Montelukast does not appear to increase the risk for neuropsychiatric adverse events in children and adolescents, according to a study published in JAMA Pediatrics.
Montelukast is a leukotriene receptor commonly used to treat asthma and allergic rhinitis. Starting in 2008, reports emerged about a possible association between montelukast use and neuropsychiatric events like depression, anxiety and suicide, which prompted the FDA to require a boxed warning in 2020 and advise against prescribing it for mild asthma and allergy symptoms. “Since the signal emerged, several studies have been conducted to evaluate it,” Viktor Wintzell, PhD, a researcher in the division of clinical epidemiology at Karolinska Institutet’s Department of Medicine in Stockholm, Sweden, and colleagues wrote. “The available evidence on this safety concern is inconclusive, and the data among children are particularly heterogeneous.”
Wintzell and colleagues tracked neuropsychiatric outcomes for 74,291 children aged 6 to 17 years (47.7% girls; mean age, 12.3 years; standard deviation, 3.3 years) who used montelukast or long-acting beta-agonists (LABAs) in Sweden from Jan. 1, 2007, to Nov. 30, 2021. The cohort study compared 26,462 children taking montelukast with 47,829 taking LABAs. Overall, the researchers reported 310 children from the montelukast group and 566 from the LABA group who experienced neuropsychiatric events up to 1 year after starting medication. This equated to a weighted incidence rate of 2.39 events per 100 patient-years for montelukast and 2.41 per 100 patient-years for LABAs. The weighted analysis showed no significant difference in the incidence of adverse events between the two medications. Additionally, Wintzell and colleagues did not find significant differences in the risk for specific outcomes, including anxiety, depression, sleep disruptions, suicide or attempted suicide, disrupted control of activity, attention and behavior, confusion or psychotic symptoms.
The researchers noted that the incidence of primary outcomes for both drugs increased from 1.69 per 100 patient-years between 2007 and 2011 to 3.03 per 100 patient-years between 2017 and 2021. They hypothesized that the increase was due to changes in screening, diagnosis and awareness of mental health issues.“Suspected neuropsychiatric adverse effects of montelukast have been a major concern for patients, clinicians and regulators,” Wintzell and colleagues wrote. “However, there is still a lack of observational studies confirming the signal; in particular, the need for pediatric evidence has been emphasized.”“In this nationwide cohort study of children and adolescents, we found no support for an association between montelukast and the risk of neuropsychiatric adverse events,” they wrote.
Dr. Kenneth Backman comments:"Since 2008, there has been concern about neuropsychiatric events related to montelukast. While the frequency of this adverse effect has been felt to be small, many practitioners, including ours here at Allergy & Asthma Care, have had patients who have experienced these adverse effects. This study calls into question whether these symptoms were truly caused by montelukast. It is important to remain vigilant for these types of symptoms, and at this point, we would still recommend discontinuing montelukast if neuropsychiatric adverse effects develop, pending further information."
