Montelukast is a leukotriene receptor antagonist (LTRA) that is one of the most common medications used for asthma and other medical conditions. LTRAs function by inhibiting inflammatory mediators of bronchoconstriction, and they are prescribed primarily as adjuvant medication to inhaled corticosteroids for patients with step 3 or higher asthma, although they might be prescribed as an alternative to inhaled corticosteroids for mild asthma.1 In 2009, the US Food and Drug Administration (FDA) warned clinicians about the use of montelukast, which included certain important observations that may involve neuropsychiatric changes.2 This study was intended to evaluate all potential side effects that have been reported or addressed by searching the MEDLINE database and focusing on neuropsychiatric attributes after starting montelukast, such as sleep disturbance, anxiety, oppositional, depression and any sort of suicidal attempt.3–4 During this decade, numerous studies were released discussing the neuropsychiatric effects of leukotrienes, but the relationship was not direct and remained controversial.5–8 Due to the high prevalence of asthma among children and the serious side effects of montelukast, we decided to investigate whether this popular medication, which is commonly used under limited conditions for pediatric patients, is associated with any neuropsychiatric event in children in five main cities in Saudi Arabia.7–10 Asthma is a common childhood condition, and its prevalence has increased in the last two decades from 8 to 23%.11,12 In the Kingdom of Saudi Arabia, the highest prevalence is reported in Hafoof (33%), and the lowest is reported in the southern region of the kingdom (Abha) (7%).13 Unfortunately, the majority of asthma cases in the Kingdom of Saudi Arabia are uncontrolled, as reported by Dr. Jahdali et al using Asthma Control Test (ACT).14 A similar study was conducted by Dr. Aslan et al., which showed that 50% of asthma cases among children were uncontrolled in a tertiary center in Riyadh.15 Asthma is an often heterogeneous disease with a wide range of presentations from mild cough to severe exacerbation with different asthma phenotypes.16,50 Asthma cases are often divided into two main groups: a younger age group and an older age group. Such classification helps health care providers diagnose and manage the patients’ conditions. In patients older than 5 years of age, it is easy to diagnose asthma, as it is straightforward based on clinical presentation. asthma medical history suggesting asthma includes intermittent cough that is often worse in winter, at night or after exercise. The cough in asthma is often dry except during exacerbation and then becomes wet and is associated with wheezing, shortness of breath, and chest tightness. Such patients respond well to asthma therapy, including bronchodilators or corticosteroids. There are different types of montelukast that are used for this group as add-ons to inhaled steroids, and they are often chewable tablets (4,5 or 10 mg) 16,17,18. However, it is a real challenge for health care providers to diagnose asthma in patients younger than 5 years, as patients of this age are unable to undergo spirometry may have similar conditions that share the same symptoms of cough, wheezing and shortness of breath. Furthermore, there are different asthma phenotypes and different presentations, which are often summarized as follows:
- a residual cough after a flu-like illness;
- coughing late at night or early in the morning, which could be the only presentation of asthma;
- recurrent or persistent wheezing; and
- bronchopneumonia, which is rare.
- Currently, the majority of asthma cases worldwide are still uncontrolled, even in Saudi Arabia, per different reports; fortunately, there has been some improvement according to recent publications.19–22 Montelukast plays an important role in the management of asthma, nasal allergies and sleep-related breathing disturbances, and the most common types of montelukast are 4 mg granules or chewable tablets.17 Allergic rhinitis and sinusitis are frequent causes of nocturnal coughing and are most often misdiagnosed as asthma. They share triggers with asthma, and there are two main types of presentation: Type 1 (non-inflammatory /watery) is the predominant type, and the child presents with clear nasal discharge, sneezing and nasal itching; and Type 2 (inflammatory) is the less common type, and the child presents with a blocked nose and signs of nasal obstruction.23,24,66 Allergic rhinitis should also be suspected if the presentation is associated with other clinical features of allergic rhinitis, such as sneezing, nasal blockage, allergic salute, or allergic shiners, or if the response to asthma medications is poor. Commonly used medications include intranasal corticosteroids and oral antihistamines.23 Intranasal antihistamines may be necessary to improve the treatment of nonallergic rhinitis with eosinophilia(NARES) or vasomotor rhinitis.24,25 Longitudinal studies have confirmed that both allergic rhinitis and positive allergic skin tests are risk factors for asthma.26 Montelukast is often used as an adjuvant to inhaled steroids for asthma with proven efficacy,27 and allergic rhinitis is often associated with asthma and called united airway disease.28 Chronic rhinosinusitis with and without nasal polyps may aggravate some symptoms, particularly coughing, which may be attributed to severe asthma. 29–30 Sleep-related breathing disorders are characterized by prolonged partial upper airway obstruction and/or intermittent complete obstructive apnea that disrupts normal ventilation during sleep and normal sleep patterns.31 Classification based on polysomnography results as proposed by Dayyat, E. et al. stated that it is essential to differentiate OSA from other disorders as the treatment and complications are different.32 OSA occurs in children of all ages, and the prevalence varies depending on the populations studied and on the stringency of the diagnostic criteria. The prevalence is 1 − 5% among children, with the peak prevalence occurring between the ages of 2 − 8 years and the peak of symptoms often occurring in the middle of the second year, which could be related to the peak growth of lymphoid tissue.33–35 While the prevalence of habitual snoring is estimated to be approximately 15%, although it has been reported to be as high as 30% in the pediatric age group, the ratio of the prevalence of habitual snoring and OSA varies from 4:1 to 6:1.36 OSA occurs equally among boys and girls during the prepubertal stage. 34, 37–40 OSA has been reported to cause significant school problems among children, such as short attention span, aggressive behavior, poor academic performance, excessive daytime sleepiness, behavioral disorders, and multiple other problems, including cardiac growth and metabolic consequences. 41–43 Inhaled steroids and montelukast are effective medical therapies for mild forms of OSA. 44–50