On Friday, Reuters published an exclusive report detailing new FDA research on montelukast presented at the annual conference of the American College of Toxicology (ACT) held this week. The FDA tests showed that montelukast can penetrate the brains of rats; they also found that the drug can bind significantly to several receptors found on brain cells. Although more research is needed to understand exactly how montelukast may increase the risk of suicide and other mental health problems associated with its use, the findings support the FDA’s recent decision not to prescribe the drug as a first-line treatment.
Montelukast was originally developed and marketed by Merck under the brand name Singulair. Approved by the FDA in 1998, this once-daily anti-inflammatory drug has become a staple treatment for millions of people, helping many prevent and control the symptoms of asthma and other allergic diseases. But over the years, some patients and their families began to report unusual episodes of aggression, depression, suicidal thoughts, and other neuropsychiatric symptoms that appeared only after they started taking the drug.
The FDA first learned about the potential link between montelukast and these symptoms in 2008. As a result of its initial investigation, the FDA introduced new labeling for montelukast and similar drugs to indicate these possible risks. But the incidents continued to pile up, and by 2019, thousands of reports about montelukast had been submitted to the FDA. Between 1998 and May 2019, the FDA received 82 reports of suicides related to the drug, with about a third of them involving children under the age of 19.
In March 2020, the FDA decided to add a black box warning, the most stringent type of warning, to Singulair and its generic versions. The new labeling further emphasizes the potential risk of suicide and other mental health effects associated with taking montelukast. The FDA has also determined that montelukast should no longer be the first choice drug for people with allergies or asthma, especially if their symptoms are mild. Rather, people should only use it when other treatments have failed to help them.
Previous studies have shown that montelukast can penetrate the brain. But the FDA’s new finding that montelukast can bind largely to receptors on brain cells is important because it provides a possible explanation for how it can cause mental health problems. Another key point is that the drug accumulates in the brain.
“These findings indicate that montelukast accumulates most in areas of the brain that are known to be involved in (psychiatric effects),” Jessica Oliphant, deputy director of the FDA’s National Center for Toxicological Studies, said at the ATC conference, discussing her findings, according to Reuters.
However, there are still important pieces of the puzzle missing. We are not sure exactly how this connection leads to the problems that some people experience while taking montelukast. And while cases of severe mental disorders caused by montelukast may be rare, we don’t know if some people are more at risk than others.
At least for now, the situation around its use will remain unchanged. An FDA spokesperson told Reuters that the new data will not change the drug’s current black box labeling. Merck did not respond to Reuters’ request for comment, but Organon, the Merck subsidiary that currently markets Singulair, responded, saying: “The label of Singulair contains full information about the advantages and disadvantages of the drug: “The Singulair product label contains relevant information regarding the benefits, risks, and reported adverse reactions of Singulair.”
Merck may yet have to answer for its initial handling of the drug. The company is reportedly still facing lawsuits from affected patients, some of whom allege that Merck knew about mental health symptoms associated with the drug and intentionally downplayed their existence to health regulators.
