Placebos (Latin: I shall please) and the placebo effect rely on and are essentially a degree of misinformation or deception that leads patients or subjects to have perceived and/or actual improvements that would not have been otherwise observed without the deception. For example, sugar pills are only effective when the individuals believe that the pills have objective medical value.
In this Lentis Chapter, we will be exploring the ways in which placebos and society affect each other. While there are myriad applications where the Placebo effects can be observed, for the purpose of this chapter and its constraints, we will be constraining ourselves to medical applications. Alternative medicine, faith healing, alcohol, drugs, and Magnetic therapy are but a few of the myriad of applications where the placebo effect is crucial to the way they shape society through consumption and marketing that could be explored. The subject of Nocebos (Latin: I shall harm), the counterparts to Placebos, is also an interesting discussion as oftentimes those effects, like placebos, can be unpredictable in powerful manners to the patients.
The healing process can be divided into three stages: autonomous response, specific response, and meaningful response. Autonomous is the body’s natural immune response, specific is response to medicinal treatment, and meaningful is the contextual response. As described later, brand names influence the healing process. When patients can identify a drug and knows how it is supposed to work, there will be a greater positive result. This part of the healing process is attributed to the patient’s attitude and understanding of the drug.
Placebos are most commonly utilized during the development of drugs. According to the FDA, a thorough investigation of the drug must include a “valid comparison with a control”. As described previously, placebos are inert substances that mimic active drugs but have no medical value. Thus, they are crucial for maintaining a control group throughout the drug investigation. Additionally, the participants should be randomly assigned to a particular treatment and the experiments should be double-blind in which neither the researchers nor the participants know which group receives the active drug and which receives the inactive placebo. This type of study is called a Randomized Controlled Trial and prevents observer-expectancy or the unintentional bias that the researcher may have to a particular outcome. During this stage of testing, the drug must display more positive results than the placebo in at least two trials. Often, many drugs fail to produce greater effects than the placebos and are withdrawn from drug development. This is referred to as crossing the futility boundary.
Societal Influences on the Placebo EffectEdit
There are several factors that influence the success of placebos including cost, color, quantity, administration method, brand name, and geography.
A study conducted by Duke University showed that people are more likely to respond positively while taking more expensive placebos as opposed to cheaper ones. This supports the cultural idea that items that are more expensive are better or more effective.
The University of Cincinnati conducted a study that focused on the effects of different colored placebos. In this study, one group took a blue placebo pill while another took a pink placebo pill. They were told that one pill increases drowsiness while the other is a stimulant. 66% of the participants which took the blue pill felt drowsier as opposed to 26% which took the pink pill. There is a clear correspondence between the color of the pill and the elicited response. Blue is a tranquilizer, yellow is an antidepressant, red is a stimulant, green is an antianxiety, and white is an antacid.
In addition to color, the quantity of pills also alters the magnitude of the placebo effect. In the University of Cincinnati study, the participants were either given one or two pills of the respective color. There was a greater response from those that received two pills than those that received one. As with cost, more is better.
The University of Mississippi concluded that injecting medicine is far superior to oral medication. Even injecting a placebo provided greater success than taking an active drug orally.
A study on headache pain relief conducted in England by Braithwaite and Cooper best illustrates the effects of brand names. In this experiment, there were four groups. Group A received a placebo labeled analgesic, group B received a placebo labeled with a brand name, group C received aspirin labeled analgesic, and group D received aspirin labeled with a brand name. The results showed that aspirin worked better than the placebos. However in comparing groups A and B, which both received placebos, the placebos labeled with a brand name greatly surpasses the effects of the placebo labeled analgesic.
Interactions between a physician and patient can greatly alter how any medical treatments are perceived. This is especially true with the use of placebos.
- In an experiment to measure the placebo effects upon removal of wisdom teeth, both patients and physicians were observed in the study. A drug called fentanyl, a pain killer, was used during this study. The physicians were informed that due to complications, the drug was not working correctly. After a week, the physicians were then informed that the drug was fixed. In both scenarios the fentanyl was actually a placebo. However, in the former study when the physicians “knew” the drug was ineffective, the pain of the patients was much greater than when the physicians “knew” the drug was effective. In turn, it can be concluded that physicians’ knowledge of the drug can cause a reaction in the patient without either group being aware.
- Additionally, the diagnosis can alter the effects of a placebo. During a study, patients in one group were given a “positive” consultation while others were given a “negative” consultation. While both groups received an inert drug, the group with the positive consultation had a 64% improvement while the group with the negative consultation only had a 39% improvement.
Patient knowledge and education often leads to an anticipated result. Acupuncture is a well-known procedure to stabilize the chi. It is sometimes used after surgeries to prevent nausea from the anesthesia. In circumstances in which the patient was unaware of the use, the acupuncture did not work. However, when the participant was aware of the procedure and had a good fundamental understanding of the technique, the outcome was successful. Thus a patient must understand how a drug works in order to completely experience the effects.
In different countries, different medical procedures and diagnoses are more common than others. For example, the US experiences a great deal of viral infection not experienced by other parts of the world. “Chinese-Americans, but not whites, die significantly earlier than normal (1.3-4.9 yr) if they have a combination of disease and birth year which Chinese astrology and medicine consider ill fated”.
Drugs tested in different parts of the world yielded different results. For example, a drug to reduce ulcers was tested in France with 76% positive results from drug treated participants and 59% positive results from placebo treated participants. However, when the same drug was tested in Brazil, 60% yielded a positive result among drug treated participants while only 10% yielded positive results among placebo treated participants.
Because the placebo effect rely on deception and misinformation that is subjective to the patients' experience, the placebo effects are inherently difficult to control and could have serious ethical consequences when applied improperly. The "Placebo Paradox" is also an interesting ethical issue; it may be unethical to deceive patients but it is also unethical to use a treatment that cures . Additionally, many companies profit from the sale of placebos to the public, raising questions about the regulation of advertising and distribution of substances that do not actually have an active component.
The Use of Placebos in MedicineEdit
A NIH survey suggests that over half (57%) of general physicians regularly prescribed placebos . However, there are no documented cases of doctors purposefully prescribing placebos for moderate to serious health threats that would require surgery or comparably aggressive treatments .
Prescribing placebos can undermine the doctor-patient relationship and violate the patients' autonomy. Sometimes, doctors could misjudge the severity of the illness and prescribe a placebo when the actual medication is necessary for the patients' health. On the other hand, people suffering from various level of hypochondriasis have imagined illnesses and symptoms that would only require a placebo to cure and prescribing them actual medication could be harmful to their health.
The Use of Placebos in Medical StudiesEdit
In certain clinical trials, the researchers implement a placebo-controlled study, where a control group is given a sham treatment. The purpose of these studies is to determine the effectiveness of the drug by controlling for the placebo effect. This eliminates the possibility that a positive outcome of the study will be merely a result of the placebo effect, rather than the actual efficacy of the active drug ingredient(s). The use of placebo-controlled studies has become standard practice, and regulatory agencies will not even approve the use of a drug if its effectiveness is not proven to be greater than that of a placebo or no treatment at all. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research ethics committee has approved the use of placebos in these trials even though the researchers know that the placebo is not expected to be the optimal treatment.
A 1980 Harvard Medical School study  was designed to test the effectiveness of aspirin in preventing myocardial infarction, or heart attacks. In a 2x2 factorial study, one group was given an active aspirin and active beta-carotene, one group was given an aspirin placebo and active beta-carotene, one group was giving active aspirin and a beta-carotene placebo, and the last group was given placebos of both compounds. The subjects submitted blood samples and filled out semi-annual questionnaires, and the researchers tracked deaths and health complications within the sample. After 9 years, it was found that the active aspirin caused a 44% decrease in heart attacks, and the aspirin placebo control groups was taken off the placebo and given aspirin for the remainder of the study. If the Harvard researchers had allowed the study to run its full course, they would have had a more complete and statistically robust body of data, but instead they chose to remove a controlled portion of the experiment when it became clear that regular active aspirin intake had beneficial health consequences.
Legal Accountability of Private CitizensEdit
In 2009, a husband and wife in Wisconsin were sentenced to 6 months in jail for the second-degree homicide of their 11-month old daughter. The daughter had an undiagnosed but treatable form of diabetes, and rather than seeking medical attention the couple chose to pray for their daughter and therefore became complicit in her eventual death. While there is conflicting evidence over the effectiveness of prayer for healing medical conditions, the court decided that the parents' actions were sufficiently negligent to warrant a prison sentence. Unfortunately, there are similar cases all around the world.
These cases represent situations where the placebo effect could not be in play in the way that any research has suggested; the patients were too young to have consciously known that they were being given medicine, and unsurprisingly their symptoms showed no signed of improvement. The adults in these cases were held accountable and punished for using known placebo treatments, even though they actually believed in the potency of their respective approaches. This contrasts with the cases where consenting adults made the choice of pursuing nontraditional treatments over modern medicine themselves and eventually suffered grave injury or death . It is unlikely that any of the people who died as a result of eschewing modern medicine in favor of unproven treatments did so with the belief that the alternative treatments were ineffective. However, with few exceptions, there have been no instances of homeopathic or traditional, non-doctor healers being given prison sentences for these deaths or injuries. The cases where jail time or fines were given were for situations that clearly involved gross negligence or outright fraud on the part of the practitioner.
In the United States, the FDA regulates the types of claims and advertising any sort of health product can make. However, it places regulatory priority on ineffective or unproven products which claim to heal serious conditions like cancer or AIDS, which are presumably more of a threat to public health because they could deceive people into not using known reliable treatments. Many forms of nontraditional medicines such as homeopathic remedies, magnetic bracelets, and herbal medicines and supplements are permitted to make broad statements about general health and pain relief even when there is no scientific evidence for their claims.
It is quite evident that we don't fully understand how Placebos work and function. We do recognize the powerful effects that it has on people and we should use caution and sound ethical judgement when it comes to applying technology that has the placebo effect in society. Lying may perhaps be always wrong, but the placebo effect clearly demonstrates that lying could better benefit society.
What is the Nocebo effect?Edit
The term nocebo (Latin for "I will harm") was first described by Walter Kennedy (1961), and it refers to the opposite of the term placebo (Latin for "I will please"). In a broad sense, a placebo is a substance (inert or active) that produces a beneficial effect in a subject—because the subject believes/expects it will do so (Stewart-Williams & Podd, 2004). Thus, nocebo can be a troublesome reaction to both real, or sham treatment. The term nocebo is often used interchangeably with non-specific side effect; the symptoms are individual and they do not dependent upon the administered dose of medication (Barsky et al 2002). Kennedy (1961) also stated that nocebo reactions should never be mixed up with the true pharmacological effects; the nocebo-effect is completely produced by the subject/patient. Consequently, not all symptoms/side-effects that occur after taking an active drug can be attributed to the drug. This has important consequences for medical treatment because adverse drug side effects often cause termination of medical treatment (Barsky et al 2002).
What main factors mediate the Nocebo effect?Edit
According to a review by Barsky et al. (2002), the main psychological mechanisms of the nocebo effect are not altogether understood, but seem to be connected to factors such as subconscious conditioning and conscious expectations. Personality factors are also worth acknowledging, and will be described in a later section. Patients who have had prior experience with adverse drug side effects can be conditioned to experience similar side effects at a later date. Liccardi at al. (2004) showed that previous experiences with adverse drug side effects were associated with heightened rate of nocebo-response in the future. Their study was conducted with 600 subjects who had a history of adverse side effects; 27% of the subjects experienced adverse non-specific side effects. Patients can also expect adverse effects if they read the long list of side effects accompanying medications, and also by recalling adverse side-effects experiences by others (Barsky et al. 2002). According to Enck et al. (2008 p. 195). “There do not seem to be only one psychobiological mechanism which can account for both the placebo and the nocebo phenomena in general. Different mechanisms seem to exist in which placebo and nocebo responses are steered across different diseases and experimental conditions.” A study by Benedetti et al. (1997) proposes that the neuropeptide cholecystokinin plays an important role in mediating the nocebo reaction. The researchers induced a nocebo-response in patients who reported mild postoperative pain. Patients agreed to increase the pain for 30 minutes, then they were given a saline solution (which does not affect pain) and told it would increase pain. A nocebo reaction was present when the inactive saline was given. However, if the cholecystokinin antagonist Proglumide was added to the saline solution, the nocebo response was absent. The researchers concluded that cholecystokinin mediated the pain increase/ nocebo response, and that this might be caused by a cholocystokinin-incuced increase in anxiety. Other researchers (e.g. Kim et al. 1998) have also emphasized the role of cholecystokinin in anxiety
The nocebo effect is a frequently occurring phenomenonEdit
The nocebo phenomenon is a common phenomenon in medical trials and also in treatment: Turner et al. (1994) showed that during placebo trials, the overall occurrence of adverse side effects in healthy volunteers was 19%. The study was a review of 109 double blind drug trials. An extensive overview of the role of expectancy in medical treatment is given by Benedetti (2009), and empirical findings on this matter are considered robust. According to a study by Mondaini et al. (2007) patients who were told about the sexual side effects of a prostate medication, reported higher sexual dysfunction compared to those who did not receive such information. A noticeable effect of negative expectations was shown by Hahn (1997); 80% of the subjects (hospitalized patients) given sugar water and told that the solution would induce vomiting, subsequently vomited. In a famous study by Schweiger et al. (1981), the researchers sent a “nonexisting” electric current through the head of student participants. 70% of the students subsequently reported headaches. These empirical accounts show that side effects are highly dependent upon the beliefs and expectations of the person. For the most part it seems like nocebo effects are mild and transient, however serious cases have been reported. Cannon (1942) describes a phenomenon that he called “voodoo death”. This appears to be a nocebo-effect turning fatal; a person who was cast a spell on, died shortly after. No organic causes could be found. Cannons work has indeed increased our modern understanding of how extreme stress caused by negative expectations can result in (fatal) illness.
Personality factors contributing to the nocebo effectEdit
The personality dimension of neuroticism seems to play an important role in nocebo proneness. Neuroticism, or negative affectivity, refers to a dimension of personality consisting of chronic negative emotions including sadness, anxiety, guilt, and anger. Moreover, neuroticism is associated with cognitive and behavioral characteristics such as low self-esteem, preoccupation, and insecurity (Digman, 1986). It is worth noting that neuroticism refers to normal individual differences, and does not imply a psychiatric diagnosis. Neuroticism is a personality dimension included in the well-acknowledged “Big 5” personality theory, and it is regarded as a fundamental trait that is stable over time (Costa & McCrae, 1987). Neuroticism appears to be a clear predictor of the nocebo-response (Davis, 1995). Also Costa & McCrae (1985) observed that neuroticism is related to the number of symptoms patients report. Mills (2006) compared measures of introversion, neuroticism and psychoticism, and found that individuals who were prone to nocebo effects had significantly higher scores on the neuroticism measure. Rief et al. (2006) suggest that neuroticism is associated with a tendency to reattribute general physical symptoms to causes such as drug side effect. Consequently, the nocebo effect could be explained as a reappraisal of already existing bodily symptoms. Khosla et al. (1992; as sited in Barsky 2002), found that 73% of 236 healthy volunteers—who were not taking medications—reported symptoms during a three-day study. The most common symptoms were fatigue, headache, and difficulty concentrating. Thus, when a patient starts taking a medication, there exist various normal/everyday symptoms that can easily be ascribed to the drug. Research linking the nocebo effect to anxiety (which is a key component of neuroticism) is steadily increasing: a study conducted on normal healthy research volunteers (NHRVs) showed that those with a high anxiety score displayed more adverse side-effects after taking the drug than those with low anxiety score (Tishler et al., 2005). Uhlenhuth et al. (1998) showed that anxious patients who had to change medication regime, frequently generated anxiety symptoms which they subsequently attributed to the medication; this tendency was stronger for patients prone to somatization. The influence of negative emotions on pain has been subjected to a lot of study (e.g. Wiech, 2009). Negative moods and emotions can cause pain or aggravate existing pain (Barsky & Klerman, 1983). Physicians have observed that the side effects reported by anxious patients often resemble the symptoms of anxiety itself; e.g. tachycardia, dyspnoea and sweating (Ferguson et al, 1993). Barsky et al (1999) have noted that a tendency toward a somatic style is related to a greater experience of non-specific side effects. “Somatic style includes: hypochondriac attitudes, somatic amplification (propensity to experience bodily sensations in general, including non-pathological bodily discomfort and normal physiological sensations- as noxious, alarming and abnormal), bodily absorption (deep involvement in sensory and imagined events, and somatization (tendency to report medically unexplainable symptoms).” (Barsky et al. 1999, P.397). Barsky et al (1988) reported that amplification was intimately related to measures of depression, anxiety and hostility.
The personality aspect of optimism/pessimism also seems to be related to the nocebo phenomenon. Although pessimism is related to other aspects of negative emotionality, particularly depression—it may also have components that are distinct (John et al., 2008) Thus; this personality aspect will be approached separately from neuroticism. Geers et al. (2005) conducted a study in which optimists and pessimists were randomly assigned into three different groups. In the first group, the subjects were given a pill, and told it would make them feel unpleasant (deceptive-expectation group). The second group, the subjects were made to believe the pill would make them feel either unpleasant or that it was an inert substance (conditional-expectation group). The final group was told they would get an inactive pill (control group). It turned out that pessimists were more likely than optimists to display a nocebo-effect when they were given a deceptive expectation, but not when given a conditional expectation. Hence, the researchers concluded that the variable of optimism–pessimism is connected to the nocebo response when individuals are given a deceptive but not a conditional expectation. This finding implies that personality and situational variables interact when it comes to nocebo responding. A subsequent study (Geers et. al, 2007) showed a positive association between optimism and response to placebo expectation. The same study also showed that as optimism increased, the nocebo response decreased.
The Nocebo effect in relation to gender and ageEdit
Effects of gender and age on the nocebo response have also been a topic of interest to researchers, however the findings are not robust and more research is needed (Rief et al 2008). One of the first to propose a female tendency for reporting more side effects was Green (1962). According to him, both the variety and frequency of side-effect symptoms were larger in women. A review of clinical trials with antidepressants showed that women reported slightly more non-specific symptoms than men (Casper et al. 2001). Klosterhalfen et al. (2008) found that women showed a stronger nocebo reaction to conditioning, while men were more likely to display a nocebo reaction as a result of expectancies (but to a lesser degree). An Italian study (Liccardi at al., 2004) also found greater nocebo propensity in women. 30% of women reported nocebo reactions, while only 19% of the male participants reported such adverse reactions. Spriet (1977) surveyed private practitioners and found that women reported more side effects: (15.2%) as compared to (11.9%) in males. Strohle, (2000) reported an increased nocebo-response in female patients diagnosed with panic disorder. An interesting sex-differrence was shown by Pennebaker (1982). A mediating variable in the non-specific symptom report was the time frame of the symptom measure. Women were found to report more symptoms than men only when the symptoms were measured in retrospect. When participants were asked to rate symptoms they were feeling at the moment (i.e. by using symptom checklists), no sex difference could be found. According to Gijsbers et.al. (1996) women score higher than men on negative affectivity measures. Watson and Pennebaker (1989) found an association between negative affectivity and reporting somatic symptoms. Correlations ranged from 0.4-0.53. Such research findings can thus be an indirect indicator of the heightened nocebo tendency in women. Perhaps the strongest “evidence” for the female propensity of reporting more side effects was found in a study conducted by Passalacqua et al. (2002). They found that 72% of their female subjects reported non-specific adverse side effects. A small number of studies suggest that elderly people are more likely to experience nocebo effect. Rosenzweig et al. (1993) reviewed 109 double-blind placebo studies including 1228 healthy volunteers, and found that the rate of reported adverse side effects were significantly higher amongst the elderly. Another study that was able to show an age difference in reporting nocebo-effects was conducted by Spriet (1977). According to this research, 10, 5% of patients under the age of 30 reported side effects, while the percentage rose to 16.3% for those patients over the age of 80. However, Costa & McCrae (1985) points out that data suggesting that hypochondrias is more pronounced in the elderly generation are likely to be bewildered, because increasing health problems are a natural result of increasing age. Moreover the researchers suggest that stable traits, such as neuroticism, are more useful than the person’s age when interpreting health complaints such as non-specific symptoms. In addition McCrae & Costa (1982) found that neuroticism (and thus the propensity to report non-specific side-effects) does not increase with age. Another study (Amanzino et al.2009) also concluded that age is not a relevant variable when it comes to reporting non-specific side effects. In sum, various factors contribute to the nocebo phenomenon; both situational and dispositional. Research linking nocebo-proneness to the personality trait of neuroticism is considered robust. Factors such as pessimism and a tendency toward a somatic style are associated with greater experience of non-specific side effects. The empirical literature shows a tendency toward a female propensity to nocebo reactions, but findings suggesting an effect of age are speculative.
Suggestions to handle/ameliorate nocebo reactionsEdit
It is a well-known fact that some of the beneficial effects of a drug can be attributed to the placebo effect, and some of the adverse non-specific effects can be attributed to the nocebo effect. Thus, when taking an active medication, some patients might report troublesome side effects because certain aspects of their personality or the nature of the situation lead them to. The nocebo effect has important medical implications in the sense that is can lead to non-adherence to medical treatment (Barsky et al 2002).
It is important for the treating physician to be aware of a potential nocebo-reaction, and not instantly attribute the non-specific adverse symptoms to the pharmacological action of the drug. According to Rief et al (2006) as much as 50% of the patients who discontinue pharmacological treatment might do so because of the nocebo phenomenon. Thus, awareness of a potential nocebo response can influence the physician’s decision to continue/discontinue treatment. Barsky et al (2002) suggests that if symptoms are especially vague or if they are typical “everyday life symptoms”, the physician should be extra suspicious of a nocebo-reaction. Such vague, everyday symptoms typically include fatigue, headache, concentration problems and nausea. Also, the physician should suspect a nocebo response if the patient has a clinical history of adverse side effects, or is overly anxious about the drug treatment and seems to expect negative side-effects.
In order to decrease the prevalence of non-specific side-effects, Barsky et al (2002) suggests that physicians should take patient variables such as neuroticism and somatization tendency into account and offer these “risky” patients extra help in comprehending, ignoring or enduring such non-specific symptoms. Asking patients in advance about prior experiences with medication is also recommendable, and bringing to the patients attention that expecting adverse side-effects can directly or indirectly causes itself to become true (self-fulfilling prophecy). Evans (2003) propose that physicians can help patients reinterpret adverse side-effects in a positive way by emphasizing that such symptoms shows that the medication is working. It is quite clear that patients who are prone to experiencing nocebo-effects (such as those with a history of mood disorders and anxiety) need to be met with extra consideration and care. Anxious patients are usually very attentive to potential harm, and adverse side effects can represent a major threat to these patients perception of control. Flaten at al (1999) calls physicians attention to the way they present the medication to the patient. If the treating physician predicts adverse side effects, a nocebo effect is more likely to take place. This has also been demonstrated by Myers et al. (1987), who observed that subjects who were warned about the common side-effects of Aspirin, were nearly three times as likely to report such side-effects. As previously mentioned, the role of expecting specific types of adverse side-effects and experiencing nocebo effect has been demonstrated by numerous researchers; e.g. Amanzino et al. (2009), Mondaini et al. (2007), Benedetti et al. (2003), and Hahn (1997). Thus, physicians should be very considerate when presenting a potential medication to a patient. It is important to achieve an optimum compromise between the ethical obligations to inform patients about expected adverse effects, and the need to reduce a nocebo expectancy effect. However, it is a delicate balance between identifying those patients most at risk of developing nocebo-effects (e.g. patients prone to neuroticism), and overgeneralization. It might be a wise choice to keep patient factors “in the back of ones head”, in addition to consulting medical literature and clinical experience with the drugs. Some researchers (e.g. Varga, 2001) have pointed out that health care professionals such as physicians and nurses could—to a greater extent—prevent non-specific side effects by being more sensitive to the individual patient, and becoming more conscious of the way in which they communicate. Many patients often have an increased level of anxiety and worrying when visiting their GP`s office, or a hospital. This state can in some sense resemble an altered state of consciousness in which the patient is more susceptible to suggestions; both positive and negative suggestions (Varga, 2011). Medical professionals use suggestive communication all day long—but most are not even aware of it. The words we use and the way we formulate sentences in the therapeutic relationship can indeed affect somatic processes. Casual negatively loaded remarks and well intended advice could sometimes have a very negative impact on the patient (Bejenke, 2010, as sited in Varga 2011). Reframing is a suggestive communicative strategy in which a different and positive interpretation is offered. As previously mentioned, Evans (2003) suggested interpreting side effects as a good thing: just a sign that the medication is working. In order for suggestive communication to work, rapport must be established between the physician and the patient. According to Hall (2009; as sited in Varga 2011) higher patient/physician rapport was achieved when the physician gave more positive statements, showed a respectful and “warm” attitude, showed undivided attention, and did not interrupt the patient. Also greeting the patient by the name is an important factor in rapport formation (one would think that is quite obvious, but it is seems like it is not!). An extensive overview of suggestive communicative techniques in the prevention/amelioration of non-specific side effects is beyond the scope of this text.
- Moerman, D.E. (2002). Meaning, medicine and the ‘placebo effect’. New York, NY: Cambridge University Press.
- FDA (2010, April 1). CFR – code of federal regulations title 21. Retrieved October 31, 2010, from http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm
- Reagan, J., Hamer, G., Wright, A., Armour, A., & Fu, J. (2005). The placebo: promise and compromise. Tennessee Medicine, 138-139.
- Gray, P. (2007). Psychology. New York: Worth Publishers.
- Silberman, S. (2009, August 24). Placebos are getting more effective. Drugmakers are desperate to know why. Wired Magazine. Retrieved November 8, 2010 from http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo_effect?currentPage=all
- Fox, M. (2008, March 4). Expensive sugar pills work better than cheap ones. Reuters. Retrieved October 31, 2010 from http://www.reuters.com/article/idUSN0446808020080304
- Blackwell, B., Bloomfield, S.S., & Buncher C.R. (1972). Demonstration to medical students of placebo responses and non-drug factors. Lancet, 1, 1279-1282.
- Grenfell, R.F, Briggs, C.J., & Holland, W.C. (1961). A double-blind study of the treatment of hypertension. Journal of the American Medical Association, 176, 124-128.
- Braithwaite, A., & Cooper, P. Analgesic effects of branding in treatment of headaches. British Medical Journal, 282, 1576-1578.
- Gracely, R.H., Dubner, R., Deeter, W.R., & Wolskee, P.J. (1985). Clinicians’ expectations influence placebo analgesia. Lancet, 1, 43.
- Thomas, K.B. (1987). General practice consultations: is there any point in being positive? British Medical Journal, 294, 1200-1202.
- Phillips, D.P., Ruth, T.E., & Wagner, L.M. (1993). Psychology an survival. Lancet, 342(8880), 1142-1145.
- Lambert, R., Bader, J.P., Bernier, J.J., Bertrand, J., Betourne, C., Gastard, J., Laverdant, C., Ribet, A., Sahel, J., & Toulet, J. (1977). Treatment of duodenal and gastric ulcer with cimetidine. A multicenter double-bind trial. Gastroenteroloie Clinique Et Biologique, 1, 855-860.
- Salgado, J.A., de Oliveira, C.A., Lima Jr., G.F., & de Paula Castro, L. (1981). Endoscopic findings after antacid, cimetidine and placebo for peptic ulcer-importance of staging the lesions. Arquivos De Gastroenterologia, 18, 51-53.
- David H. Newman (2008). Hippocrates' Shadow. Scribner. pp. 134–159. ISBN 1-4165-5153-0.
- BMJ-British Medical Journal (2008, October 25). U.S. Doctors Regularly Prescribe Real Drugs As Placebo Treatments, Study Claims.ScienceDaily. Retrieved December 3, 2010, from http://www.sciencedaily.com/releases/2008/10/081023195216.htm.
- Physicians' health study i. (2009). Informally published manuscript, Department of Biomedical Research, Harvard University, Cambridge, Massachusetts. Retrieved from http://phs.bwh.harvard.edu/phs1.htm
- Imrie, R. (2009, October 6). Couple get 6-month jail sentence in prayer death. JSOnline, Retrieved from http://www.jsonline.com/news/wisconsin/63632882.html
- Brandeis University (2009, June 18). The Healing Power Of Prayer?. ScienceDaily. Retrieved December 3, 2010, from http://www.sciencedaily.com/releases/2009/06/090617154401.htm
- What's the harm?. (n.d.). Retrieved from http://whatstheharm.net/alternativemedicine.html
- Hepatitis outbreak gp struck off. (2000, November 15).BBC News, Retrieved from http://news.bbc.co.uk/2/hi/health/1024753.stm#top
- Arena, S. (2000, November 15). Cancer doc hit for $2.5m-plus.NY Daily News, Retrieved from http://www.nydailynews.com/archives/news/1997/03/31/1997-03-31_cancer_doc_hit_for__2_5m-plus.html
- Barrett, S. (2009). Homeopathy: the ultimate fake. Retrieved from http://www.quackwatch.org/01QuackeryRelatedTopics/homeo.html
Amanzino, M., Corazzini, L.L., Vase, L and Benedetti, F. (2009) A systematic review of Adverse events in placebo group of anti-migraine clinical trails. Pain, 146:261-269
Barsky, A.J., Klerman, G.L (1983) Overview: Hypochondriasis, bodily complaints, and somatic styles. American Journal of Psychiatry, 140: 273-283
Barsky, A.J., Goodson, J.D., Lane, R.S., Cleary, P.D. (1988) The amplification of somatic symptoms. Psychosomatic Medicine, 50: 510-519
Barsky, A.J., Orav, J.E., Ahem, D.K., et al (1999) Somatic style and symptom reporting in rheumatoid arthritis. Psychosomatics, 40: 396-403
Barsky, A.J., Saintfort, R., Rogers, M.P. & Borus, J.F. (2002) Nonspecific Medication Side Effects and the Nocebo Phenomenon, Journal of the American Medical Association, 287(5): 622-627
Benedetti, F., Amanzio, M., Casadio, C et al. (1997) Blockade of nocebo hyperalgesia by Cholecystokinin antagonist Proglumide. Pain, 71: 135-140.
Benedetti, F., Pollo, A, Lopiano, L et al. (2003) Conscious Expectations and Unconscious Conditioning in Analgesic, Motor, and Hormonal Placebo/Nocebo Responses The Journal of Neoroscience, 23(10): 4315-4323
Benedetti, F. (2009) Placebo Effects: Understanding the mechanisms in health and disease. New York: Oxford University Press
Cannon, W.B. (1942) “Voodoo” American Anthropologist, 44(2): 169-181
Casper, R.C., Tollefson, G.D., Nilsson, M.E. (2001) No gender differences in placebo responses of patients with major depressive disorder. Biol Psychiatry ;49:158-160.
Costa, P.T, McCrae, R. R. (1985). Hypochondriasis, Neuroticism, and Aging: When are Somatic Complaints Unfounded. American Psychologict, 40: 19-28
Costa, P.T, McCrae, R. R. (1987). Neuroticism, somatic complaints, and disease: Is the bark worse than the bite? Journal of 'Personality, 55, 299-316.
Davis, C., Ralevski, E., Kennedy, S.H., Neitzert, C. (1995). The role of personality factors in reporting of side effect complaints to moclobemide and placebo: a study of healthy male and female volunteers. Journal of Clinical Psychopharmacology, 15: 347-352
Digman, J. M., Inouye, J. (1986). Further specification of the five robust factors of personality. Journal of Personality and Social Psychology, 50, 116-123.
Enck, P., Benedetti, F., Schedlowski, M (2008) New insights into the Placebo and Nocebo Responses. Neuron, 59(2): 195-206)
Evans, R. (2003) Letter to the editor: The nocebo-response: Can Migrane Medication Efficacy be Enhanced. Headache, 43(6): 693
Ferguson, J.M. (1993) Alprazolam XR: patient acceptability, safety, and tolerability. Psychiatry Annual, 23: 20-26
Flaten, M.A., Simonsen, T., Olsen, H. (1999) Drug related information generates placebo & Nocebo responses that modify the drug response. Psychosomatic Med., 61: 250-255
Geers, A., Helfer, S., Kosbab, K., Weiland, P., Landry, S. (2005) Reconsidering the role of personality in placebo effects: Dispositional optimism, situational expectations, the placebo response. Journal of Psychosomatic Research, 58(2): 121-127
Geers, A., Kosbab, K., Helfer, S. (2007) Further evidence for individual differences in placebo responding: An interactionist perspective. Journal of Psychosomatic Research, 62(5): 563-570
Gijsbers van Wijk, C.M., Kolk, A.M. (1996) Psychometric Evaluation Of Symptom Perception Related Measures. Person. Individ. Diff., 20(1):55-70
Green, D.M (1962) Side effects. Federation Proceedings, 21:179
Hahn, R.A. (1997) The Nocebo Phenomenon: The Concept, Evidence, and Implications for Public Health. Preventive Medicine, 26(5): 607-611
John, O.P., Robins, R.N., Pervin, L.A. (2008) Personality and Health: A Lifespan Perspective. In: Handbook of Personality: Theory & Research. (pp.770-794) NewYork: The Guilford Press
Kennedy, W.P. (1961) The Nocebo reaction. Medical World: 95, 203-205
Kim, Y.H., Shim. J.C. (1998) Neuropeptides in Clinical Psychiatric Research: Endorphins and Cholecystokinins. Korean Journal of Biological Psychiatry, 5(1): 34-45
Klosterhalfen, S., Kellermann, S., Braun, S., Kowalski, A., Schrauth, M., Zipfel, S., Enck, P. (2008) Gender and the nocebo response following conditioning and expectancy. Journal of Psychosomatic Research, Journal of Psychosomatic Research, 66(4): 323-328
Liccardi G, Senna G, Russo M, Bonadonna P, Crivellaro M, Dama A, et al. (2004) Evaluation of the nocebo effect during oral challenge in patients with adverse drug reactions. J Investig Allergol Clin Immunol;14:104-107.
McCrae R.R., Costa, P.T. (1982) Self-concept and the stability of personality: Cross-sectional Comparisons of self reports and ratings. Journal of Personality and Social Psychology, 43: 1282-1292
Mills, B.S. (2006) The nocebo effect: Identification of discrete causal personality traits in a nonclinical population. Dissertation, Regent University, 87 pages.
Mondaini, N., Gontero, P., Giubilei, G. et al. (2007) Finasteride 5mg and Sexual Side Effects: How Many of these are Related to a Nocebo Phenomenon? Journal of Sexual Medicine, 4: 1708-1712
Myers, M.G, Cairns J.A, Singer J. (1987) The consent form as a possible cause of side effects. Clin Pharmacol Ther ;42:250-253.
Passalacqua, G., Milanese, M., Mincarini, M. et al. (2002) Single-Dose Oral Tolerance Test with Alternative Compounds for the Management of Adverse Reactions to Drugs. Allergy Immunol. 129: 242-247
Pennebaker, J.W., Brittingham, G.L. (1982) Environmental and sensory cues affecting the perception of physical symptoms. In Baum A. & Singer J.E (Eds.), Advances in environmental psychology: Environmental health. (Vol. 4, pp. 115-136). Hillsdale, HJ: Erlbaum
Rief, W., Avorn, J., Barsky, A.J. (2006) Medication-attributed adverse effect in placebo groups. Implications for assessment of adverse effects. Archives of Internal Medicine, 166(2): 155-160)
Rief, W., Hofmann, S.G , Nestoriuc, Y. (2008) The power of Expectation- Understanding the Placebo and Nocebo Phenomenon. Social and Personality Psychology Compass 2(4): 1624-1637
Rosenzweig P, Brohier S, Zipfel A. (1993) The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. Clin Pharmacol Ther ; 54:578-583.
Schweiger, A., Parducci, A. (1981) Nocebo: the psychological induction of pain. Pav J Biol Sci, 16: 140-143
Spriet, A., Spriet, C., Larousse, D., Chigot, M., Simon, P. (1977) Methodology and results of a survey of adverse reactions to drugs in private practice. Eur Clin Pharmacol, 11: 181-192
Stewart-Williams, S., Podd, J. (2004) The Placebo effect: Dissolving the Expectancy Versus Conditioning Debate. Psychological Bulletin 130(2) 324-340.
Strohle, A. (2000) Increased response to a putative panicogenic nocebo administration in female patients with panic disorder. J Psychiatr. Res, 34: 439-442
Tishler, C., Bartholomae, S., Rhodes, A. (2005) Personality profiles of normal healthy volunteers: a potential concern for clinical drug-trial investigations. Medical Hypotheses, 65(1): 1-7
Turner, J. A., Deyo, R. A., Loeser, J. D., Von Korft, M., Fordyce, W.E. (1994) The Importance of Placebo Effects in Pain Treatment and Research. Journal of the American Medical Association, 271(20): 1609-1614
Uhlenhuth, E.H., Alexander, P.E., Dempsey, G.M. et al. (1998) Medication side-effects in anxious patients: Negative placebo responses? Journal of Affective Disorders, 47: 183-190
Varga,.K (Ed.) (2011) Beyond the Words: Communication and Suggestion in Medical Practice. New York: Nova Science Publishers, Inc.
Watson, D., Pennebaker, J.W. (1989) Health complaints, stress and distress: Exploring the central role of negative affectivity. Psychological Review, 96: 234-254
Wiech, K., Tracey, I. (2009) The influence on negative emotions on pain: Behavioral effects and neural mechanisms. NeuroImage, 47(3): 987-94