Potentially Overlooked Risk for Neuropsychiatric Symptoms in Children: Montelukast Treatment

Abstract

Background: Montelukast is a leukotriene receptor antagonist commonly used in allergic diseases. In this study, we investigated the frequency, severity and risk factors for neuropsychiatric side effects and sleep disorders associated with montelukast in children.

Method: Children aged 6 months to 17 years prescribed montelukast for allergic rhinitis or asthma at 31 Paediatric Allergy and Immunology centres were enrolled in this cohort study. At enrollment, sociodemographic characteristics, prior diagnoses of neuropsychiatric diseases or sleep disorders, and indications for montelukast treatment were recorded, and the primary caregivers completed a baseline questionnaire about neuropsychiatric symptoms (insomnia, nightmares and depressed mood) of their children. All participants were followed up for 1 month, and a post-treatment follow-up questionnaire on neuropsychiatric symptoms was completed at the end of this period. Moreover, caregivers were instructed to contact the clinic if neuropsychiatric side effects or sleep disorders were observed during this period.

Results: Total of 1163 children were enrolled. There was a significant increase in the frequency of insomnia, nightmares, night terrors, drowsiness, behavioural problems, irritability, depressive mood, agitation, anxiety, hyperactivity, learning difficulties and headache during the 1 month period after montelukast treatment compared to the previous 1 month (p < 0.001 for all). Overall, caregiver reports of neuropsychiatric symptoms in children increased from 172 (14.8%) to 399 (34.3%) after 1 month of montelukast treatment (p < 0.001).

Conclusions: Montelukast treatment increases the risk of neuropsychiatric symptoms and sleep disorders in children with allergic diseases, especially if there is concomitant use of antihistamines.

Keywords: allergy; antihistamine; asthma; montelukast treatment; neuropsychiatric symptoms.

FIGURE 1

A total of 1542 patients included in the study. Of these, 379 patients were excluded because they did not complete the follow‐up questionnaire, were duplicate enrollments, or had missing data. The data of 1163 cases who met all the inclusion criteria and who completed the follow‐up were included in the study. The 399 children developed neuropsychiatric symptoms but completed the follow‐up questionnaire at the end of one‐month follow‐up.

FIGURE 2

(A) Model findings of neuropsychiatric side effects or sleep disorders reported in the National Montelukast Cohort in allergic children due to the past reporting of these events. Amongst children who reported neuropsychiatric symptoms or sleep disorders in the past, headache and drowsiness (somnolence) were associated with the highest increase in occurrence risk with montelukast use (9.2‐fold and 8.2‐fold increase in risk, respectively). Increase in the risk of nightmares, learning disabilities and behavioural symptoms were also observed (Adjusted risk ratios of 6.3, 5.6 and 5.3, respectively). Ins: Insomnia, Nmr: Nightmare, Nter: Night terror, Drws: Drowsiness, Bpb: Behavioural problems, Irt: Irritability, Dps: Depressive mood, Agt: Agitation, Anx: Anxiety, Exa: Excess activity, Ldf: Learning difficulty, Hch: Headache, Lrl: Lower range limit, Url: Upper range limit, OR: Odds Ratio. (B) Model findings of neuropsychiatric side effects or sleep disorders reported in the National Montelukast Cohort in allergic children due to antihistaminic drug use at the baseline. Antihistamine use at admission independently was associated with an increase in many neuropsychiatric side effects caused by montelukast treatment, including lethargy (OR = 1.67), behavioural problems (OR = 1.59), hyperactivity (OR = 1.55), learning disability (OR = 1.77) and headache (OR = 1.59). Ins: Insomnia, Nmr: Nightmare, Nter: Night terror, Drws: Drowsiness, Bpb: Behavioural problems, Irt: Irritability, Dps: Depressive mood, Agt: Agitation, Anx: Anxiety, Exa: Excess activity, Ldf: Learning difficulty, Hch: Headache, Lrl: Lower range limit, Url: Upper range limit, OR: Odds Ratio.