Peer Reviewed

The Placebo Effect & Ménière's disease

What is the placebo effect?

First described in the early 1900s, the placebo effect is defined by Oxford Languages as a beneficial effect produced by an inactive drug or treatment that cannot be attributed to the properties of the intervention itself. This effect has been shown to be prevalent in many different conditions, affecting many different symptoms.

The placebo effect typically has the most impact on patient-reported metrics like survey responses and symptom reporting. Signs of disease like those found on a doctor’s examination or imaging are less likely to be affected. This is also layered with a component of time. The more time that passes, the weaker the placebo effect.

Placebo in Clinical Trials

In practicality, the placebo effect most often gets discussed in the context of clinical trials (scientific research involving patient subjects) where new therapies like medicines and surgeries are being investigated. It is used to control for factors that are not directly related to the active therapy being studied. Generally, this relies on blinding, which means that patients do not know if they are receiving the placebo or the active therapy. While this may seem deceitful, this is the only way to preserve the effects of the placebo. Many times, the clinicians are also blinded to preserve their neutrality.

Patients receiving placebo treatment are integral to the success of critical trials. As mentioned, they help make sure that the differences that are found between groups are due to effects of the study’s intervention and not due to the placebo effect. It is appreciated that these effects wane over time, which means that duration of follow-up can be important. This may be why patients participating in clinical trials are seen for multiple follow-up visits. Some studies may use much longer follow-up times, meaning that people can be enrolled in the study for up to a year or more. The hope from the researcher’s point of view is that the benefit of the treatment intervention of the study may be appreciated after more time has passed, allowing the placebo effect to weaken. How a clinical trial is designed may play a role, as well.

Why participate in clinical trials if you might end up in the placebo group?

The thought of being enrolled in a study and not receiving an active medication is scary for some patients and can be a deterrent to enrollment. If you are thinking about participating in a study that uses a placebo, talk to the clinicians that are offering the study to determine the study design. Some studies have multiple phases, where all participants receive both the placebo drug and the active drug at different time periods. Other studies may simply randomly assign you to receive one or the other.

Ultimately this decision comes down to whether or not you want to contribute to what we know about your condition and how to most optimally treat it. Although there is no guarantee that you will get any direct benefit from enrollment in a study, you will help future patients with your condition. You could potentially be contributing to your own future treatment plan.

The most important thing to know about enrollment in studies is that they are completely voluntary from beginning to end. They are voluntary to join and you can drop out of the study at any point if you do not wish to continue.

How does the placebo effect impact people outside of clinical trials?

When not enrolled in clinical trials, the picture of the impact of the placebo effect is less clear. There is undoubtedly benefit, but it is difficult to quantify. This is especially true in the short term. It is also seen when evaluating success after a change in treatment plan in some conditions. People that have experienced treatment success in the past may be more likely to experience success in future treatments. The reciprocal also appears to be true: people that have not experienced success may be less likely to do so.

What does the placebo effect look like in Meniere’s Disease?

Meniere’s Disease (MD) is a condition that has been determined to be highly susceptible to the placebo effect given the subjective nature of most of the symptoms experienced by patients. Many studies that evaluate MD focus on surveys and other severity of disease measures. This is an active area of research. A study from late 2023 estimated that patients with MD had more than a 50% improvement in vertigo episodes and other patient-reported outcome measures, even though they were on the placebo. It is expected that this effect slowly wears off over time.

What does this mean for you as a vestibular patient?

You play a part in the course of your disease! The neurobiology of the placebo effect is complex and may be modulated by individual traits. Patients with an optimistic outlook may experience more improvement in symptoms than those with a pessimistic outlook. If you are gracious enough to join a clinical trial with a placebo component for a new medication or intervention, future patients will have better treatment because of the generosity of your time and participation.

Authors: Neil Monaghan,1,2 Brian Keith,1,3 Habib Rizk MD MSc1

Affiliations: 1. Department of Otolaryngology – Head and Neck Surgery, 2. College of Medicine, Medical University of South Carolina, Charleston, SC, USA, 3. School of Osteopathic Medicine, Campbell University, Lillington, NC, USA.

Reference: Taniguchi AN, Sutton SR, Mills JF, Nguyen SA, Rizk HG, Meyer TA, Nguyen JP, Lambert PR. Placebo effect in randomized controlled trials for Meniere’s disease: A meta-analysis. Am J Otolaryngol. 2024 Mar-Apr;45(2):104178. doi: 10.1016/j.amjoto.2023.104178. Epub 2023 Dec 11. PMID: 38101129.

References

  1. Girach A, Aamir A, Zis P. The neurobiology under the placebo effect. Drugs Today (Barc). 2019 Jul;55(7):469-476. doi: 10.1358/dot.2019.55.7.3010575. PMID: 31347615.

  2. Enck P, Klosterhalfen S. Placebos and the Placebo Effect in Drug Trials. Handb Exp Pharmacol. 2019;260:399-431. doi: 10.1007/164_2019_269. PMID: 31463606.

  3. Požgain I, Požgain Z, Degmečić D. Placebo and nocebo effect: a mini-review. Psychiatr Danub. 2014 Jun;26(2):100-7. PMID: 24909245.

  4. Hafliðadóttir SH, Juhl CB, Nielsen SM, Henriksen M, Harris IA, Bliddal H, Christensen R. Placebo response and effect in randomized clinical trials: meta-research with focus on contextual effects. Trials. 2021 Jul 26;22(1):493. doi: 10.1186/s13063-021-05454-8. PMID: 34311793; PMCID: PMC8314506.

  5. Morral A, Urrutia G, Bonfill X. Placebo effect and therapeutic context: A challenge in clinical research. Med Clin (Barc). 2017 Jul 7;149(1):26-31. English, Spanish. doi: 10.1016/j.medcli.2017.03.034. Epub 2017 May 15. PMID: 28521961.

  6. Tavel ME. The placebo effect: the good, the bad, and the ugly. Am J Med. 2014 Jun;127(6):484-8. doi: 10.1016/j.amjmed.2014.02.002. Epub 2014 Feb 8. PMID: 24518105.

  7. Taniguchi AN, Sutton SR, Mills JF, Nguyen SA, Rizk HG, Meyer TA, Nguyen JP, Lambert PR. Placebo effect in randomized controlled trials for Meniere’s disease: A meta-analysis. Am J Otolaryngol. 2023 Dec 11;45(2):104178. doi: 10.1016/j.amjoto.2023.104178. Epub ahead of print. PMID: 38101129.

  8. Pipaliya RM, Duckett KA, Monaghan NP, Miller EM, Young G, Brennan EA, Nguyen SA, Soler ZM, Schlosser RJ. The placebo effect in randomized-controlled trials of medical treatments for chronic rhinosinusitis: A systematic review and meta-analysis. Int Forum Allergy Rhinol. 2023 Nov 20. doi: 10.1002/alr.23302. Epub ahead of print. PMID: 37985206.

  9. Hróbjartsson A, Gøtzsche PC. Placebo interventions for all clinical conditions. Cochrane Database Syst Rev. 2004;(3):CD003974. doi: 10.1002/14651858.CD003974.pub2. Update in: Cochrane Database Syst Rev. 2010;(1):CD003974. PMID: 15266510.