The Placebo Effect: Untapped Potential?

    The mind and body have a complex relationship that is still being studied and researched by scientists today. While much is known about this relationship, there is still so much to learn; The Placebo Effect is an example of how elementary our knowledge is of the human mind and its potential in healing the human body. The Placebo Effect was first recognized in 1799 by a British Physician, John Haygarth, who determined his placebo device was just as effective as the authentic medical device (Howick). As science progresses and neuroscientists become fascinated with the Placebo Effect and its potential in medicine, it has become increasingly more researched and developed; the Placebo Effect is suggested to be able to have a large impact on mental illnesses like depression and anxiety, and can possibly combat the use of antidepressants and other prescribed medications. Despite this potential to fight the problem of over-prescription, there is a large obstacle in using placebos in clinical settings: the ethics behind the deception needed for placebo effectiveness.

    Placebos can range anywhere from sugar pills to sham surgeries to placebo chemotherapy, etc., and are considered the control in an experiment. Placebos are administered with the intention of imitating a real drug or procedure and are done without the knowledge of the patient– a patient is unaware the pill being ingested does not contain the actual drug, or an incision is made to delude the patient into thinking the procedure was performed. The effects of the placebo versus that of the actual drug, treatment, or procedure are then studied. In a clinical setting, double-blind clinical trials are performed in order to determine whether treatments work more effectively than the placebo effect. As a result of such research, there is an overwhelming amount of evidence that proves that placebos can have the same therapeutic effects as active treatments, if not better– such research will be discussed later in this paper. In contrast, placebos may also have adverse effects on a patient – which has been coined as the phrase ‘nocebo’ (Colagiuri). Research shows that there are certain cues in a patient that can influence how susceptible they are to the success or demise of a placebo; 

When a patient encounters a treatment (whether active or placebo), the verbal, contextual, and social cues present to cause the individual to recollect the sensations experienced in prior situations, which in turn develops into an expectancy for what is likely to be experienced in response to the current treatment (Colagiuri).

This is important in understanding how the human mind and body are connected. More specifically, it has been determined that more optimistic people are likely to encounter the Placebo Effect, while more pessimistic people are more vulnerable to the Nocebo Effect. This knowledge of the other influences can play an important role in the future success of placebos. More specifically, doctors could potentially be able to use such information to maximize the possible therapeutic effects of treating their patients with a placebo rather than by prescribing medication. 

    An extensive amount of research is being done to analyze how placebos can play a role in treating mental illnesses such as anxiety and depression. These mental illnesses affect millions of individuals. However, even though these mental illnesses are so widespread, each person encounters a different degree of symptoms, making it difficult to treat each patient the same way (Carek). Doctors are cautious to prescribe antidepressants and anxiety medication because of their efficacy issues as well as the dangerous side effects of taking the drug. In research conducted with thousands of randomized trials, it was determined that “...antidepressants may be less effective than their wide marketing suggests. Short-term benefits are small and long-term balance of benefits and harms is understudied” (Ioannidis). The negative side effects of using antidepressants and anxiety medications for an extensive period of time are also extremely common; such side effects may include “stroke, death, falls and fractures, epileptic seizures in the elderly, sexual dysfunction, withdrawal, diabetes, deep vein thrombosis, and gastrointestinal and intracranial bleeding” (Kirsch). As a result, scientists are pouring research into the use of placebos in the treatment of such illnesses and have made headway in the effectiveness of doing so. In research, it was found that placebos among patients suffering from depression are between 30% and 40%, and for those who have only just recently begun experiencing symptoms of depression, the placebo response rate is almost 50% (Brown). These results are comparable to the response rate results of antidepressants. In Figure 1. shown below, there is evidence in studies that prove placebos can be just as effective as antidepressants in patients who have never been prescribed antidepressants, however, placebos are half as effective in those individuals who have taken antidepressants in the past.

Figure 1. Effectiveness of Placebos in Contrast to Antidepressants (AD) in Patients in 2010 and Revisited in 2015

Additionally, along with the effectiveness on less severe patients, the National Insitute of Mental Health Treatment of Depression Collaborative Research Program determined that there is a drastically higher relapse rate for patients who were prescribed antidepressants versus those treated in other ways [by placebo]; ~36% as compared to 50% relapse rate for antidepressant users (Kirsch). As a result of these findings, the short and long-term effects of placebos are evident. While there are varying responses to placebos, they have been just as effective for some patients as antidepressants, which suggests that placebos could have untapped potential in the treatment of some mental illnesses. 

The Placebo Effect has also been studied in treating other varying psychiatric illnesses such as OCD, psychosis, PTSD, etc. Findings show that:

The magnitude of placebo response and drug response was heterogeneous and were statistically significantly different among various psychiatric disorders. Although a noticeable degree of heterogeneity was detected in the drug–placebo ratio among various disorders, the differences did not reach statistical significance. This finding suggests that placebo use should be continued for newer agents being tested for all of psychiatric disorders (Khan).

    In a separate trial, patients who experience chronic migraines were separated into four groups for the effectiveness of a placebo pill to be studied. The first would receive a placebo drug with no brand indication on the pill. The second would receive a placebo drug marked with a well-known brand name for such a drug. The third would receive an unlabeled drug. The fourth would receive a drug labeled with the popularized brand name. The results of the study are as follows: “the aspirin was more effective than placebo… brand-name aspirin was more effective than generic aspirin, and brand-name placebo was more effective than generic placebo” (Moerman). These results give insight into the idea of pill efficacy, and how the mind plays a role in enhancing drug response. Since it is understood that the well-known brand drug will relieve one’s headaches, the label on the pill indicates that the body will be ingesting that drug, allowing the placebo to have a more positive effect than if the placebo was unlabeled. Even though the placebo contained no true drug to relieve the headache, the brain was able to enhance its supposed effects. This study gives insight into the fact that there are other components that can influence a patient’s response to a placebo.

Four distinct areas of the brain have been studied in order to determine if brain density has any degree of effect on placebo predisposition. The study used two groups– placebo responders and nonresponders– and studied the differentiations between the brain densities. The results showed that “the highest significant difference was seen for the right mid frontal gyrus (r-MFG)...showed higher connectivity to the rest of the brain for responders across all densities, with most significant difference seen at 10% density. At this density, average per voxel degree count within r-MFG was twice as high in responders as in nonresponders” (Vachon-Presseau). These results demonstrate that there is a physical difference between patients who are more likely to respond to placebos and those who are not; this difference in brain density in responders versus nonresponders is illustrated in Figure 2. 

Figure 2. The Brain of Placebo Responders versus Nonresponders

Therefore, there is potential for the ability to predict placebo response in a clinical setting by studying a patient’s brain connectivity and propensities. In doing so, doctors would be able to decrease the number of patients that are being put on medication, by administering placebos as a first-resort therapeutic option. Then, if a placebo is ineffective, the doctor could move forward with prescribing medications.

    While the use of a placebo seems to be a viable alternative to medications, there are ethical issues that have halted the use of placebos clinically. There are ethical codes that must be followed in medicine, in which the absence of deception is a large principle of ethical practice. While there is ample evidence to back the fact that placebos are more likely to be effective if a patient is unaware that the pill, procedure, etc. is a placebo, many feel that this necessary deception is “a threat to the integrity of medicine” (De Craen). Opinions adverse to the use of placebos claim “...clinical use of placebo usually involves deception and is therefore ethically problematic…[which can] have a tremendous effect on our practice regarding truth-telling and informed consent” (Asai). Additionally, in the ethics of medicine, the patient’s beneficence must be intended. While the administration of placebos is with the same intent as other true medications, oftentimes, the patient is not being given the actual treatment which is proven to work in an effective manner. Instead, they are being deceived and the result of the patient experiencing the Placebo Effect is only a possibility. In turn, the improvement of their health is being left “up to chance.” However, since the doctor is not contradicting their oath to ‘do no harm,’ and “provided that placebo effects are used as additional effects to best practice medicine” (Bystad), others find the use of placebos in a clinical setting to be ethical. These differing opinions shed light on the issue behind the controversy of placebos. 

    While the issue behind the use of placebos from an ethical mindset needs to be resolved, it is evident that placebos have untapped potential in the medical field. Placebos can be used in order to treat many different mental illnesses and have been proven to be just as effective as prescription medications. Additionally, placebos can have with-standing effects in the long term, just as medications can. If placebos were to be used on a clinical basis at a wider scale, they could potentially be a strong catalyst used to combat the problem of over-medication.

Michella Chiaramonte

Works Cited

Asai, A., & Kadooka, Y. (2013). Reexamination of the ethics of placebo use in clinical practice. 

Bioethics, 27(4), 186-193.

Brown, W. A. (1994). Placebo as a treatment for depression. Neuropsychopharmacology, 10(4), 

265-269.

Bystad, M., Bystad, C., & Wynn, R. (2015). How can placebo effects best be applied in clinical 

practice? A narrative review. Psychology Research and Behavior Management, 8, 41. 

Carek, P. J., Laibstain, S. E., & Carek, S. M. (2011). Exercise for the treatment of depression and 

anxiety. The international journal of psychiatry in medicine, 41(1), 15-28.

Colagiuri, B., Schenk, L. A., Kessler, M. D., Dorsey, S. G., & Colloca, L. (2015). The placebo 

effect: from concepts to genes. Neuroscience, 307, 171-190.

De Craen, A. J., Kaptchuk, T. J., Tijssen, J. G., & Kleijnen, J. (1999). Placebos and placebo 

effects in medicine: historical overview. Journal of the Royal Society of Medicine, 92(10), 511-515.

Ioannidis, J. (2008). Effectiveness of antidepressants: an evidence myth constructed from a 

thousand randomized trials?. Philosophy, Ethics, and Humanities in Medicine, 3(1), 1-9.

Jeremy Howick Director of the Oxford Empathy Programme. “The Fascinating Story of 

Placebos – and Why Doctors Should Use Them More Often.” The Conversation, 13 Sept. 2022, https://theconversation.com/the-fascinating-story-of-placebos-and-why-doctors-should-use-them-more-often-149945. 

Khan, A., Kolts, R. L., Rapaport, M. H., Krishnan, K. R. R., Brodhead, A. E., & Brown, W. A. 

(2005). Magnitude of placebo response and drug–placebo differences across psychiatric disorders. Psychological Medicine, 35(5), 743-749.

Kirsch, I. (2019). Placebo effect in the treatment of depression and anxiety. Frontiers in 

Psychiatry, 10, 407.

Moerman, D. E., & Harrington, A. (2005, March). Making space for the placebo effect in pain 

medicine. In Seminars in Pain Medicine (Vol. 3, No. 1, pp. 2-6). WB Saunders.

Vachon-Presseau, E., Berger, S. E., Abdullah, T. B., Huang, L., Cecchi, G. A., Griffith, J. W., ... 

& Apkarian, A. V. (2018). Brain and psychological determinants of placebo pill response in chronic pain patients. Nature communications, 9(1), 1-15.