Singulair: Making Sense of the FDA's Suicide Investigation

In early Spring 2008, the FDA announced it was investigating the asthma drug Singulair for links to depression, changes in mood and suicide. Dr. Fred Little, an asthma specialist, weighs in on the debate.

Dr. Fred Little

What is the concern about Singulair (montelukast)?
Singulair is a major drug in asthma treatment – it is important to review recent developments and put these findings in perspective of overall asthma care for individual patients.

Singulair (montelukast)
Singulair (manufactured and marketed by Merck and Co.) is a drug of the so-called anti-leukotriene class that is used for control of symptoms of asthma and allergic rhinitis (hay fever). It was initially approved by the U.S. Food and Drug Administration (FDA) for use in asthma in 1998 (its indication was broadened to include treatment of allergic rhinitis in 2003). In the two broad classes of asthma medications --  quick-relief (typically bronchodilators, such as Xopenex or Foradil) and long-term controllers (typically anti-inflammatory medications such as Azmacort or Medrol) -- Singulair falls in the latter class. The anti-leukotrienes block the action of several molecules that not only cause inflammation in the breathing tubes of asthmatics but also contribute to airway narrowing (bronchospasm). Together these effects reduce wheezing and shortness of breath in asthmatics.

What happened?
In the Spring of 2008, the FDA released an Early Communication on Singulair based on so-called post-marketing reports (i.e. after the drug has been approved for use by the FDA) on a possible association between the use of Singulair and varied alterations in mood and behavior, including tremor, depression, suicide, and anxiousness. In one notable case, a 15-year-old boy with allergies had switched from an antihistamine to Singulair. Within two weeks, his parents noted that their son began to have sleep difficulties and he became agitated. Seventeen days after starting the medication, he committed suicide. These events were directly communicated by the parents at a hearing at the FDA in Washington DC. Over the past year, these findings had been noted in the Merck’s product information sheets that accompany drug packaging.

In light of these events, the FDA is working in earnest with Merck to review post-marketing data (both from the company and directly from consumers) on any associations between use of Singulair and changes in mood or behavior. The FDA is expanding its surveillance to other medications in the anti-leukotriene class – which include Accolate (zafirlukast), Zyflo (zileuton), and Zyflo CR (a long-acting preparation of zileuton).
To be clear, the FDA has not issued a ”warning” about the use of these drugs, as the association is not firmly established or definitive from a statistical standpoint. The main purpose of these Early Communications is to alert the public and health professionals to monitor patients closely for the development of adverse side effects of Singulair and related medications.

Professional Society Recommendations

Clearly, these concerns need to be addressed and investigated in detail, as anti-leukotriene medications are effective and used by many patients with asthma and allergic rhinitis. To guide patients and health care professionals, professional societies released statements on their interpretation of the association between Singulair and suicide risk. Two of the nation's major societies that represent asthma and allergy care providers, the American Academy of Allergy, Asthma and Immunology, and the American College of Allergy, Asthma and Immunology, released a joint statement cautioning discontinuation of anti-leukotriene medications as the evidence is not definitive and for concern of declines in asthma control amongst many patients who benefit from these medications: "There are no data from well-designed studies to indicate a link between Singulair and suicide [and] (t)he concern expressed by the FDA is based entirely on case reports and there is no indication that such effects apply to other leukotriene-modifying medications."

Closing thoughts
I have many patients taking anti-leukotriene medications for asthma, allergic rhinitis, and in many cases, both. These are effective medications that can be part of an overall treatment plan that includes medicines and patient education. My approach is not to discontinue Singulair or related medicines in patients who have been taking them for many months, unless they have noticed clear changes in mood or behavior. For patients in whom I am considering starting an anti-leukotriene medication, I discuss the recent findings with them and have them monitor their mood closely if we start the medicine. If there is cause for concern, I would discontinue the medication and seek alternatives.

To be clear, no advice can replace direct communication between you and your doctors about your asthma. If you have concerns about these medications you should discuss this specifically with them.


See also:

Asthma and Allergy Doctors Say, Keep Taking Singulair

Not Worrying About Taking Singulair

Singulair Side Effects 

Ask a Question

Get answers from our experts and community members.

View all questions (1141) >