For decades, people with asthma have turned to the drug montelukast for relief. But new data collected by the Food and Drug Administration is the latest to show this treatment is more dangerous than once assumed—particularly to our brains.
On Friday, Reuters released an exclusive report detailing the FDA’s new research on montelukast, presented at the annual American College of Toxicology (ACT) conference that week. The FDA’s tests reportedly showed that montelukast could enter the brains of rats; they also found that the drug could significantly bind to several receptors found on brain cells. While more research is needed to understand exactly how montelukast can raise the risk of suicide and other mental health problems associated with its use, the findings support the FDA’s recent decision to discourage prescribing the drug as a first-line treatment.
Montelukast was originally developed and sold by Merck, under the brand name Singulair. Approved by the FDA in 1998, the anti-inflammatory drug—taken an once-daily pill—became a mainstay treatment for millions, helping many people prevent and control their symptoms of asthma and other allergies. But over the years, some patients and their families began to report unusual episodes of aggression, depression, suicide ideation, and other neuropsychiatric symptoms that emerged only after they started taking the drug.
The FDA first caught wind of a potential link between montelukast and these symptoms in 2008. As a result of their initial investigation, the FDA mandated new labeling on montelukast and similar drugs that disclosed these possible risks. But the incidents continued to pile up, and by 2019, thousands of reports on montelukast had been sent to the FDA. Between 1998 to May 2019, the FDA had received 82 reports of suicide tied to the drug’s use, with about a third involving children under 19.
In March 2020, the FDA decided to add a black box warning, the strongest type of warning, to Singulair and its generic versions. The new labeling more strongly emphasized the potential risk of suicide and other mental health effects from taking montelukast. The FDA also determined that montelukast should no longer be a first drug of choice for people with allergy or asthma, particularly if their symptoms are mild. Rather, people should only use it if other treatments have failed to help them.
Previous research has shown that montelukast can reach the brain. But the FDA’s new finding that montelukast can significantly bind to brain cell receptors is important since it provides a possible explanation for how it can cause mental health problems. Another key point is where the drug was found accumulating in the brain.
“These data indicate that montelukast is highest in brain regions known to be involved in (psychiatric effects),” said Jessica Oliphant, a deputy director at FDA’s National Center for Toxicological Research, at the ATC conference discussing their findings, according to Reuters.
There are still crucial pieces of the puzzle missing, however. We’re not sure exactly how this binding leads to the problems that some people experience while taking montelukast. And while cases of severe mental illness from montelukast may be rare, we don’t know if some people are more susceptible to the risk than others.
For now, at least, the situation surrounding its use will remain the same. An FDA spokesperson told Reuters that the new data would not change the FDA’s current black box labeling of the drug. Merck did not respond to a request for comment from Reuters, but Organon, a spinoff of Merck that now markets Singulair, did, stating: “The product label for Singulair contains appropriate information regarding Singulair benefits, risks and reported adverse reactions.”
Merck may yet have to answer for its original handling of the drug. The company is reportedly still facing lawsuits from affected patients, some of which have alleged that Merck knew early on about the mental health symptoms associated with the drug and deliberately downplayed their existence to health regulators.
