Relationship between montelukast and behavioral problems in preschool children with asthma

Main Article Content

Eda Özata
Zülfikar Akelma
Sacit Günbey

Keywords

Preschool children, Asthma, Montelukast, Check Behavior Checklist, Behavior Problems

Abstract

Background: There is insufficient clarity regarding whether or not drugs used in asthma cause behavioral problems in children.


Methods: A total of 155 individuals, categorized into an asthma group (n = 95) and a control group (n = 60), were enrolled in the current prospective controlled study. The asthma group consisted of patients receiving treatment (inhaled corticosteroids [ICS] or montelukast) for at least 1 month. Check Behavior Checklist (CBCL) for ages 1.5–5 scores for the asthma and controls were compared. The asthma group was divided into two subgroups based on prophylactic therapy received, ICS and montelukast, and these groups’ CBCL scores were also compared.


Results: The asthma group consisted of 95 children (ICS subgroup 45, montelukast subgroup 50) and the healthy control group of 60 cases. The mean total CBCL score was higher in the asthma group than in the control group (42 vs 32, respectively, P = 0.001). Internalization and externalization scores were also higher in the asthma group compared to the control group (P = 0.004 and P = 0.005, respectively). No significant difference was determined in terms of CBCL scores between the ICS and montelukast groups (P = 0.3). Montelukast was discontinued in one asthmatic child due to hallucination.


Conclusion: This study determined a higher rate of behavioral problems in preschool children with asthma compared to healthy children. In contrast to other studies in the literature, we determined no difference in terms of total CBCL, and internalization and externalization scores of children with asthma who received ICS and montelukast. Nevertheless, it should be kept in mind that montelukast may cause serious neuropsychiatric events such as hallucination.

Abstract 90 | PDF Downloads 55 HTML Downloads 4 XML Downloads 4

References

1. Soriano JB, Abajobir AA, Abate KH, Abera SF, Agarwal A, Ahmed MB, et al. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir Med. 2017;5(9):691–706. 10.1016/S2213-2600(17)30293-X

2. Calam R, Gregg L, Simpson B, Morris J, Woodcock A, Custovic A. Childhood asthma, behavior problems, and family functioning. J Allergy Clin Immunol. 2003;112(3):499–504. 10.1016/S0091-6749(03)01606-3

3. McQuaid EL, Kopel SJ, Nassau JH. Behavioral adjustment in children with asthma: A meta-analysis. J Dev Behav Pediatr. 2001;22(6):430–9. 10.1097/00004703-200112000-00011

4. Scadding GK, Kariyawasam HH, Scadding G, Mirakian R, Buckley RJ, Dixon T, et al. BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis (Revised Edition 2017; First edition 2007). Clin Exp Allergy. 2017;47(7):856–89. 10.1111/cea.12953

5. Aldea Perona A, García-Sáiz M, Sanz Álvarez E. Psychiatric disorders and montelukast in children: A disproportionality analysis of the VigiBase®. Drug Saf. 2016;39(1):69–78. 10.1007/s40264-015-0360-2

6. Haarman MG, van Hunsel F, de Vries TW. Adverse drug reactions of montelukast in children and adults. Pharmacol Res Perspect. 2017;5(5):e00341. 10.1002/prp2.341

7. Benard B, Bastien V, Vinet B, Yang R, Krajinovic M, Ducharme FM. Neuropsychiatric adverse drug reactions in children initiated on montelukast in real-life practice. Eur Respir J. 2017;50(2):1700148. 10.1183/13993003.00148-2017

8. Glockler-Lauf SD, Finkelstein Y, Zhu J, Feldman LY, To T. Montelukast and neuropsychiatric events in children with asthma: A nested case–control study. J Pediatr. 2019;209:176–82.e4. 10.1016/j.jpeds.2019.02.009

9. Philip G, Hustad CM, Malice MP, Noonan G, Ezekowitz A, Reiss TF, et al. Analysis of behavior-related adverse experiences in clinical trials of montelukast. J Allergy Clin Immunol. 2009;124(4):699–706.e8. 10.1016/j.jaci.2009.08.011

10. Philip G, Hustad C, Noonan G, Malice MP, Ezekowitz A, Reiss TF, et al. Reports of suicidality in clinical trials of montelukast. J Allergy Clin Immunol. 2009;124(4):691–6.e6. 10.1016/j.jaci.2009.08.010

11. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. Søren Pedersen M, Helen K Reddel, MBBS PhD, Editor; 2017.

12. Achenbach TM, Rescorla LA. Manual for the ASEBA preschool forms and profiles: An integrated system of multi-informant assessment. Burlington, VT: University of Vermont Department of Psychiatry; 2000.

13. Mirabelli MC, Hsu J, Gower WA. Comorbidities of asthma in U.S. children.Respir Med. 2016;116:34–40. 10.1016/j.rmed.2016.05.008

14. Del Giacco SR, Cappai A, Gambula L, Cabras S, Perra S, Manconi PE, et al. The asthma-anxiety connection. Respir Med. 2016;120:44–53. 10.1016/j.rmed.2016.09.014

15. Vila G, Nollet-Clemençon C, De Blic J, Mouren-Simeoni MC, Scheinmann P. Prevalence of DSM IV anxiety and affective disorders in a pediatric population of asthmatic children and adolescents. J Affect Disord. 2000;58(3):223–31. 10.1016/S0165-0327(99)00110-X

16. Booster GD, Oland AA, Bender BG. Psychosocial factors in severe pediatric asthma. Immunol Allergy Clin North Am. 2016;36(3):449–60. 10.1016/j.iac.2016.03.012

17. Quak W, Klok T, Kaptein AA, Duiverman EJ, Brand PLP. Preschool children with high adherence to inhaled corticosteroids for asthma do not show behavioural problems. Acta Paediatr Int J Paediatr. 2012;101(11):1156–60. 10.1111/j.1651-2227.2012.02805.x

18. US Food and Drug Administration. Updated information on leukotriene inhibitors: Montelukast (marketed as Singulair), Zafirlukast (marketed as Accolate) and Z (marketed as Z and ZC. U.S. Food and Drug Administration. Available from: https://wayback.archive-it.org/7993/20170111080414/http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm165489.htm. 10.1201/b19633