Australia’s Therapeutic Goods Administration (TGA) recently issued a safety alert requiring extra warnings to be included with the asthma and hay fever drug montelukast (brand names include Asthakast, Lukafast, Montelair and Singulair).

The warnings are for users and their families to look for signs of serious behaviour and mood-related changes, such as suicidal thoughts and depression. The new warnings need to be printed at the start of information leaflets given to both patients and health-care providers (sometimes called a “boxed” warning).

So why did the TGA issue this warning? Here’s what you need to know.

What is the link to depression and suicide?

The possibility that this drug may cause behavioural changes is not new information. Manufacturers knew this as early as 2007 and issued warnings for possible side-effects including depression, suicidality and anxiousness. 

The United Kingdom’s Medicines and Healthcare products Regulatory Agency has required a warning since 2008 but mandated a more detailed warning in 2019. The United States’ Food and Drug Administration has required boxed warnings for the drug since 2020. 

Montelukast is known to potentially induce a number of behaviour and mood changes, including agitation, anxiety, depression, irritability, obsessive-compulsive symptoms, and suicidal thoughts and actions. 

Initially a 2009 study that analysed data from 157 clinical trials involving more than 20,000 patients concluded there were no completed suicides due to taking the drug, and only a rare risk of suicide thoughts or attempts. 

The most recent study, published in November 2024, examined data from more than 100,000 children aged 3–17 with asthma or hay fever who either took montelukast or used only inhaled corticosteroids. 

It found montelukast use was associated with a 32% higher incidence of behavioural changes. The behaviour change with the strongest association was sleep disturbance, but montelukast use was also linked to increases in anxiety and mood disorders. 

In the past ten years, around 200 incidences of behavioural side-effects have been reported to the TGA in connection with montelukast. This includes 57 cases of depression, 60 cases of suicidal thoughts and 17 suicide attempts or incidents of intentional self-injury. There were seven cases where patients taking the drug did complete a suicide. 

This is of course tragic. But these numbers need to be seen in the context of the number of people taking the drug. Over the same time period, more than 200,000 scripts for montelukast have been filled under the Pharmaceutical Benefits Scheme. 

Overall, we don’t know conclusively that montelukast causes depression and suicide, just that it seems to increase the risk for some people. 

And if it does change behaviour, we don’t fully understand how this happens. One hypothesis is that the drug and its breakdown products (or metabolites) affect brain chemistry. 

Specifically, it might interfere with how the brain detoxifies the antioxidant glutathione or alter the regulation of other brain chemicals, such as neurotransmitters.

Why is the TGA making this change now?

The new risk warning requirement comes from a meeting of the Australian Advisory Committee on Medicines where they were asked to provide advice on ways to minimise the risk for the drug given current international recommendations. 

Even though the 2024 review didn’t highlight any new risks, to align with international recommendations, and help address consumer concerns, the advisory committee recommended a boxed warning be added to drug information sheets.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Note: This article has been slightly edited for a health professional audience, with permission from the author.