Do cultures influence placebo response?

Individuals are born in, work in and live in cultures, which have a profound effect on their lives and functioning. Cultures determine cognitive schema and also how individuals express and deal with distress – whether it is physical or emotional. Cultures determine explanatory models of illness that individuals hold and allocate health resources as well as encourage individuals to follow certain pathways into care and accept or reject health care. Cultural variations in presentation of various psychiatric disorders have been studied, but not treatment responses as widely. It is inevitable that dietary habits, simultaneous use of alternative and complementary medicines and other factors such as pharmacodynamics and pharmacokinetics play a major role in acceptance of pharmaceutical agents and treatment outcomes across cultures. In various cultural settings, patients and their carers have varying expectations. In this editorial, we explore the role of placebo response. The placebo response itself is affected by a number of factors 1. These include colour, name, appearance, route of administration of drugs as well as personality traits of patients 2. Both classical conditioning 3 and information processing 4 have been described as influencing placebo effect. The term placebo derives from Latin, with its literal meaning being 'I please'. Placebos have been used for millennia and the term carries multiple meanings and interpretations 5. The term does carry negative meanings as well 6. It has been argued that in spite of its perceived 'inertness', patients do get better 7. These authors note that Beecher's original observation 8 that placebo may work as a psychological instrument and as a resource for the doctor and to study the mechanisms of drug action still stands. From the early days of randomised controlled trials where placebos and 'active' medications were compared, the actual impact of placebo has not been clear, and some of the reasons for this are described below. Placebos have been used as controls 9. Price et al. 10 define the placebo effect as the average placebo response in a group of individuals and a placebo response as the change in symptom or condition occurring as a result of placebo. Media and lay interpretations of placebo play an important role in its acceptance. Culture itself is described as the milieu within which one is brought up and has distinct frameworks, values and systems which not only give the individual a sense of belonging but also provide a sense of world view and values. It is critical that we bear in mind that individuals carry multiple cultural identities or micro-identities, which may reflect in a number of ways, such as gender, institutions, workplace and sexual orientation. Cultures determine cognitive schema and interpretation of symbols of relevance and importance within that culture. This is the crux of understanding placebo response. However, this aspect of placebo response must be seen in the context of how patients perceive their illness experiences – what names and explanatory models they give to it, but also the actual therapeutic communication and encounter. It is clear that all these are strongly affected by cultures. Disease and illness: Doctors are trained to diagnose and treat diseases, whereas the social impact of diseases is embedded in illnesses. Doctors focus on organs and their dysfunction, whereas patients see the impact of disease in their states of being and social function 11. Diseases and illnesses do not map distinctly onto each other 12. Thus, seeing the social implications in the cultural context is important. It is also likely that patients are keen to seek healing for their illnesses and these may be more attractive because they take into account individual models of distress 13. Cultures also influence explanatory models and Kleinman 13 noted that in Taiwan patients expected allopathic doctors to provide injections, whereas Chinese doctors were expected to provide herbal treatments, thus highlighting different expectations. Culture and Placebo: It has been argued that placebos affect the illness more than they affect the disease 14. Classical conditioning 15 and expectancy 16 are key aspects of placebo response. Thompson et al. see expectancy as the patient's level of expectation that they will be helped by the treatment. These authors argue that expectancy is a fairly robust and comprehensive model, thereby recognising the importance of the therapeutic context through supporting expectancy and triggering a placebo effect. In order to kick off such responses, verbal instructions play a role, thus confirming the role of communication in therapeutic engagement. In many cultures, patients expect their doctors to make the right decisions and look after them, making the responsibility clear, whereas in others, patients want to be given information and expect joint decision-making where they have equal say. Thompson et al. 7 suggest that a related concept to expectancy is self-efficacy. This depends upon the belief that one can successfully perform actions needed to achieve valued outcomes. Caspi 17 puts forward a model which sees the therapeutic relationship between clinician and patient as the key trigger to placebo response. Caspi 17 proposes that clinicians may thus use the process of the therapeutic encounter to reframe the patient's concerns and health status in ways that can instil hope. Brody 18 argues that the practitioner plays a key role in providing an explanation of what is wrong with the patient and holding out a promise for the patient that no matter how bad things are, they will get better. This dealing with ambiguity and holding hope for the patient are key responsibilities of the psychiatrist 19. The key is what meaning patients give to their experiences and distress which are culturally influenced. Two explanations have been offered in understanding the placebo effect – its dynamic effect and, secondly, that the placebo effect interacts synergistically with other therapeutic elements 20. Placebo effect has also been seen as offering a meaning response, which means the psychological or physiological effects of meaning in treatment of illness 21. Visual perceptions and world views differ across cultures, and the links between biology and culture require further exploration. It is possible that cultural variations in pharmacodynamics and pharmacokinetics will affect responses to placebo. Colour of medication: Patients' compliance of medication and treatment is strongly influenced by the role (they think) medicine plays 22. The size and colour of the tablets are significant factors. Blue is seen as depressant-sedative, and yellow as stimulant antidepressants 23. Blue preparations are more soothing; and red, pink or yellow as more stimulating 24. De Craen et al. 25 confirmed that stimulation was associated with medicine which was marketed in hot colours (red, orange, yellow), and antidepressants were marketed in cold colours (blue, green, purple). In a study with volunteer medical students, similar observations were made 26. Expectations thus drive the placebo effect 27. Where patients see their illness as hot or cold, they will only accept medication which deals with the heat or cold. Buckalew and Coffield 23 demonstrated that white capsules were seen as analgesics by Caucasians, but as stimulants by African Americans, whereas black capsules were seen as stimulants by Caucasians and as analgesics by African Americans. Interestingly, among passive individuals who were intellectually oriented, sedative agents produced higher (than expected) levels of sedation 2. Regrettably, in drug trials, these factors are not taken into account. It has been demonstrated that holidays and year of birth play a role in patient responses 28, but drug trials do not appear to take these factors into account. In clinical practice a few decades ago, Neki et al. (29, 30) observed that African patients had varying expectations from psychiatrists in comparison with shamans who offered traditional healing practices. In African cultures, there was a clearly observed discrepancy between the African illness and expectations from European clinicians. The challenge for modern psychiatry is to look at cultural variations and cultural differences and place these in the context of clinical practice, patient expectations and therapeutic encounters. Ninnemann 31 raises some interesting points about the role of ethnopsychopharmacology in placebo effects. There is no doubt that discussion of ethnic and racial differences and identities are charged with irrational emotions. The emphasis on genomics and development of psychopharmacogenomics raises some significant issues, and cultural differences therefore deserve further exploration in the cultural, sociological and anthropological contexts. Kleinman 32 noted that, in spite of increasing data from treatment outcome studies on the effects of psychopharmacological medications, the evidence remains less impressive. He emphatically argues that cultural and psychosocial factors deserve more and better attention. Thus, there is a clear challenge for regulators like the Federal Drug Administration that any drug trials take into account psychosocial impact of drug trials and focus on cultural relativism. We know that drug trials previously conducted had recommended doses which were inappropriate for many ethnic groups. Now, as ever increasing numbers of trials are being conducted in eastern Europe, China and India, it will be of special interest to see whether recommended doses as a result of these trials will work for other ethnic populations elsewhere. In social and cultural psychiatry, numerous factors have often been ignored and require further exploration. It is important that medical and patient understanding of expectations of each other deserve further exploration, especially in drug trials. Healing, its meanings and its rituals, must be understood in the context of 'modern' allopathic medicine. Cultural symbols and their meanings, for example preference of some cultural groups for syrups or injections or capsules, have to be understood. All drug trials must explore these meanings while conducting the trials. A stronger positive effort is required to understand patient perspectives of their distress, their expectations of (therapeutic or otherwise) interventions and expectations of the therapeutic encounter itself. This requires cross-cultural work with many cultures in rapid transition as a consequence of globalisation, rapid industrialisation and urbanisation. Use of complementary and alternative medicines and their simultaneous use will further make therapeutic interactions complex. To conclude, cultural factors are at the heart of any individual's functioning. Therapeutic expectations and therapeutic responses need to be understood in the context of biocultural variations. The cultural meanings of symbols embedded in the medical treatment have to be explored and understood in order to achieve better therapeutic engagements and outcomes. Understanding patients' explanatory models, their expectations and pathways into care will provide better outcomes. Taking into account that more drug trials are being conducted in Eastern Europe and Asia, the time is ripe to explore mind–body interactions and pharmacokinetic and pharmacodynamics differences and place these in the context of placebo response. Dietary habits, smoking patterns and the use of other substances must be taken into account when conducting drug trials.