Regulators in the USA has set up a probe into a potential link between Merck & Co’s big-selling asthma treatment Singulair and suicidial behaviour.

The US Food and Drug Administration said that it is investigating a possible association between the use of Singulair (montelukast) and behaviour/mood changes, suicidal thinking and suicide in patients who have taken the leukotriene receptor antagonist. Singulair is approved to treat asthma and the symptoms of allergic rhinitis, such as sneezing, stuffy and runny nose.

The FDA said it is reviewing the drug after receiving postmarketing reports of mood changes and suicidality in patients who took Singulair, although it was not specific as to how many reports it is studying. The agency did note, however, that “due to the complexity of the analyses”, it anticipates taking up to nine months to complete the ongoing evaluations.

The FDA added that it is also looking at reports of behavioural changes in patients taking AstraZeneca’s Accolate (zafirlukast) which is also a leukotriene receptor antagonist and Zyflo/Zyflo CR (zileuton), Clinical Therapeutics’ leukotriene synthesis inhibitor. It will assess “whether further investigation is warranted”, on those treatments but the last year has already seen a number of changes to the label on Singulair, which had fourth-quarter sales of $1.2 billion.

Merck has updated the prescribing information to include tremor (March 2007), depression (April), suicidality (October) and anxiousness (February 2008). The company is also working with the FDA to evaluate Singulair study data for more information about suicidality and suicide.

However both the agency and the firm pointed out that no connection between Singulair and suicidiality has been established. Merck said that the label updates in the past year were based on “a very limited number of post-marketing adverse event reports” and do not “reflect a conclusion” that the event is caused by Singulair.

Furthermore, in a cumulative analysis recently provided to the FDA of Merck's clinical trials, which included over 11,000 adults and children in over 40 studies who were treated with Singulair, there were no reports of suicidal thoughts or actions or completed suicides. In another study, of 3,900 people on the Merck drug and 3,400 treated with other asthma therapies, one patient who attempted suicide received Singulair, while the figure for those on other treatments (such as inhaled corticosteroids and long-acting beta-agonists) was three.