In total, 774 cases of nightmares were reported, with 467 of the cases occurring in patients aged 19 years and younger using montelukast.
Montelukast (Singulair, Merck), a guideline-recommended therapy for asthma in both children and adults, has been shown to cause severe neuropsychiatric symptoms, including nightmares, shortly after starting the treatment.
Led by Meindina Haarman (pictured), MD, of the University Medical Center Groningen in the Netherlands, the study sought to examine the safety profile of the drug in order to give prescribing physicians a better understanding of the adverse drug reactions (ADRs) experienced by patients.
The data showed that depression in adults, aggression in children, headaches, and nightmares were reportedly the most common adverse events in the patient population. The data on reports of disproportionality (ROR), used to determine a link between montelukast and ADRs, were obtained by using retrospective analysis of studies involving the global VigiBase database and a Dutch database, as well as VigiLyse, a search and analysis tool.
"In our study, we gave prescribing physicians the advice to be alert for signs and symptoms for allergic granulomatous angiitis and for severe neuropsychiatric symptoms," Haarman told MD Magazine. "The patient and doctor still decide whether or not to treat with montelukast. The most important thing people need to know from our study is that they should be aware of neuropsychiatric symptoms when using montelukast. People using montelukast should consult their physician in time if they have any doubts about this medication or possible side effects."
The study found 331 reports of ADRs related to montelukast in the Dutch database, 37.5% (n=124) of which were reported in men and 61.3% (n=203) in women. Children aged 0 to 18 years were involved in 32.3% (n=107) of cases, and adults 19 years and older were involved in 64.7% (n=214) of cases.
In total, 45 (13.6%) cases were reported as “serious”, including 2 deaths: 1 involving a pulmonary embolism with doubtful relation to montelukast and 1 involving renal failure with possible relation to the drug. Hospitalization occurred in 26 cases, with 10 patients recovering, 7 remaining in the hospital at the end of the study, 3 failing to recover, and 6 with an unknown status. None of the hospitalized patients died.
In the VigiBase, there were 17723 reports of ADRs, with 6960 (39.3%) in men and 9732 (54.9%) in women. Children aged 18 and younger were involved in 32.4% (n=5743) of cases, with 20.7% (n=3665) of cases not reporting age.
Haarman and colleagues found that neuropsychiatric symptoms, such as depression, suicidal ideation, aggression, abnormal behaviors, and nightmares, were significantly and frequently observed in both children and adults. The RORs were also markedly high, indicating a strong relationship between the drug and the events, according to the researchers.
The authors wrote that “severe neuropsychiatric symptoms can occur after montelukast in both adults and children for whom montelukast was prescribed; especially nightmares may occur soon after starting montelukast.”
Nightmares were experienced by both children and adults, with 749 reported cases in VigiBase (448 in children <19 years) and 25 in the Dutch database (13 in children <19 years). In the VigiBase, nightmares had RORs of 22.48 (95% CI: 20.8—24.2) and 78.04 (95% CI: 70.0–87.1), for the entire population and children under 19 years, respectively. In the Dutch database, RORs were 19.29 (95% CI: 12.8-29.2) for all cases and 56.72 (95% CI: 56.1-57.4) for children <19 years of age.
"The US drug label for montelukast also states that neuropsychiatric events have been reported in adult, adolescent, and pediatric patients taking montelukast," Haarman said. "Post-marketing reports with montelukast use include agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism, suicidal thinking and behavior (including suicide), tic, and tremor. The clinical details of some post-marketing reports involving montelukast appear consistent with a drug-induced effect."
Aside from nightmares, aggression (ROR 24.99; 95% CI: 23.5-26.6), suicidal ideation (ROR 20.4; 95% CI: 19—22), and abnormal behavior (34.05; 95% CI: 31.8–36.5) had the highest reported RORs. Headaches, insomnia, anxiety, dyspnea, and dizziness were also reportedly present.
Depression was the most frequently reported ADR in the global population (ROR 6.93; 95% CI: 6.5-7.4), while aggression was the highest in children globally (ROR 29.77; 95% CI: 27.5-32.2).
Additionally, a previous study found that montelukast was associated with a 4.5-fold increase in the risk of allergic granulomatous angiitis onset within 3 months. The condition was reported in 563 patients in the VigiBase.