TCS Daily


Turn Your Head and Cough

By John Luik - February 21, 2006 12:00 AM

About the last thing millions of people suffering from colds this winter need to hear right now is that cough medicines are not only useless but dangerous, especially for kids. But that's the latest message from the American College of Chest Physicians (ACCP), which has just published new guidelines on managing coughs.

According to the ACCP, over the counter (OTC) cough remedies containing dextromethorphan (listed as DM on most cough medicines) don't work for adults and are dangerous for children. As the Guidelines committee chairman Dr. Richard Irwin of the University of Massachusetts Medical School put it:

"There is no clinical evidence that over-the counter cough expectorants or suppressants actually relieve cough. ... Cough and cold medicines are not useful in children and can actually be harmful."

Dextromethorphan-based cough medicines account for about 75% of the annual sales of OTC cough remedies. According to Irwin, if cough sufferers want to take something, they should consider the older, sleep-inducing antihistamines, for which there is stronger evidence of effectiveness. "There is considerable evidence that older type antihistamines help to reduce cough," he said, according to the BBC, "so ... why not take something that has been proven to work?"

Irwin's claims must have come as a bit of a surprise to most consumers, not to say to the makers of cough medicines. The Consumer Healthcare Products Association, which represents the makers and distributors of OTC products, responded:

"Over-the-counter, or OTC, cough/cold products provide relief to millions of consumers each year. The United Sates Food and Drug Administration... and other regulatory agencies world-wide support the use of over-the counter cough/cold products for providing relief of coughs and other symptoms associated with the common cold, and studies support the symptom relief among consumers using these products."

Indeed, the bottle of Maximum Strength Robitussin in my medicine cabinet makes the following claims: "Controls Coughs, 6-8 Hours" and "Relieves Cold Symptoms" If Dr. Irwin and the ACCP are correct, is this false advertising? Should we just throw them out?

A closer look at the science behind the ACCP's new guidelines is in order.

The guidelines are not based on any new science or original research performed by the ACCP. Rather, they are simply an assessment of the existing science by a panel of 15 physicians who rated the scientific evidence for each of their recommendations. And, in their reading, the panel rates the level of evidence supporting the recommendation not to use cough medicines with DM because they are ineffective as only "fair."

Puzzled by this, I called one of the contacts on the ACCP press release, Jennifer Stawarz, who works at the ACCP headquarters in Northbrook, Ill. I wanted to know just how the ACCP had come to the conclusion that DM-based cough medicines didn't work, why they thought they were harmful to children, and why they weren't recommending to the FDA that the medicines that were both ineffective and harmful be pulled from the shelves. Jennifer suggested that I speak to the chair of the ACCP's committee on pediatric cough, Dr. Anne Chang. She assured me that Dr. Chang was very willing to answer questions and explain the basis for the ACCP's recommendations. Unfortunately, Dr. Chang lives in Brisbane, Australia, so I sent her an email with my questions. But I heard nothing from her.

Just a bit puzzled by the ACCP brush-off I decided to take a closer look at what the science behind the new cough guidelines actually says. And once I did it became obvious why the scientific support is only rated "fair."

A quick MEDLINE search turned up a dozen studies, in addition to the FDA's own efficacy and safety review, on the effectiveness of OTC cough medicines in adults.

For example, in a 1999 study in the British Journal of Clinical Pharmacology, R. Abdul Manap et al found that dextromethorphan demonstrated a "significant antitussive effect." Manap cites several clinical and experimental cough studies going back to the 1950s that found dextromethorphan effective.

In a 1996 review of the scientific literature, L. Parvez et al looked at a series of randomized, double blind, placebo-controlled studies -- the gold standard of scientific research -- of the effectiveness of cough medicines containing DM. They found that after a single 30 milligram dose, there were "reproducible cough suppressant effects" using "objective measures of cough counts, latency and total effort."

Similar indications of effectiveness were found in studies by M.S. Croughan-Minihane et al, which found that DM and guaifenesin -- also labeled ineffective by the ACCP -- were "equally effective in relieving cough symptoms," and P. Karttunen et al, where cough threshold levels rose at statistically significant levels compared with placebo after administration of DM.

In a meta-analysis of six studies on the effectiveness of DM, L. Pavesi et al, in a 2001 article published in CHEST, the official journal of the ACCP, found that a single 30 mg dose "demonstrated significantly greater overall reductions in cough bouts, cough components, and cough effort ... than those treated with placebo."

Even one of the skeptics of DM, Ian M. Paul from Pennsylvania State University reported in a small 2004 study of the use of DM in children as young as two that the medicine provided "symptomatic relief".

And finally, two reviews by none other than the guideline committee chairman Richard Irwin (R.S. Irwin et al, Drugs, 1993 46: 80-91 Appropriate use of antitussives and protussives: A practical review, and R.S. Irwin et al, European Journal of Respiratory Diseases. Supplement. 1987: 153: 173-181 The effects of drugs on cough), reported that in double-blind, placebo-controlled, randomized studies, dextromethorphan has been shown to be effective.

Part of the problem is that most of the studies on the effectiveness of DM-based cough medicines are too small to reach statistical significance and thus provide a good basis for treatment guidelines. The ACCP's main piece of evidence, a review by K. Schroeder and T. Fahey ("Over-the-counter medications for acute cough in children and adults in ambulatory settings" Cochrane Database of Systematic Reviews 2001: 3) cautions: "There is no good evidence for or against the effectiveness of OTC medicines in acute cough. ... The numbers of studies in each group were small, and studies often showed conflicting results."

As for children, the evidence of effectiveness was equally mixed.

Only one study looked at antitussives and it found that they were no more effective than placebo. Another trial examined two pediatric cough syrups and found, compared to placebo, that both "showed a satisfactory response" in 46% and 56% of the children compared to only 21% in the placebo group. All in all, that's a somewhat slender basis on which to make the sweeping claim that cough medicine is useless, particularly given that the reviewers themselves did not come to that conclusion. It seems that the ACCP might have confused no evidence of effect with evidence of no effect.

Another problem is that the ACCP seems to believe that cough medicines should treat the underlying cause of a cough -- and that's the basis for judging them effective -- whereas most cough sufferers and indeed most doctors simply want symptomatic relief for the few days that a cough hangs around, something that the medicines seem to provide. They understand that nothing makes the cough go away, but they also realize that there is nothing wrong with a bit of relief.

As James Walmsley, writing in the British Medical Journal (2002: 324 1158 Letters: "The fact that people keep buying the medicines is itself evidence"), noted that's all that physicians can really offer for the common cold. As he observes: "Patients derive enough benefit from over the counter cough medicines to purchase them in the first place and to keep returning for more."

Indeed, if people start to think that cough medicines are ineffective and dangerous, they might just turn up at their family doctor for help every time they get a cough and cold, something that everyone concedes is not only a vast waste of time and scarce health care resources, but likely to increase the already overuse of antibiotics.

Pediatric lung specialist William Glomb, who helped write the new guidelines for cough in children, told WebMD that he frequently treats children with products such as Robitussin -- which contains DM -- and will continue to do so, even though the ACCP's guidelines recommend against this. "I have discussed this with every pediatric pulmonologist that I know, and we all use it," he says. "It works wonderfully to clear the mucus out."

Though he disagrees with some of the wording in the new guidelines, Glomb does agree that coughs in children should not necessarily be treated. "When children cough it is generally because they need to get out whatever it is that is in there," he says. That stance was echoed by Kenneth J. Reid Jr., a pediatrician who objected to the advice from the American Academy of Pediatrics on the use of DM for children in 1997, in a letter to Pediatrics that "children, like adults, should have the benefit of reduction of pain and discomfort."

But not at the expense of safety, of course. And according to the ACCP, cough medicines should not be used with children as they "may experience significant morbidity and mortality."

These medicines are deadly? How so?

The ACCP refers to three pieces of evidence: The AAP's "Use of Codeine- and Dextromethorphan-Containing Remedies in Children," a study by Veronica Gunn et al on the risks of OTC cough medicines and a general study by C. Chien et al about the risks of all OTC medications and children.

The AAP report, contra the ACCP, says that cough medicine containing DM is "efficacious for cough suppression in adults." The risks for children from cough medicines, meanwhile, mostly are from the older codeine-based medicines. It references one report in which children receiving dosages greater than 5 mg/kilogram/day (100 mg for a 44 pound child) died. However, it makes clear that these deaths were associated with overdosage: "Dosages of codeine less than 2 mg/kg (40 mg for a 44 pound child) are unlikely to be associated with significant adverse reactions."

Dextromethorphan is not codeine. This is its great advantage, for children and adults. The AAP report notes that DM can also pose a risk such as "behavioral disturbances" and "respiratory depression," but only in cases of "acute overdosage." In other words, the AAP evidence about the risks of DM is about the risks of overdosage -- not use as directed. It found no studies of pediatric mortality from using DM.

The Gunn study presented "3 cases of children who suffered significant morbidity from OTC cough and cold preparations. ..." In two of the cases, the children had not been given dextromethorphan, so they are not relevant to the ACCP's claim of significant morbidity and mortality risks. In the third case where the child had been given dextromethorphan, the risks were again due to an exceptionally high dosage.

As for the third study, it is about risks of unintentional ingestion of over the counter medications by children, with the harm largely coming from children getting into medicines that don't have child proof closures.

Most significantly, one of the ACCP's major pieces of evidence against cough medicine effectiveness in children, the Schroeder and Fahey study "Should we advise parents to administer over the counter cough medicines for acute cough?" reported, contra the ACCP's alarmism, that "most drugs appeared to be well tolerated with a low incidence of mostly minor adverse effects." The adverse effects reported for DM included hyperactivity and diarrhea, which is a bit removed from "significant morbidity and mortality".

So, what of the ACCP's claim that DM based cough medicines pose a significant morbidity and mortality risk for children? The evidence suggests that such is only in cases of excessive overdoses, which can occur with many kinds of medicines.

Just about everyone can agree on two things about coughs: everyone gets them and everyone wants them to go away as quickly as possible. As for the ACCP's latest bit of cough wisdom, well, the only thing that can be added is something we all already know: Don't exceed the recommended doses of any medicine for children.

John Luik is writing a book about health policy.

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6 Comments

Turn your head and cough?
The only time I was asked to do that was at a recruiting depot...and it didn't have anything to do with a cold rememdy.

Cough Be Gone
“They understand that nothing makes the cough go away…”

Based on my non-scientific personal experience, the above statement is mostly untrue. Further, OTC cough medicines are NOT an effective treatment for acute cough’s…the kind often accompanied by fever, headaches, body aches, and significant chest congestion. However, prescription cough medicines have proven to directly relieve the congestion, mitigate the accompanying symptoms and eventually result in the ability to resume normal activity. In other words, there are medicines that work, it is just that they are unavailable without a prescription.

The ACCP has claimed that certain OTC cough/cold medicines are ineffective and/or harmful… without suggesting a remedial course of action. If the ACCP’s goal was to improve the condition of the sick, they should have identified those medicines with proven effectiveness, and proposed that they be made available OTC.

Caution: Luik is not a doctor
It is clear why the pharmaceutical industry might not like that another renowned objective review of the medical evidence has found little sound clinical evidence to support the use of dextromethorphan. Luik's little Medline search does not instill confidence, as he didn't critically exam the studies' methodologies. He picked and choosed lines from abstracts to support what he wanted readers to believe.

So, let's turn to one of the most well-respected reviews of clinical research, relied upon by the scientific and medical community for its objective and critical examinations of available clinical, randomized controlled trials: Cochrane. It found: "The evidence for effectiveness of over-the-counter cough medicines is weak."

"The results of this review suggest that there is no good evidence for or against the effectiveness of OTC medications in acute cough....Many studies were of low quality and very different from each other, making evaluation of overall efficacy difficult."

That is very similar to the review by the ACCP which Luik and the drug companies find threatening:
"There is no clinical evidence that over-the counter cough expectorants or suppressants actually relieve cough. … Cough and cold medicines are not useful in children and can actually be harmful."

But that's okay, if you can get people to believe your drug works, then any placebo is okay to sell. This is a free country, after all.

So What?
So what if the author isn't a doctor? It doesn't take a doctor to understand the results of these studies, or to read the conclusions of doctors.

And just because the pharmaceutical industry may like the conclusions of this article does NOT make the article wrong.

-Bob

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