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Only since recent time, is the scientific sphere increasingly diverting some of its attention to the placebo. While an established element in the conduction of research, and an embedded entity in the ‘gold-standard’ random controlled trial, the placebo remains a controversy.
Since its establishment as part of research methodology, it has “received inadequate attention, poor methodology, and a-priori assumptions” [5]. Yet, while being considered an inert medication or intervention that resembles the active drug or procedure, placebo, in fact, has specific effects of its own [1].


Prior to the use of placebo in research, a medical intervention was deemed effective if outcomes provided such evidence, yet since the introduction of placebo, the legitimacy of an intervention was only granted if outcomes of research showed superiority to a designated placebo [5]. A placebo control has since been employed to reduce bias on account of “ancillary effects” of a trialled intervention or regimen [6]. Its aim has been to “challenge, debunk, and discard ineffective and harmful treatments” [2].


Yet, with recent research drawn to investigate the effects from placebo, it has become evident that placebo itself has the ability of influencing trial participants [2]. Such findings render the placebo a tool that is “unscientific and caused by bias and prejudice” [2], and as such instigate an essential need to redefine placebo and its application [1].


Placebo effects are not the effects of the inert drug as which it is frequently defined, but are the alterations patients perceive in their states of health, caused by aspects related to non-medicinal or non-interventional sources. They are “genuine biopsychosocial phenomena” largely attributed to the therapeutic relationship, its proceedings and the patient-practitioner encounter [2]. Yet, such restrictive attribution is inappropriate. Trials have shown that placebo acts even where the impact from the therapeutic relationship and associated ritual are removed, or extended equally to all three trial arms, active verum, placebo and no-treatment arm. Either way, research outcomes have shown that the produced effects of placebo are greater than those reported from the no-treatment arm [3]. Furthermore, research has shown that effect sizes of placebo in conventional research, are as extensive over no-treatment, as verum is over placebo [1], and that placebo responsiveness is higher in trial conditions that use continuous, that is, non-specific, subjective outcomes [1].


In this light it is controversial, if not paradoxical, to employ placebo in trial investigations, as it fails to control bias, and impacts the efficacy outcomes [6]. Future studies employing placebo must include a third trial arm that investigates the outcomes from a ‘no treatment’ group, as a control for the placebo arm, and the chosen placebo must be appropriately selected for the particular type of trial to be conducted. It must be devoid of the potential to, itself, impact outcomes [6].


While, placebo, according to the current knowledge, is thought to be unable to provide entire cure, it is considered capable of altering symptoms and disease progress. As such it has the capacity to impact the efficacy of medicinal or clinical therapy and regimen [2].


Yet, there is the implication that placebo may be positive or negative. Nocebo, the negative placebo tilts patient perception from the positive anticipation of a treatment to a negative one, that is, the treatment results in a lack of effect, or is concomitant to experiences considered as undesired or adverse by the patient [2, 4].


Furthermore, the use of placebo in clinical practice is, by its nature, very controversial, as the ethical implication of informed consent is limited by its use. The use of the ‘inert’ pill or intervention becomes a deceptive act [2]. For a prescribed placebo to unfold its effect, this prescription has to be founded on the lie that the patient is receiving an active medication [3]. This is challenging in the medical/healing sphere, where “trust and transparency” are imperative to medical practice [2, 4].


Interestingly enough, when researchers investigated the impact on trial participants when these were told they would be receiving a placebo, their reaction to the faux pill was equally as effective as when it was not disclosed to them that they were receiving an inert drug [3]. Following such prior disclosure, the prescription of placebo rules out the ethical objectives of informed consent, and the ethical dilemma is overcome [3].


The use of placebo requires to be reconsidered, both for research and in clinical practice. Adjustments to the ethical paradigm are necessary in order to elucidate the use of placebo as a prescription to patients, and research must measure the placebo effect in its trials and studies, in order to identify its magnitude and make correct statements on the efficacy of drugs and interventions trialed in a placebo controlled manner [3].


Placebos are of an invaluable worth, as they demonstrate that physical ailment can be impacted psychologically [3]. Yet, it is not a healing response coming from the pill, but actually from the patient upon taking it [3]. The current conclusion on this phenomenon is an interesting one, namely, that the human body has an inherent power to heal itself [3]. Yet, we are nowhere near the end of exploration and explanation of the placebo and its effect.




[1] Howick , J., Friedemann, C., Tsakok,M., Watson, R., Tsakok, T., Thomas, J., Perera, R., Fleming, S., & Heneghan, C. (2013) ‘Are Treatments More Effective than Placebos? A Systematic Review and Meta-Analysis’, PLOS one [Online]. Available at: DOI: 10.1371/journal.pone.0062599 (Accessed: June 2013).
[2] Kaptchuk, T. & Miller, F. (2015) ‘Placebo Effects in Medicine’, N Engl J Med, 373(), pp. 8-9 [Online]. Available at: DOI: 10.1056/NEJMp1504023 (Accessed: July 2015).
[3] Silberman, S. (2010) ‘Meet the Ethical Placebo: A Story that Heals’, PLOS Blogs [Online]. Available at: http://blogs.plos.org/neurotribes/2010/12/22/meet-the-ethical-placebo-a-story-that-heals/ (Accessed: November 2013).
[4] Strausz, M (2012) ‘Nocebo: Der böse Bruder von Placebo’, DocCheck News [Online]. Available at: http://news.doccheck.com/de/326/nocebo-der-bose-bruder-von-placebo/ (Accessed: August 2015).
[5] Kaptchuk, T. (1998) ‘Powerful placebo: the dark side of the randomised controlled trial’, The Lancet, 351(9117), pp. 1722–1725 [Online]. Available at: DOI: http://dx.doi.org/10.1016/S0140-6736(97)10111-8 (Accessed: November 2015).
[6] Horn, B., Balk, J. & Gold, J. (2011) ‘Revisiting the sham: Is it all smoke and mirrors?’, Evidence-based complementary and alternative medicine, 2011, 4 pages. doi:10.1093/ecam/neq074