No excess suicide risk found with asthma drugs

In 2008, the Food and Drug Administration (FDA) said it was investigating reports of mood and behavior changes, suicidal thinking and suicide among people taking asthma medications known as leukotriene modifiers.

The drugs include Singulair (known generically as montelukast), Accolate (zafirlukast) and Zyflo (zileuton).

After reviewing clinical trial data on the drugs, the FDA concluded there was no evidence of a link to suicidal behavior. Still, in 2009 the agency asked manufacturers to add a precaution in the drugs' prescribing instructions about reports of suicide and other psychiatric problems.

But single reports of serious effects among medication users can only hint at a problem.

"Case reports don't prove there actually is an association between a drug and an adverse event, because there are so many other factors that could be at work," said Glen T. Schumock, a professor of pharmacy practice at the University of Illinois at Chicago who led the new study.

So Schumock's team looked through information from a U.S. insurance claims database. From a group of 195,000 five- to 24-year-olds on asthma medication, the researchers found 344 cases of attempted suicide.

They matched each of those young people with 10 others who had no suicide attempts.

Not surprisingly, Schumock and his colleagues found the suicidal group had higher rates of mental health conditions and substance abuse, and those youths were more likely to be on psychiatric drugs including antidepressants.

Overall, 5.5 percent had been on a leukotriene modifier at the time of their suicide attempt. That compared with 6.5 percent of the young asthma patients with no suicide attempts who were taking those medications.

When the researchers accounted for mental health problems and other factors, they found no connection between leukotriene modifiers and suicide risk, according to findings published in the Journal of Allergy and Clinical Immunology.

There have been reports, though, of other problems tied to the drugs - including depression, insomnia and aggressive behavior. And Schumock said this study cannot speak to those risks.

Nor is it the final word on leukotriene modifiers and suicide. "There still needs to be more work done," Schumock said. "One study is never enough."

One of the limits of the study is its reliance on information from medical claims. That may not capture all suicide attempts, or accurately reflect whether young people actually took their asthma medications.

But Schumock said the findings should give doctors, parents and patients some reassurance.

He noted that leukotriene modifiers are considered an important option for children with asthma because they are taken in pill form, rather than through an inhaler.

As for the precautions in the drugs' labeling, Schumock said he does not know whether these findings might change anything.

And it's not clear that anything should change, he added. "I think people should have all the information that's out there," Schumock said.

The FDA declined to comment on the findings directly, but a spokesperson said it "continues to monitor post-marketing reports of neuropsychiatric events and leukotriene modifiers."

As for why the asthma drugs themselves would have mental health effects, there is no known potential reason, according to Schumock.

The medications do appear able to cross from the blood into the brain, but there's no evidence they cause harm once they get there. On the other hand, no one can say for sure that the drugs are completely safe, Schumock noted.

He said it might be wise for a young person with risk factors for suicide - like a past suicide attempt - to avoid the medications for now.

One of Schumock's colleagues on the study is a consultant to Merck, which makes Singulair. None of the other researchers reports any conflicts of interest.

SOURCE: bit.ly/LNrob7 Journal of Allergy and Clinical Immunology, online June 14, 2012.