the best predictor…

Posted on Wednesday 30 October 2013

In September, I noticed yet another John Mann/Robert Gibbons article in a major journal proposing that an FDA Warning be ignored [Varenicline, Smoking Cessation, and Neuropsychiatric Adverse Events] [very monotonous…]. I wrote then:
When you happen onto a really long blog post with lots of quotes, you can usually count on the fact that the blogger is out to prove something and getting his/her facts in a row. I usually skip to the end [or move on], being an impatient scanner myself. So I thought I’d start with the conclusion. Drs. Robert Gibbons and J. John Mann are making a career of attacking the FDA’s Black Box Warnings of potential suicidality from certain medications. Their articles generally rely on special access to datasets made available by pharmaceutical connections, yet they list their research support as coming from public grants. It smells like three day old fish to me, and I wonder why the journals keep publishing them…
What I left out was the ad campaign that followed the articles about suicidality with Prozac®/Effexor® [Suicidal Thoughts and Behavior With Antidepressant Treatment]:
Now, with this most recent article attacking the FDA Warning about Chantix®, we’re greeted with the same thing – an article in PsychiatricNews that reads like something from one of those check-out counter magazines at the supermarket:
by Vabren Watts
October 24, 2013

A reanalysis of previous data on the neuropsychiatric effects of the smoking-cessation drug Chantix may change some minds about its use. As Pfizer Pharmaceuticals pays out millions of dollars in claims related to depression and suicide associated with the antismoking drug Chantix, a study published September 13 in AJP in Advance found that the drug may be no more harmful than other smoking-cessation therapies.

Researchers in the Department of Psychiatry at the University of Chicago and at Columbia University conducted the largest randomized controlled trial to date evaluating the safety and efficacy of varenicline— a nicotine receptor partial agonist and the active ingredient in the product Chantix. J. John Mann, M.D., and Robert Gibbons, Ph.D., reanalyzed previous data concerning varenicline and found it was not linked to suicide events, depression, or aggression. According to study authors J. John Mann, M.D., and Robert Gibbons, Ph.D., since the Food and Drug Administration issued a black-box warning for Chantix in 2009, varenicline has been extensively studied for its association with neuropsychiatric events, but results have been inconsistent, and the studies have had major limitations.

“There are very few meta-analyses evaluating the effect of varenicline at a personal level,” Mann told Psychiatric News. He said that it is important to conduct more studies in clinical settings with limited exclusionary criteria, which will allow assessments of more-realistic outcomes. “In reality, we see people who want to quit smoking with unstable diabetes, heart disease, taking medication for 10 different conditions. Conducting randomized controlled trials in the clinic is important because the patterns of findings may be different”…

With information from more than 40,000 subjects, the authors reanalyzed data from 17 placebo-controlled trials conducted by Pfizer to assess smoking abstinence, suicidal ideation, depression, aggression, and nausea in participants with and without a history of psychiatric illness. In addition, data from the Department of Defense were evaluated to compare the rates of neuropsychiatric events and psychiatric symptoms among military health system patients receiving varenicline or nicotine-replacement therapy. The data showed that varenicline was highly associated with inducing nausea among patients, but not with suicide events, depression, or aggression. Current or past psychiatric illness increased the risk of neuropsychiatric events equally among the varenicline and placebo groups…

When Psychiatric News asked Mann why he thinks thousands of varenicline users have reported adverse psychiatric effects, he replied, “People who smoke have more pronounced aggressive and impulsive traits—smoking is associated with suicidal behavior and mood change — [and] sometimes the side effects or adverse effects reported are due to nicotine withdrawal or the loss of the cognitive-enhancing effects of nicotine.” Mann also noted that when any medication receives negative media attention for adverse events, clinicians are more likely to inquire about these side effects, and patients are more likely to report them. “Some reports are due to the patient being alert to the possibility [of a side effect] and [thus] more likely to report its occurrence, and sometimes the person feels that they have the complication, but objective examination fails to confirm this,” Mann said.

The study was funded by the National Institute of Mental Health. Gibbons served as an expert witness for Pfizer in a case related to varenicline and neuropsychiatric adverse events. Pfizer provided no financial support.
Again, from very monotonous…:
It would appear that Dr. Gibbons and Dr. Mann never met an FDA Black Box Warning they really cared much for. And as I said, there’s more in common with these three articles than just the shared authorship of Drs. Gibbons and Mann and their monotonous opinion of FDA warnings. They had special access to datasets to analyze, unavailable to the rest of us.
We can add something else – an ad campaign based on an article in a medical journal. For that matter, that little bit of mass psychoanalysis at the end explaining away patient reports sounds mighty familiar too. Since I have no way to vet this, "Pfizer provided no financial support," I can’t follow up on my "smells like three day old fish to me" comment. But I can say that Neurontin®, Effexor®, and Chantix® are all Pfizer products. And I can reiterate my comment:
I object, however, to their releasing information the rest of us can’t see to Drs. Gibbons and Mann to publish with the COI burden they have and absolutely no way for practicing or dissenting physicians to look into things for ourselves. It’s just not right. And, by the way, do our public granting institutions keep up with where their our money is being spent?
There’s a saying, "the best predictor of future behavior is past behavior," that belongs in here somewhere…
    Steve Lucas
    October 30, 2013 | 8:40 AM

    This link may be of interest as it shows the impact of marketing in a closed system.

    In this instance we see how in certain VA facilities a more expensive drug is being used over less expensive alternatives even thought he VA tightly controls drug rep access and formulary. The take away is that marketing outside the normal hospital channels has an impact on sales, and sales are the only thing pharma cares about.

    Steve Lucas

    October 30, 2013 | 2:34 PM

    Whoa, Steve— they got past the lower cost gate at the VA? Wow. Perhaps, after trying the other two, they were desperate for something that would work better. A lot of veterans were trained to smoke.

    I found this on a lawsuit website

    Numbers regarding similar drugs bear out the claims that the company brought a dangerous drug to market. In the first year that Chantix was on the market, there was the same number of adverse effects reported to the FDA regarding Chantix depression as there were for Zyban and Wellbutrin over the previous 10 years. Considering that the latter two are also prescribed widely for depression and related mental health problems, the disparity is significant, although many plaintiffs argued that Pfizer did little to indicate the risks when it aggressively marketed the drug.

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