Why will a common asthma drug now come with additional safety warnings about depression?

The Australian Therapeutic Goods Administration (TGA) recently issued a demanding safety alert additional warnings should be included in the medicine montelukast used to treat asthma and hay fever.

Warnings are for users and their families to be alert for signs of solemn changes in behavior and mood, such as suicidal thoughts and depression. The novel warnings should be printed at the top of information leaflets distributed to both patients and healthcare providers (sometimes called a “boxed” warning).

So why did the TGA issue this warning? Is there any cause for concern if you or a member of your family are using montelukast? Here’s what you need to know.

First of all, what is montelukast?

Montelukast is a prescription drug also known by brand names that include Asthakast, Lukafast, Montelair, and Singulair. It is used to treat the symptoms of delicate to moderate asthma and seasonal hay fever children and adults.

Asthma occurs when the airways narrow and produce additional mucus that makes it complex for air to enter the lungs. Similarly, a runny nose is characteristic of hay fever occurs due to overproduction of mucus.

Leukotrienes is an essential family of chemicals found in the respiratory tract and involved in both mucus production and airway constriction. Montelukast is a cysteinyl leukotriene receptor antagonist, which means it blocks the site in the airway where leukotrienes act.

Montelukast cannot be used to treat acute asthma (asthma attack) because it takes time for the tablet to break down in the stomach and be absorbed in the body. On the contrary, it should be taken daily to prevent symptoms of asthma or seasonal hay fever.

It can be used together with asthma medications containing corticosteroids and medications such as salbutamol (Ventolin) for acute attacks.

What is the connection with depression and suicide?

The possibility that this drug may cause behavioral changes is not novel information. The producers knew this already in 2007 and issued warnings about possible side effects, including depression, suicidal thoughts and anxiety.

The UK Medicines and Healthcare products Regulatory Agency requested a warning since 2008 but ordered a more detailed warning to be issued in 2019. It was required by the US Food and Drug Administration boxed warnings for the drug from 2020

Montelukast is known to potentially cause a number of: changes in behavior and moodincluding agitation, anxiety, depression, irritability, obsessive-compulsive symptoms, and suicidal thoughts and actions.

Initially a 2009 study al., who analyzed data from 157 clinical trials involving over 20,000 patients, concluded that there were no suicides committed as a result of taking the drug, and the risk of suicidal thoughts or attempts occurred only rarely.

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

Montelukast utilize was found to be associated with a 32% higher incidence of behavioral changes. The most significant behavioral change was sleep disturbance, but montelukast utilize was also associated with an augment in anxiety and mood disturbances.

There have been approximately 200 cases of behavioral side effects reported in the last ten years reported to the TGA in connection with montelukast. This included 57 cases of depression, 60 cases of suicidal ideation and 17 cases of suicide attempt or intentional self-harm. In seven cases, patients taking the drug committed suicide.

This, of course, is tragic. However, these numbers must be seen in the context of the number of people using the drug. In the same period, over 200,000 scripts for montelukast were completed under the Pharmaceutical Benefits Scheme.

Overall, we do not know conclusively that montelukast causes depression and suicide, only that it increases the risk in some people.

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

Specifically, it may interfere with the way 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 novel risk warning requirement comes from the Risk Council meeting Australian Medicines Advisory Committee where they were asked for advice on how to minimize the risks associated with the utilize of the medicine, taking into account current international recommendations.

Although the 2024 review found no novel risks, to bring it in line with international recommendations and facilitate address consumer concerns, the advisory committee recommended adding a boxed warning to drug information sheets.

If you have asthma and you (or your child) are taking montelukast, you should not simply stop taking the medicine, as this may put you at risk of an attack, which could be life-threatening. If you are concerned, talk to your doctor, who can discuss the risks and benefits of the medicine and, if necessary, prescribe a different medicine.

If this article has raised concerns for you, or if you are worried about someone you know, please call Lifeline on 13 11 14.