Allergies occur when the immune system overreacts and treats an essentially harmless foreign protein as a dangerous invader capable of causing infection. The immune system mounts a full-scale response to the triggering protein. This response involves a cascade of inflammatory chemicals, which recruit the involvement of other cells, and promote still more inflammation. Symptoms of allergic rhinitis may include swelling in the nasal passages, increased mucus production, stuffy (or runny) nose, itching, and more.

Leukotrienes are fatty immune system chemicals derived from dietary omega-3 and omega-6 fatty acids. They play a key role in some of the more troubling symptoms of allergic rhinitis and allergy-induced asthma. By binding with certain receptors on muscle cells, they can cause the smooth muscles of the windpipe to contract, which accounts for their role in allergy-induced asthma. Asthma patients suffer from shortness of breath and wheezing caused by constriction of the airways. 

Drugs that modify the production or activity of leukotriene are known as leukotriene inhibitors (they are also called leukotriene receptor antagonists or leukotriene modifiers). Some of these drugs work by limiting the production of leukotrienes by cells such as leukocytes (a type of white blood cell), while others block leukotrienes from binding with their receptors on smooth muscle cells. If the fatty signaling molecules cannot bind with their cellular targets, they cannot trigger muscle contraction. 

Montelukast (Singulair)

Drugs such as montelukast (Singulair) and zafirlukast (Accolate) are widely prescribed for the treatment of exercise and allergy-induced asthma. A third drug, zileuton (Zyflo), indirectly inhibits leukotriene synthesis, and thus is also in the leukotriene-modifier class of drugs. Singulair is also prescribed for the treatment of perennial (year-round) and seasonal (recurring, yet temporary) allergic rhinitis. Of course, allergic rhinitis is characterized by stuffy, runny, or itchy nose, among other symptoms. These drugs are usually taken by mouth, once a day.

Leukotriene inhibitors are yet another class of drugs to be used in the fight against allergies and allergy-related illnesses, but they are still considered second-line treatment. Inhaled corticosteroids are the most effective treatment, offering comprehensive relief from the various symptoms of allergic rhinitis, so they are considered first-line treatment. However, in cases where patients suffer from both allergy-induced asthma and allergic rhinitis, leukotriene modifiers may be considered first-line treatment. 

With their introduction in the 1990s, leukotriene inhibitors became the first new class of drugs for the treatment of asthma and some symptoms of allergic rhinitis in about 30 years. Although inhaled corticosteroids remain the international standard for first-line treatment of mild asthma, some studies have shown that leukotriene modifiers provide effective singular, first-line therapy for the control of mild asthma in children. 

Side Effects of Leukotriene inhibitors

Although they are widely prescribed, and considered relatively safe, leukotriene inhibitors have been associated with side effects among some users. Possible side effects listed for the drug, Singulair, for instance, include alterations in mood and increased suicidal thoughts.

The Food and Drug Administration (FDA) initiated an inquiry into these and other neuropsychiatric effects in 2008. In 2009, they concluded that existing clinical trials reveal an increased risk of developing insomnia among users of this class of drugs, compared to placebo.

According to the FDA, information gathered from patients after the public release of the drugs indicates an increased risk of:

  • agitation
  • aggression
  • anxiety
  • dream abnormalities and hallucinations
  • depression
  • insomnia
  • irritability
  • restlessness
  • suicidal thinking and behavior (including suicide)
  • tremor

The FDA concluded its review by noting, “neuropsychiatric events were not commonly observed,” at least not in clinical trials, although the FDA also noted that these trials were not specifically designed to detect such reactions. Singulair does not interact significantly with other drugs, such as the asthma drug theophylline.