A popular asthma drug may cause brain damage

For decades, people with asthma have turned to montelukast for relief. But new data from the Food and Drug Administration is the latest to show this treatment is more dangerous than previously thought — especially to our brains.

Reuters on Friday released an exclusive report detailing the FDA’s new research on montelukast, presented this week at the American College of Toxicology (ACT) annual conference. FDA testing has reportedly shown that montelukast can enter the brains of rats; they also found that the drug could 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 to discourage prescribing of this 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 once-daily anti-inflammatory drug has become a primary treatment for millions of people, helping many prevent and control the symptoms of asthma and other allergies. However, over the years, some patients and their families began to report unusual episodes of aggression, depression, suicidal thoughts, and other neuropsychiatric symptoms that did not appear until they started taking the drug.

First the FDA caught the wind a potential link between montelukast and these symptoms in 2008 following a preliminary FDA study ordered new signage regarding montelukast and similar medicines, which revealed these possible risks. However, incidents continued to increase, and by 2019, thousands of reports about montelukast were submitted to the FDA. Between 1998 and May 2019, the FDA received 82 reports of drug-related suicides, approximately one-third of which involved children under 19 years of age.

In March 2020, the FDA decided 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 associated with the use of montelukast. The FDA also determined that montelukast should no longer be a first-line treatment for people with allergies or asthma, especially if their symptoms are mild. Rather, people should only use it when other treatments have not helped.

Previous research has shown that montelukast can reach the brain. However, the FDA’s new finding that montelukast can significantly bind to brain cell receptors is important because it provides a possible explanation for how it may cause mental problems. Another key issue is where the drug has been found to accumulate in the brain.

“These data indicate that montelukast concentrations occur most frequently in areas of the brain known to be involved in (psychiatric effects),” Jessica Oliphant, deputy director of the FDA’s National Toxicology Research Center, said at an ATC conference discussing its findings, according to Reuters.

However, key pieces of the puzzle are still missing. We are not sure how this binding leads to the problems some people experience when taking montelukast. And while cases of severe mental illness caused by montelukast may be rare, we don’t know whether some people are more susceptible to this risk than others.

At least for now, the situation surrounding its use will remain the same. An FDA spokesman told Reuters the new data would not change the drug’s current FDA black box labeling. Merck did not respond to Reuters’ request for comment, but Organon, the Merck spinoff that currently markets Singulair, did, stating: “The Singulair product label provides appropriate information regarding the benefits, risks and reported adverse effects of Singulair.”

Merck may yet have to answer for its original handling of the drug. According to reports, the company is still facing difficulties lawsuits from affected patientssome of which claimed that Merck had early knowledge of the drug’s mental health symptoms and deliberately downplayed their existence to health regulators.