Government researchers have found that a widely prescribed asthma drug originally sold by Merck & Co may be linked to serious mental health problems in some patients, according to a scientific presentation reviewed by Reuters.
The American researchers discovered that the drug, sold under the brand name Singulair and commonly as montelukast, attaches to multiple brain receptors that are crucial for psychiatric functioning.
Singulair was a blockbuster product for Merck after its launch in 1998, offering relief in pill form as an alternative to an inhaler. In early advertising, the company said the side effects were so benign they were “similar to a sugar pill,” while the label said the spread in the brain was “minimal.” Generic versions are still prescribed to millions of adults and children every year.
But by 2019, thousands of reports of neuropsychiatric episodes, including dozens of suicides, in patients prescribed the drug had piled up on internet forums and in the U.S. Food and Drug Administration’s tracking system. Such “side effect” reports do not prove a causal relationship between a drug and an adverse event, but are used by the FDA to determine whether more research into a drug’s risks is warranted.
After years of analysis, the reports and new scientific research led the FDA in 2020 to add a “black box” warning to the montelukast prescription label, flagging serious mental health risks such as suicidal thoughts or actions .
The agency also convened a group of internal experts around the same time to investigate why the drug might cause neuropsychiatric side effects.
The results of the group’s work, which are preliminary and have not previously been reported or publicly released, were presented to a limited audience Wednesday at the meeting of the American College of Toxicology in Austin, Texas.
The FDA said it does not plan to update the drug’s label based on data from the presentation.
‘Something that is worrying’
Montelukast’s behavior appears similar to that of 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 investigations are still ongoing and results have not yet been finalized.
When the FDA added the black box, it cited research by Julia Marschallinger and Ludwig Aigner of the Austrian Institute for Molecular Regenerative Medicine.
The two scientists told Reuters on Thursday that the new data showed significant amounts of montelukast were present in the brain. The receptors involved play a role in regulating mood, impulse control, cognition and sleep, among other things, they said.
The research does not show whether this binding mechanism directly leads to harmful effects in individual patients, or in those who are at particular risk, the two scientists said. However, Marschallinger said the new data reinforces reports from people who reported experiencing side effects.
“It definitely does something that is concerning,” she said.
A Merck representative did not respond to questions. Organon, a Merck spin-off that now markets Singulair, said in a statement that it was confident in the drug’s safety profile.
“The product label for Singulair contains appropriate information about the benefits, risks and reported side effects of Singulair,” the company said.
Reuters reported last year that the FDA had received thousands of reports of patients, many of them children, who experienced depression, suicidal thoughts and behaviors or other psychiatric problems after starting to take montelukast.
In 2019, the FDA counted 82 suicides linked to Singulair and its generic versions reported in the adverse drug reaction database since 1998. At least 31 of those reports involved someone 19 years old or younger.
Robert England’s 22-year-old son, Nick, committed suicide in 2017, less than two weeks after starting montelukast. England recalled that his son had trouble sleeping before he died, and said he was perfectly healthy and had no mental health problems before taking the drug.
“He was only on that drug for a few days, literally just a few days,” England said. “It completely changed the trajectory of our lives.”
The Reuters report also details lawsuits alleging that Merck knew from its early research that the drug could affect the brain and minimize the potential for psychiatric problems in statements to regulators. Many of those lawsuits are still pending.
If you are struggling with thoughts of suicide or experiencing a mental health crisis and live in New York City, you can call 1-888-NYC-WELL for free and confidential crisis counseling. If you live outside the five boroughs, you can call the 24/7 National Suicide Prevention hotline on 988 or visit SuicidePreventionLifeline.org.