After evaluating 328 citations and abstracts from all sources, we included 15 trials involving 2166 participants (figure).16–30
Table shows the main characteristics of the included randomised controlled trials. The number of studies for each type of drug was small, ranging from one to five. Outcomes included frequency and severity of cough and were measured in many different ways—for example, self report, physician assessment, cough sound pressure levels, and tape recordings. Ten studies reported data on adverse effects.
Characteristics of randomised controlled trials of over the counter cough preparations versus placebo for acute cough
The methodological quality of included studies in terms of randomisation, blinding, and reports of losses to follow up was variable and generally not high (table ). Four of the 15 studies reported the randomisation process, which was adequate in three trials. Only two studies reported blinding of outcome assessors. It was unclear for three trials whether participants or treatment providers were blinded. Loss to follow up was well documented in 12 studies, with differential loss to follow up in both treatment arms reported in four studies. One trial reported a power calculation, and only one study fulfilled all the quality criteria. Many trials were too small to detect clinically important differences.
Quantitative data synthesis
We could not pool the results because there was clear clinical heterogeneity between trials in terms of participants, interventions, and outcome measurements. Furthermore, the number of trials in each category was small and the amount of quantitative data available limited.
Five trials tested antitussives versus placebo (table ). Two studies tested codeine and found it no more effective than placebo. One of two studies of dextromethorphan favoured active treatment over placebo (differences in mean changes of cough counts 19% to 36% in three substudies, P<0.05), whereas the other found no significant effect. Moguisteine (one trial) led to mean differences in cough scores of about 0.5 in groups with severe cough on days 2 and 3 (P<0.05), but there were no differences between groups at final follow up. Only two trials reported adverse effects.17,20
Nausea, vomiting, and abdominal pain were more common in participants treated with moguisteine than placebo (22% v
and in one trial participants did not report any adverse effects from dextromethorphan.20
Participants in one study found guaifenesin more helpful than placebo (75% v
However, a second trial found no significant differences between the groups (table ).22
Guaifenesin led to a low incidence of nausea and urticaria in the active treatment group in one trial21
; the other did not report on adverse effects.22
In the only study of mucolytics, frequent cough was less prevalent in the Bisolvon linctus group than the placebo group (8.6% v
This study did not report on adverse effects.
One of the two trials of antihistamine-decongestant combinations showed a lower mean severity cough score in the active treatment group on days 3-5 (1.4 in active group v
2.0 in placebo group, P<0.05).24
The other trial found no significant differences between the two treatments (table ).25
Antihistamine-decongestant combinations seemed to have a slightly higher incidence of adverse effects than placebo. These included dry mouth, dizziness, headache, and insomnia.
Other drug combinations
We included three studies of medicines containing fixed drug combinations (table ).26–28
These studies were very heterogeneous and used different drug preparations, limiting their comparability. In a study of EM-Vier, more participants in the treatment group improved within the first three days than in the placebo group (26/58 v
In a crossover trial of Vicks Medinite syrup, 58% of participants rated active treatment good or better in relieving cough symptoms compared with 32% for placebo.27
Dextromethorphan plus salbutamol was better than placebo or dextromethorphan alone in relieving cough at night but there were no significant differences for cough symptoms during the day.28
Adverse effects for all preparations were rare and usually mild.
Based on two trials, terfenadine was no more effective than placebo in relieving cough symptoms (table ).29,30
The incidence of adverse effects, which included excess fatigue and headache, was low with no significant differences between the groups.