FDA Singulair Warning Cautions Patients of Psychiatric Risks

By James Parker

The U.S. Food and Drug Administration (FDA) has added a black box warning label to the asthma medication montelukast, better known by its brand name Singulair. The FDA Singulair warning addressed a troubling connection between the medication and an increased risk of neuropsychiatric events, including agitation and depression. 

Singulair is a prescription medication used to treat a variety of asthmas in adults and children. Used by millions of Americans, it’s also taken to treat allergic rhinitis (hay fever) and control the nasal symptoms of seasonal outdoor allergies.

Approved in 1998, Singulair is commonly prescribed to control mild symptoms. Singulair is considered effective in improving symptoms of asthma and allergic rhinitis by preemptively blocking pollen, dust and other foreign materials prompting reactions in the body. 

The first notice of an increased risk of neuropsychiatric events came in 2008. After increased adverse event reports, observational studies and an advisory committee meeting in September 2019, the agency issued a safety communication in March 2020. 

In the news release, the agency noted “the risks of montelukast may outweigh the benefits in some patients.” A boxed warning is the FDA’s most stringent level of protection, and the agency has encouraged patients with milder symptoms to seek alternative therapies whenever possible. 

Singulair Mental Health Adverse Events 

While reviewing Singulair adverse event reports in the FDA Adverse Event Reporting Systems (FAERS) database, MedTruth found more than 42,822 adverse event reports were filed from its approval in 1998 until March 31, 2020.  

Multiple symptoms can be contained in a single report. The reports contained an estimated 25 separate mental health symptoms associated with Singulair and its generic versions, including: 

1. Depression
2. Anxiety
3. Suicidal Ideation
4. Aggression
5. Insomnia
6. Abnormal Behavior
7. Anger
8. Crying
9. Irritability
10. Agitation
11. Mood Swings
12. Sleep Disorder
13. Sleep Terrors
14. Mood Altered
15. Depressed Mood
16. Attempted Suicide
17. Hallucinations
18. Suicidal Contemplation
19. Abnormal Dreams
20. Fear
21. Emotional Disorder
22. Intentional Self Injury
23. Mental Disorder
24. Personality Change
25. Disturbance in Attention

Each adverse mental health symptom, listed in order of most to least common, occurred in at least 100 patients. Reports were consistent between Singulair and its generic versions.

A combined total of more than 30,735 distinct mental health effects, or incidences, were reported by patients taking Singulair or its generics forms. 

According to the FAERS database, the five most commonly reported psychiatric side effects of Singulair include: 

• Depression - 3,351 reports
• Anxiety - 3,136 reports
• Suicidal Ideation - 2,806 reports
• Aggression - 2,478 reports
• Insomnia - 2,277 reports

These adverse events, in addition to study data presented at the FDA Meeting of the Pediatric and Drug Safety and Risk Management Committees in September 2019, have led to an increased effort to inform patients of potential serious risks. In its most recent safety communication, the agency acknowledged the incidence of adverse events is “unknown.” 

Singulair is a commonly prescribed drug, prompting the FDA to change prescription recommendations. The agency indicates Singulair “should only be reserved to treat allergic rhinitis in patients who are not treated effectively with or cannot tolerate other allergy medicines.” 

The FDA lists “neuropsychiatric events” as the primary focus of its Singulair warning label update, but it has explicitly stated the drug is no longer recommended for patients with mild symptoms.

The FDA added a boxed warning included an update to the folded Patient Medication Guide that accompanies the prescription. The update was added to Warnings and Precautions section 5.4.