The Powerful Placebo Effect in Cough: Relevance to Treatment and Clinical Trials

Abstract

Interest in the placebo effect of medicines has developed from the use of placebo treatments as controls in clinical trials into a whole new area of research around how placebos fit into a psychosocial model of therapeutics. The large placebo effect associated with cough medicines is both a problem and an opportunity for researchers: a problem for clinical trials on new actives as the active must beat the large placebo effect, and an opportunity for harnessing the placebo effect to produce effective cough medicines without any pharmacologically active ingredient. This review discusses the mechanisms associated with the placebo effect of cough medicines and distinguishes between a 'perceived placebo effect' and a true 'placebo effect'. The efficacy of sweeteners in cough syrups is discussed as well as viscosity, mucoadhesion, and flavoring. The complexity of modern cough medicines is demonstrated by an example of a medicine which contains one active ingredient, and eighteen excipients which provide a complex and intense sensory experience to enhance the placebo effect and complement the pharmacological activity of the medicine.

What is the Role of Over 100 Excipients in Over the Counter (OTC) Cough Medicines?

“…It will be important to consider if in the future these medicines are used to treat acute cough if they will be administered to patients as tablets or if pharmaceutical companies will harness the power of excipients to enhance the efficacy of these new medicines. If new cough medicines are to be marketed as syrups rather than tablets, then this may complicate clinical trials on these new medicines, as the placebo effect and other actions of excipients may be the major component of the efficacy of the new cough product [1,26]. The easiest way forward is to conduct the clinical trials on tablet formulations and to conduct consumer market research on how patients will react to a new cough medicine in tablet form.…”

“…The color of tablets has been shown to influence the perception of their properties as sedatives or stimulants with red yellow and orange associated with stimulant effects, and blue and green colors with tranquilizing effects [25]. The color of a cough medicine may influence perception about its efficacy and enhance its placebo effect, although no published research has been found on the effect of color on the placebo effect of cough medicines [26].…”

Recent progress in the management of chronic cough

“…4, July 2020 servational studies [71,72]. Cough is frequently self-limiting and prone to placebo effects [73], which may underlie the large discrepancy between placebo-controlled and uncontrolled (observational) studies.…”

“…However, placebo-controlled studies indicate that true therapeutic benefits gained from treating these conditions may be much less than the findings suggested from observational studies [ 71 , 72 ]. Cough is frequently self-limiting and prone to placebo effects [ 73 ], which may underlie the large discrepancy between placebo-controlled and uncontrolled (observational) studies.…”

LUNG Year in Review: 2020

“…Thankfully, the last decade has seen a great increase in cough-related research which has led to multiple antitussive drug development programs currently underway [ 9 ]. Cough-related articles featured in 2020 included State-of-the-Art reviews on the placebo effect in cough clinical trials [ 2 ], the role of excipients in antitussive preparations [ 11 ], and an update on the status of chronic cough in China [ 3 ]. Other topics covered were drug-associated cough [ 82 ], therapeutic strategies for chronic cough [ 79 , 83 ], the role of cough assessment in monitoring patients with asthma [ 36 ] and COPD [ 47 ], the question of whether there will be an emergence of a post-COVID-19 chronic cough [ 23 ], and abstracts from the Seventh American Cough Conference [ 84 ].…”