Many were never told asthma drug could induce despair

FDA issued warning on side effects in 2020

In early 2020, the Food and Drug Administration responded to decades of escalating concerns about a commonly prescribed drug for asthma and allergies by deploying one of its most potent tools: a stark warning on the drug’s label that it could cause aggression, agitation, and even suicidal thoughts.

The agency’s label, which was primarily aimed at doctors, was supposed to sound an alert about the 25-year-old medication, Singulair, also known by its generic name, montelukast. But it barely dented use: The drug was still prescribed to 12 million people in the United States in 2022.

Children face the greatest risks of the drug’s ill effects, and while usage by minors did decline, it was still taken by 1.6 million of them — including Nicole Sims’ son. Sims had no idea why, at 6, her son started having nightmares and hallucinations of a woman in the window. When he told her that he wanted to die, Sims went online, desperate for answers.

Only then did she learn about the FDA warning. She also found a Facebook support group with 20,000 members for people who had experienced side effects of the drug. Members of the group recounted a haunting toll that they linked to the drug with the help of peers, not their doctors.

“It’s a mental health crisis that nobody is recognizing,” said Anna Maria Rosenberg, an administrator of the group.

The FDA’s handling of Singulair illustrates systemic gaps in the agency’s approach to addressing troubling side effects from medicines approved long ago — and to warning the public and doctors when serious issues arise. The agency had flagged the 2020 warning label, known as a “boxed warning,” to physicians’ groups, but it had not required that doctors be educated about the drug’s side effects.

Federal regulators in 1998 initially dismissed evidence that emerged during the approval process about the drug’s potential to affect the brain and did not revise their assessment until two decades later. The FDA was slow to alert the public as reports of psychiatric problems surfaced, highlighting deficiencies of a drug-monitoring system that puts the onus on drugmakers to report problems.

Federal regulators themselves can be blind to the full scale of a problem: The FDA discovered nearly a decade ago that Merck, the maker of Singulair, received thousands more reports of side effects from the drug than the agency or its global counterpart. And after a teenager’s high-profile suicide in 2007, the FDA stopped short of forcing Merck to conduct more rigorous and expensive studies that could have made clear how common bad reactions were.

Prescribing of the drug has remained at high levels, raising questions about whether the alert reached enough doctors and patients, who often don’t read the fine print on the drug’s tightly folded label, tucked into a bag at the pharmacy.

Many doctors support the drug’s availability and see existing cautions as sufficient. But researchers have grown increasingly alarmed about its effects, especially on children, and about what they see as the FDA’s failure to determine how many have been harmed or to get the word out to doctors.

“What are the great studies that tell us how often it happens? There aren’t any,” said Thomas Moore, of the Johns Hopkins Center for Drug Safety and Effectiveness, who has long tracked reports of montelukast’s psychiatric effects. “This is a structural problem.”

Dr. Reshma Ramachandran, a Yale University assistant professor and family doctor, said the warning had not broken through to channels that doctors notice and that the agency “needs to do much more in terms of direct communication to clinicians and through more active channels.”

In issuing the warning in March 2020, the FDA required pharmacists to hand out a medication guide and added the warning, with a thin black line as a border, to the drug label. The agency also sent a safety alert to email subscribers, flagged the warning to dozens of professional and patient groups, and published an article in a medical journal on its reasoning.