannot be attributed to the intervention being studied, the measured effect is made up of numerous possible components. The importance of these components varies depending on the study design and types of observations. Although there is some evidence that placebo interventions can change hormone, endocannabinoid, or endogenous opioid levels, other notable components include expectancy effects, regression to the mean, and flawed research methodologies.

Expectations and psychological conditioning

The placebo effect is related to the patient's expectations and perceptions. If a substance is considered beneficial, it can heal, but if it is considered harmful, it can cause Negative consequences which are known as the nocebo effect. In 1985, Irving Kirsch proposed that placebo effects are produced by self-fulfilling response duration effects, in which the belief that one is feeling differently leads one to actually feel differently. According to this theory, the belief that a person has received active treatment can produce subjective changes that are believed to be produced by the actual treatment method. A placebo can act similarly through classical conditioning, in which the actual stimulus and dummy drug are not used simultaneously as long as it is associated with the effect of the actual stimulus. Conditioning and expectations play important roles in the placebo effect and contribute in different ways. Psychological conditioning has a longer lasting effect and can affect more early stages information processing. Those who believe the treatment will work have a stronger placebo effect than those who don't, according to an acupuncture study.

A placebo presented as a stimulant will have this effect on heart rate and blood pressure, but when administered as a depressant, it has the opposite effect. Perceived as ergogenic aids, they may increase endurance, speed, and weightlifting ability, leading to the question of whether placebos should be allowed in athletic competition.

Since placebos depend on perceptions and expectations, various factors, changing perception can increase the magnitude of the reaction to it. For example, research has shown that the color and size of the pill matter, with warm-colored pills working better as stimulants, while cool-colored pills working better as depressants. Capsules seem to be more effective than tablets, and size is also important. One researcher found that big tablets the effect is enhanced, while another argues that even cultural background influences the effect.

Motivation may contribute to the placebo effect. An individual's active goals alter somatic experience by altering the detection and expectation interpretation of congruent symptoms and by altering the behavioral strategies pursued by the individual. Motivation can be linked to the meaning through which people perceive illness and treatment. This meaning comes from the culture in which they live and which informs them about the nature of the disease and how it responds to treatment. Research into the treatment of stomach and duodenum placebos show significant fluctuations in society. The placebo effect in the treatment of stomach ulcers is low in Brazil, higher in northern Europe (Denmark, Netherlands) and very high in Germany. However, the placebo effect in the treatment of hypertension in Germany is lower than in other countries.

The placebo effect and the brain

Functional imaging of placebo pain relief shows that it is associated with activation and increased functional correlation between this activation in the anterior cingulate cortex, prefrontal, orbitofrontal and insular cortices, nucleus accumbens, amygdala, periaqueductal gray matter and spinal cord.

The higher brain works by regulating subcortical processes. High placebo responses are associated with increased dopamine and mu-opioid activity in the reward response and motivated behavior circuitry of the nucleus accumbens, and conversely, anti-pain-relieving nocebo responses have been associated with a shutdown of dopamine and opioid release in this part of the brain. Since 1978, it has been known that placebo analgesia is dependent on the release of endogenous opioids in the brain. Such analgesic activation by placebo alters processing downstream in the brain by increasing inhibition of descending via the periaqueductal gray matter of the brain on spinal nociceptive reflexes, while expectations from anti- nocebo painkillers act in the opposite direction to block this.

The brain is also involved in less studied ways of the non-analgesic effects of placebo:

• Parkinson's disease: placebo relief linked to dopamine release in brain
• Depression: Depression-reducing placebos affect many of the same areas activated by antidepressants, with the addition of the prefrontal cortex
• Caffeine: Coffee with placebo caffeine increases bilateral dopamine release in the thalamus.
• Glucose: Waiting for an intravenous glucose injection increases dopamine release in the basal ganglia of men (but not women).

Methylphenidate: Anticipation of intravenous administration of this drug in inexperienced drug users increases dopamine release in the ventral cingulate cortex and nucleus accumbens.

Functional imaging generalizations to placebo analgesia have shown that the placebo response is mediated by top-down processes dependent on frontal cortical areas that generate and maintain cognitive expectations. Dopaminergic reward pathways may underlie these expectations. Diseases that lack important top-down or cortical regulation may be less likely to experience placebo-related improvements.

Brain and body

The brain has control over the body processes that are affected by placebos.

In psychological conditioning, a neutral stimulus, saccharin, is added to a drink with a drug that produces an unconditioned response. For example, this drug may be cyclophosphamide, which causes immunosuppression. In a person exposed to this combination, the taste of saccharin itself is capable of causing immunosuppression, like a new conditioned reflex through top-down neural control. Such conditioning has been found to influence a diverse set of not only the basic physiological processes of the immune system, but also processes such as levels serum iron, level of oxidative DNA damage and insulin secretion. Recent reviews claim that the placebo effect is due to top-down brain control for immunity and pain. Pacheco-Lopez and colleagues raised the possibility that the neocortical-sympathetic-immune axis provides neuroanatomical substrates that may explain the relationship between placebo/conditioning and placebo/expectancy responses.

A recent fMRI study found that a placebo can reduce pain associated with neural activity in the spinal cord, suggesting that placebo effects may extend beyond the brain.

Dopaminergic pathways have been implicated in placebo responses in pain and depression.

Developed health regulation

Evolutionary medicine identifies many symptoms, such as fever, pain, and illness patterns, as learned responses to protect or enhance recovery from infection and injury. Fever, for example, is a developed self-medication method that removes bacteria or viruses through elevated body temperature. However, these developed reactions also have their own price, which, depending on the circumstances, may outweigh their benefits (in this regard, for example, there is a decrease in fever due to malnutrition or later pregnancy). According to Nicholas Humphrey's theory of the health management system, the brain was selected to ensure that learned responses were engaged only when cost and efficiency were biologically beneficial. To this end, the brain is factored into various information sources, including probability derived from the belief that the body will recover without deploying its costly learned responses. One such source of information is knowledge about how to provide the body with care and treatment. In this view, the placebo effect occurs when misinformation about medications misleads the health management system about the likelihood of improvement, so that it decides not to engage in self-medication.

Clinical utility

Hrobjartson and Goetzsch published a study in 2001 and a follow-up study in 2004 questioning the nature of the dummy product's effect. The studies were conducted in two meta-analyses. They found that in studies with a binary outcome, meaning patients were classified as either improved or not improved, the placebo group showed no statistically significant improvement compared to the no-treatment group. In addition, there was no significant placebo effect in studies in which objective outcomes (eg, blood pressure) were measured by an independent observer. The placebo effect can only be documented in studies in which the results (improvement or failure to improve) were not self-reported by the subjects. The authors concluded that the placebo effect did not have “powerful clinical effects” (objective effects) and patient-reported pain improvement (subjective effects) was small and could not be clearly separated from reporting bias. Other researchers (Wampold et al.) reanalyzed the same data from the 2001 meta-analysis and concluded that placebo effects for measures of objective symptoms were comparable to those for subjective symptoms. In addition, this effect may exceed the effect of active treatment in the 20% of disorders that respond to placebo. Another group of researchers noted completely different conclusions between these two groups of authors with almost identical meta-analytic results, and suggested that placebo effects are indeed significant, but small in magnitude.

Hrobjartson and Goetzsch's conclusion has been criticized on several grounds. Their meta-analysis covered studies in a very mixed group of conditions. It has been reported that for assessment in peripheral organs, the placebo effect appears to be more effective in achieving improvements in physical parameters (eg, reduction in hypertension, increase in FEV1 in asthmatics, or reduction in prostatic hyperplasia or anal fissure) compared with improvements in biochemical parameters (cholesterol or cortisol levels). ) for various conditions such as venous ulcers, Crohn's disease, infections urinary tract and chronic heart failure. Additionally, placebos work differently than clinical trials because subjects don't know whether they might be getting the real treatment or a sham treatment. The placebo effect occurs in studies in which people, when given an inert drug, think they are receiving a real treatment (not just a possibility). Other authors argue that this effect can be reliably demonstrated under appropriate conditions.

Another update by Hrobjartson and Goetzsch, published in the 2010 Cochrane systematic review, which confirms and modifies their previous work, included more than 200 studies 60 clinical conditions. Again, placebo interventions were not found to have important clinical effects overall, but they were able to influence patient-reported outcomes in some situations, particularly pain and nausea, although it was difficult to distinguish between patient-reported effects , from response bias. The pooled relative risk they calculated for placebo was 0.93 (only a 7% effect), but it was still significant. Effects were also found for phobia and asthma, but researchers are unsure due to high risk bias. In other conditions with three or more trials, no statistically significant effect was found for smoking, depression, dementia, hypertension, obesity, anxiety and insomnia, despite wide confidence intervals. Several clinical (physical placebos, patient-involved outcomes, false information to patients that there was no dummy treatment) and methodological (small sample size, explicit intent to study effect) factors were associated with increased placebo effects. Given the overall low effects and risk of bias, the authors did acknowledge that large effects of a placebo intervention are possible in certain situations.

In 2013, Jeremy Howick and colleagues used data from Hrobjartson and Goetzsch to compare the magnitude of placebo effects with the magnitude of treatment effects. They found a statistically significant difference between placebo and treatment effect sizes in trials with binary outcomes, but not in trials with subjective measures.

Negative effects

Similar to the placebo effect, inert substances have the potential to cause negative effects through the “nocebo effect” (Latin “nocebo” = “I will cause harm”). In this regard, the introduction of an inert substance has negative consequences.

Another negative consequence is that the dummy product may cause side effects related to actual treatment. An example is the situation with people who have already taken an opiate and who may experience respiratory depression, it is possible to reintroduce it to them in the form of a placebo.

Withdrawal symptoms may also occur after placebo treatment. For example, this happened after the completion of the Initiative's research women's health with hormone replacement therapy for menopause. The women received the placebo for an average of 5.7 years. Moderate or severe withdrawal symptoms were reported by 4.8% of those in the placebo group compared with 21.3% of those receiving hormone replacement therapy.

The use of placebos as treatments in practice is also often ethically challenging.

Doctor-patient relationship

In a study of Danish doctors general practice it was demonstrated that 48% of them had been prescribed placebo at least 10 times in the past year. The most commonly prescribed dummy products were antibiotics for viral infections and vitamins for fatigue. Specialists and hospital doctors reported much lower levels of use of such products. A 2004 study published in the British Medical Journal found that 60% of doctors in Israel used them in their medical practice, most often to “discourage” requests for unreasonable appointment medications or reassure the patient. The accompanying editorial concluded: "We cannot afford to do without some treatment that works, even if we are not sure how it does." Other researchers argue that openly providing placebos for ADHD treatment in children may be effective in maintaining children's ADHD for more low doses stimulants in the short term.

Critics of this practice argue that prescribing a treatment that doesn't work is unethical and that a doctor telling a patient (as opposed to a trial subject) that a placebo is a real cure is deceiving and damaging the relationship with the patient in the long run. Critics also argue that using a pacifier may delay production. correct diagnosis and treatment of serious illnesses.

Disadvantages associated with placebo include:

• Roughly only 30% of the population is susceptible to its effects, and it is impossible to determine in advance whether it will work or not. However, the placebo effect equal to zero in blood poisoning studies and up to 80% in duodenal wound studies.
• Patients rightfully want immediate relief or improvement of their disease or symptoms. A non-placebo can do what a placebo cannot.
• Legitimate doctors and pharmacists may open themselves up to accusations of fraud, since sugar pills will cost pennies per bottle, but the price of the "real" medicine must be charged to prevent the patient from becoming suspicious.

About 25% of doctors in the Danish and Israeli studies used a placebo as a diagnostic tool to determine whether a patient's symptoms were real or whether the patient was faking it. Both critics and advocates of the medical use of placebos agreed that it was unethical. An editorial in the British Medical Journal states: "Just because a patient experiences pain relief from a placebo does not mean that the pain was not real or organic in origin... the use of placebos to 'diagnose' whether pain is real or not introduces misleading."

Placebo administration may be a useful treatment option in some specific cases where recommended medications cannot be used. For example, burned patients who have breathing problems often should not be given opioids (morphine) or opioid derivatives (pethidine) as they can cause further respiratory depression. In such cases, placebo injections (normal saline, etc.) are useful in relieving actual pain in non-delirious burn patients if they are told that they are receiving a strong dose of painkiller.

Regarding homeopathy specifically, the UK House of Commons Science and Technology Committee said homeopathy is a dud treatment and the government should have a placebo prescribing policy. The British government has been reluctant to consider the appropriateness and ethics of prescribing placebos to patients, which usually relies on some degree of patient deception. Such prescribing is not consistent with informed patient choice, which the government says is important because it means patients are not getting the full benefit. necessary information to make meaningful choices.

Ethical issues and the integrity of the doctor-patient relationship aside, prescribing pure placebos is bad medicine. Their action is unreliable and unpredictable and cannot serve as the sole basis of any treatment in a health care system.

Depression

In 2008, psychologist Irving Kirsch concluded in a controversial meta-analysis of FDA data that 82% of reactions to antidepressants were due to placebo. However, there are serious concerns about the methods used and the interpretation of the results, in particular the use of 0.5 as the percentage threshold for the effect size. A full re-analysis of the recalculation based on the same FDA data found that Kirsch's study suffered from important flaws in the calculations. The authors concluded that while most responses to placebo were due to anticipation, this was not true for the active drug. In addition to confirming the drug's effectiveness, they found that the drug's effects were not related to the severity of depression.

Another meta-analysis found that 79% of depressed patients treated with placebo maintained wellness(within 12 weeks after successful initial therapy of 6-8 weeks) compared with 93% of those receiving antidepressants. However, in the continuation phase, patients receiving placebo relapsed significantly more often than patients receiving antidepressants. A 2009 meta-analysis reported that in 2005, 68% of antidepressant effects were due to the placebo effect, more than twice the rate of placebo reactions in 1980.

While some say that full consent, or even consent to an unspecified treatment for a given patient given in advance, is ethical, others say patients should always receive specific information about the name of the drug they are receiving, its side effects, and other treatment options. There may be times when patients do not want to be informed, but healthcare professionals are ethically obligated to provide correct information about this treatment. There is controversy over the use of placebos because although they are used to the benefit of many to ensure that drugs work, some argue that it is unethical to deprive individual patients of effective drugs.

Chronic fatigue syndrome

It has previously been suggested that placebo responses in patients with chronic fatigue syndrome (CFS) are unusually high, at least 30-50%, due to the subjective reporting of symptoms and the fluctuating nature of the condition. According to the meta-analysis and contrary to popular belief, the pooled response rate in the placebo group was 19.6%, which is even lower than for some other medical conditions. The authors suggested possible explanations for these results: it is generally accepted that CFS with turmoil is treatable, which may reduce expectations of improvement. In the context of data suggesting that placebo does not have powerful clinical effects compared with no treatment, the low rate of spontaneous remission in CFS may contribute to the reduced rate of improvement in the inert group. The type of intervention also contributes to heterogeneity in response. Low patient and clinician expectations for physiological treatment may explain low responses to dummy treatments in psychiatric treatment in particular.

List of medical conditions

The effectiveness of placebo treatment (inert tablet unless otherwise stated) was studied for the following medical conditions. Much of this relates to research showing that active treatments are effective, but there are also placebo effects.

• anxiety disorders;
• autism: speech and behavior problems;
• asthma;
• benign prostate enlargement;
• compulsive gluttony;
• bipolar mania;
• burning mouth syndrome;
• cough;
• depression;
• Crohn's disease;
• dyspepsia and gastric motility;
• food allergy: the ability to ingest unhealthy foods;
• headache;
• congestive heart failure;
• ulcers of the stomach and duodenum;
• mental impairment;
• irritable bowel syndrome;
• lower urinary tract symptoms;
• migraine prevention;
• nausea due to gastric activity;
• postoperative nausea and vomiting (sham acupuncture);
• arthrosis;
• nausea due to chemotherapy;
• multiple sclerosis ;
• hyperactive bladder;
• pain;
• panic disorders;
• Parkinson's disease;
• reflux esophagitis;
• psoriatic arthritis;
• restless legs syndrome;
• rheumatic diseases;
• sexual dysfunction in women;
• social phobia;
• ulcerative colitis.

History and research

The word "placebo" in Latin means "will give pleasure" and goes back to the Latin translation of the Bible by St. Jerome. In 1811, Hooper's Quincy's Lexicon-Medicum defined placebo as "any medicine which will give the patient more pleasure than benefit."

John Haygarth was the first to study the effectiveness of the placebo effect in the 18th century. He tested a then-popular treatment method called "Perkins traction devices" and concluded that the remedy was ineffective, demonstrating that the results from the dummy remedy were as beneficial as those from the supposedly "active" counterpart.

Emile Couet, a French pharmacist who worked as a pharmacist in Troyes between 1882 and 1910, also advocated the effectiveness of the "placebo effect". He became famous for reassuring his clients by praising the effectiveness of each medicine and leaving little positive notes with each medicine dispensed. His book Self-Control through Conscious Self-Hypnosis was published in England (1920) and the USA (1922).

Placebos remained widespread in medicine until the 20th century, and are sometimes approved as a necessary deception. In 1903, Richard Cabot said that he was raised to use placebos, but he eventually came to the conclusion that he had not yet found a single situation in which lying was more beneficial than harmful.

In modern times, T.K. Graves first defined the “placebo effect” in an article published in The Lancet in 1920. He spoke of the “placebo effects of drugs,” which occur when a genuine psychotherapeutic effect appears to have been produced. In 1961, Henry C. Beecher concluded that surgeons he classified as enthusiastic surgeons were better at solving chest and heart pain problems in patients than skeptical surgeons. Beginning in the 1960s, the placebo effect became widely accepted and placebo-controlled trials became the norm in the approval of new drugs.

Placebo-controlled studies

The placebo effect makes it difficult to evaluate new treatments. Clinical trials monitor this effect by including a group of subjects who receive a dummy treatment. Subjects in such studies do not know whether they are receiving treatment or a placebo. If a person is given a placebo under one name and reacts to it, he will react to it in the same way on more late stage under the same name, but not under another. Clinical trials are often double-blind, so researchers also don't know which subjects are receiving the active treatment or a placebo. The placebo effect in such clinical trials is weaker than in conventional therapy because subjects are unsure whether the treatment they are receiving is active.

Deliberate administration of placebo when available effective treatment is a complex issue from a bioethical point of view. While placebo-controlled studies can provide information about the effectiveness of treatment, they deny that some patients may have the best available (if unproven) treatment. For research to be considered ethical, informed consent is generally required, including disclosure of the fact that some subjects will receive a placebo.

The ethics of placebo-controlled studies were discussed during the revision of the Declaration of Helsinki. Of particular concern were the differences between trials that compared inert placebos to an experimental treatment versus the best available treatment versus an experimental treatment, as well as differences in trials in the sponsor's developed countries versus the study's target developing countries.

Nocebo

In the opposite effect, a patient who does not believe in treatment may experience worsening symptoms. This effect, now called by analogy a nocebo (Latin for “to cause harm”), can be measured in the same way as a placebo effect, for example when control group participants given an inert substance report worsening symptoms. Recipients of an inert substance may negate the intended placebo effect simply because of their negative attitude toward the effectiveness of the prescribed substance, often resulting in a nocebo effect that is not caused by the substance but by other factors, such as the patient's mentality regarding the ability to recover or even purely random worsening of symptoms.

Placebo ingredients

In some cases, placebos used in clinical trials have had unintended consequences. A report published in the Annals of Internal Medicine, which reviewed details of 150 clinical trials, found that some placebos used in the trials affected the results. For example, one study of cholesterol-lowering drugs used olive oil and corn oil in dummy tablets. However, according to the report, this may lead to an underestimation of the drugs' benefits: the monounsaturated and polyunsaturated fatty acids of these placebo drugs and their antioxidant and anti-inflammatory effects may reduce lipid levels and heart disease. Another example the researchers cited in their work was a clinical trial of a new treatment for cancer patients suffering from anorexia. The placebo used contained lactose. However, since such patients are most often at increased risk of lactose intolerance, the pills may have actually caused unexpected side effects that made the experimental drug look better in comparison.

A placebo (from Latin placebo, “to please, please,” from placeō, “to give pleasure”) is a medically ineffective method of treating a disease. A patient receiving a placebo believes in its effectiveness. A person with such ineffective treatment often experiences a subjectively perceived or real improvement in his condition. This phenomenon is commonly referred to as the placebo effect or placebo response. Several different elements contribute to the placebo effect, and how the placebo is administered can be just as important as its administration.

Placebos are an important methodological tool in medical research. Placebos often include inert pills (such as sugar pills), infusions of inactive ingredients, sham surgery, and other procedures based on false information. However, in a 2010 study, patients who knew they were receiving placebo pills showed greater improvement compared to those who did not know they were receiving a placebo. In addition, it has been shown that using treatments that patients are unaware of is less effective than using treatments that patients are informed about. The placebo effect is the subject of scientific research aimed at understanding the underlying neurobiological mechanisms in the relief of pain, immune suppression, Parkinson's disease and depression. Brain imaging techniques by Emeran Mayer, Joanna Jarko, and Matt Lieberman have shown that placebos can have real, measurable effects on physiological changes in the brain. A placebo may produce some objective physiological changes, such as changes in heart rate, blood pressure and brain chemical activity, in cases associated with pain, depression, anxiety, fatigue and some symptoms of Parkinson's disease. In other cases, such as asthma, the effect is purely subjective, with the patient reporting improvement despite no objective change in the underlying condition. The placebo effect is very common. In fact, it is part of the response to any active medical intervention. The placebo effect points to the importance of perception and the influence of the brain on physical health. The use of placebos as a treatment in clinical medicine (as opposed to laboratory research) is ethically problematic because it involves deliberate misleading of the patient. The UK Parliamentary Committee on Science and Technology stated that “prescribing placebos...usually involves some degree of deception of the patient” and “prescribing pure placebos is a poor practice. The effect will be unreliable and unpredictable and cannot serve as the sole basis of treatment in National system health care." In 1955, Henry C. Beecher suggested that the use of placebos could have clinically important effects. This view was particularly challenged when a 2001 systematic review clinical trials concluded that placebo did not show any clinically important effects, with the possible exception of pain management and effectiveness when observing subjective treatment outcomes. The article faced a barrage of criticism, but the authors later published a Cochrane Collaboration review with similar findings (updated as of 2010). In most studies, the difference from baseline to the end of the trial was attributed to a placebo effect, but reviewers examined studies that included both a placebo and an untreated group in order to separate the placebo effect from natural disease progression.

Types of placebo

Placebos are defined as “substances or procedures… that objectively do not have a specific effect on the condition being treated.” By this definition, a wide variety of things can be called placebo, and many things can have a placebo effect. However, the placebo effect can be part of true pharmacological therapy: infusions of painkillers and anti-anxiety drugs secretly, without the patient's knowledge, are less effective than if the patient knows he is receiving them. In addition, the effects of stimulation from implanted electrodes in the brains of Parkinson's patients are more pronounced if the patients know that they are receiving this stimulation. Sometimes administering or prescribing a placebo turns into medical fraud. Usually, “sugar pills” or injections are used as a placebo. saline solution. Sometimes fake transactions are also carried out. An example is the Finish Meniscal Legion Study Group trial, published in the New England Journal of Medicine, which found that sham meniscus surgery was as effective as the actual procedure. While examples of placebo treatments can be found, the definition of the placebo concept remains imprecise.

Effects

The placebo effect is sometimes defined as a physiological effect caused by a placebo, but Morman and Jonas note that this seems counterintuitive since a placebo is an inert substance that does not directly cause any effects. Instead, they coined the term “meaningful response”—the response that the brain associates with a placebo, which causes the physiological placebo effect. They suggested that the use of placebos, which may be unethical, could be avoided entirely if doctors provided more support and encouragement to their patients. Ernst and Resch also attempted to distinguish between "true" and "perceived" placebo effects, as they argued that some of the effects attributed to the placebo effect may be due to other factors. Research has shown that, for psychological reasons, some placebos are more effective than others. Large tablets are more effective than small tablets, colored tablets are more effective than white tablets, injections are more effective than tablets, and surgical intervention produces a stronger placebo effect than injections.

Ethics

The placebo effect has always been considered controversial issue. Famous medical organizations approved the use of placebos, but in 1903 Richard Cabot stated that the use of placebos in medicine should be avoided because the method involved deception. Newman points out the “placebo paradox”: it may be unethical to use a placebo, but it is also unethical to “not use something that cures.” He proposes a solution to this dilemma by introducing the concept of a "meaningful effect", that is, the judicious use of the placebo effect, as long as "the patient... accepts the placebo honestly, openly, and believes in its potential healing power."

Mechanism of action of placebo

Because the placebo response is simply a patient reaction that cannot be explained by the pill, there are numerous possible components of the measured placebo effect. These components have varying significance depending on the type of study and types of observations. While there is some evidence that placebos can alter levels of hormones, endocannabinoids, or endogenous opioids, other known components of measuring the placebo effect include mean duration of exposure, regression to the mean, and flawed study methodologies.

Expectation and conditioned reflex

The placebo effect is related to the patient's perceptions and expectations; if a substance is viewed as beneficial, it may have a therapeutic effect; if it is viewed as harmful, it may cause negative effects, which are known as the “nocebo effect.” In 1985, Irving Kirsch hypothesized that placebo effects are produced by self-fulfilling response expectancy effects, in which a patient's belief that they will feel differently leads the person to actually feel differently. According to this theory, the belief that a patient has received an active drug can produce subjective changes in his or her health status. A placebo can act in a similar way to classical conditioning, in which a placebo and an actual stimulus are used simultaneously until the placebo becomes associated with the effect of the actual stimulus. Both conditioning and expectation play a role in the placebo effect. The conditioned reflex has a longer lasting effect and can affect more early stages information processing. Patients who are confident that a treatment will work show a stronger placebo effect than patients who do not believe that a treatment will work, as shown in studies using acupuncture. A placebo disguised as a stimulant will have a stimulating effect on heart rate and blood pressure, but when administered as a depressant it will have the opposite effect. If a person believes they are taking an ergogenic drug, they may experience increased endurance, speed, and ability to lift. heavy weights. All this leads to the question of whether the use of placebos should be allowed in sports competitions. Because placebos are dependent on perception and expectancy, various factors that alter perception can increase placebo response. For example, studies have shown that the color and size of the placebo pill makes a difference. Pills of “warm” colors act more strongly as stimulants, while tablets of “cool” colors act as depressants. Capsules are more effective than tablets. Size can also matter. One of the researchers found that larger tablets increased the effect, while another argued that the effect depended on the patient's cultural background. Motivation may contribute to the placebo effect. An individual's active goals change his somatic experience by changing the detection and interpretation of symptoms congruent with expectations, as well as by changing the person's behavioral strategy. Motivation may be related to the meaning of how people experience illness and treatment. This meaning is derived from the culture in which a person lives and which informs him about the nature of the disease and how it responds to treatment. Research into the treatment of gastric and duodenal ulcers with placebos shows that the effect varies widely among different societies. The placebo effect in the treatment of stomach ulcers is low in Brazil, higher in Northern Europe (Denmark, Netherlands), and extremely high in Germany. However, the placebo effect in treating hypertension is lower in Germany than in other countries. Although the placebo effect is typically associated with deception associated with positive expectations, research conducted by Harvard Medical School has shown that placebos can work even without deception. In an attempt to use a placebo fairly, 80 patients suffering from IBS (irritable bowel syndrome) were divided into two groups, one of which received no treatment while the other was given placebo pills. Although patients were told that the tablets contained no active ingredient, patients reported relief from symptoms. Another similar study, in which patients suffering from migraines were given pills labeled “placebo”, found that patients reported an improvement in symptoms.

The placebo effect and the brain

Functional imaging of placebo analgesia shows that it is associated with activation and increased functional correlation between this activation in the anterior cingulate cortex, prefrontal, orbitofrontal and insular cortices, nucleus accumbens, amygdala, central gray matter and spinal cord. The higher brain center regulates subcortical processes. High placebo responses are associated with increased dopamine and mu-opioid activity during responses to reward and motivated behavior in the nucleus accumbens, and, in contrast, anti-analgesic responses to nocebo have been associated with deactivation of dopamine and opioid release in this part of the brain. (It has been known since 1978 that placebo pain relief depends on the release of endogenous opioids in the brain). This placebo analgesia alters information processing downstream in the brain by increasing descending inhibition through the periaqueductal gray matter in the brain on spinal nociceptive reflexes, while anti-analgesic nocebo expectations act in the opposite direction. The brain is also involved in less studied ways in the non-analgesic effects of placebos: Parkinson's disease: Placebo relief is associated with the release of dopamine in the brain. Depression: Depression-reducing placebos affect many of the same areas that are activated by antidepressants with the addition of the prefrontal cortex. Caffeine: Decaffeinated coffee, when users are unaware of its caffeine content, results in increased bilateral dopamine release in the thalamus. Glucose: Anticipation of intravenous glucose increases dopamine release in the basal ganglia in men (but not women). Methylphenidate: Waiting for intravenous administration of this drug in inexperienced users increases dopamine release in the ventral cingulate cortex and nucleus accumbens, with this effect being greatest in patients with no prior experience with the drug. Functional imaging with placebo shows that the placebo response “is mediated by top-down processes dependent on frontal cortical areas that create and maintain cognitive expectations. Dopaminergic reward pathways may underlie these expectations.” “Diseases that lack this top-down or cortical regulation may be less associated with improvement with placebo.”

Brain and body

The brain controls the body processes that are affected by placebos. When creating a conditioned response, the neutral stimulus saccharin is introduced into a drink with an agent that produces an unconditioned response. For example, this agent may be cyclophosphamide, which causes immunosuppression. After this, the taste of saccharin itself will cause immunosuppression, as a new conditioned reflex, through top-down neural control. This conditioned reflex affects wide range not only the basic physiological processes of the immune system, but also processes such as serum iron levels, levels of oxidative DNA damage, and insulin secretion. Recent reviews argue that the placebo effect is associated with top-down control regarding immunity and pain. Pacheco-Lopez and colleagues raised the possibility of a "neocortex-sympathetic immune axis providing neuroanatomical substrates that may explain the relationship between placebo/conditioned reflexes and placebo/expectancy responses." A recent MRI study found that a placebo can reduce pain associated with neural activity in the spinal cord, suggesting that placebo effects may extend beyond the brain. Dopaminergic pathways are involved in the placebo response in pain and depression.

Evolutionary regulation of health

Evolutionary medicine identifies many symptoms, such as fever, pain, and illness behavior, as evolved responses to protect or enhance recovery from infection and injury. Fever, for example, is an evolved self-medication that kills bacteria or viruses through elevated body temperature. These evolved responses, however, also come at a cost, which, depending on the circumstances, may outweigh the benefits (due to, for example, a decrease in temperature during malnutrition or at the end of pregnancy). According to Nicholas Humphrey's theory of health system management, the brain serves to provide responses only when the cost-benefit ratio is biologically beneficial. To do this, brain factors use various information sources, including, but not limited to, probabilities derived from the belief that the body will recover without deploying its costly evolutionary responses. One such source of information is knowledge that the body is receiving care and treatment. The placebo effect, in this view, occurs when misinformation about medications misleads the health management system about the likelihood of recovery, so that the body chooses not to deploy evolutionary self-medication.

Clinical utility

Clinical relevance

Asbjørn Hróbjartsson and Peter Gotzsche published a study in 2001, and a follow-up study in 2004, that questioned the nature of the placebo effect. The studies were conducted in two meta-analyses. They found that in studies with a binary outcome, that is, where the outcome was classified as improvement or no improvement, the placebo group showed no statistically significant improvement compared with the no-treatment group. Likewise, no significant placebo effect was observed in studies in which objective data (such as blood pressure) were measured by an independent observer. The placebo effect can only be documented in studies in which the results (improvement or non-improvement) were self-reported by the subjects. The authors concluded that the placebo effect did not have “powerful clinical effects” (objective effects) and that patient-reported improvements (subjective effects) in pain were small and could not be clearly distinguished from reporting bias. Other researchers (Wampold et al.) reanalyzed the data from the 2001 meta-analysis and concluded that the placebo effect on objective symptom measures is comparable to the placebo effect on subjective measures and that the placebo effect may exceed the effect of active treatment by 20% in diseases susceptible to the placebo effect. Another group of researchers noted strikingly different conclusions between the two groups of authors, despite nearly identical meta-analytic results, and suggested that the placebo effect was indeed significant but small in magnitude. The conclusion of Hróbjartsson and Gotzsche has been criticized for several reasons. Their meta-analysis covered studies in a highly mixed group of conditions. It has been reported that for measurements in peripheral organs, the placebo effect appears to be more effective in achieving improvements in physical parameters (such as reduction in hypertension, improvement in FEV1 in patients with bronchial asthma, or reduction in prostate hyperplasia or anal fissure) than in improving biochemical parameters (such as cholesterol or cortisol) in various diseases such as venous ulcers lower limbs, Crohn's disease, urinary tract infections and chronic heart failure. Placebos also don't work as well in clinical trials because patients don't know whether they're getting the real treatment or a dummy one. When placebo studies are conducted in which people think they are receiving the actual treatment (not just the possibility of it), the placebo effect is observed. Other authors argue that the placebo effect can be reliably demonstrated under appropriate conditions. Another publication by Hróbjartsson and Gotzsche, published in 2010 as a systematic review by the Cochrane Collaboration, confirms and modifies their previous work. The meta-analysis included more than 200 trials investigating 60 clinical conditions. Placebo interventions again failed to show important clinical effects overall, but may have influenced patient-reported outcomes in some situations, particularly pain and nausea, although it was "difficult to distinguish patient-reported placebo effects from response bias." The pooled relative risk they calculated for placebo was 0.93 (only a 7% effect), but significant. Effects were also found for phobia and asthma, but were imprecise due to the high risk of bias. In other conditions involving three or more trials, no statistically significant effect was found for smoking, dementia, depression, obesity, hypertension, insomnia and anxiety, although the confidence intervals were wide. Several clinical (physical placebos, patient outcomes, misinformation to patients that there was no placebo) and methodological (small sample size, explicit purpose of studying the placebo effect) factors were associated with higher placebo effects. Despite the overall low effects and risk of bias, the authors acknowledged that there may be a strong placebo effect in certain situations. In 2013, Jeremy Howick and colleagues used data from Hróbjartsson and Gotzsche to compare the size of the placebo effect with the size of the treatment effect. They found a statistically significant difference between the size of the placebo effect and the treatment effect in trials with binary outcomes, but not in trials with subjective outcomes.

Negative effects

Similar to the placebo effect, inert substances have the potential to cause negative effects through the “nocebo effect” (Latin: Nocebo: “I will harm”). In this case, taking an inert substance will have negative consequences. Another negative consequence is that placebos may cause side effects associated with the actual treatment. One example of this is giving people who have already been given an opiate, giving it as a placebo, and seeing them experience respiratory depression. Withdrawal symptoms may also occur after placebo treatment. This was found, for example, after the Women's Health Initiative discontinued menopausal hormone replacement therapy. Women used placebo for an average of 5.7 years. Moderate or severe withdrawal symptoms were reported by 4.8% of patients in the placebo group compared with 21.3% of those on hormone replacement therapy. In addition, the use of placebos as a form of treatment is often ethically difficult to practice.

Doctor-patient relationship

A study of Danish general practitioners found that 48% of doctors prescribed placebos at least 10 times in the past year. The most commonly prescribed placebos were pacifiers disguised as antibiotics used for viral infections, as well as vitamins for fatigue. Specialists and hospital physicians reported much lower rates of placebo use. A 2004 study in the British Medical Journal of Physicians in Israel found that 60% of doctors used placebos in their medical practices, most often to counter requests for unnecessary drug prescribing or to reassure patients. The accompanying editorial states, "We can't afford to go without some treatment that works, even if we're not sure exactly how it does." Other researchers argue that open-label provision of placebos for the treatment of ADHD in children may be effective in keeping children with ADHD on lower doses of stimulants in the short term. Critics of this practice respond that it is unethical to prescribe a treatment that is not effective, and that telling a patient (as opposed to the research subject) that a placebo is the real treatment is deceptive and harms the doctor-patient relationship in the long run. Critics also argue that using placebos may delay proper diagnosis and treatment serious illnesses. Doctors and pharmacists may face fraud or malpractice charges when using placebos. About 25% of doctors in studies in Denmark and Israel used a placebo as a diagnostic tool to determine whether a patient's symptoms were real or faking them. Both critics and advocates of the medical use of placebos agreed that it was unethical. The editors of the British Medical Journal stated: "Just because a patient experiences pain relief from a placebo does not mean that the pain is not real or organic in origin... Using a placebo to 'diagnose' whether the pain is real is erroneous." The use of placebo may be a useful treatment option in some specific cases where recommended medications cannot be used. For example, burn patients who experience breathing problems often cannot be prescribed opioids (morphine) or opioid derivatives (pethidine) as this may cause further respiratory depression. In such cases, placebo injections (normal saline, etc.) are useful in providing real pain relief in burn patients if non-delirious patients are told that they are being given a strong dose of painkiller. Regarding homeopathy specifically, the UK House of Commons Science and Technology Committee stated: In the Committee's view, homeopathy is a placebo treatment and the government should have a placebo prescribing policy. The government has been reluctant to address the appropriateness and ethics of prescribing placebos to patients, which usually involves some degree of deception of the patient. Prescribing a placebo is inconsistent with informed patient choice, which the government considers very important because it means patients do not have all the information they need to make a choice. Besides ethical problems and the integrity of the physician-patient relationship, prescribing pure placebos is poor practice. Their effect is unreliable and unpredictable and cannot form the sole basis of any treatment on the NHS. A study of over 10,000 doctors in the United States found that while 24% of doctors prescribe a treatment that is a placebo simply because the patient wants the treatment, 58% do not, and for the remaining 18%, it depends circumstances.

Changes over time

A review published in JAMA Psychiatry found that in trials antipsychotic drugs, the change in placebo response increased significantly between 1960 and 2013. The authors of the Review identified several factors that may influence this change, including inflation basic indicators and the participation of fewer severely ill patients. Another analysis published in Pain in 2015 found that placebo responses increased significantly in neuropathic pain clinical trials conducted in the United States from 1990 to 2013. The researchers suggested that this may be because such trials "increased in study size and duration" during this time period.

Patients

Who is affected by the placebo effect?

Placebos don't work for everyone. Henry C. Beecher, in a paper published in 1955, suggested that placebo effects occur in approximately 35% of people. However, this article was criticized for failing to distinguish the placebo effect from other factors, and thus encouraged an inflated understanding of the placebo effect.

Individual differences

In the 1950s, significant research was conducted to determine whether a particular personality type responded to placebo treatment. The findings could not be reproduced and are now considered to have no effect. The desire for pain relief, “goal motivation,” and how much pain relief is expected increases placebo pain relief. Another factor in increasing the effectiveness of placebos is the degree to which a person pays attention to symptoms, “somatic focus.” Individual differences in response to placebo analgesics have been linked to regional neurochemical differences in the internal affective state of individuals experiencing pain. Patients with Alzheimer's disease lose the ability to perceive placebos, and this is associated with a loss of the ability to have expectations, dependent on the prefrontal cortex. Children show greater placebo responses than adults.

Genes

In social anxiety disorder (SAD), an inherited variant of the gene for tryptophan hydroxylase 2 (an enzyme that synthesizes the neurotransmitter serotonin) is associated with decreased activity tonsils and greater sensitivity to the placebo effect. The authors note that “it is necessary extra work to determine the generalizability of the findings.” In a 2012 study, variations in the COMT (catechol-O-methyltransferase) genes associated with dopamine release played a critical role in the placebo effect in irritable bowel syndrome patients participating in the study, according to the research team at Harvard Medical School. Patients with the met/met variant, having two copies of the methionine allele, showed a greater likelihood of responding to placebo treatment, while the val/val variant, due to two copies of the valine allele, showed least likely. The response of patients with one copy of methionine and valine was moderate. Dopamine release in patients with met/met variation is thought to be associated with reward and “confirmation bias,” which enhance the feeling that treatment is working. The role of COMT gene variations is expected to be more prominent in studies in which patients report more subjective conditions, such as pain and fatigue, rather than objective physiological measures.

Symptoms and conditions

The placebo effect is stronger in some conditions than in others. Dylan Evans suggested that placebos were most effective for conditions such as pain, swelling, stomach ulcers, depression and anxiety, which were associated with activation of the acute phase response.

Pain

The placebo effect is thought to reduce pain—a phenomenon known as placebo analgesia—by two different ways. One way is that the placebo triggers the release of endorphins, which are natural painkillers produced by the brain. Another way is that the placebo changes the patient's perception of pain. “A person may reinterpret sharp pain as an uncomfortable tingling sensation.” One way in which the magnitude of placebo analgesia can be measured is by conducting "open/covert" studies, in which some patients receive an analgesic and report that they will receive it (an open study) while others are administered the same drug. without their notification (hidden research). Such studies have shown that analgesics are significantly more effective when the patient knows that he is receiving them. When administered orally, placebo has clinically significant effects in reducing back pain.

Depression

In 2008, a controversial meta-analysis conducted by psychologist Irving Kirsch analyzing FDA data found that 82% of the response to antidepressants was to placebo. However, there are serious concerns about the methods used and the interpretation of the results, in particular the use of an effect size of 0.5 as a cut-off point. A complete reanalysis and recalculation based on the same data, the FDA found that Kirsch's study had important calculation flaws. The authors concluded that although the large response rate to placebo was due to expectancy, this was not true for the active drug. In addition to confirming the effectiveness of the drugs, they found that the effect of the drug was not associated with the severity of depression. Another meta-analysis found that 79% of depressed patients treated with placebo felt well (12 weeks after an initial 6-8 weeks of successful treatment), compared with 93% of patients treated with antidepressants. In the continuation phase, however, patients receiving placebo relapsed significantly more often than patients receiving antidepressants. A 2009 meta-analysis found that in 2005, 68% of antidepressant effects were due to placebo, more than double the placebo response rate in 1980. While some argue that general consent for an unspecified treatment given in advance by a patient is ethical, others say that patients should always receive specific information about the name of the drug they are receiving, its side effects, and other treatment options. Although some patients are reluctant to receive information, healthcare professionals have an ethical obligation to provide adequate information about a given treatment. There is such debate about the use of placebos because while placebos are used for the benefit of society to test the effectiveness of drugs, some argue that it is unethical to deprive individual patients of effective drugs.

Chronic fatigue syndrome

It has previously been suggested that placebo response rates in patients with chronic fatigue syndrome (CFS) are unusually high, "at least 30% to 50%", due to the subjective presentation of symptoms and the fluctuating nature of the condition. According to the meta-analysis and contrary to conventional wisdom, general indicator The response rate in the placebo group was 19.6%, which is even lower than for some other medical conditions. The authors offer possible explanations for this result: CFS is widely understood as a difficult condition to treat, which will lead to lower expectations of improvement. In the context of evidence showing that placebo does not have powerful clinical effects compared with no treatment, the low rate of spontaneous remission in CFS may contribute to the slower rate of improvement in the placebo group. The type of intervention also contributed to the heterogeneity of response. Low patient and clinician expectations for psychological treatment may explain particularly low placebo responses in psychiatric treatment.

List of medical conditions

The effect of placebo treatment (inert tablets unless otherwise stated) has been studied for the following diseases. Many of these quotes refer to studies showing that active treatments are effective, but placebo effects also exist.

Anxiety disorders

Autism: language and behavioral problems

Benign prostate enlargement

Compulsive overeating

Bipolar mania

Burning mouth syndrome

• Crohn's disease

  Depression

  Dyspepsia and gastric motility

  Epilepsy

  erectile disfunction

  Food allergies

  Stomach and duodenal ulcers

  Headache

  Heart failure, congestive

  Mental retardation

  Irritable bowel syndrome

  Lower Urinary Tract Symptoms

  Migraine prevention

  Multiple sclerosis

  Nausea: gastric activity

  Nausea: chemotherapy

  Nausea and vomiting: post-operative (sham acupuncture)

  Osteoarthritis

  Overactive bladder

  Panic disorders

  Parkinson's disease

  Psoriatic arthritis

  Reflux esophagitis

  Restless legs syndrome

  Rheumatic diseases

  Sexual dysfunction: women

  Social phobia

  Ulcerative colitis

Story

The word placebo, which in Latin means “I will please,” dates back to the Latin translations of the Bible by St. Jerome. In 1811, Hooper's Lexicon-Medicum defined placebo as "[any medicine] more adapted to the convenience, rather than to the benefit, of the patient." Early implementations of placebo control groups date back to the 16th century in Europe, when Catholics made efforts to discredit exorcism. Individuals who claimed to be possessed by demonic powers were given false shrines. If the person reacted with violent convulsions, it was concluded that the possession was purely a figment of the imagination. John Haygarth was the first person to study the effectiveness of the placebo effect in the 18th century. He tested a popular medical remedy of his time called Perkins sticks and concluded that the remedy was ineffective, demonstrating that the results of treatment with counterfeit Perkins sticks were the same as those from the original sticks. Emile Couet, a French pharmacist, working as an apothecary in Troyes between 1882 and 1910, also advocated the effectiveness of the "placebo effect". He became known for reassuring his customers by praising the effectiveness of each drug and leaving a small positive notice on every drug he sold. His book Self-Control through Conscious Self-Hypnosis was published in England (1920) and the USA (1922). Placebos remained a widespread medical practice until the 20th century, and the use of placebos was sometimes approved as a necessary deception. In 1903, Richard Cabot said that he had been taught to use placebos, but eventually came to a conclusion, saying that “I have yet to come across a single case in which a lie has not done more harm than good.” In modern times, T. C. Graves first defined the "placebo effect" in a published article in The Lancet in 1920. He spoke of the “placebo effect of drugs,” which occurs when “there appears to be a real psychotherapeutic effect.” In 1961, Henry C. Beecher concluded that surgeons he classified as enthusiastic were more effective in relieving their patients' chest pain and heart problems than skeptical surgeons. Beginning in the 1960s, the placebo effect became widely accepted and placebo-controlled trials became the norm in the approval of new drugs.

Placebo-controlled studies

The placebo effect makes it difficult to evaluate new treatments. Clinical trials are testing this effect by enrolling patients in a dummy treatment. Patients in such studies do not know whether they are receiving treatment or a placebo. If a person receives a placebo under one name, and if there is positive effect, the person will react in the same way later to this placebo under the same name, but not under another. Clinical trials are often double-blind, where researchers also don't know which subjects are receiving the active treatment and which are receiving a placebo. The placebo effect in such clinical trials is weaker than with conventional therapy because patients do not know whether the drug they are receiving is active. Knowingly giving a person a placebo if there is an effective affordable treatment, is ethical difficult question. While placebo-controlled studies can provide information about the effectiveness of treatment, they do not provide some study patients with the best possible outcome. available methods treatment. Informed consent is generally required from patients, including informing patients that some subjects will receive placebo treatment. The ethics of placebo-controlled studies were discussed during the revision of the Declaration of Helsinki. Of particular concern are the differences between studies comparing inert placebos with an experimental treatment versus comparing the best available treatment with an experimental treatment, as well as the differences between trials in the sponsor's developed countries and those in the target developing countries.

Nocebo

A nocebo is the opposite of a placebo effect, where the patient believes that treatment will cause symptoms to worsen. This effect, now called nocebo by analogy, can be measured in the same way as the placebo effect, for example when members of a control group receiving an inert substance report worsening symptoms. Recipients of an inert substance can negate the placebo effect simply by having a negative attitude toward the substance's effectiveness, often resulting in a nocebo effect that is not caused by the substance but is due to other factors, such as the patient's attitude toward their ability to recover, or even purely by chance worsening symptoms.

Placebo ingredients

Placebos used in clinical trials sometimes have unintended effects. A report in the Annals of Internal Medicine looking at 150 clinical trials found that some placebos used in the trials affected the results. For example, one study of cholesterol-lowering agents used olive oil and corn oil in placebo pills. However, according to the report, this "may cause the active drug to appear less advantageous than placebo: the monounsaturated and polyunsaturated fatty acids from these 'placebos' and their antioxidant and anti-inflammatory effects may cause lower lipid levels and risk cardiovascular diseases" Another example the researchers reported was a clinical trial of a new treatment for cancer patients suffering from anorexia. The placebo that was used included lactose. However, since cancer patients typically face a higher risk of lactose intolerance, the placebo pills may have actually caused unintended side effects that made the experimental drug look better.

“The doctor’s faith in the treatment and the patient’s faith in the doctor have a mutually reinforcing effect, the result is a powerful remedy that is almost guaranteed to lead to improvement and sometimes cure.”– Petr Skrabanek and James McCormick, Follies and Fallacies in Medicine, p. 13.

A placebo effect is a measurable, observable improvement in health or behavior that is independent of the medication or invasive treatment that was given.

Placebo (from Latin placebo - I will like, satisfy) is a pharmacologically inert and harmless drug or medical procedure. Placebos often include glucose, saline, or vitamins. Even imaginary surgery and sham psychotherapy can have a placebo effect.

The idea of ​​a placebo in modern times was proposed by HK Beecher. He evaluated 15 clinical trials involving various diseases and found that 35% of 1082 patients were satisfactorily treated by placebo (“Powerful Placebo,” 1955). Later studies estimated the placebo effect to be even higher than Beecher's. Studies have shown that placebos are effective in 50 or 60 percent of cases with certain conditions, such as “pain, depression, some heart disease, peptic ulcer stomach and gastric problems.” * Placebos are also effective as a psychotropic drug in the treatment of various brain diseases, some researchers even argue that there is not adequate data to prove that new pharmaceutical drugs are more effective than placebos.

Beecher began a series of studies aimed at understanding how something (improving health in in this case) can come from nothing (placebo). Unfortunately, many studies are not of very high quality. Kienle and Kiene in 1997 opined that a reanalysis of Beecher's data found “no evidence of a placebo effect in any of the studies cited.” The health improvements were real, but were due to other reasons that gave the “false impression of a placebo effect.” Re-analysis of Beecher's data shows that the improvements were:

Spontaneous improvement, fluctuations in symptoms, and return to normal are only conditionally associated with the placebo effect. Beecher's results are obtained by rounding , incorrect result variables, polite responses from subjects, adjustment of experimental conditions, neurotic or psychotic miscalculations, psychosomatic phenomena, incorrect citations, etc.

Reanalysis shows that there are a number of factors that can influence treatment outcomes and the assessment of these outcomes, so it is very difficult to be certain that it is an intervention that leads to improvement. We must also consider “artifacts such as the natural history of illness (that is, the tendency of people to get better without any treatment at all), the fact that people behave differently when they are participating in an experiment than when they are sick at home, the desire to please experimenters by giving desired responses…” (Bausell 2007: 27), and a variety of other factors unrelated to the drug we are studying and independent of any proposed mechanism that produces the observed effect.

In May 2001, The New England Journal of Medicine published an article questioning the validity of the placebo effect. In the article “Is the Placebo Powerless? An Analysis of Clinical Trials Comparing Placebo with No Treatment,” Danish researchers Asbj?rn Hr?bjartsson and Peter C. G?tzsche “found little evidence that placebo has powerful clinical effects.” Their meta-analysis of 114 studies found that “compared with no treatment, placebo had no significant effect on binary outcomes, regardless of whether those outcomes were subjective or objective. In trials with continuous results, placebo shows a beneficial effect, but the effect decreases with larger sample sizes, indicating possible bias due to the effects of small studies.” (Most of the studies reviewed by Hr?bjartsson and G?tzsche were small: 82 of the studies had a mean group size of 27 and the other 32 studies had a mean group size of 51).

“The high level of placebo effect, which has been repeatedly reported in many papers, is, in our view, the result of shortcomings in the study methodology,” said Dr Hr?bjartsson, professor of medical philosophy and research methodology at the University of Copenhagen. *

Hr?bjartsson cites the work of surgeon J. Bruce Moseley, who performed a sham knee operation, as a typical flawed study in eight out of ten patients.(In a sham operation, a small incision is made on the knee and stitched up). Six months after surgery, all patients were satisfied with the result.Rather than concluding that the patients did not require surgery or were cured on their own, he concluded that the healing of eight patients was due to a placebo effect, although the two patients who had surgery were significantly better off.Irving Kirsch and Guy Sapirstein made a similar methodological error in their controversial meta-analysis, which showed that antidepressants work as placebos instead of antidepressants being unnecessary and useless.

Another example shows that better methodology for placebo effect research is needed.

Forty years ago, a young cardiologist in Seattle named Leonard Cobb conducted unique experience, then widely used in the treatment of angina, doctors made small incisions in the chest area and tied two arteries in knots to increase blood flow to the heart.It was a popular technique—90% of patients reported that it worked—but when Cobb compared it to the results of placebo surgery, in which he made cuts but did not tie off the arteries, the sham surgeries were just as successful. The procedure, known as internal mammary stapling, was soon abandoned.(“The Placebo Prescription” by Margaret Talbot, New York Times Magazine, January 9, 2000). *

Did Cobb show that this kind of surgery works as a placebo effect? Or did he show that surgery was not necessary because most patients healed on their own if nothing was done?

To rule out natural history or reversion to normal, many researchers use a third group (control) that receives no treatment at all. If the placebo group shows better results than the control group, then the placebo is effective.Hr?bjartsson and G?tzsche think that most of these studies also have shortcomings, mainly with too small groups or due to patient reports that suit the researcher in advance.

After the publication of the study by Hr?bjartsson and G?tzsche, doctor John C. Bailar III stated in an editorial accompanying the study: “people who claim that the placebo effect exists will have to prove it.”It is necessary, he says, for large, well-designed studies to clearly define and measure the effects of drugs and treatments compared with placebo and compared with no intervention at all.These studies must clearly distinguish between objective measures (e.g. arterial pressure, cholesterol level, etc.) and subjective measures (for example, reports of pain or evaluative observations of the researcher, for example, “I see that your tumor has shrunk” or “I see that you are not as depressed as before”).

The research that Dr. Bailar called for has been done and several such studies are discussed in Chapter Nine of R. Barker Bausell's Snake Oil Science (2007): “How do we know that Placebo exists.”One thing is worth considering here.It was published in Journal Paintwo months after the article by Hr?bjartsson and G?tzsche. In progress“Feelings of Hope in the Placebo Group and Its Clinical Implications for Pain Management” Antonella Polo and co-authorsshowed that a placebo can help people with severe pain.Below is their summary:

Patients received buprenorphine[potent pain reliever] on demand for 3 consecutive days, along with IV saline.However, the three groups reported the saline administration differently.The first group was not told anything about any analgesic effect (the natural course of the disease). INThe second group was told that the infusion was either a powerful pain reliever or a placebo.The third group was told that the solution was a powerful pain reliever (a deceptive message).Thus, while analgesic treatment was the same in the three groups, verbal instructions about basal infusion differed.The placebo effect of the basal infusion was measured by recording the number of buprenorphine doses required over three days of treatment.We found that the second group showed a decrease in requests for buprenorphine compared to the first.However, this decrease was even greater in the third group.Overall, after 3 days of placebo, the first group received 11.55 mg of buprenorphine, the second group received 9.15 mg, and the third group received 7.65 mg.Despite these dose differences, pain relief was similar in the three groups.These results indicate that different verbal instructions about definite and uncertain expectations of pain relief produce different placebo analgesic effects, which in turn produce acute behavioral changes leading to significant reductions in opioid consumption.

Patients who thought they were being given a powerful painkiller asked for 34% less of the actual drug than patients who were told nothing and 16% less than patients who were told they were taking either a painkiller or a placebo. Each group ended up receiving the same amount of painkiller, but their analgesic requests differed dramatically.The only thing significant difference between the three groups was the nature of verbal instructions regarding basal infusion.The study was too short to explain differences from natural history or other alternatives found by Hr?bjartsson and G?tzsche.

A few things are worth noting about this experiment. Patient placement involves treatment by medical staff in a medical facility.This attunement usually involves a strong desire for recovery on the part of the patient, as well as a belief that the treatment will be effective.Different verbal instructions about basal infusion resulted in different expectations.Belief, motivation and expectations are essential to the placebo effect.Together they are called the subjective expectancy effect.. Classical conditioningand the suggestion of a reputable healer seem to be the “trigger” of the placebo effect (Bausell 2007: 131).

Psychological hypothesis is all in your mind

Some believe that the placebo effect is psychological in nature and is based on a subjective feeling of relief or the belief that the treatment can provide significant help. Irving Kirsch, a psychologist at the University of Connecticut, is convinced that the beneficial effects of Prozac and similar drugs are primarily due to the placebo effect. Irving Kirsch and Guy Shapirstein analyzed 19 cases clinical application antidepressants and concluded that 75% of the effectiveness of these drugs was due to the expectation of improvement rather than the regulation of brain chemistry (Kirsch, 1998). “The decisive role,” says Kirsch, “is our attunement to a certain outcome. Medicines may have nothing to do with the patient noticing positive changes.” In his early work Shapirstein analyzed the case histories of 39 depressed patients from 1974 to 1995. Each patient was prescribed medical supplies or psychotherapy, or both in combination.

Patient expectations and belief in the effectiveness of treatment, combined with suggestibility, can lead to significant biochemical changes. Sensory experiences and thoughts can influence neurochemical processes in the body. The neurochemical system influences other biochemical systems of the body and, in turn, is affected by them. Thus, all this is consistent with modern knowledge that a person's positive attitude and attitude have a significant impact on improving his physical condition.

However, it may also be that the placebo effect refers primarily to the effect of the brain not on the body, but on human behavior. The fact is that a certain amount of the behavior of a “sick” person is acquired. This means that a certain amount of role-playing is observed in the behavior of a sick or in pain person. Role-playing is not the same thing as pretending or pretending. The behavior of a sick or suffering person is based on a certain social and cultural basis. The placebo effect allows you to “measure” the proportion of changed behavior that is caused by the belief in the positive effects of treatment, including a change in the patient’s attitude towards his own actions and words about well-being, which can also affect brain chemistry.

Apparently, the psychological explanation for this phenomenon is more convincing. This is why many people are disheartened when they learn that the effective medicine they are taking is nothing more than a placebo. This leads them to believe that the problem is obsessive thoughts, “sitting in their head” and that in reality nothing terrible happens to them. In addition, since numerous studies have found that placebos play a significant role in improving health, this suggests a psychological nature of its effects.

In one experiment, doctors rid their patients of warts by painting them with brightly colored inactive dyes and promising the patients that the warts would disappear as soon as the dye came off. In observing asthmatics, researchers found that patients' airways dilated if they were told they were taking bronchodilators, even though the drugs they were given were not. Patients experiencing pain after wisdom tooth extraction receive equal relief from real or sham ultrasound, as long as the patient and physician are confident that the ultrasound device is turned on. Based on the results of 11 different studies, 52% of people suffering from colitis who used a placebo during treatment felt relief. When objectively assessing the condition of the inflamed organs, in 50% of cases a real improvement was noted (“The Placebo Prescription” by Margaret Talbot, New York Times Magazine, January 9, 2000).

It is unlikely that such effects are due to psychological factors alone.

In fact, Martina Amanzio and her colleagues(2001) showed that “at least part of the physiological basis of the placebo effect is endogenous opiates” (Bausell 2007: 160).We can reflexivelyrelease endorphins, catecholamines, cortisol and adrenaline into the blood.One of the reasons why acupuncture or sham acupuncture treatment is successful is the placebo effect, which stimulates the internal opioid systems.

Faith Healing

Another popular theory is that the healing process, which is accompanied by increased attention, care and kindness towards the patient, a process that is encouraging and reassuring, can stimulate physical reactions in the body that stimulate recovery. Dr. Walter A. Brown, a psychiatrist at Brown University, says:

...there is certain data suggesting that the very immersion in the treatment process leads to certain consequences. Depressed patients who simply take their prescribed medications do not do as well as those who are given a placebo. And - this seems very impressive to me - when a placebo is used as a pain reliever, pain begins to decrease in the same way as under the influence of the active drug. Peak pain relief occurs one hour after taking the placebo, just as it does with the real drug. If the use of a placebo analgesic were equivalent to the patient taking no medication at all, then the course of the disease would be more unpredictable (Ibid.).

Dr. Brown and others believe that the placebo effect is mostly, if not entirely, physical in nature and occurs through physical changes that promote healing or well-being. According to Brown and his associates, the participation, concern, attention and other manifestations of goodwill that represent the component of research in a controlled setting (and even the therapeutic principle itself), along with optimism and encouragement emanating from the experimenter or doctor, influence the patient's mood, which , in turn, initiates changes in his body, such as the release of endorphins. This process reduces stress by creating hope or reducing doubts about treatment options or possible outcomes. Weakening stress state helps prevent harmful changes in the body or slow them down.

Genetic connection

Because the placebo effect shows a deep dependence on people's personalities, some researchers have sought evidence genetic predisposition and susceptibility to placebo. Andrew Leichter and colleaguespostulated that placebo acts through central monoamine modulation pathways, which are under strong genetic control.Their findings “support the hypothesis that genetic polymorphisms in the modulation of monoaminergic tones are associated with the degree of placebo effectiveness in the treatment of depressive disorder.”The researchers emphasized that genetics is not the only explanation for placebo response, which is likely to be influenced by several biological and psychosocial factors.*

Ethical dilemma

The power of the placebo effect has led to an ethical dilemma. There is no need to deceive other people, but we need to alleviate the pain and suffering of our patients. Should you use deception to benefit your patients? Could it be unethical for a doctor to knowingly prescribe a placebo without telling the patient? If informing the patient reduces the effectiveness of the placebo, does this justify deception, even if the patient benefits? Some doctors believe that the use of placebos is justified in cases where a strong placebo effect has been proven. * Others think that it is always wrong to deceive the patient and that the patient's informed consent to placebo treatment is necessary. Others, especially complementary and alternative medicine (CAM) practitioners, don't even want to know whether a treatment is a placebo or not. They believe that as long as the treatment is effective, who cares whether it is a placebo or not?

While it may be unethical to knowingly prescribe or sell placebos as magical treatments, CAMs believe otherwise because they truly believe in their chi energies, meridians, yin, yang, prana, vata, pitta, kapha, auras, chakras and other unobservable processes. which supposedly have all sorts of magical, analgesic and healing functions.

Is placebo dangerous?

Although skeptics may reject faith, prayerand “alternative” medical practices,Their beneficial effects cannot be ruled out.It is clear that they cannot cure cancer and cannot prolong life, giving hope and relief from suffering, as is sometimes believed.But the practitioner of placebo therapy involves interacting with the patient in a caring, attentive manner, and this can provide some degree of comfort.However, for those who say “what difference does it make how it works, the main thing is that it works”my answer is that it is likely that there is something that works even better, and may even be cheaper.But what is much worse is that some people seek a quack to treat a serious disorder that does not depend on quack therapy but can be alleviated or cured by scientific medicine.Additionally, placebos may not always be beneficial or harmless. John Dodes notes:

Patients may become dependent on uneducated healers who practice placebo therapy. Such patients may end up believing that they are suffering from imaginary reactive hypoglycemia,11 non-existent allergies and fungal infections, being “poisoned” by the composition of their dental filling, or that they are under the influence of chi energy or the influence of aliens. And patients will be reassured that their illnesses are amenable only to a specific type of treatment offered by special people.

In other words, using placebos can open the door to quackery. R. Barker Bausell suggests that in alternative medicine, practitioners mainly feed the patient hope (2007: 294), “such treatments may generate little more than the expectation that they will reduce pain; all treatments are promises and rituals” (p. 149). Placebos in fancy packaging are big business and are likely to get even bigger. The only thing that can slow down the spread of quack medicine is the sudden appearance of terrible side effects.

I would say that the likelihood of this happening is about the same as the likelihood of mediums John Edward or James Van Praagh telling the audience that a spirit is telling them that the client who pays is a murderer.

How is the effectiveness of a medicine checked?

What's happened?

In the debate between Anatoly Chubais and Alexei Navalny, a dispute arose again about the effectiveness of Kagocel, one of the most popular Russian medications for flu and colds. Navalny argued that the drug had not undergone proper clinical trials and had not been published in respected scientific journals. In response, Chubais provided links to publications with the results of testing the drug. Meduza asked Tarusa Hospital doctor Artemy Okhotin to tell us how the effectiveness of new treatment methods is assessed and how convincing the research presented by Chubais is.

Kagocel helps me. This is not enough?

No. This argument does not work even for a doctor who sees dozens of patients - “Kagocel helps my patients.” Many diseases go away on their own or occur in waves: the state of health either improves or worsens. In these cases, any medicine will “help,” even a placebo (dummy), especially if the patient believes in the drug. This is called the placebo effect.

How then can you assess whether the medicine is helping?

To exclude the placebo effect and other subjective factors, methods have been developed, united by the concept of “evidence-based medicine”. The standard of evaluation is a double-blind, randomized, placebo-controlled trial. This is a study in which a drug is compared with a placebo, and neither the doctor nor the patient knows who exactly is receiving the study drug and who is receiving a seemingly indistinguishable dummy.

So, are all treatments tested this way?

Unfortunately no. Previously, it was considered perfectly acceptable to conduct a study in which all patients received a new drug. The flawed logic of such research is well conveyed in a quote attributed to Galen (2nd century AD): “All the sick who took this remedy soon recovered, except those for whom it did not help - they died. Hence it is obvious that this remedy helps in all cases except hopeless ones.” Understanding how dangerous misconceptions arise from simply observing the effects of drugs came in the 1960s and 1970s. When placebo control began to be used to evaluate drugs, it turned out that many conventional drugs not only do not help, but also cause harm. For example, the CAST study showed that drugs used in myocardial infarction to stabilize the heart rhythm do stabilize the rhythm, but increase mortality.

Why is double blinding and randomization needed?

To exclude the placebo effect and physician intervention when forming groups receiving the drug or placebo. If a doctor has doubts about a new drug, he may subconsciously refer milder patients to the drug group. The attitude of the doctor and the patient towards the drug will also influence the assessment of its effectiveness, especially when assessing such informal indicators as general health or severity of cough. Therefore, neither the doctor nor the patient should know who is taking the medicine and who is taking the placebo. This allows the doctor to evaluate the condition without knowing whether the patient received the drug.

If the study is carried out according to all the rules and published, can the drug be considered effective?

No, publication means providing data for judgment by the professional community. The results are discussed, rechecked and criticized. Analysis and criticism of clinical trials constitutes a significant portion of publications in good medical journals. The principles of evidence-based medicine are developing; what we have named are the basics, without which the work will not be read and will not be accepted into a decent journal. But not only the research methodology is important, but also its statistical significance, which excludes the randomness of the results.

How can the results be random?

Very simple. Let's say we invented a way to only flip tails in a heads-or-tails game. If we make three tosses and get heads three times, the probability that we were just lucky is 1/8. Such a result will not be accepted in a medical journal; the probability of a case is too high. If we toss a coin six times and get heads each time, the probability of randomness is only 1/64 - this is already suitable for publication. But treatments rarely produce the desired effect 100% of the time, so large samples are needed to obtain statistically significant results. For example, to show that oseltamivir (Tamiflu) speeds up recovery from influenza by a day, the study required recruiting more than 700 patients.

And if the results of the study show that the drug is ineffective, will we know about it?

We may not know unless the authors publish their results. This problem is called publication selectivity. If we repeat a series of experiments with a coin many times, sooner or later we will get six heads in a row and we can publish this result. No one will know about unsuccessful experiments, which will create a false impression that the method is effective. To combat publication selectivity, pre-registration of clinical trials was invented, requiring publication of any results. It is interesting that studies with negative results are often published in English-language journals, while this is not accepted in Russian-language publications, which greatly undermines their credibility.

Sometimes these studies are just as interesting as the studies with positive results. Among the most high-profile such publications in recent years is the COURAGE study, published in the prestigious New England Journal of Medicine. It showed that coronary angioplasty - a procedure to restore blood flow in the arteries of the heart - does not reduce the risk of heart attack and death in stable patients; they can be treated with pills. The study became major cardiology news for many years.

Who checks how well the research is conducted and whether errors are possible?

There are several levels of verification. Statisticians should participate in the preparation of publications. Before publication, the article is reviewed by the editorial office of the journal (such journals are called peer-reviewed). However, erroneous or inaccurate results may be published. Therefore, medical publications are subject to rather harsh criticism by the professional community. If the criticism is sufficiently convincing, researchers may be required to provide primary data. Another level of verification is the state supervisory authorities (Ministry of Health in Russia, FDA in America), but they, as a rule, rely on the same professional community in their conclusions.

Does a doctor really need to know all the studies in order to prescribe effective treatment?

The volume of medical information is enormous and constantly growing. At best, you can keep track of your narrow specialty. But professional organizations come to the rescue by examining existing data, assessing its reliability and publishing practical recommendations. They indicate the degree of validity of a particular recommendation.

It turns out that evidence-based medicine turns the art of healing into work according to instructions?

No, this is a very superficial view. Recommendations describe standard situations in which you can actually act according to the instructions. But you need experience and knowledge to understand which instructions to act on at the moment. In addition, not all patients fit into the standard. Often, in order to understand what will help the patient, the doctor himself needs to analyze the published data. The ability to work with data is as important a skill for a doctor as talking to a patient, recognizing symptoms, or performing therapeutic procedures.

But aren't all the studies and journals bought by the pharmaceutical mafia?

No. But drug manufacturers sometimes try to influence research results. Therefore, manufacturer-sponsored studies are less trusted. When such influence is revealed, a scandal ensues, from which not only the company suffers, but also the authors of the studies. This was the case with the painkiller Rofecoxib from Merck. Studies have shown that the drug slightly increases the risk of heart attack, but the authors presented this data in a very innocent light. When it turned out that this was done intentionally, and some of the data was also hidden by the researchers, the company had to pay several billion dollars and stop sales of the popular drug. That is, not everything has been bought: where there is a judicial system and a professional medical community, the pharmacological mafia can be fought - like any crime.

So what about Kagocel, does it help or not?

This is unknown. So far, no publications have appeared in respected medical publications confirming or refuting the effectiveness of Kagocel. Medline, a database of publications in all major biomedical journals, does not have a single link to clinical trials of the drug. The studies cited by Anatoly Chubais were published in rather marginal publications. Most of the articles were written by the same authors, some of the studies were unavailable, and the available publications had small samples and, most importantly, did not indicate the statistical methods used. It also does not help credibility that the results of these studies were not critically analyzed by outside authors. However, the situation with many over-the-counter antiviral drugs not better. For a doctor who is accustomed to focusing his practice on the principles of evidence-based medicine, Kagocel simply does not exist yet.

How does treatment with sugar, starch and saline help, and why do even doctors resort to placebos?

How it works

Dummy drugs contain substances that, it would seem, should not cause any therapeutic effects: sugar, starch, water, saline solution.

However, many studies have shown that . These medications help cope with chronic pain, cough, anxiety disorders, symptoms, erectile dysfunction, improve the condition of patients with epilepsy.

The secret is simple. When a person takes medicine, he expects to feel better. This leads to changes in hormone levels and performance nervous system- the “chief conductor” who directs all processes in the body. In the brain, areas responsible for motivation and reward are reflexively activated.

To a large extent, the effect of placebos is based on conditioned reflexes. The patient can be compared to Pavlov's dog, which begins to salivate in response to a signal.

What conditioned reflexes is the brain capable of? For example, it can activate, “turn off” fever. And much more .

Experiments conducted in 2012 showed that counterfeit pills act “bypassing” consciousness. Often we don’t even have time to consciously believe in the effectiveness of a placebo - but it already acts due to the power of the subconscious.

There are other explanations for the “effectiveness” of placebos. Some illnesses are so minor that they would go away without treatment, but the person believes that a “magic pill” certainly helped. Sometimes they start taking a pacifier if all other options have been exhausted, and in the meantime the illness has passed its peak period and has begun to decline. There are diseases that occur cyclically, and the start of taking a placebo could come at the end of the next exacerbation.

Placebo and children

In 2014, scientists from the Penn State College of Medicine found that a placebo helped reduce coughing in young children (under 4 years of age).

Placebotherapy is recognized as a better solution than expectant management. This is especially true when you consider the fact that many cough and cold remedies are contraindicated at a young age.

Placebo treatment is also successfully practiced by many mothers. Little children know that in order for a stubbed finger to stop hurting, it “must be kissed.”

Which placebo “helps” better?

A pill with the same starch can be painted in different colors - each of them will “treat” in its own way. Scientists have found that yellow pills They help best with depression, red ones are highly stimulating, green ones relax and calm, white ones reduce the symptoms of gastritis and ulcers (especially if the tablet says “antacid”).

How does a “pure” placebo differ from an “impure” placebo?

In the usual understanding, a placebo is a “dummy”, that is, a drug that does not contain any active substances. For example, a sugar pill or a saline injection does not cure anything, they only have a psychological effect. This type of placebo is called a “pure” placebo.

An “impure” placebo contains active substances, but their effectiveness has not been proven. For example, an antibiotic for a viral infection and vitamins for cancer are “unclean” placebos.

How often do doctors prescribe placebos?

In 2013, scientists from Oxford and Southampton decided to ask 783 doctors how they felt about placebos. The survey results showed that 97% of doctors prescribed pacifier treatment at least once in their practice, and deliberately prescribed a drug that was obviously ineffective.

Doctors do not prescribe placebo therapy to deceive patients. They expect that the dummy pill will be useful as a psychotherapeutic agent and will help calm the patient when he insists on being prescribed at least something.

Earlier, in 2008, American researchers found that therapists and rheumatologists in the United States often resort to placebos. Medical workers from different countries believe that placebos provide benefits through psychological effects, and there is nothing wrong with prescribing such drugs in certain situations. However, the issue has another - ethical - side. Is it fair to the patient to prescribe a “dummy” under the guise of effective medicine, for which a person must pay?
Experts from the UK Medical Council (GMC General Medical Council) urge doctors to honestly inform patients about prescriptions.

The opposite of placebo: nocebo

The human brain can generate not only therapeutic, but also placebo side effects. The doctor may tell the patient that a lump of sugar or starch heals headache, but often leads to dizziness and nausea. Many patients will report feeling “dizzy” after taking a pacifier, and some will even vomit.

This effect - when there are no negative effects, but a person believes in them and experiences them - is called nocebo. Doctors and scientists have mixed feelings about it. Some experts consider the term “nocebo” to be incorrect, since it is essentially the same as a placebo. For example, immune suppression may be beneficial (placebo) for patients with autoimmune diseases but harmful (nocebo) for infections. Both effects can be caused by the same drugs, and they are realized by similar mechanisms. The only difference is in subjective perception.

In everyday life, such types of nocebo as belief in “”, “evil eye” are common. There is another reason to think: are some “sores” caused by such “dummies”?