On March 27, 2008 the FDA issued a safety alert regarding the asthma medication Singulair (montelukast). The alert was issued in order to inform healthcare professionals and patients about the agency's investigation into the possible link between Singulair use and depression and suicidality.
During clinical trials, depression was not reported as a side effect, however, drug makers are required to keep track of side effects reported to them after drugs go to market. During the past year, Merck & Co, Inc., which manufactures Singular, had received reports of tremor, depression, suicidality and anxiousness. In February of this year, Merck and the FDA began discussing how to disseminate this information to the public and the decision was made to interact face-to-face with prescribers and provide them with patient information leaflets to distribute.
In January 2009, the FDA announced that an investigation into Merck's clinical trial data did not discover a link between Singulair (montelukast) and suicidal behavior. The investigation, which began 9 months before, was prompted by a number of reported suicides, especially that of 15-year-old Cody Miller who took the drug and appeared to have no history of mood or behavioral problems. (It is worth noting here that Singulair "is the top-selling drug for people under 17 years old" and Merck's biggest seller with annual sales of close to $4.5 billion.)
In attempt to assess Merck's data better, the FDA also investigated AstraZeneca's Accolate (zafirlukast) and Cornerstone Therapeutics's Zyflo (zileuton). Although the FDA did imply that "the data were inadequate to draw a firm conclusion" and said that the clinical trials were not set up to observe any psychiatric behavior. Here are the data the FDA discovered during their review of these trials:
Singulair: 41 placebo-controlled trials that included 9,929 patients
Singulair: 41 placebo-controlled trials that included 9,929 patients
- Reports of suicidal thoughts: 1 (treated with Singulair)
- Attempted suicides: None reported
- Completed suicides: None reported
Accolate: 45 placebo-controlled trials that included 7,540 patients
- Reports of suicidal thoughts: 1 (placebo group)
- Attempted suicides: 1 (placebo group)
- Completed suicides: None reported
Zyflo: 11 placebo-controlled trials (number of patients unknown)
- Reports of suicidal thoughts: None reported
- Attempted suicides: None reported
- Completed suicides: None reported
However, On June 12, 2009 the FDA announced that Singulair (montelukast) as well as some other less popular leukotriene inhibitors -- Accolate (zafirlukast) as well as Zyflo and Zyflo CR (zileuton) -- must start to include a warning on its package insert, or label, regarding an increased risk of neuropsychiatric events including suicide and depression.
This June 2009 FDA warning about Singulair is seemingly a reversal from an earlier position taken by the FDA in January 2009 when the agency said their review of clinical trials did not suggest Merck's Singulair asthma drug caused suicide or suicidal thoughts.
From a June 12, 2009 MedPage Today article, "FDA: Leukotriene Inhibitors Associated with Suicide, Depression":
Leukotriene inhibitors must include a warning regarding increased risk of neuropsychiatric events including suicide and depression, according to the FDA.
The requirement applies to montelukast (Singulair), zafirlukast (Accolate), and zileuton (Zyflo and Zyflo CR). All are approved to treat asthma, and montelukast is also approved to treat symptoms of allergic rhinitis and to prevent exercise-induced asthma.
The requirement applies to montelukast (Singulair), zafirlukast (Accolate), and zileuton (Zyflo and Zyflo CR). All are approved to treat asthma, and montelukast is also approved to treat symptoms of allergic rhinitis and to prevent exercise-induced asthma.
Upon completing a review of the agents in April, the FDA found reports of agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicide, suicidal ideation, and tremor associated with use of the drugs.
The FDA based its review on postmarket reports and clinical trial data submitted by the manufacturers of the drugs....
The FDA said physicians should consider discontinuing the medications if patients develop neuropsychiatric symptoms.
The FDA said physicians should consider discontinuing the medications if patients develop neuropsychiatric symptoms.
