Lack of effect of codeine in the treatment of cough associated with acute upper respiratory tract infection

Abstract

Codeine is often used as a standard antitussive against which new antitussives are compared. However there is little information available about the effects of codeine on cough associated with upper respiratory tract infection. The present study investigated the effects of codeine syrup B.P. (30 mg/10 ml, q.d.s.) or syrup vehicle on cough frequency and the subjective severity of cough during a 3-h laboratory phase and a 4-day home phase of treatment. Cough frequency and subjective scores of cough severity were significantly decreased during the 3-h laboratory phase but at no time point was there a significant difference between the codeine- and placebo-treated groups. The results of the 4-day home phase diary were similar to those of the laboratory phase as at no time point was there a significant difference between the mean scores for the codeine- and placebo-treated groups. The results indicate that codeine, either as a single 30-mg dose or in a total daily dose of 120 mg, is no more effective than the syrup vehicle in controlling cough associated with acute upper respiratory tract infection.

Antitussive Drugs—Past, Present, and Future

“…In contrast, Dicpinigaitis et al (1997) observed significantly greater suppression of capsaicininduced cough 2 hours after ingestion of 30 mg of codeine compared with placebo. In citric acid-induced cough, 20 mg of codeine was associated with significantly greater cough suppression than placebo (Empey et al, 1979) In two exemplary studies investigating cough due to URTIs, Eccles et al (1992) found that codeine at an initial dose of 30 mg, followed by 4 days of dosing at 30 mg four times a day, had no effect greater than placebo syrup, either on objective initial cough recording or on subsequent self-reported cough. In the second study by the same group, oral codeine (50 mg) was compared with placebo syrup in 82 subjects in a parallel group design using three measures of cough assessment (Freestone et al, 1996).…”

ERS guidelines on the assessment of cough

“…Having recruited a study population, there is an inevitable marked spontaneous regression back to normality. This, coupled with a particularly powerful placebo effect [165,166], makes the study of subjects with acute cough highly challenging. These factors, but particularly the daily variation in baseline, make crossover studies virtually impossible.…”

Functional neuroimaging of placebo inhibition in capsaicin induced urge-to-cough

“…While there is evidence that placebo effects may play a part in the effectiveness of many antitussives (Eccles et al, 1992;Freestone & Eccles, 1997;Schroeder & Fahey, 2004;Taylor et al, 1993), this has not been studied systematically. A logical next step would be to examine placebo responses in patients with cough disorders.…”

“…A number of recent double blind, placebo-controlled studies have shown that codeine is not significantly more effective than placebo in suppressing cough due to upper airway disorders (Bolser & Davenport, 2007;Eccles, Morris, & Jawad, 1992).…”

“…Consistent with this, cough is highly susceptible to placebo suppression. Indeed, many currently available antitussive therapies, including codeine and dextromethorphan, offer minimal therapeutic effect over placebo in treating cough (Eccles et al, 1992;Lee et al, 2005;Smith, Owen, Earis, & Woodcock, 2006;Tukiainen et al, 1986). Given that antitussive therapies provide symptom relief, these observations suggest a high propensity of cough neural pathways to be regulated by higher order inhibitory control mechanisms.…”