FDA: No link between Singulair and suicidal behavior

On Tuesday, 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 ago, 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:

SingulairSingulair: 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

AccolateAccolate: 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

ZyfloZyflo: 11 placebo-controlled trials (number of patients unknown)

  • Reports of suicidal thoughts: None reported
  • Attempted suicides: None reported
  • Completed suicides: None reported

Forgive me for being cynical but the data sounds fishy. I can’t pinpoint why but it does. The suicide numbers and patient involvement data seem to deviate some from the numbers listed in Merck’s PR issued last March. (I’m seeing 11,000+ patients vs. 9,929 patients.) Regardless of the clinical trial data, it appears that the FDA as of yet have not reviewed post-marketing data.

Scott Korn, a senior safety surveillance executive for Merck said in an article for Reuters:

“‘At the time we did not believe, and we still don’t think a link has been established’ between Singulair and the suicides.”

In the same article, Sanford Berstein analyst Tim Anderson had this to say about the possibility of the FDA finding a link:

“If the… safety review leads to a stern warning about behavioral changes in the Singulair label, this could frighten users of the drug or their parents and give Merck’s competitors ammunition to attack the brand.”

The Washington Post has Dr. David Weldon, director of the Allergy and Pulmonary Lab Services at Scott & White in College Station, Texas, on record saying that he had not “seen any increase in psychiatric problems with the drug but that some patients had complained of nightmares after starting on Singulair.” (Note: It appears that the closest conflict of interest Weldon would have here is that he served as a consultant and is honoraria for AstraZeneca.)

Dr. Rauno Joks, head of the SUNY Downstate division of allergy and immunology, made an interesting point in the Washington Post article:

“The physician really needs to review whether there are symptoms that have developed since patients started taking the medication, if there’s an underlying depression that was there before medication started.

Also, seasonal allergies in and of themselves can cause fatigue and lethargy, which makes it harder to assess, because those are some of the symptoms you have with depression.”

The FDA says they’ve completed analyses of submitted clinical trial data but their “safety review will continue” for several more months before they come to a concrete conclusion. For customer testimonials, check out medications.com that has over 2,300 people reporting side effects and askapatient.com that has an average 2.3 rating from 524 reviewers. The most commonly reported mood-related side effect on both of the sites is irritability.

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2-Year Anniversary: The Long and Winding Road

I’m aware that my blog has taken a significantly dark turn.  This may alienate some of my readers who seek happier, brighter topics. I don’t think my posts have been negative; on the contrary, I think they’ve been positive. Positive and educational.

I’ve been exploring the topic of suicide recently because it’s a subject that’s quite near and dear to me, now more than ever before.

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Word of the Day: Paroniria

Paroniria: Terrifying dreams causing sleep disturbances.

I was looking at the Allegra Web site to double-check whether my recent mixed-mood episodes might have been induced since I began taking the allergy drug regularly. (It’s not a far-fetched idea. Think Singulair.) "Sleep disturbances and paroniria" are a few of the many adverse effects listed for the drug.

Brief update on Singulair-suicide link

Merck issued a press release today responding to the FDA’s investigation. Along with the standard "we didn’t know about this problem until after it the market" disclaimer, the PR mentioned:

In a cumulative analysis recently provided to the FDA of Merck’s randomized, double-blind, placebo-controlled clinical trials, which included over 11,000 adults and children in over 40 studies who were treated with SINGULAIR, there were no reports of suicidal thoughts or actions and no completed suicides in the patients who received SINGULAIR.

Additionally, in a cumulative analysis recently provided to the FDA of Merck’s randomized, double-blind, clinical trials that compared SINGULAIR with other active agents to treat asthma (which included over 3,900 adults and children who were treated with SINGULAIR and over 3,400 who were treated with other asthma therapies), there was 1 patient who attempted suicide who received SINGULAIR, and there were 3 patients who attempted suicide who received other asthma therapies (including inhaled corticosteroids and long-acting beta-agonists).  These studies were not designed to compare the rate of suicide in patients taking SINGULAIR with the rate of suicide in patients taking these other asthma agents.

Did Merck report that one suicidal attempt when compared to "other active agents to treat asthma"? It doesn’t say anything in their patient safety or prescribing information when I checked. Perhaps someone can find out whether they reported this in their clinical trials?

In the meantime, the Singulair section of medications.com is ablaze with parents who are now expressing concern over their children’s well-being on the drug. Apparently, issues have cropped up with the drug even before the FDA announced their investigation.

Singulair and Suicidal Behavior

SingulairIn a particularly odd link, the FDA is looking into Singulair, the asthma and allergy drug and its correlation with suicidal behavior. I’ve taken Singulair in the past and not once did it ever occur to me to think about an allergy medication being linked to suicidal behavior. The FDA also says that it could cause mood and behavior changes. The situation that alerted the FDA to this possibility is the story of 15-year-old Cody Miller who killed himself 17 days after switching from allergy medication Allegra to Singulair. Miller’s mother, Kate, approached his medication switch with extreme caution and informed herself of the possible side effects:

She checked the Merck website and the information sheet she got from the pharmacist on Singulair and found no red flags, so they were stumped when Cody started acting out of character.

I have to hand it to Merck: Once the Millers reported Cody’s death, they immediately updated Singulair’s warnings to include suicidal thoughts and actions. However, Cody died on August 4, 2007. Merck updated their information two months later. As of February 29, 2008, the FDA still hadn’t taken any action. Despite the updated warnings, however, doctors and pharmacists were unaware of the new information.

The Singulair website carries the updated side effects, but you have to search it out in the patient information PDF on the fourth of five pages.

If you check with the FDA, you’ll find nothing. That’s because they admit they haven’t updated their website on Singulair since 2001.

According to the FDA’s MedWatch safety information, they have only begun their investigation today. They say it will take 9 months for them to “complete their investigation.” We may not hear of the FDA’s conclusions until early 2009. If this is a single, isolated incident, the FDA may just say the results are inconclusive and allow Merck rip the warning off their patient safety information. It is also important to note, however, that Singulair has also been linked to depression and anxiety.

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