The Powerful Placebo in Cough Studies?
Authors: R Eccles
Journal: Pulmonary Pharmacology & Therapeutics (2002)
Discipline: CLINICAL MEDICINE
Keywords: Placebo treatment; clinical trials; antitussive medicines; cough; upper respiratory tract infection

Abstract:  Placebo treatment has been reported to improve subjective and objective measures of disease in up to 30-40% of patients with a wide range of clinical conditions. A review of 8 clinical trials on the effects of antitussive medicines on cough associated with acute upper respiratory tract infection shows that 85% of the reduction in cough is related to treatment with placebo, and only 15% attributable to the active ingredient Treatment with a cough medicine can be viewed as consisting of three components: pharmacological, physiological (demulcent) and placebo. The placebo effect is related to belief in the effectiveness of the treatment and this idea must in some way influence the central control of cough. Studies on the placebo effect of analgesics indicate that the placebo effect may be mediated by endogenous opioid neurotransmitters and this may explain the analgesic potency of opioid medicines such as morphine. In the present paper a model is proposed to explain the antitussive effects of placebo treatment on the basis of endogenous opioid neurotransmitters. With active pharmacological ingredients contributing only 15% to the effects of cough treatment it seems reasonable to conduct more research on the other components of treatment such as placebo. 

Retracted: No

PubPeer comments:
 The regression to the man effect should almost always be considered when talking about  placebo effects . In fact, this article discusses this effect. Good point. In that section the author calls for a third treatment arm, namely a  no treatment arm, to allow for dissociation between regression to the mean and, say, psychologically-explained placebo effects. Good point. Then the author tells about a trial that included such no treatment group, Ref 20; he is listed as last author of that paper, said to have been published in 2001 (NB the current article is form 2002). However, there is no such publication in the Br J Clin Pharmacol. Instead there is a publication from an almost identical group with a similar title, published in 2005 in Psychosom Med (DOI: 10.1097 01.psy.0000155667.59662.92). That trial was a 2 arm trial, placebo vs. no treatment, and the placebo was in fact vitamin E (hence violating the ICH E10 definition), there was no active comparator to show sensitivity. It appears that that trial had not been registered. How could the author tell about a trial that was published 3 years later? Was it rejected in 2001 by Br J Clin Pharmacol due to too many questions? How can the conclusions from the review now be supported? Namely that regression to the mean would not sufficiently explain the  placebo effect on coughing. In fact, the review provides nothing else. As it stands now the review cannot support the relevance of  placebo effects that could be explained psychologically or by  endogenous opioid neurotransmitters . , 
 #1 The article referred to is published in the British Journal of Pharmacology under proceedings of the BPS as it was presented at a meeting in December 2000 prior to full publication in Psychosom Med in 2005. Vitamin E was used as a placebo and I agree that this is somewhat controversial and did involve some deception as regards the patient information as the patients were told that the study involved testing vitamin E to see if it had any effect on cough. There was some debate in the Journal correspondence on this topic ,