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.

Ghostwriting

According to the International Herald Tribune (IHT), the Journal of the American Medical Association (JAMA) has published an article about Merck’s practice of writing research studies and then asking doctors to slap their names on them. This practice has called into question Merck’s marketing of Vioxx, a profitable cardiovascular drug that was pulled off the shelves due to its link to heart attacks.

Merck acknowledged Tuesday that it sometimes hired outside medical writers to draft research reports before handing them over to the doctors whose names eventually appear on the publication. But the company disputed the article’s conclusion that the authors do little of the actual research or analysis.

Continue reading:

One paper involved a study of Vioxx as a possible deterrent to Alzheimer’s progression.

The draft of the paper, dated August 2003, identified the lead writer as "External author?" But when it was published in 2005 in the journal Neuropsychopharmacology, the lead author was listed as Dr. Leon Thal, a well-known Alzheimer’s researcher at the University of California, San Diego.

The second author listed on the published Alzheimer’s paper, whose name had not been on the draft, was Ferris, the New York University professor. Ferris, reached by telephone Tuesday, said he had played an active role in the research and he was substantially involved in helping shape the final draft.
"It’s simply false that we didn’t contribute to the final publication," Ferris said.

A third author, also not named on the initial draft, was Dr. Louis Kirby, currently the medical director for the company Provista Life Sciences. In an e-mail message on Tuesday, Kirby said that as a clinical investigator for the study he had enrolled more patients, 109, than any of the other researchers. He also said he made revisions to the final document.

"The fact that the draft was written by a Merck employee for later discussion by all the authors does not in and of itself constitute ghostwriting," Kirby’s e-mail message said.

Uh, yeah it does.

Read the rest of this entry »

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.

Loose Screws Mental Health News

Wow. I learned something new – “Women are over-represented in all cases of” depression, anxiety, dysthymia and panic attacks. Read more here.


An interesting observation from Gretchen Rubin, blogger of The Happiness Project.

“Studies showed that depressed people have as many nice experiences as non-depressed people, but they remember them less well.”


Graham’s Blog has linked to interesting fashion jewelry: Made with Molecules. For only $20, you can:

“Display your favorite neurotransmitters close to your brain!”

Erhm. The very thought of this disturbs me. Also feel free to purchase a serotonin-happiness card or a dopamine-heart card – just in time for Valentine’s Day.

dopamine heart card

Pfizer is cutting 10,000 from its workforce citing nothing other than loss of profits:

“The drug giant Pfizer said Monday that it would lay off 10,000 workers and close several manufacturing and research sites in an effort to bolster earnings hurt by the loss of patent protection on certain drugs and by setbacks in developing new products.”

I’ve mentioned patent protection before but it seems that Pfizer isn’t generating enough “structurally related” drugs to prevent the loss of its profits to generics. The two biggest losses: Zoloft and Zithromax.

“Pfizer said the moves would save $1.5 billion to $2 billion a year in pretax expenses.

Pharmaceutical industry analysts have generally been welcoming cutbacks by Pfizer but have said that while cost-cutting is beneficial, the company needs to resume growth by bringing new products to market.”

Pfizer’s a big company; I’m sure they’ll have no problems rebounding. However, I have no doubt that the failed torcetrapib factored into Pfizer’s decision to cut staffers.


A Philly plaintiff in the Vioxx suit against Merck has willingly withdrawn her suit. She cannot refile against Merck.

“Merck has consistently said it will fight each case on a one by one basis rather than submit to a large settlement.

In trials that have reached a jury verdict so far, Merck has won nine and lost four, including one Merck victory that since has been thrown out.”

The legal fees surrounding the Merck case must be astounding, but is it really worth it for Merck to drag these cases out against 27,000 other plaintiffs? I would assume on Merck’s part that it would be cheaper to settle. But then again, maybe it’s the whole “we need to clear our name” thing. That’s a fast way to lose profits for a pharma company.