METHODS

Searching

We identified original randomised controlled trials (RCTs) by searching the Cochrane Acute Respiratory Infections Group specialised register, the Cochrane Controlled Trials Register (The Cochrane Library issue 2, 2000), Medline (up to December 1999), Embase (up to December 1999), the UK Department of Health National Research Register (December 2000), our personal collections of references, and reference lists of all retrieved articles (search strategy shown in box). We wrote to authors of original studies, pharmaceutical companies, and the Proprietory Association of Great Britain for information on unpublished studies and made no constraints based on language or publication status.

Study selection and validity assessment

We selected studies for review if: (1) the population of interest was composed of children and adolescents (less than 16 years of age) with acute cough (less than three weeks' duration) as a result of URTI in an ambulatory setting; (2) the interventions were OTC cough preparations; (3) a reported outcome was cough (for example, frequency, duration); and (4) studies were RCTs with a contemporaneous control group receiving a placebo.

We excluded studies if: (1) they tested OTC cough medicines in chronic cough (more than three weeks' duration or caused by a chronic underlying disease such as asthma or tuberculosis); (2) cough was induced artificially in healthy volunteers; (3) they used non-conventional (for example, herbal or homoeopathic) or non-oral preparations.

We (KS and TF) screened potentially relevant citations independently and applied the selection criteria using an in/out/pending sheet in duplicate. We resolved any differences at any stage of the review through discussion. To be included a study had to meet all our inclusion criteria. We extracted data and assessed the quality of studies independently. We contacted investigators for additional information if necessary and obtained translations of abstracts or papers written in languages other than English or German. We were not masked with regard to trial authors or journals and instead of applying a trial quality score, we listed data on potential sources of bias such as randomisation, blinding, and follow up in a separate table (table 2).

RESULTS

Trial flow

We evaluated 328 citations and abstracts from all sources, of which six trials involving 438 children met all our inclusion criteria (fig 1).^9–14

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Figure 1

Progress through the stages of the systematic review.

Study characteristics

Table 3 summarises the characteristics of included RCTs which we grouped into five drug classes (see table 1). The number of trials in each group ranged from one to a maximum of two. Cough outcomes included frequency and severity and were reported by the parents using cough scores. Four studies reported data on adverse effects.

The methodological quality of included studies was generally low (table 2). None of the six RCT reports stated the randomisation process. In four studies the outcome assessors were blind to treatment allocation, and three studies did not report whether participants and/or treatment providers were blinded. Loss to follow up was documented in three studies, with differential loss to follow up in the treatment arms reported in only one study. None of the studies fulfilled all the quality criteria. Three trials reported a power calculation.

Quantitative data synthesis

We felt that pooling of the results was inappropriate because of the small numbers of trials in each category, the limited quantitative data available, and the notable differences between trials in terms of participants, interventions, and outcome measurements.

Effects on cough

Table 3 summarises the impact of OTC cough preparations on cough outcome.

Antitussives

One study involving 57 children with night cough compared a single dose for three nights of dextromethorphan and codeine with placebo.⁹ Mean cough and composite scores decreased in each of the three treatment groups on each day of the study. Neither dextromethorphan (cough score reduction of 2.1, p = 0.41) nor codeine (cough score reduction of 2.2, p = 0.70) was more effective than placebo (cough score reduction of 2.2) on day 3. Adverse effects included drowsiness, diarrhoea, and hyperactivity with no statistically significant differences between the three groups.

Mucolytics

One study involving 40 children compared the mucolytic letosteine with placebo.¹⁰ The symptom score on a four point scale favoured active treatment from day 4 until day 10, with an average difference of about 0.2 points (p < 0.01). No adverse effects were reported in both groups.

Antihistamine–decongestant combinations

Two studies involving 155 children compared antihistamine–decongestant combinations with placebo.^11,12 Brompheniramine/phenylpropanolamine was no more effective than placebo in reducing the number of children coughing two hours after each dose (49.0% v 43.1%, p = 0.66). A higher proportion of children were reported asleep in the active treatment group (46.6%) than in the placebo group (26.5%, p = 0.53), and no other adverse effects were reported.¹¹

In the second study (n = 96), brompheniramine/phenylephrine/phenylpropanolamine was no more effective than placebo or no treatment in improving cough symptoms (67% v 58% and 70%, p = 0.5 and p = 0.8 respectively).¹²

Other drug combinations

One trial involving 43 children tested two paediatric cough syrups (Triaminicol syrup and Dorcol pediatric cough syrup).¹³ Compared to placebo, 69% of children in both active treatment groups showed a satisfactory response reported by their parents compared to 57% of children in the placebo group (p = 0.5). Adverse effects were not reported.

Antihistamines

One trial involving 143 children compared the antihistamines clemastine and chlorpheniramine with placebo.¹⁴ There was spontaneous improvement in all groups. In both active treatment groups, cough scores observed by physicians and participants improved in 39.6% of individuals compared with 27.6% in the placebo group (p = 0.2). Drowsiness and sleepiness were reported in 20% of children, with no statistically significant difference between the groups.

DISCUSSION

Summary of key findings

In this systematic review we found that there is no good evidence for or against the effectiveness of OTC cough medicines in acute cough. This concurs with the findings of previous reviews.^6,7 In the only study showing a statistically significant result, the effect size was small and of doubtful clinical relevance. OTC cough preparations were generally well tolerated and did not lead to major adverse effects. Many of the reported adverse effects could in fact have been a result of the underlying URTI.

Study limitations and potential sources of bias

The results of this systematic review have to be interpreted with caution, as the number of trials in each category was small. Studies were very different with regard to settings, populations, interventions (drugs, doses, and frequency) and outcome measures, making them difficult to compare. Individual RCTs were of variable methodological quality with respect to randomisation, blinding of outcome assessment, and losses to follow up. Many studies described differences in cough scores between the treatment groups, which are difficult to interpret for the purpose of making informed treatment decisions.

Although we attempted to obtain information on unpublished studies, we received little response from pharmaceutical companies and study authors. If studies with negative results were less likely to be submitted for publication, this could have led to publication bias.

Implications

Cough caused by URTI can be a very troublesome symptom for a child, and for a health professional, not to offer any treatment may seem unacceptable to many parents and lay people. However, as this systematic review shows, there is very little evidence to suggest that OTC cough medicines are effective. For this reason, we cannot recommend these as first line treatment for acute cough. It is, however, vital that paediatricians, GPs, and other health care workers take the symptoms of acute cough seriously, taking a careful history and performing a thorough physical examination to search for possible underlying diagnoses. If a viral URTI seems the most likely diagnosis, the treatment options and the lack of evidence for the effectiveness of OTC cough medicines should be discussed carefully with parents. Whether a child is being treated or not, parents should always be offered a further appointment in case the cough persists, which may suggest the possibility of another underlying condition.

At present, the NHS encourages self medication for acute self limiting illnesses and the use of cough preparations as a home remedy.⁴ Though OTC cough preparations appear to be relatively free from adverse effects, their safety in children has been questioned.¹⁵ In addition, purchase of OTC cough medicines may lead to an unnecessary financial burden for health care consumers.

If health professionals want to recommend OTC cough medicines to parents of children who suffer from cough caused by acute URTI, advice should be restricted to less expensive preparations until more evidence about their effectiveness becomes available.

Suggestions for future research

Health professionals need more evidence from carefully designed RCTs before recommending OTC cough medicines to their patients. Identification of effective self care treatments may help reduce suffering in children with cough as well as the number of consultations in primary care. Future studies should therefore use outcome measures that can be easily used in a primary care setting and that produce clinically meaningful results.

Conclusions

We conclude from the limited evidence available that OTC cough medicines do not appear to be more effective than placebo in acute cough caused by URTI and should not be recommended as a first line treatment for the resolution of acute cough. Although these medicines are generally well tolerated, their use may lead to unnecessary expenses for health care consumers.