Nocebo effect

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The nocebo effect (from Latin nocere ' to harm', nocebo 'I will harm') is - analogous to the placebo effect ( Latin placebo , I will like ') - a negative health effect after exposure to an agent, e.g. B. by a drug or some other external influence, without a direct and immediate causal relationship between agent and effect seems to exist, whereby the effects are mostly attributed to psychological causes. In contrast to the positive effect of the placebo effect, the nocebo effect produces a negative reaction. The nocebo effect also describes a negative reaction to what is rumored to have a lasting negative effect on health or well-being of an environmentally-changing measure.

definition

The nocebo effect was discovered in the course of clinical tests of pharmaceuticals when, after administration of active ingredient-free preparations - so-called placebos - negative health effects, and in some cases also disease-causing effects, occurred. If the negative effect predominates, it is correctly referred to as a nocebo (instead of placebo). In medical-scientific usage today, all other measures or any influencing variables that can cause a negative reaction without scientific evidence of a specific effect are also referred to in a broader sense. A nocebo effect can also add up to negative effects that can be explained in other ways.

The nocebo effect - often also referred to as the negative placebo effect - is based, like the placebo effect, on, among other things, certain expectations . The expectations can therefore also be unconscious and rely on learning mechanisms such as B. Conditioning based. In this way, the patient can fear that certain external influences “make him sick”. These people then actually become ill, or the corresponding symptoms can be observed and also measured in them. Another popular model According to the statement, these are a negative self-fulfilling prophecy (self-fulfilling prophecy) . Triggers or amplifiers may include a. (Incorrect) diagnoses by doctors or detailed explanations of possible side effects (e.g. in scientific studies or in the often long list of side effects in the leaflet for many drugs).

Symptoms

The side effects complained about by those affected are mostly illnesses to which a high degree of psychosomatic causes is generally ascribed. The nocebo effect is usually expressed through subjective symptoms , such as nausea , headache , exhaustion or drowsiness . In addition, however, objective symptoms can also be diagnosed. Most importantly , these are skin rashes , increased blood pressure and increased heart rate . These symptoms can be mild and temporary, but they can also be chronic and in extreme cases even fatal . The nocebo effect shows itself most clearly in a sick fear of imaginary dangers.

Nocebo symptoms are significantly more common in women than in men. Older people are more likely to experience the nocebo effect than younger people.

Mechanisms

The psychological mechanism underlying the nocebo effect is largely unknown. According to the current state of knowledge, conditioning and expectations play an essential role.

Physiological components related to the nocebo effect can also be identified. Obviously, the neurotransmitter cholecystokinin (CCK) formed in the intestinal mucous membrane plays a role in mentally-related pain . It triggers a pain reaction in the brain and also has a decisive function in phobias . This fear-triggered messenger substance is presumably responsible for the fact that side effects occur more frequently when the patient expects them to occur.

Examples

The nocebo effect can be observed especially in placebo-controlled double-blind studies for the approval of new drugs . In these studies, all patients are informed about possible expected side effects of the active ingredient - regardless of whether they receive this active ingredient or a placebo. Around a quarter of the placebo recipients then complain about the side effects explained to them. An example is the occurrence of hypervagotonia , which manifested itself in a double-blind study of a calcium antagonist in patients with cardiac arrhythmia , although they had only received the placebo. In another study, 19 percent of the subjects who had received the placebo in a placebo-controlled double-blind study with a total of 109 healthy subjects complained of side effects. In an earlier study in which 67 placebo-controlled clinical studies were evaluated, an average of 23 percent of subjects who had only received the placebo complained of at least one disturbing side effect. The proportion of test subjects who complained of side effects after taking the placebo had a significantly higher incidence of 27 to 71 percent when asked about the side effects.

Just as the placebo effect of the control group is subtracted from the effect of the actual active ingredient to assess the effect of a drug in a placebo-controlled double-blind study, the nocebo effect of the control group can in principle also be subtracted to determine the actual side effects of the active ingredient.

According to hypotheses - about which there is no current scientific consensus - the nocebo effect should also play a role in negative perceptions in connection with radio masts (" electrosmog ") or nuclear power plants.

The nocebo effect can also be observed in animals.

After simulated rear-end collisions, in which the car was only supposedly accelerated, a significant proportion of test persons complains of complaints in the cervical spine area that can last for several days. Obviously pain is expected and it will come.

Examples from clinical studies

Framingham Heart Study

In the very wide and generations-scale Framingham Heart Study of the United States Public Health Service has found that women who said of himself that they suffer more than other women from heart disease, actually an observation period of 20 years, almost four times Showed a likelihood of having a myocardial infarction or sudden cardiac death - even when the results were corrected for the variables tobacco use , high blood pressure, and high cholesterol .

chemotherapy

An example of conditioning, or the influence of psychological factors, is that patients receiving chemotherapy for breast cancer can develop profound nausea when they enter a room that is the same color as the infusion room in which they received chemotherapy. In one study, this was the case in a third of the patients.

Food allergy

In a double-blind study, patients who complained of a food allergy received injections of saline solution , which they - deliberately incorrectly - was described as an allergen . A quarter of these patients showed allergic reactions after the injection.

Side effects to drugs

In Italy, a large-scale study was carried out in 2004 with a total of 600 patients who had previously complained of adverse drug effects (side effects) when taking drugs. Some of the patients received a placebo, the other part an active ingredient, each administered orally. In the group that received the placebo, 27% of the patients experienced the nocebo effect. A later study comes to similar results, but with a significantly lower frequency (three percent).

Headache from lack of electrical currents

In a study from the early 1980s, the following experiment was performed on 34 students: The students were told that an electrical current was being sent through their head and that it could cause a headache. Without any current flow, more than two thirds of the students complained of headaches.

A similar study was published in 1993. 99 test persons were connected to two electrodes below the eye, which were connected to a device labeled "shock generator". It was explained to the test persons that a non-measurable current was passed through their head. In reality, however, the device only produced a tone that became louder when shifting up. The result:

  • 25 test persons complained of pain
  • a further 23 test persons had punctual pain, but denied experiencing pain in a subsequent questioning
  • 3 subjects had other sensations such as dry mouth or tension in the neck
  • 7 test persons had pain only in the area of ​​the electrodes
  • 7 test persons had pain in the extended electrode area
  • 11 subjects had pain in the electrode and other areas
  • 28 subjects had pain in other areas of the head

Electrosmog

In a three-year study by the University of Essex , 44 people took part who complained of health problems from the proximity of cell phone transmitters, as well as 114 people who had never noticed negative effects from cell phone networks. In a laboratory, these people were exposed to electromagnetic radiation with frequencies in the GSM and UMTS range in various experiments .

In the double-blind study , the test participants were told that an antenna with the corresponding radiation would be in operation for 50 minutes. The subjects who considered themselves to be radiation-sensitive (from the group of 44) then complained of nausea, headaches or flu-like symptoms. Doctors were also able to measure changes in heart rate and skin moisture in those affected . These subjectively perceived complaints and measurable symptoms were, however, completely independent of whether the antenna was actually in operation or not. Twelve people had to stop the test because of massive health problems.

Wind turbines and infrasound

In the area of wind turbines , infrasound is suspected to be the cause of various diseases, but there is no real evidence for this. Double-blind studies showed that similar symptoms could be triggered both with actual exposure to sound and by mere imagination without actual infrasound exposure, if the test participants expected symptoms due to previous exposure. People who did not expect any negative influences from infrasound, on the other hand, did not develop any symptoms in the experiment.

Voodoo curse

An example of an extreme nocebo effect are death sentences imposed by voodoo priests . It is assumed that the victims, in their belief, become sick of resignation and fear and ultimately actually die.

Suicide attempt with placebos

The nocebo phenomenon has not been as well studied as the placebo effects. However, “expectation” and “conditioning” seem to be triggered by the same mechanisms of action. A case report of a student who attempted suicide ingesting an entire month's supply of a drug obtained through participation in a drug study is sensational . He was under medical treatment and although the drug was only placebo tablets, his condition was critical. Only after learning of the true nature of the tablets did his values ​​return to normal.

Epidemic hysteria

If a single person shows clear symptoms of an illness, this will be perceived by their social environment. This leads to sympathy and, under certain circumstances, a transfer of symptoms to the environment. In extreme cases this can lead to mass hysteria . One example is the Arjenyattah epidemic , which occurred in the West Bank in 1983 and the cause of which can essentially be attributed to the nocebo effect. A similar phenomenon was " Mohl's disease ".

Animal experiment

In a classic animal test the hypothesis of conditioning by Pavlov was rats with saccharin given offset drinking water before cyclophosphamide injected got. Cyclophosphamide causes immunosuppression , among other things . To the surprise of the experimenters, the saccharin alone had an immunosuppressive effect after the conditioning phase.

Problem

Just as the placebo portion adds up to the positive overall effect of a drug in verum treatment , the nocebo effect is responsible for a not inconsiderable part of the undesirable effects of drugs ( side effects ). In this context, studying the patient information leaflet in detail or talking to a doctor or pharmacist about side effects can be extremely problematic. Sensitive or depressed people, in particular, often imagine the worst scenarios.

The nocebo effect represents a significant cost factor for the health system , and thus for the national economy . According to a study by the University of Arizona, the cost of drug-related side effects in the United States alone was an estimated 76.6 billion  US dollars in 1995 . A significant proportion, currently not quantifiable, is caused by the nocebo effect. So far, however, only psychosomatic symptoms (headache, nausea) due to the nocebo effect have been proven beyond doubt in the laboratory .

history

The term nocebo was coined by Walter P. Kennedy in 1961 and is much less well known than the placebo effect.

While a great deal has been and is being published about the placebo effect, there is significantly less literature and scientific studies on the nocebo effect. Scientific interest has increased significantly since 2000. In PubMed In total 99 publications with the keyword "nocebo" found until 19 February, 2009. Of these, 72 were published after 2000 and only 10 before 1990.

There are only very limited clinical studies. One of the reasons for this is that it is ethically difficult to induce disease in healthy people via the nocebo effect.

In 2001, three quarters of all patients in the USA were not aware of the nocebo effect or are not aware of it. The proportion of employees in the health sector is similarly high.

literature

  • Stewart Justman: The Nocebo Effect. Springer, 2016, ISBN 978-1-137-52329-7 ( limited preview in Google book search).
  • M. de la Cruz, D. Hui, HA Parsons, E. Bruera: Placebo and nocebo effects in randomized double-blind clinical trials of agents for the therapy for fatigue in patients with advanced cancer. In: Cancer . 116, 2010, pp. 766-774 PMID 19918921 PMC 281507 (free full text).
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  • F. Benedetti et al. a .: When words are painful: unraveling the mechanisms of the nocebo effect. In: Neuroscience. 147, 2007, pp. 260-271. PMID 17379417
  • AL Geers et al. a .: Further evidence for individual differences in placebo responding: An interactionist perspective. In: Journal of Psychosomatic Research. 62, 2007, pp. 563-570. PMID 17467411
  • B. Olshansky: Placebo and Nocebo in Cardiovascular Health: Implications for Healthcare, Research, and the Doctor-Patient Relationship. In: J Am Coll Cardiol 49, 2007, pp. 415-421. PMID 17258086
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  • F. Benedetti et al. a .: Conscious Expectation and Unconscious Conditioning in Analgesic, Motor, and Hormonal Placebo / Nocebo Responses. In: J Neurosci. 23, 2003, pp. 4315-4323. PMID 12764120
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Web links

Individual evidence

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