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Cough Update: Beneficial effects of diphenhydramine and ammonium chloride in reducing cough

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eMediNexus    30 December 2020

Epidemiological surveys suggest that approximately one in five people are affected acute cough in Western countries and is considered as one of the most common reasons to consult a general practitioner. It has been observed that most acute coughs improve spontaneously, however, many patients use over-the-counter (OTC) medicine for relief. The current study examined the therapeutic potential and safety of CS1002, an over-the-counter cough treatment comprising diphenhydramine, ammonium chloride and levomenthol in a cocoa-based demulcent. Diphenhydramine, an antihistamine has the potential to decrease the heightened cough reflex sensitivity in patients with cough associated with an upper respiratory tract infections. While ammonium chloride is an acid-forming salt which causes an expectorant effect by loosening sputum.

This multicentre, randomised, controlled study included patients with acute cough of <7 days duration, aged ≥18 years. Moreover, they were enrolled with criterion of cough with severity ≥60 mm on a 0–100 mm visual analogue scale (VAS), whereas current smokers or history of smoking within the past 12 months were the exclusion criteria. Hence, a total of 163 participants were included in the study with mean participant age 38 years. These patients were randomised to CS1002 (Unicough) or simple linctus (SL), a commonly used cough treatment, and for a period of 7 days or until resolution of cough. The primary analysis was intention-to-treat and included cough severity assessed using a VAS after 3 days treatment. In addition, the authors also examined the cough frequency, sleep disruption, health status using Leicester Cough Questionnaire (LCQ-acute) and cough resolution.

The outcome of the study at day 4 revealed that the adjusted mean difference in cough severity VAS between CS1002 and SL was −5.9 mm (−14.4 to 2.7). Moreover, the mean difference in cough severity VAS reduced to −4.2 mm (−12.2 to 3.9) at the end of the study or day 7. CS1002 showed greater reduction in cough sleep disruption (mean difference −11.6 mm (−20.6 to 2.7) and cough frequency (mean difference −8.1 mm (−16.2 to 0.1) in contrast to SL. A greater amelioration in LCQ-acute quality of life scores was observed with CS1002 in comparison to SL with a mean difference 1.2 (0.05 to 2.36) after 5 days treatment. Therefore, more patients prematurely discontinued treatment due to cough improvement in the CS1002 group in comparison to SL group (24.4% versus 10.7%). However, incidence of adverse events were also found to be slightly lesser in CS1002 group than SL group (20.5% versus 27.6%). 

Thus, based on the findings, it can be concluded that the combination therapy including diphenhydramine and ammonium chloride has the potential to reduce cough frequency, sleep disruption and ameliorate overall health status. Thus, these agents can benefit in the treatment of the treatment of cough associated with upper respiratory tract infections.

Source: Birring SS, Brew J, Kilbourn A, Edwards V, Wilson R, Morice AH. Rococo study: a real-world evaluation of an over-the-counter medicine in acute cough (a multicentre, randomised, controlled study). BMJ Open. 2017;7(1):e014112. Published 2017 Jan 16. 

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