Search

Despite their ubiquitous presence, placebos and placebo effects retain an ambiguous and unsettling presence in biomedicine. Specifically focused on chronic pain, this review examines the effect of placebo treatment under three distinct frameworks: double blind, deception, and open label honestly prescribed. These specific conditions do not necessarily differentially modify placebo outcomes. Psychological, clinical, and neurological theories of placebo effects are scrutinized. In chronic pain, conscious expectation does not reliably predict placebo effects. A supportive patient-physician relationship may enhance placebo effects. This review highlights “predictive coding” and “bayesian brain” as emerging models derived from computational neurobiology that offer a unified framework to explain the heterogeneous evidence on placebos. These models invert the dogma of the brain as a stimulus driven organ to one in which perception relies heavily on learnt, top down, cortical predictions to infer the source of incoming sensory data. In predictive coding/bayesian brain, both chronic pain (significantly modulated by central sensitization) and its alleviation with placebo treatment are explicated as centrally encoded, mostly non-conscious, bayesian biases. The review then evaluates seven ways in which placebos are used in clinical practice and research and their bioethical implications. In this way, it shows that placebo effects are evidence based, clinically relevant, and potentially ethical tools for relieving chronic pain.

Results from small clinical trials suggesting that placebos can be ethically and effectively used in clinical practice warrant further study, argue Ted Kaptchuk and Franklin Miller

Lack of knowledge about placebos affects participants’ understanding of trials and breaches the ethical obligations of researchers, argue C R Blease, F L Bishop, and T J Kaptchuk

Objective To provide the first quantitative data on the use of the term “placebo” in the 19th century. Design Computer search of BMJ’s archival database from January 1840 (the first issue) through December 1899 for uses of the words “placebo(s).” Grounded theory was used to categorise the implications of uses of the term. Results 71 citations contained the term “placebo(s).” Of these, 22 (31%) used the term to mean “no effect” or as a general pejorative term, 18 (25%) portrayed placebo treatment as permitting the unfolding of the natural history (the normal waxing and waning of illness), 14 (20%) described placebo as important to satisfy patients, 7 (10%) described it as fulfilling a physician’s performance role, 3 (4%) described its use to buy time, 3 (4%) described its use for financial gain, 2 (3%) used it in a manner similar to a placebo control, and only one implied that placebo could have a clinical effect. Only one citation mentioned telling the patient about his placebo treatment. Conclusion Nineteenth century physicians had diverse a priori assumptions about placebos. These findings remind us that contemporary medicine needs to use rigorous science to separate fact from its own beliefs concerning the “provision of care.” As in previous generations, ethical issues concerning placebos continue to challenge medicine.

Objective To describe the attitudes and behaviours regarding placebo treatments, defined as a treatment whose benefits derive from positive patient expectations and not from the physiological mechanism of the treatment itself. Design Cross sectional mailed survey. Setting Physicians’ clinical practices. Participants 1200 practising internists and rheumatologists in the United States. Main outcome measures Investigators measured physicians’ self reported behaviours and attitudes concerning the use of placebo treatments, including measures of whether they would use or had recommended a “placebo treatment,” their ethical judgments about the practice, what they recommended as placebo treatments, and how they typically communicate with patients about the practice. Results 679 physicians (57%) responded to the survey. About half of the surveyed internists and rheumatologists reported prescribing placebo treatments on a regular basis (46-58%, depending on how the question was phrased). Most physicians (399, 62%) believed the practice to be ethically permissible. Few reported using saline (18, 3%) or sugar pills (12, 2%) as placebo treatments, while large proportions reported using over the counter analgesics (267, 41%) and vitamins (243, 38%) as placebo treatments within the past year. A small but notable proportion of physicians reported using antibiotics (86, 13%) and sedatives (86, 13%) as placebo treatments during the same period. Furthermore, physicians who use placebo treatments most commonly describe them to patients as a potentially beneficial medicine or treatment not typically used for their condition (241, 68%); only rarely do they explicitly describe them as placebos (18, 5%). Conclusions Prescribing placebo treatments seems to be common and is viewed as ethically permissible among the surveyed US internists and rheumatologists. Vitamins and over the counter analgesics are the most commonly used treatments. Physicians might not be fully transparent with their patients about the use of placebos and might have mixed motivations for recommending such treatments.

To investigate whether placebo effects can experimentally be separated into the response to three components-assessment and observation, a therapeutic ritual (placebo treatment), and a supportive patient-practitioner relationship-and then progressively combined to produce incremental clinical improvement in patients with irritable bowel syndrome. To assess the relative magnitude of these components.A six week single blind three arm randomised controlled trial.Academic medical centre.262 adults (76% women), mean (SD) age 39 (14), diagnosed by Rome II criteria for and with a score ofor =150 on the symptom severity scale.For three weeks either waiting list (observation), placebo acupuncture alone ("limited"), or placebo acupuncture with a patient-practitioner relationship augmented by warmth, attention, and confidence ("augmented"). At three weeks, half of the patients were randomly assigned to continue in their originally assigned group for an additional three weeks.Global improvement scale (range 1-7), adequate relief of symptoms, symptom severity score, and quality of life.At three weeks, scores on the global improvement scale were 3.8 (SD 1.0) v 4.3 (SD 1.4) v 5.0 (SD 1.3) for waiting list versus "limited" versus "augmented," respectively (P0.001 for trend). The proportion of patients reporting adequate relief showed a similar pattern: 28% on waiting list, 44% in limited group, and 62% in augmented group (P0.001 for trend). The same trend in response existed in symptom severity score (30 (63) v 42 (67) v 82 (89), P0.001) and quality of life (3.6 (8.1) v 4.1 (9.4) v 9.3 (14.0), P0.001). All pairwise comparisons between augmented and limited patient-practitioner relationship were significant: global improvement scale (P0.001), adequate relief of symptoms (P0.001), symptom severity score (P=0.007), quality of life (P=0.01). Results were similar at six week follow-up.Factors contributing to the placebo effect can be progressively combined in a manner resembling a graded dose escalation of component parts. Non-specific effects can produce statistically and clinically significant outcomes and the patient-practitioner relationship is the most robust component.Clinical Trials NCT00065403.