Locations:
Search IconSearch
February 28, 2018/Pulmonary/Asthma

Are Leukotriene-Modifying Agents Associated with Suicidality?

Asthma Center Co-Director gives the short answer

18-PUL-XXXX-Khatri-Hero-Image-650x450pxl

By Sumita Khatri, MD

Advertisement

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

My colleagues and I recently published a review of the literature examining a possible association between leukotriene-modifying agents (LTMA) and suicidality, and we found neither sufficient evidence to affirm the association nor enough clarity to conclusively disprove it. In short, I think the association is weak at best.

The LTMA montelukast is one of our most effective pharmacologic therapies for allergic asthma. In 2008, the Federal Drug Administration issued a warning based on a case report involving the death by suicide of a teenager with no prior mental health history and drastic mood and emotional changes following commencement of montelukast. Later, the warnings were extended to other LTMAs like zileuton and zafirlukast. Because no clear pharmacophysiological link can explain an association between LTMAs and suicide, the warnings were quite controversial.

Our extensive literature review revealed that most of the data indicating a potential association between suicidality and LTMA use is from individual case reports. Any research studies have been inconclusive. Confounding factors include other medications that increase the risk of suicidality (like steroids) and the increased incidence of suicide mortality for patients with asthma compared with controls. Other factors that make this association unlikely include:

  • Reporting bias in spontaneous event-reporting systems
  • Absence of positive evidence from clinical trials
  • Negative evidence from ecological studies
  • Absence of pharmacological mechanisms supporting the association

Advertisement

While we have strong evidence that suicide outcomes and LTMAs are not positively associated at the population level, I hesitate to generalize to individual cases. With any patient I see for asthma, I consider the whole person, including barriers to care and other possible confounding conditions such as depression. When patients are well treated for depression, the use of LTMAs may not be a concern. However, I am more likely now to ask whether changes in medication in the past might have resulted in any changes in mood or depression, and I may avoid continuing or restarting LTMAs in those instances.

Dr. Khatri is Co-Director of the Asthma Center.

Advertisement

Related Articles

asthma inhaler
August 16, 2024/Pulmonary/Asthma
Leveraging Machine Learning to Enhance Asthma Phenotyping: Implications for Precision Medicine

New research classifies asthma into five clinically important subphenotypes

Asthma
September 15, 2023/Pulmonary/Asthma
Measuring Exhaled Nitric Oxide When Diagnosing and Managing Asthma

Cleveland Clinic pulmonologists address the role of measuring exhaled nitric oxide in the diagnosis and management of asthma and provide guidance for its appropriate use

Patient with chest pain
January 24, 2022/Pulmonary/Asthma
Using Fractional Exhaled Nitric Oxide Tests to Make Treatment Decisions for Patients with Asthma

New guidelines from the American Thoracic Society provide clarity on when to use the test, though some questions remain

650×450-Lungs
May 5, 2021/Pulmonary/Asthma
Androgens May Have Airway Benefits for Patients With Asthma

Study links androgen-receptor expression with less inflammation and better lung function

18-PUL-4998-Aronica-Hero-Image-650x450pxl[1]
April 30, 2020/Pulmonary/Asthma
Genetic Study Opens the Door for Treatment of Glucocorticoid-Resistant Asthma

Gene variant holds key to those needing a different treatment

650×450-Eosinophil
February 12, 2019/Pulmonary/Asthma
Mepolizumab in Patients with Severe Eosinophilic Asthma

Long-term safety and efficacy assessed

17-PUL-3831-Khatri-Hero-Image-650x450pxl
November 30, 2017/Pulmonary/Asthma
Is Spirometry Necessary to Diagnose and Control Asthma?

Without it, we underdiagnose

Ad