According to a Reuters investigation, parents trying to sue Merck were “stymied by one of Corporate America’s most effective liability shields: the doctrine of federal preemption” which says federal law and federal regulations supersede state laws, but some are now moving forward.
Dozens of patients, including many children, died by suicide or suffered from neuropsychiatric problems after taking Singulair, Merck’s allergy and asthma medication, according to lawsuits that are finally proceeding, after decades of delays and legal challenges, Reuters reported.
Merck is accused of downplaying early evidence of Singulair’s impact on the brain. These claims “later faced intense scrutiny,” leading to “a raft of lawsuits alleging [Merck] knew … that the drug could impact the brain and that it minimized the potential for psychiatric problems in statements to regulators.”
Singulair, also known as montelukast, is available to adults and children as a medication for severe allergies and asthma. The drug “blocks chemicals, called leukotrienes, in the body,” according to Dr. Michelle Perro, a pediatrician. Leukotrienes “can be involved in the precipitation of asthma and can cause respiratory symptoms, as well as inflammation of the airways,” Perro told The Defender.
Numerous public comments about Singulair’s side effects were submitted in 2019, prior to the Sept. 27, 2019, joint meeting of the U.S. Food and Drug Administration’s (FDA) Pediatric and Drug Safety and Risk Management Advisory Committees charged with reviewing the drug’s safety.
Many of the comments were submitted by “vocal parents” of children adversely affected by Singulair.
Rolf Hazlehurst, senior staff attorney with Children’s Health Defense (CHD), told The Defender he “worked closely” with several of these parents.
The public comments, along with thousands of reports submitted over several years to the FDA Adverse Event Reporting System (FAERS) plus a 2015 research study finding that a “substantial amount” of Singulair entered the brain, forced the FDA to take action.
On March 4, 2020, the FDA required Singulair to carry a “black box” label — the FDA’s most serious warning, for “serious mental health side effects,” according to Drugwatch.
Black box warnings list “important side effect information surrounded by a thick black border and bold lettering to warn of permanent, serious or fatal side effects.”
In the case of Singulair, the label links the drug to “suicide, depression, aggression, agitation, suicidal thoughts and sleep disturbances.”
The black box label was at least two decades in coming, according to Hazlehurst, who said it “took over a decade’s worth of work by persistent parents, armed with overwhelming evidence of the serious neuropsychiatric side effects, urging the FDA to take action.”
According to Drugwatch, lawsuits now pending against Merck claim the drugmaker “knew or should have known before it started selling Singulair in 1998 that the drug could cause neuropsychiatric injuries during treatment and even after stopping.”
Dr. Liz Mumper, a pediatrician, said she has been “aware of the potential neuropsychiatric side effects of montelukast for many years,” adding that her patients “are instructed to stop the medicine if they notice a change in their mental health.”
“Over the years, parents have reported personality changes in their children, rapid changes in mood and irritability,” Mumper told The Defender. “Typically, these symptoms resolve once off montelukast.”
Since March 2020, when the FDA applied the black box warning to Singulair, numerous lawsuits have been filed against Merck. The lawsuits allege Merck designed “a defective drug,” in addition to claiming “negligence and failure to warn about the risk of mental problems,” according to Drugwatch.
A Reuters investigative report revealed the lawsuits also allege “that the company’s own early research indicated the drug could impact the brain but that Merck downplayed any risks in statements to regulators.”
The Reuters investigation states that plaintiffs faced a legal hurdle commonly used by Big Pharma — known as a “preemption defense” — based on a legal argument that federal law and federal regulations supersede state laws, including state product liability laws that traditionally served as the basis for lawsuits like those against Merck.
As a result, “companies increasingly argue that federally regulated products or services should be immune from lawsuits alleging state-law violations,” and plaintiffs “must often demonstrate that a company failed to disclose safety information to federal regulators — and that the information could have spurred new government restrictions or warnings before the alleged harm occurred.”
This has made it particularly difficult to sue manufacturers of generic versions of Singulair and other drugs, because generic drugmakers simply follow the primary manufacturer’s FDA-approved labeling, while the primary drugmaker can’t be sued by claimants if they or their family members took the generic version.
Perro told The Defender that a combination of an abrogation on the part of federal regulators, a lack of integrity on the part of drugmakers and complex legal maneuvering makes it difficult for doctors to prescribe safe treatments to their patients.
She said:
“A medical practitioner now needs to understand their patient, the illness, any prescribed medications, what Pharma reports about their drug, the real science behind the drug, and unfortunately, the legal doctrine of preemption, which is the principle based on federal law trumping state law.
“It is a dark time in medicine when the physician must question the integrity of what is written on the prescription pad.”
The FDA claims it has “diligently monitored reports of side effects possibly associated with montelukast, as well as communicated findings and taken regulatory action, when appropriate,” and that it “continues to monitor and investigate this important issue.”
Merck’s patent on Singulair expired in 2012, allowing generic drugmakers to begin producing and marketing the drug. Still, according to Reuters, Singulair “has provided Merck with about $50 billion in revenue.”
However, once Merck’s patent expired, “The number of patients prescribed the medicine climbed from about 7 million annually to more than 9 million” — with up to half of recipients age 16 or younger.
At least 82 suicides connected to Singular before FDA added black box warning
The Reuters investigation noted that “in the case of Singulair’s potentially deadly side effects, the FDA waited years, despite thousands of reported psychiatric problems, to require its most serious warning on the drug’s label.”
During this time, dozens of individuals taking Singulair committed suicide or faced other neuropsychiatric problems.
For instance, in 2017, 22-year-old Nicholas England, a Virginia resident, shot himself in the head less than two weeks after starting a generic version of the medication. He had no history of mental health problems — and his family had no legal recourse against Merck due to the preemption defense.
In 2007, a 15-year-old boy in New York committed suicide, 17 days after first taking Singulair. According to Reuters, this incident led Merck to propose — and the FDA to accept — an amendment to the drug’s label to add suicidal thinking and behavior to the product’s listed adverse events.
However, this adverse event “appeared in the middle of a list of more than three dozen side effects,” the Reuters investigation found. “Parent advocates argue the new label was grossly inadequate to warn of such a grave risk.”
“Neuropsychiatric side effects are listed in the documentation of potential side effects, but not always prominently,” Mumper told The Defender. And despite the new label, she said, parents searching for its package insert online will find older versions “without a prominent black box warning.”
According to Drugwatch, the change to Singulair’s label was made in August 2009, when the label was updated to also include other neuropsychiatric events including “postmarket cases of agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness … and tremor.”
In 2008, the FDA said it was investigating “a possible association between the use of Singulair and behavior/mood changes, suicidality … and suicide,” Drugwatch reported.
In another example, the 3-year-old son of Jan Gilpin was prescribed Singulair for asthma in 2003. He “soon seemed withdrawn and sullen” and “started talking about death,” according to Reuters.
Gilpin initially did not suspect Singulair — until she discovered online posts by parents stating that their children were exhibiting similar behavior while on this medication. She pulled her son off Singular and soon “noticed he began to skip and laugh,” while his “obsessive thoughts about death disappeared after he quit the medicine.”
Indeed, “reports of related neuropsychiatric episodes piled up on internet forums and in the FDA’s early-warning detection system” starting in 1998, Reuters reported. Yet, by the time of England’s suicide in 2017, the FDA was still “reviewing” this data.
According to Reuters, in 2011, the FDA “rejected a petition from Gilpin and other parents seeking a black box warning, citing what it called insufficient evidence that the drug caused suicidal behavior.”
“Parents who argue Singulair endangered their children view the FDA’s 2020 decision to add a black box warning as vindication, but many still want to sue Merck for not acting sooner,” Reuters also reported.
In 2014, an FDA panel acknowledged that neuropsychiatric side effects among Singulair users were a “known safety issue,” but cited this reason and “feasibility concerns” in its decision not to order new studies, according to Reuters.
Yet, as reports of suicides continued to be filed — with 82 suicides linked to Singulair and its generic versions, including at least 31 involving people age 19 and younger, a new FDA advisory panel was convened in 2019.
According to Reuters, “agency staffers again said there was not enough evidence” to merit this. However, with Merck’s patent having expired, an FDA official told the advisory committee that the company may opt to pull Singulair from the market rather than fund expensive new studies to investigate the product’s safety.
This resulted in the March 2020 decision to add the black box label to Singulair.
‘Substantial amount’ of Singulair enters human brain
In its 2020 decision, the FDA cited independent research conducted in 2015 by cell biologist Julia Marschallinger and other researchers at Austria’s Institute of Molecular Regenerative Medicine.
They found that Singulair’s distribution into the brain was more significant than what was stated on the product label, which described its brain distribution as “minimal.”
Merck had claimed, in documents it submitted to FDA for the drug’s approval in 1998, that “only a trace amount” of the drug could be found in the brain and that its presence “declined over time.” Merck’s public marketing of the product later described side effects as “generally mild” and “similar to a sugar pill.”
However, Marschallinger’s team found that while Singulair’s presence decreased almost everywhere in the body within 24 hours after administration, the opposite was true in the brain, where “a substantial amount” of the drug was identified.
In its 1996 patent application for Singulair, Merck also claimed the drug could be used as a treatment for “cerebral spasms” — indicating “knowledge of the drug’s potential brain impacts.” Lawyers for plaintiffs filing Singulair lawsuits against Merck have cited this argument, as well as Marschallinger’s study.
The FDA has confirmed the study’s findings, acknowledging that claims regarding the declining presence of Singulair in all tissues “did not fully reflect the data.”
However, according to Reuters, the FDA also characterized findings of “a substantial amount” of the drug in the brain “a subjective characterization that is not necessarily incompatible with the ‘minimal’ descriptor in other contexts.”
“The FDA could have asked Merck to repeat the experiment or do it for an even longer period of time,” Marschallinger told Reuters. “It’s not hard to do.”
Perro said, “For those children who have been harmed by this drug,” due to the FDA’s 22-year delay in adding a black box warning, “there will not be any compensation because of pharmaceutical protection by our own government and liability shields.”
The FDA’s inaction has resulted in many deaths, Sue Peters, Ph.D., a CHD science fellow, told The Defender:
“The FDA has placed pharmaceutical profits over the safety and mental health of our children. It’s a never-ending cycle, with increased rates of chronic illness, like asthma, leading to pharmaceutical treatments which have not been properly safety-tested.
“These drugs put young people, with critical brain myelination continuing past 25 years of age, at risk of developing mental health disorders, leading to polypharmacy with psychiatric medications, and contributing to iatrogenic deaths as a leading cause of death in the U.S.”
Perro called for an overhaul of the FDA, telling The Defender:
“It is clear who our government — including the judicial system — is protecting. A solution to the lack of action by regulatory agencies? Overhaul.
“In the meantime, there are safer pharmaceutical alternatives for asthma in children. Not to mention, this is yet another reason to examine the root causes as to why so many children now have asthma, and address the real culprits, such as air pollution.”
For Mumper, a new approach to treating ailments such as asthma is needed. “Although montelukast is a valuable medication in my toolbox for treating allergies, the prescription should come after other measures, including working on gut health,” she said.
Similarly, Peters called for a “careful analysis” of the role of drugs in the treatment of common disorders and their role in precipitating mental health disorders and even deaths. She told The Defender:
“The tragic increase in the rate of mental health disorders in children in the United States, requires careful analysis of the role of iatrogenic death.
“Failing to consider the role of pharmaceutical drugs and medical treatments in the development of mental health disorders in children, has led to the loss of valuable research time, wasted research dollars, and ultimately the loss of life. Clearly, our current system is broken.”
Preemption defense lets Big Pharma avoid directly addressing safety claims
According to the Reuters investigative report, most of the Singulair lawsuits pending against Merck are still in their early stages.
Drugwatch reported that, as of May 16, “there have been no scheduled trials or court-approved global settlement in Singulair litigation.” Many of the suits against Merck were filed in New Jersey, where in January 2022, they were consolidated into multicounty litigation in the Superior Court of New Jersey Law Division: Atlantic County.
And in April, U.S. District Judge Timothy S. Hillman in Massachusetts denied Merck’s motion to dismiss a Singulair lawsuit “for lack of personal jurisdiction,” Drugwatch reported. Judge Hillman argued Merck manufactured, marketed and sold the drug in the state and allowed the case to continue.
Two U.S. Supreme Court rulings in 2011 and 2013 strengthened the preemption defense.
In Pliva, Inc. v. Mensing (2011), the Supreme Court held that state law requiring “generic drug manufacturers to provide adequate warning labels was preempted where federal law required manufacturers to use the same labels as their brand-name counterparts.”
And in Mutual Pharmaceutical Co. v. Bartlett (2013), the Supreme Court held that design-defect claims questioning the adequacy of a drug’s warnings under state law are preempted by the Federal Food, Drug, and Cosmetic Act and the Pliva v. Mensing ruling.
According to Reuters, the preemption doctrine rests on the U.S. Constitution’s Supremacy Clause, which states that the Constitution and federal law take precedence over state laws and state constitutions.
As a result, “Preemption defenses often deliver companies a swift procedural win, allowing them to avoid addressing the substance of plaintiffs’ allegations.”
While the defense has been used across multiple industries, it “has had a particularly profound impact in the pharmaceutical industry,” particularly as FDA data cited by Reuters indicates that generic drugs account for 91% of U.S. prescriptions.
Reuters, in its review of 257 U.S. Supreme Court and federal appeals court rulings since 2001, found that “judges ruled two-thirds of the time to weaken or kill lawsuits alleging deaths or injuries caused by corporate negligence or defective products.”
Moreover, “The number of potential lawsuits that were never filed” serves as “Another industry benefit” that “can’t be quantified,” according to Reuters.
Preemption defenses became a centerpiece of the George W. Bush administration — and FDA policy under his presidency, Reuters reports. This was part of the Bush campaign’s promise to address what it described as “frivolous” lawsuits.
Daniel Troy, the FDA’s chief counsel under the Bush administration, “interpreted preemption to mean that courts can’t undermine federal regulators based on alleged state-law violations,” Reuters reported, adding that he “aimed to make that argument in high-profile lawsuits” and briefed drug industry lawyers on the strategy in 2003.
Troy — who is now a pharmaceutical industry lawyer — told Reuters, “If you believe in a strong FDA, we can’t have state courts, especially juries, second-guessing and undercutting the FDA’s judgments.”
Hazlehurst told The Defender Troy’s argument is the same one used by Wyeth (Pfizer) before the Supreme Court in Bruesewitz v. Wyeth (2011). The Supreme Court’s decision in this case prohibited design defect lawsuits against vaccine manufacturers.
The U.S. Department of Health and Human Services, the parent agency of the FDA and the Centers for Disease Control and Prevention, supported Wyeth’s 2011 argument.
Similarly, Mumper told The Defender that pharmaceutical companies “have a history of avoiding liability through various legislative protection,” including the preemption defense and the National Childhood Vaccine Injury Act of 1986.
And in 2006, “The FDA formally changed its view of preemption in a 2006 regulation, stating the agency now believed that FDA labeling approval ‘preempts conflicting or contrary State law,’” Reuters reported.
Hazlehurst told The Defender, “CHD is proud to have played a role in advocating and assisting these parents on the journey to hold Merck accountable,” but “one thing rings loud and clear: the FDA is a captured agency, and this is a fundamental problem.”
Some parents have questioned whether the black box warning for Singulair was enough to save lives, citing the damage already done, continued legal obstacles, and Merck’s strong marketing campaign for the drug.
“Due to tremendous financial conflicts of interest, the pharmaceutical industry has tremendous influence over the FDA,” Hazlehurst said. “As a result, the FDA protects the pharmaceutical industry first and people second — this story is just one example.:
He added: “One must wonder, how many lives could have been spared if the FDA had timely done its job of properly investigating and regulating the pharmaceutical industry?”