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, we can report.

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 minimised 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 paediatrician. Leukotrienes “can be involved in the precipitation of asthma and can cause respiratory symptoms, as well as inflammation of the airways,” Perro says.

Numerous public comments about Singulair’s side-effects were submitted in 2019, prior to the September 27, 2019, joint meeting of the US Food and Drug Administration’s (FDA) Paediatric 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 Defence (CHD), says 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 paediatrician, 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 reports. “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 “pre-emption defence” – 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 labelling, while the primary drugmaker can’t be sued by claimants if they or their family members took the generic version.

Perro says a combination of an abrogation on the part of federal regulators, a lack of integrity on the part of drugmakers and complex legal manoeuvring 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 pre-emption, 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 seven million annually to more than nine million” – with up to half of recipients age 16 or younger.

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 pre-emption defence.

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 behaviour 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 “post-market 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 behaviour and mood changes, suicidality … and suicide,” Drugwatch reported.

In another example, the three-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 behaviour 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 behaviour.”

“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.

• The Defender report / By Dr Michael Nevradakis