Reuters has seen a scientific presentation reporting how US government researchers discovered that a frequently prescribed asthma medicine initially supplied by Merck & Co (MRK.N) may be associated with major mental health issues in certain patients.

Researchers uncovered how the medicine, available under the name Singulair and generically as montelukast, binds to brain receptors important for psychiatric function.

Merck's Singulair, launched in 1998, quickly became a popular treatment due to its tablet form instead of an inhaler. Early ads claimed mild side effects, likening them to a sugar pill, while the label stated minimal brain impact. Even today, generic versions are prescribed to millions annually.

By 2019, numerous reports of neuropsychiatric side effects, including suicides, linked to Singulair (montelukast) were filed with the FDA. Although these reports don't establish direct causality, they prompted further investigation. In 2020, after years of study, the FDA added a "black box" warning to the medication's label, highlighting significant mental health risks such as suicidal thoughts and behaviors.

Around the same time, the government formed an internal expert panel to investigate why the medicine may cause neuropsychiatric adverse effects, with findings presented for the first time this week at the American College of Toxicology meeting in Texas. 

Jessica Oliphant from the FDA's National Center for Toxicological Research highlighted that laboratory tests showed montelukast significantly binds to brain receptors. Further studies confirmed that the drug reaches the brains of rats, particularly in regions linked to psychiatric effects. However, the FDA has not indicated any immediate plans to update the drug's labeling based on these findings.

According to FDA slides acquired by Reuters, montelukast's behavior appears to be comparable to that of other medications with neuropsychiatric effects, such as the antipsychotic risperidone. The FDA has stated that its tests are still underway and that the results have not yet been finalized.

When the FDA introduced the black box, it referenced studies by Julia Marschallinger and Ludwig Aigner of Austria's Institute of Molecular Regenerative Medicine.

Both told Reuters on Thursday that the new data revealed "significant binding" of montelukast to receptors in the brain. According to the researchers, the receptors involved regulate mood, impulse control, cognition, and sleep, among other tasks.

Negative effects 'concerning'

According to the two experts, the research does not establish if that binding mechanism actually causes negative consequences in individuals or people particularly at risk. However, Marschallinger stated that the new evidence supports claims from persons who have had negative effects.

"It's definitely doing something that's concerning," according to Marschallinger.

Organon, a Merck subsidiary that currently markets Singulair, issued a statement expressing confidence in the drug's safety profile, saying the label contains "appropriate information regarding Singulair benefits, risks, and reported adverse reactions."

Reuters reported last year that the FDA received hundreds of reports of patients, including many minors reporting depression, suicidal thoughts and acts, or other psychological issues after starting montelukast.

By 2019, the FDA had recorded 82 suicides associated with Singulair and its generic variants in its adverse-event database since 1998. At least 31 of the complaints concerned individuals aged 19 or younger.

Nick, Robert England's 22-year-old son, committed suicide in 2017 less than two weeks after taking montelukast. England recalls his son having difficulty sleeping before he died, but claims he was totally healthy and had no mental health issues previous to taking the medicine.

"He was on that medication for just days, literally just days," England recalled. "It completely changed the trajectory of our lives."

The Reuters investigation also revealed complaints saying that Merck knew from early studies that the medicine may affect the brain and understated the risk of mental issues in regulatory declarations. Many of the lawsuits are still pending.