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.

Calls for VA's top official to resign

I’d been meaning to talk about this story but it’s progressed faster than my typing hands can keep up.

An e-mail sent around at the Veterans Health Administration among Dr. Ira Katz, the VA mental health director, and other officials, discussed the issue of hiding the number of suicides committed by veterans from the public—an estimated five out 18 of them being under VA care. Now, a number of senators (and bloggers) are calling for Katz’s resignation.

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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.

Suicide: Understanding and Intervening – Part I

Black’s Common Features of Suicidal Thinking

  1. Bitterness
  2. Anger
  3. An unwillingness to forgive
  4. The “last word” in argument
  5. A way to punish someone

“Romans 1 suggests that a person – believer or unbeliever – who contemplates suicide must actively suppress the Spirit’s testimony that he is a creature made in the image of God, living in dependence on him.”

“Actively suppress” is a strong statement. If it means a person is aware of this suppression, then I’d disagree. Some people may be aware of this but that isn’t always the case. Black emphasizes suicidal believers are made in the image of God and insinuates that suicidal attempts are willful acts of disobedience:

“We want to demolish the idea that someone who takes his life is a sad, wounded, and weakened victim, and that suicide is a noble expression of his fragility and God’s failure to rescue him.”

While suicide is not a noble expression of fragility, suicide shows a suicidal person and those around him how weak he is. This is not “weak” that describes someone with a character flaw; those referred to as weak are those who need emotional help. Those who are emotionally stronger are able to encourage someone who is emotionally weak. A man who takes his life may have been sad, may have been wounded, and may have been weak – but God’s grace was not beyond him and what is perceived as God’s “failure” to rescue him was still within God’s control. (I won’t get into the fine details of why He allows some people to live and some to die in this post.)

Suicide debates rage

Wow. I never realized all the responses that my post on “Suicide” would garner me. Again, I am not proud of my tendencies toward suicidal actions. I have some opinions on the following comments that I’ll reserve until afterward.

First, a comment from Amy:

“My brother committed suicide via hanging in our garage. My parents will never be the same some 17 years later.

Suicide is selfish and to be brutally honest, if you are going to do it do it somewhere where your dearest family and friends will not find you first. The aftermath and lingering nightmares are just too much.”

A follow-up comment from Anna:

“Amy,

I have attempted suicide, unsuccessfully; my sister killed herself, my grandfather killed himself with arsenic, my sister-in-law's mother gassed herself, my step-father's mother took an overdose. We do suicide in my family. All of us have been severely affected by it; I still cry at the thought of walking into my sister's flat and finding the dried pool of blood – an image I will never get out of my head, some 15 years later.

I have kept myself alive through all the pain because I have 3 children who I could not bear the thought of damaging in that way; I have been living for them, not for me.
However, I have tremendous sympathy for all those who attempt or succeed at committing suicide – I say succeed with emphasis. Any person who has ever felt the depths of despair of not being able to face another hour of the intolerable pain of deep depression, would understand the longing to end that pain. Living through it takes an unselfishness which is arguably admirable, arguably the biggest form of self-harm and denial possible. For someone to continue to live with that pain so as to avoid giving someone else the pain of grieving is not necessarily the kindest act; watching your loved one living (or rather "existing") with the pain of depression is arguably as bad, if not worse, than grieving for their death. They are existing in hell for that period of time it takes for them to crawl out of that hell. Nobody wants the person they love to live in hell – why keep them there???

Who is being selfish: the person who takes their life to end their suffering, or the person who watches that person suffering day in day out and doesn't want them to die because they themselves cannot stand the idea of their own grief and suffering when their loved one commits suicide? I personally cannot "judge" which person is being the more selfish.
I wouldn't want my worst enemy to have to endure that pain, day in day out, and to know that the only reason they are keeping themselves alive is for my benefit. Ultimately each of us has the choice to live or die and that choice deserves respect and compassion, not condemnation.

I understand that families left behind are often distraught as my own family has been; I have been, but I also understand why someone does it. If you can develop that understanding, it eases the pain, lessens the blame and enables all who are affected to feel compassion – a vital element in loving and being loved.”

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Who I Am

I am a 26-year-old black female who suffers from bipolar disorder. I was diagnosed with the illness in November 2006. I’d been diagnosed as suffering from major depressive disorder (MDD) beginning at the age of 14. I still consider myself to suffer primarily from depression although I do have occasional manic episodes.

This blog has helped me to recognize many of the things that I am. That
I truly am more than my diagnosis and that my diagnosis does not define
me. I am not just a person with manic and depressive episodes. I am a person with a personality. I’m smart, witty, drop-dead gorgeous—okay, I wish, but I’m not ugly—musically inclined, and ambitious. And that’s just scratching the surface.

I can be happy, sad, angry, and joyful. I have so many emotions that could classify me as anything. I have a short attention span, for instance. The docs missed the attention-deficit hyperactivity disorder (ADHD) diagnosis (although I lack the hyperactivity).  I suffer from anxiety as well but not a single medical record lists me as suffering from generalized anxiety disorder (GAD). So I self-diagnose. It helps me to realize that all of my flaws can pigeonhole me into any diagnosis I choose. I accept my flaws – “diagnosable” or not – and my strengths. This is my journey to learn more about myself, my diagnosis, my medical treatment, and anything relating to my personal life and general mental health.

I’m skeptical of pharmaceutical companies. I don’t hate them; however, many of their practices are shady and I—along with some of my favorite medical blogs —hope to shed light on the “unfavorable” news they choose to keep hidden from the public.

I highlight celebrities who admit to mental illnesses. Many of them suffer from depression, which is the fashionable mental illness of the moment, but others truly suffer from problems that are worth talking about.

I also write about my personal life relating to mental illness. I struggle with constant thoughts of suicide. Readers of this blog will note a pronounced emphasis on suicidal thoughts and behaviors.

Feel free to read on to the next entry about my Perfectionistic Tendencies. Chronicling my journey to managing and treating my illness can hopefully aid me. And eventually, someone else.