The Food and Drug Administration (FDA) has completed a review of clinical trial data and postmarketing case reports indicating that some patients taking the leukotriene inhibitors montelukast (Singulair), zafirlukast (Accolate), and zileuton (Zyflo and Zyflo CR)-used in the treatment of asthma and allergic rhinitis-have experienced neuropsychiatric events (changes in behavior and mood). These events include agitation, aggression, anxiety, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicidal thoughts and behavior, and tremors.

After examining the clinical trial data submitted by the drugs' manufacturers, however, the FDA found that these adverse effects occurred very rarely, possibly because the trials were not designed to identify them. The risk of suicidality, for example, was found to be extremely rare. Study results submitted by Merck show that of the 9,929 montelukast-treated patients in 41 placebo-controlled clinical trials, only one adult (0.01%) had suicidal ideation and none had committed suicide (among the 7,780 patients in the placebo arm, none had suicidal ideation or committed suicide). Of the 7,540 patients treated with zafirlukast in 45 placebo-controlled clinical trials submitted by AstraZeneca, none had suicidal ideation or committed suicide, whereas two (0.04%) of the 4,659 patients in the placebo group exhibited suicidality (one suicide attempt and one instance of suicidal ideation). Results of 11 clinical trials were submitted by Cornerstone Therapeutics, in which out of 1,745 patients treated with zileuton and 1,063 treated with a placebo, no patients had suicidal ideation or committed suicide.

The revised leukotriene inhibitor product labeling is expected to include a new precaution stating that neuropsychiatric events have been reported, but the FDA is not recommending that use of the medications be stopped at this time. The agency instead advises patients and health care providers to be aware that these adverse effects might occur and to discontinue the medication if they do. Patients should inform their health care provider of the occurrence of any of the identified neuropsychiatric events. For more information, go to http://bit.ly/UnqoP and http://bit.ly/10cBXF.