This asthma drug is taken by millions. Now scientists have found it in the brain

When Johanna Barry noticed her daughter Makenzie lashing out, she put it down to the “terrible twos”.

Then came the night terrors. “She just would not go to sleep,” Barry recalls. “She would wake up in this trance-like state. She’d be screaming, and no matter how much we just hugged her, [the terrors] could last over an hour.”

Makenzie was too young to speak at the time, but later told her parents what she remembered of her hallucinations: one in which monsters crawled up her walls, another in which she watched her skin fall off, and occasions when she saw visions of people who weren’t in the room.

Now nine years old, Makenzie has just started sleeping in her own room again, five years since her parents took her off montelukast – a chewable flavoured tablet used to treat asthma but increasingly linked to depression, aggression and suicidal thoughts.

Barry was one of a group of parents who wrote to Health Minister Mark Butler at the weekend, urging him to intervene in a drawn-out process to add warning labels to the medication.

Here’s why.

The news

US government researchers unveiled at a conference last week early results from laboratory tests showing the medication, sold under the brand name Singulair and generically as montelukast, binds to various brain receptors critical to psychiatric function.

While the findings, first reported by news agency Reuters, have not been published or peer-reviewed, they are the first glimpse of detailed research being undertaken by the US Food and Drug Administration.

The researchers told patient groups the finalised data would not be published for a while but their participation in the conference was “our way of trying to get this information to the public”.

What is montelukast?

When montelukast hit pharmacy shelves in 1998 under the brand name Singulair, it was a blockbuster product for pharmaceutical company Merck, offering relief in a pill 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 any distribution in the brain was minimal.

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 FDA’s tracking system.

In Australia, drugs containing montelukast have been associated with more than 200 adverse events reported to the Therapeutic Goods Administration in the past decade. There have been 15 events reported this year alone, including three suicides.

Montelukast was the only drug the three people who took their own lives were known to have been taking at the time of their deaths. However, “adverse event” reports are not confirmed by the TGA and do not prove a causal link between a medicine and a side effect.

In 2020, increasing adverse event reports in the US, combined with new scientific research, led the FDA to add a “black box” warning to the montelukast prescribing label, signalling serious mental health risks.

The agency also convened a group of internal experts about the same time to look into why the drug might trigger neuropsychiatric side effects.

Australians have been prescribed drugs containing montelukast on more than 40,000 occasions in the past year, Pharmaceutical Benefits Scheme data reveals.

What has the FDA found?

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

Jessica Oliphant, a deputy director at the FDA’s National Centre for Toxicological Research, told the conference that laboratory tests showed “significant binding” of montelukast to receptors in the brain.

The FDA confirmed earlier scientific research showing montelukast penetrates the brains of rats. “These data indicate that montelukast is highest in brain regions known to be involved in [psychiatric effects],” Oliphant said.

The behaviour 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 cautioned that its studies are ongoing, and results have not been finalised.

What have Australian authorities said?

An action group including almost 1200 Australians has been lobbying the TGA to enforce the black box warning mandated in other countries, including the US.

A spokesman said the TGA reviewed montelukast risks again earlier this year. That review did not find any new neuropsychiatric risks but did recommend a boxed warning “in acknowledgment of consumer concerns”.

The Pharmaceutical Society of Australia is reviewing the possibility of creating a cautionary label that pharmacists can stick on the medication when given to patients.

Associate Professor Fei Sim, the industry body’s national president, said coming up with cautionary labels was a “complex process” and there was no timeline for when one would be introduced.

With Reuters

Lifeline 13 11 14 or lifeline.org.au

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