The asthma drug Singulair may be linked to mental health problems

Government researchers have found that a widely prescribed asthma drug originally sold by Merck & Co may be linked to serious mental health problems for some patients, according to a scientific presentation reviewed by Reuters.

US researchers found that the drug, sold under the brand name Singulair and generically as montelukast, attaches to multiple brain receptors critical to psychiatric functioning.

Singulair was a successful product for Merck after its launch in 1998, offering relief in a pill as an alternative to an inhaler. In early advertising, the company said the side effects were so good they were “similar to a sugar pill,” while the label said any delivery to the brain was “minimal.” Generic versions are still prescribed to millions of adults and children each year.

But by 2019, thousands of reports of neuropsychiatric episodes, including dozens of suicides, in patients given the drug had piled up on Internet forums and the US Food and Drug Administration’s tracking system. Such “adverse event” reports do not prove a causal link between a drug and a side effect, but are used by the FDA to determine whether more study of a drug’s risks is required.

After years of analysis, reports and new scientific research led the FDA in 2020 to add a “black box” warning to montelukast’s prescription label, noting serious mental health risks such as suicidal thoughts or actions.

The agency also assembled a group of internal experts at the same time to look at why the drug might cause neuropsychiatric side effects.

The results of the group’s work, which are preliminary and have not been previously reported or published, were presented to a limited audience at the American College of Toxicology meeting in Austin, Texas on Wednesday.

The FDA said it does not plan to update the drug’s label based on data from the presentation.

‘Something that is disturbing’

The behavior of montelukast appears similar to other drugs known to have neuropsychiatric effects, such as the antipsychotic risperidone, according to FDA slides reviewed by Reuters. The FDA has warned that its studies are ongoing and the results have not been finalized.

When the FDA added the black box, it cited research by Julia Marschallinger and Ludwig Aigner at Austria’s Institute of Regenerative Molecular Medicine.

The two scientists told Reuters on Thursday that the new data showed significant amounts of montelukast present in the brain. The receptors involved play a role in governing mood, impulse control, cognition and sleep, among other functions, they said.

The research does not show whether this binding mechanism directly leads to harmful effects in individual patients, or who is particularly at risk, the two scientists said. However, Marschallinger said the new data bolsters reports from people who reported suffering side effects.

“He’s definitely doing something disturbing,” she said.

A Merck representative did not respond to questions. Organon, a Merck spinoff that now markets Singulair, said in a statement it was confident in the drug’s safety profile.

“The product label for Singulair contains the correct information about Singulair’s benefits, risks and reported side effects,” the company said.

Reuters reported last year that the FDA had received thousands of reports of patients, including many children, experiencing depression, suicidal thoughts and behaviors, or other psychiatric problems after starting montelukast.

As of 2019, the FDA counted 82 suicides linked to Singulair and its generic versions reported in its adverse event database since 1998. At least 31 of those reports involved someone 19 years of age or younger .

Robert England’s 22-year-old son, Nick, killed himself in 2017 less than two weeks after starting montelukast. England recalls his son having trouble sleeping before he died and said he was perfectly healthy and had no mental health issues before taking the drug.

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

The Reuters report also detailed lawsuits alleging that Merck knew from its early research that the drug could affect the brain and downplayed the potential for psychiatric problems in statements to regulators. Many of these lawsuits are still pending.

If you are struggling with suicidal thoughts or are experiencing a mental health crisis and live in New York City, you can call 1-888-NYC-WELL for free, confidential crisis counseling. If you live outside the five boroughs, you can call the National Suicide Prevention Lifeline 24/7 at 988 or go to SuicidePreventionLifeline.org.