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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CCEF 2008 Annual Conference: The Addict In Us All

CCEF 2008 Annual Conference

I’ve previously mentioned that I receive (currently weekly) counseling at CCEF in Glenside, PA. They hold a conference every year on various topics. Last year’s subject was overcoming fear and my husband and I found it to be immensely helpful. This year’s topic focuses on addiction. I received a PR from them and am posting it below.


Christian Counseling & Educational Foundation (CCEF) Announces
2008 Annual Conference – The Addict in Us All

Addiction sounds ominous, and it is. Addictions to drugs, alcohol, and gambling tear families apart and ruin lives. But this conference is about more than the junkie scoring dope or the alcoholic hiding vodka around the house. Even the average person gets stuck in negative behavior patterns. Overeating, shopping, sexual temptation, people’s approval, even love…everyone struggles with something. And everyone faces moments of despair and thinking that change is not possible.

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.

Decision Resources attempts to restore confidence in Big Pharma's atypicals

Zyprexa

Whee for self-promotion!

“Eli Lilly’s Zyprexa Will Remain the Clinical Gold Standard for the Treatment of Schizophrenia Through 2015”

“Clinical Gold Standard,” huh?

I can’t bring anything new to the table on this. Maybe I’m wrong, but here I go:

“For almost three decades, Decision Resources has provided in-depth research on the trends, emerging developments, and market potential in various healthcare industry sectors.  Our client base is diverse – including large pharmaceutical companies, emerging biotechnology concerns, financial services, managed care organizations, and medical device manufacturers who turn to Decision Resources to help shape their strategy and master their chosen markets.

The privately-owned company offers a rich array of research publications advisory services, and consulting that make it second to none for quality, analytical depth and insight. With access to almost 10,000 thought leaders, specialists, HMO formulary directors, and general practitioners, Decision Resources’ highly-credentialed analysts are able to reconcile real-world practice with hard numbers from the industry’s most respected data sources.  The resulting analysis and insights drive business decisions and commercial success within the biopharmaceutical, managed care, medical device, and financial markets.”

Here’s my assessment, take it with a grain of salt: In an attempt to fight the decline in sales from the NYT-induced Zyprexa backlash, Eli Lilly has gone on the offensive and hired Decision Resources to reinvent its star medication.

Decision Resources (DR), a privately owned company (no hyphen if a modifier ends in “-ly”), has a client base that includes large pharmaceutical companies. Ta-da! Don’t get it?

Decision Resources is not a public company; hence, in addition to not receiving federal money, it doesn’t need to report its financial dealings to the SEC. Therefore, no publicly accessible financial records of DR’s clients. They haven’t said they are an “independent” organization. Perhaps this is implied. Whatever the case may be, DR gets paid by its client base to research their products and “help shape their strategy and master their chosen markets.”

This isn’t brain science; this is on their “About Us” section of their Web site. Therefore, if Eli Lilly turns to DR and pays them to – I like DR’s wording here – “shape their strategy and master their chosen markets,” then DR is essentially a PR loudspeaker letting everyone know that Zyprexa is the “clinical gold standard” for schizophrenia.

What a bunch of hooey.

Not too long ago, it seems that AstraZeneca (AZ) may have had DR engineer its new marketing strategy to give Seroquel a boost. Why not? Mental health media watchdogs are hatin’ on the atypical antipsychotics.

“According to a new report entitled Schizophrenia: Turning Physician Insight into Projected Patient Share, Zyprexa is superior in efficacy to all other current therapies, particularly on measures that are most important to prescribers, such as impact on global symptoms and responder rate.”

Holla at me if you’ve got your hands on that report mentioned above.

“In spite of scoring* less favorable than the other drugs in terms of safety and lower than risperidone in terms of delivery features, Zyprexa is the gold standard.”

OK – so it’s not safe and it doesn’t deliver as well as Risperdal – whatever that means – but Zyprexa is still “the gold standard”?

“This overall advantage for a drug with significant safety concerns highlights the importance of efficacy to prescribers.”

I want you to reread that: ” This overall advantage for a drug with significant safety concerns highlights the importance of efficacy to prescribers.” Let’s attempt to paraphrase this: The benefit of this potentially harmful drug shows the importance of how effective it is to those who receive the drug. Although Zyprexa has “significant safety concerns,” the drug works well enough for doctors to prescribe it to patients. Uh, no. Positives don’t outweigh the negatives. It was nice jargon for a second there, though. (If this is effed up enough for adults, why subject children to this crap?)

“The report also finds that the most commercially important emerging antipsychotics (Janssen’s Invega, Organon BioSciences’ asenapine, and Wyeth/Solvay/Lundbeck’s bifeprunox) score* lower than Zyprexa, indicating that Zyprexa will remain unsurpassed during Decision Resources’ forecast period.”

I know I’m doing a play-by-play but this is important. I need to find out how DR decided that Zyprexa would be the “gold standard” until 2015. (What’s the significance of this year? Does EL’s patent on Zyprexa expire then? Nope, Eli Lilly’s patent on Zyprexa expires in 2011. Expect a similar molecularly structured olanzapine before then. Biolexapine?) So basically, in this report, DR’s conclusion is Zyprexa beats every other atypical antipsychotic for schizophrenia by far. Notice that AZ’s Seroquel (the soon-to-be “gold standard” of bipolar meds),  an atypical also used for schizophrenia, is not listed. Not coincidence.

The little asterisk (*) next to the word “score” prompts me to wonder: Just how did they come up with these scores? Well, the asterisk tells me that I need to contact DR for the methodology behind the product scores. I just might. Then send it off to CL Psych or Furious Seasons to decipher the crap out of it.

Another thing to note on this PR:

“”Invega is a metabolite of risperidone and is likely to have efficacy similar to that of risperidone, which scored* slightly lower than Zyprexa overall,” said Nitasha Manchanda, Ph.D., analyst at Decision Resources. “Asenapine also lacks the differentiation to replace Zyprexa as the gold standard because it does not make as significant an impact on global symptoms, and bifeprunox is significantly inferior to Zyprexa in all primary efficacy measures and is not capable of surpassing Zyprexa.””

Dr. Manchanda, analyst for DR, pulled bifeprunox – not yet on the drug market – into the Zyprexa comparison and somehow was able to call it “significantly inferior to Zyprexa” with an incapability to “surpass” it. How many people have used bifeprunox, Ms. Manchanda? OK, now tell me how many people have used Zyprexa? And you’re telling me that a drug that hasn’t yet hit the market is “significantly inferior” to a drug that has been on the market for the past couple of years and has 1,200 lawsuits still pending in addition to the millions that have already been paid?

As for AZ, DR has determined that Seroquel will become the “gold standard” for bipolar medication by 2010, knocking Lamictal out of its current “gold standard” status. Like Furious Seasons, I had NO idea Lamictal was held up so highly for bipolar meds. Considering that lithium has always been the king of bipolar meds and treats both acute mania and depression better than Lamictal, I’m surprised to read this.

“According to the new DecisionBase report entitled Bipolar Depression: Turning Physician Insight into Projected Market Share, Seroquel’s advantages over Lamictal include the more profound effect on depressive symptoms seen in short-term trials.”

My doctor precribed Lamictal to me for management of depressive symptoms in bipolar disorder. He conversely prescribed Seroquel for mania (and to help me get sleep).  Getting back to the short-term trials, Lamictal was tested for 18 months for long-term management of bipolar disorder. Seroquel, however, was tested for 8 weeks. Effective for the short-term? Perhaps. But most patients on atypicals take them long-term. And that’s precisely where Seroquel fails.

“The drug’s efficacy on this measure differentiates it from other therapies, according to thought-leading psychiatrists, and the importance assigned to this measure by prescribing psychiatrists drives Seroquel’s product score above Lamictal’s.*”

According to thought-leading psychiatrists who probably function as consultants and analysts for “large pharmaceutical companies.” Seroquel may have the potential to sell more than Lamictal by 2010 – if this is what DR’s gauging. However, it seems like DR is trying to push Seroquel, not just as a better market share, but as a better product. In this “report,” DR also fails to compare Seroquel’s efficacy to Zyprexa’s. What a convenient absence for a product used for psychosis in bipolar disorder.

(ignore any spelling errors in this post. it’s late and i bumped my forehead against the edge of a car door in the rain. ouch.)