Headlines about the link between montelukast and suicide attempts in young children have recently splashed across local and international news pages, but the evidence is tenuous. Should the popular asthma medicine still be prescribed?

One woman based in the US, where montelukast (Singulair) has a ‘black box warning’, told the New York Times that her son started having nightmares and hallucinations of a woman in the window at 6 years of age.

She is one of 20,000 members of a Facebook support group for those who have experienced adverse effects from montelukast.

Locally, Harrison Sellick, who used montelukast from the age of 2, attempted suicide at 5, later surviving several other attempts. Three Australians who have used montelukast have also taken their own lives since 2020.

What are the indications for montelukast?

Montelukast is listed by the Therapeutic Goods Administration (TGA) for use as an asthma treatment in children aged 2 years and older, and for the symptomatic management of allergic rhinitis.

It’s mostly used to treat mild-to-moderate asthma as an alternative to inhaled corticosteroids (ICS), particularly in children with recurrent wheeze, said National Asthma Council Australia Director and respiratory physician, Professor Peter Wark.

‘It has also been used as an add-on treatment to inhaled corticosteroids and inhaled corticosteroid/ long-acting beta agonists (ICS/LABA),’ he said. 

Efficacy for montelukast is typically low – with only around 20–30% of children responding to treatment.

While montelukast is more effective than placebo in association with as-needed short acting beta agonists (SABA), Prof Wark said the evidence does not point to its use as a first-line treatment for any age group with asthma. 

‘When trials control for things such as adherence in head-to-head comparisons, montelukast consistently performs less well than ICS use on a regular basis, or in adolescents and adults ICS/LABA,’ he said. 

Why do parents prefer montelukast?

Prof Wark said there has ‘always been’ a preference among some parents and doctors for montelukast as a:

• chewable oral agent
• non-corticosteroid option.

The ‘lingering concerns’ around potential ICS adverse effects, including evidence that regular use is associated with a slowing in the rate of growth, could be a deterrent for some. 

‘However, ICS are the most effective form of treatment for asthma and all side effects can be mitigated with appropriate low doses that are sufficient for the majority of people with asthma,’ he said.

There are also perceptions that montelukast is easier to administer. 

‘There’s a preference for oral agents where there’s perceived difficulty in getting people to use inhaled therapies,’ said Prof Wark. ‘But virtually all children can use inhalers with a spacer, even at a very young age.’

Montelukast can treat allergic rhinitis symptoms that ICS will not, but the most effective treatment for allergic rhinitis is the use of intranasal low-dose corticosteroids, said Prof Wark.  

The medicine has also been used sometimes as an as-needed treatment, especially with virus-induced wheeze.

‘The only evidence for as-needed treatments exists with ICS and a fast-acting bronchodilator, with ICS/formoterol, available for people with mild asthma aged 12 and above under the PBS,’ he said. 

How common are neuropsychiatric adverse effects?

The adverse effects of montelukast recently highlighted in the media are not new, said University of Sydney Associate Professor Claire O’Reilly FPS. 

‘Within the last 5–10 years, the risk of neuropsychiatric adverse effects from montelukast have been well known,’ she said.

Montelukast’s reported neuropsychiatric adverse effects include:

• agitation and irritability
• aggressive behaviour
• anxiety and depression
• dream abnormalities, insomnia and sleepwalking 
• hallucinations
• restlessness and tremor
• suicidal thinking and behaviour.

While serious in nature, there’s not a strong evidence base for the prevalence of these adverse effects associated with montelukast, said Prof Wark.

‘The recent large systematic review could only attach associations with anxiety and insomnia.’

In fact, the review found older adults may be more susceptible to neuropsychiatric events related to montelukast than children, said A/Prof O’Reilly.

‘No significant association between montelukast use and suicide-related events was found, so the data for this association is a bit unclear,’ she said.

Meanwhile, a recent case-control study reported a ‘statistically significant’ link between leukotriene receptor antagonists and suicide attempts in patients aged 19–24 years. 

However, when adjustments were made to account for previous exposure to other asthma medicines and medicines associated with suicide, the link was no longer significant.

Prof Wark said the evidence is also not clear enough to link increased risks of adverse effects from montelukast to those with existing neuropsychiatric or mental health conditions.

‘However, it would be reasonable to look out for these events in that group of individuals in whom the effects could be worse,’ he said.

If a patient with a pre-existing condition, such as anxiety or depression, presents to the pharmacy with a prescription for montelukast, A/Prof O’Reilly recommends assessing whether the prescriber has warned them about the risk of adverse effects.

‘If they haven’t, that might warrant a conversation directly with the prescriber to ensure they’re comfortable with the patient using the medicine,’ she said.

When should pharmacists check in with patients?

While the neuropsychiatric adverse effects from montelukast are uncommon, it’s important patients are informed and aware of that risk, and they’re aware of what to look out for, said A/Prof O‘Reilly.

The most important time to check in with patients about any behavioural changes or potential adverse events is when initiating montelukast or increasing the dose, she said.

‘If a patient or parent reports those adverse effects, pharmacists should link them back with their prescribing doctor for review as soon as possible.’

The Australian Asthma Handbook recommends advising all patients and carers about possible adverse effects and conducting a review 4–6 weeks after treatment is initiated.

But the use of montelukast should primarily be based on efficacy grounds, said Prof Wark.

‘It’s not a first-line treatment and it would be far better and safer to consider the use of low-dose ICS and salbutamol as needed.’ 

How can the risks versus benefits be assessed?

The best way to help patients and parents assess the risks versus benefits of using montelukast is through raising awareness of the potential adverse effects, said Prof Wark.

When patients present with a script for montelukast, Prof Wark said it’s reasonable to discuss:

• what treatments have been used previously
• what montelukast is being used for
• whether asthma is well-controlled
• what the alternative treatment options are.

‘It’s a good opportunity to consider whether it’s an appropriate [medicine] to treat their asthma,’ he said.

‘If patients have concerns around montelukast, the question then becomes, “why aren’t you using an ICS-based regime?”’

If montelukast needs to be used, Prof Wark advises explaining in the vast majority of people, it can be used safely and discussing the risk in the context of that individual.

CAL calls for montelukast

The last safety review conducted by the TGA into montelukast took place in 2018. Now, the TGA is considering updating the product information. The PSA’s CAL Review Group is currently considering a proposal for a new CAL for montelukast, and is conducting thorough consultation with stakeholders including health professionals and consumers.

The benefit of having a focused CAL for this type of adverse effect is to prompt pharmacists to ensure they counsel patients about the risks, said A/Prof O’Reilly, who is providing advice on the proposed CAL.

‘It will give some visibility to the possible concern, and serve as a reminder as to what to look out for and how to manage those side effects if they do appear,’ she said.