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A prospective, randomized, placebo-controlled, double-blind study of montelukast's effect on persistent middle ear effusion.


We conducted a prospective, randomized, placebo-controlled, double-blind study to determine if the leukotriene inhibitor montelukast is effective in eliminating persistent middle ear drainage in patients with otitis media with effusion (OME). Our study population was made up of patients aged 2 to 6 years who had had confirmed OME in one or both ears for at least 2 months. Patients were randomized to receive either placebo or 4 mg of montelukast daily for 1 month. The main outcome measure was clearance of middle ear effusion as demonstrated by otoscopy and tympanometry 1 month after the initiation of treatment. Our goal was to recruit 120 patients; however, an interim analysis was conducted after 38 patients had completed their regimen (19 patients in each group) when it became apparent that montelukast was not having any effect in clearing the effusions. Indeed, the OME had cleared in only 3 montelukast patients (15.8%) and 4 controls (21.1%); the difference was not statistically significant (p > 0.90). Based on this early trend, the study was terminated at this point. We conclude that montelukast appears to be no more effective than placebo in eliminating persistent middle ear effusion.


Proven nonsurgical therapies for persistent otitis media with effusion (OME) are nonexistent. In fact, the only conservative management strategy available is watchful waiting. Obviously, the clinical and economic benefits of an effective medical treatment for OME would be significant.

One common denominator among children with persistent OME is eustachian tube dysfunction. Leukotrienes have been implicated in the pathogenesis of eustachian tube dysfunction, (1-4) and a leukotriene receptor antagonist has been shown to be beneficial in preventing the development of middle ear fluid after an inflammatory challenge in the guinea pig model. (5)

In humans, a randomized, controlled study by Combs showed that the leukotriene receptor antagonist montelukast in combination with amoxicillin was significantly more efficacious in clearing persistent OME than was amoxicillin and placebo (clearance rates: 58 and 16%, respectively). (6) However, because that study involved the use of two medical interventions, it could not be concluded with certainty that the clearing effect was indeed attributable to the montelukast or if it was actually attributable to the amoxicillin. Therefore, we conducted a prospective, randomized, placebo-controlled, double-blind study of montelukast alone to determine if it has any beneficial effect in clearing middle ear effusion.

Patients and methods

Our study population was recruited from among all new patients aged 2 to 6 years old who had presented with persistent middle ear fluid of at least 2 months' duration. The presence of middle ear fluid in at least one ear was confirmed by otoscopy by a single otolaryngologist (S.R.S.) and validated independently via tympanometry performed by a research nurse (A.W.). Patients were recruited from among the patient population at the Connecticut Children's Medical Center in Hartford and regional offices in Avon, Conn., and Glastonbury, Conn., from September 2005 through February 2007. Recruitment was conducted throughout the year so that in terms of the timing of presentation, all seasons were represented.

Exclusion criteria included a history of allergy, current use of montelukast for asthma or allergic rhinitis, a previous adverse reaction to montelukast, the presence of a craniofacial disorder, the use of a systemic steroid within 1 month prior to presentation, the presence of acute otitis media (AOM) at presentation, and a parental desire that the child remain on prophylactic antibiotic treatment as prescribed by a primary care provider.

Eligible patients were randomized to receive either placebo or 4 mg of oral montelukast once each evening for 1 month.After 1 month of treatment, repeat otoscopy and tympanometry were scheduled for all participants. At the follow-up, the research nurse determined adherence to the medication regimen by counting the number of returned pills; compliance was defined as the administration of at least 50% of the scheduled doses.

Statistical analysis was performed with the Fisher exact test. The study protocol was approved by the Institutional Review Board at the Connecticut Children's Medical Center.


Early in the study, it became apparent that the montelukast regimen was not having any effect. After 38 patients had completed their regimen (19 in each group), an interim analysis was performed. At this point, OME clearance was seen in only 3 montelukast patients (15.8%) and 4 controls (21.1%); the difference between the two groups was not statistically significant (p > 0.90). Based on this early trend, the study was terminated by the funding sponsor.

No significant adverse effects were observed during the study.


Although leukotrienes have been implicated in the pathogenesis of eustachian tube dysfunction, our study did not demonstrate that the leukotriene inhibitor montelukast had any effect in clearing middle ear fluid. The initial enthusiasm for montelukast, which had been based in part on the results of the study by Combs, (6) was not supported by our findings. It is possible that the 58% clearance rate in the Combs study was attributable to the effects of some synergy between montelukast and amoxicillin. Another possible explanation for the difference in outcomes between the two studies is that the patients in the Combs study were somewhat older--2 to 12 years as opposed to 2 to 6 years in our study. Finally, the eligibility criteria in the Combs study allowed for the inclusion of patients with AOM, a condition that is associated with higher rates of spontaneous and posttreatment clearance than is OME, lasting 2 months or more. Therefore, it is likely that our study more accurately reflects the natural course of persistent OME than did the Combs study.

The results of medical treatment of persistent middle ear effusion have been disappointing. Treatments with decongestants, antihistamines, and oral and topical nasal steroids have produced only very limited success, and no appreciable benefit over observation alone has been seen. (7) Therefore, when persistent OME causes significant conductive hearing impairment, the only practical solution remains drainage and ventilation. Certainly, every attempt should be made to find a means to clear OME with medication. Unfortunately, montelukast does not appear to be efficacious for this purpose.


The authors thank Lisa Benson and Bertha Robbins of the Clinical Trials Unit at the Connecticut Children's Medical Center for their help in preparing the protocol for IRB approval, and Trudy Lerer of the same unit for performing the statistical analyses.


(1.) Jung TT. Prostaglandins, leukotrienes, and other arachidonic acid metabolites in the pathogenesis of otitis media. Laryngoscope 1988;98(9):980-93.

(2.) Brodsky L, Faden H, Bernstein J, et al. Arachidonic acid metabolites in middle ear effusions o f children. Ann Otol Rhinol Laryngol 1991; 100(7):589-92.

(3.) Ganbo T, Hisamatsu K, Shimomura S, et al. Inhibition of mucociliary clearance of the eustachian tube by leukotrienes C4 and D4. Ann Otol Rhinol Laryngol 1995;104(3):231-6.

(4.) Enomoto F, Ichikawa G, Nagaoka I, Yamashita T. Measurement of leukotrienes C4 and D4 in the effusion of otitis media. In: Mogi G, Honjo I, Ishii T, eds. Recent Advances in Otitis Media. Proceedings of the Second Extraordinary International Symposium. Otia, Japan; Amsterdam, Netherlands: Kugler Publications; 1994:655-9.

(5.) Sutbeyaz Y, Yakan B, Ozdemir H, et al. Effect of SC-41930, a potent leukotriene B4 receptor antagonist, in the guinea pig model of middle ear inflammation. Ann Otol Rhinol Laryngol 1996;105(6):476-80.

(6.) Combs JT. The effect of montelukast sodium on the duration of effusion of otitis media. Clin Pediatr (Phila) 2004;43(6):529-33.

(7.) Thomas CL, Simpson S, Buffer CC, van derVoort JH. Oral or topical nasal steroids for hearing loss associated with otitis media with effusion in children. Cochrane Database Syst Rev 2006;3:CD001935.

Scott R. Schoem, MD; Alice Willard, RN; Jerome T. Combs, MD

From the Department of Otolaryngology-Head and Neck Surgery (Dr. Schoem) and the Clinical Trials Unit (Ms. Willard), Connecticut Children's Medical Center, Hartford; and the Department of Pediatrics, University of Connecticut School of Health Sciences, Farmington (Dr. Combs).

Corresponding author: Scott R. Schoem, MD, Department of Otolaryngology-Head and Neck Surgery, Connecticut Children's Medical Center, 282 Washington St., Hartford, CT 06106. E-mail:

Previous presentation: The information in this article has been updated from its original presentation at the annual meeting of the American Society of Pediatric Otolaryngology; May 4, 2008; Orlando, Fla.

Funding/support: This study was sponsored by a Medical School Research Grant from Merck & Co.
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Article Details
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Author:Schoem, Scott R.; Willard, Alice; Combs, Jerome T.
Publication:Ear, Nose and Throat Journal
Article Type:Clinical report
Geographic Code:1USA
Date:Sep 1, 2010
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