Montelukast for Children with Obstructive Sleep Apnea: Results of a Double-Blind, Randomized, Placebo-Controlled Trial

Abstract

Rationale: Obstructive sleep apnea (OSA) is highly prevalent in children and is usually treated by adenotonsillectomy. Nonsurgical therapies for OSA consist primarily of antiinflammatory approaches and have gained popularity, but their efficacy remains to be critically examined.

Objectives: To determine the effect of montelukast on pediatric OSA.

Methods: A prospective randomized double-blind controlled trial of polysomnographically diagnosed OSA in children ages 2-10 years who were treated with either oral montelukast (4 or 5 mg daily) or placebo for 16 weeks. Adherence to the medication was ascertained using automated timed pill dispensers along with weekly telephonic reminders.

Measurements and main results: Ninety-two children diagnosed with OSA were approached, and 64 (69.6%) agreed to participate. Of these, 57 (89.0%) completed the 16-week trial, 28 in the montelukast group and 29 in the placebo group. Age, sex, and percentage of obesity were similar in the two groups, as were initial apnea-hypopnea index (AHI) scores. Overall, intention-to-treat analyses revealed that beneficial effects occurred in 20 children receiving montelukast (71.4%), whereas only 2 (6.9%) of the children receiving placebo showed reductions in AHI score (P < 0.001). Indeed, AHI decreased from 9.2 ± 4.1/hour total sleep time (TST) to 4.2 ± 2.8/hour TST (P < 0.0001) in montelukast-treated children, whereas in children receiving placebo, the AHI did not change (from 8.2 ± 5.0/h TST before to 8.7 ± 4.9/h TST at completion of the trial).

Conclusions: When compared with placebo, montelukast for 16 weeks effectively reduced the severity of obstructive sleep apnea in children 2-10 years of age. These results support a therapeutic role for leukotriene modifiers in pediatric OSA provided that long-term trials confirm current findings. Clinical trial registered with www.clinicaltrials.gov (NCT 00599534).

Trial registration: ClinicalTrials.gov NCT00599534.

Keywords: adenotonsillar hypertrophy; inflammation; leukotrienes; obstructive sleep apnea; tonsils.

Figure 1.

Schematic flow diagram illustrating the trial recruitment process. OM = oral montelukast; P = placebo.

Figure 2.

Effects of a 16-week treatment with oral montelukast or placebo on the severity of sleep-disordered breathing. (A) Individual apnea–hypopnea indices before (solid symbols) and after (open symbols) treatment with oral montelukast (squares) or placebo (circles). (B) Boxplots illustrating median and 95% confidence intervals of apnea–hypopnea indices in response to montelukast or placebo, based on intention-to-treat analyses (P < 0.0001).