Doctors Continue to Prescribe Asthma Medication to Children Despite Possible Mental Health Concerns

Back in 1998, a new medicine for allergies and asthma came into the picture in the U.S. It was called montelukast but went by the more familiar name Singulair. Advertisements with flowers and cats soon filled the airwaves, claiming it was a "different way to treat allergies." Over the next twenty years, many doctors favored this pill, especially for kids, as it spared them the hassle of using inhalers.

For most, it was like taking vitamins, as noted by Andrei Constantinescu, a pediatric pulmonologist at Columbia University Medical Center. However, not everyone had a smooth experience. Some who took montelukast found themselves facing unexpected mental health challenges. Unusual irritability, hallucinations, insomnia, and even thoughts of harming oneself were reported. This disturbing trend was more prevalent in children, leading the Food and Drug Administration to add a serious label warning, known as a "black box," in 2020.

With public awareness growing, scientists are now investigating the extent of these side effects and unraveling how exactly an allergy drug is playing with people's minds. Montelukast falls under the category of leukotriene modifiers, a type of medicine that blocks chemicals produced when the body encounters allergens. This prevents these chemicals, called leukotrienes, from causing unpleasant symptoms like excessive mucus, coughing, and throat tightness.

Despite the concerns, montelukast remains widely used for allergy and asthma treatment worldwide. In 2021, an estimated 31 million people in the U.S. alone were prescribed some form of the drug. The puzzle scientists are trying to solve is how a drug that shouldn't cross the blood-brain barrier is ending up in the brain. Reports to the drug's original manufacturer, Merck (now made by Organon), indicated instances of extreme agitation, insomnia, disturbing nightmares, aggression, anxiety, and suicidal thoughts—most troublingly, in children.

A parent shared a concerning incident involving their three-year-old child on a generic version of montelukast, as documented by the National Center for Toxicological Research. The child displayed distressing behavior, such as banging his head on the wall and hiding kitchen knives under his pillow—fortunately, only accessible butter knives. These testimonials prompted the FDA to issue a black box warning for the drug. The FDA spokesperson assured ongoing scrutiny, with a commitment to update the label based on pertinent data.

The alarming number and intensity of such reports caught the attention of researchers, including Seena Fazel, a psychiatrist from the University of Oxford. Collaborating with forensic psychiatrists, pediatricians, and public health experts, Fazel conducted a study published in JAMA Network Open in 2022. Analyzing health records of over 72,000 asthma patients and nearly 82,500 allergy sufferers on montelukast, the team found a 14% increased likelihood of insomnia diagnosis within a year and a 16 to 17% rise in antidepressant prescriptions.

Fazel emphasizes the relatively small individual risk but underscores its significance on a larger scale. He advocates for further research to comprehend the complete impact of the drug, referring to their findings as a crucial part of the puzzle.

Though the exact workings of montelukast in the brain remain elusive, recent mouse studies propose alterations in dopamine and serotonin levels, potentially impacting mood. Cátia Marques, a systems pharmacologist at the University of Pennsylvania, suggests that children might be more vulnerable to psychiatric side effects due to their developing brains. The drug could function similarly to other allergy medications, crossing the blood-brain barrier.

The question arises: why did these side effects go unnoticed for so long? Retrospectively, early rat studies hinted at montelukast accumulating in rodent brains even 24 hours post-dosing. However, rodent results may not always mirror human trials. The slow development of psychiatric symptoms, which can fluctuate daily, may have eluded notice during initial clinical investigations. Moreover, safety tests primarily focused on acute physical health effects, assuming minimal distribution to the brain at the time.