{"id":40116,"date":"2013-09-19T11:31:05","date_gmt":"2013-09-19T15:31:05","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=40116"},"modified":"2013-09-19T18:13:57","modified_gmt":"2013-09-19T22:13:57","slug":"very-monotonous","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2013\/09\/19\/very-monotonous\/","title":{"rendered":"very monotonous…"},"content":{"rendered":"
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.<\/div>\n

There are three examples – two are Pfizer Drugs [Chantix®<\/font><\/strong> and Neurontin®<\/font><\/strong>], and one is about Lilly and Wyeth\/Pfizer drugs [Prozac®<\/font><\/strong> and Effexor®<\/font><\/strong>]. I’m not going to comment on the content of their articles. The post would reach to the floor. I’m just going to document what I said in the last paragraph and let you come to your own conclusions about the Conflict of Interest problems and the special treatment by industry on NIMH funded research. First, the most recent example.<\/p>\n

Chantix®<\/font><\/strong> [Varenicline] was introduced as a smoking cessation aid in 2006<\/font><\/strong>. In 2009<\/font><\/strong>, the FDA issued a black box warning of possible side effects including depression, suicidal thoughts, and suicidal actions. Moore, Glemullen et al reported on their analysis of the FDA records in several subsequent articles in PLoS ONE:<\/div>\n
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Prescription Drugs Associated with Reports of Violence Towards Others<\/a> <\/div>\n
by Thomas J. Moore, Joseph Glenmullen, and Curt D. Furberg <\/div>\n
PLoS ONE<\/font><\/strong>. 2010<\/font><\/strong> 5[12]: e15337. doi:10.1371\/journal.pone.0015337.<\/div>\n
[full text on-line<\/a>] <\/div>\n

<\/p>\n

Context<\/font><\/strong>: Violence towards others is a seldom-studied adverse drug event and an atypical one because the risk of injury extends to others.<\/div>\n
Objective<\/font><\/strong>: To identify the primary suspects in adverse drug event reports describing thoughts or acts of violence towards others, and assess the strength of the association. <\/p>\n
<\/div>\n

C<\/font><\/strong>onclusions<\/font><\/strong>: Acts of violence towards others are a genuine and serious adverse drug event associated with a relatively small group of drugs. Varenicline, which increases the availability of dopamine, and antidepressants with serotonergic effects were the most strongly and consistently implicated drugs. Prospective studies to evaluate systematically this side effect are needed to establish the incidence, confirm differences among drugs and identify additional common features.<\/div>\n<\/blockquote>\n

\n
Suicidal Behavior and Depression in Smoking Cessation Treatments<\/a><\/div>\n
by Thomas J. Moore, Curt D. Furberg, Joseph Glenmullen, John T. Maltsberger, and Sonal Singh.<\/div>\n
PLoS ONE<\/font><\/strong>. 2011<\/font><\/strong> 6[11]: e27016. doi:10.1371\/journal.pone.0027016.<\/div>\n
[full text on-line<\/a>] <\/div>\n

<\/p>\n

Background<\/font><\/strong>: Two treatments for smoking cessation — varenicline and bupropion — carry Boxed Warnings from the U.S. Food and Drug Administration [FDA] about suicidal\/self-injurious behavior and depression. However, some epidemiological studies report an increased risk in smoking or smoking cessation independent of treatment, and differences between drugs are unknown. <\/p>\n
<\/div>\n

C<\/font><\/strong>onclusions<\/font><\/strong>: Varenicline shows a substantial, statistically significant increased risk of reported depression and suicidal\/self-injurious behavior. Bupropion for smoking cessation had smaller increased risks. The findings for varenicline, combined with other problems with its safety profile, render it unsuitable for first-line use in smoking cessation.<\/div>\n<\/blockquote>\n

Now this published on-line in the American Journal of Psychiatry<\/font><\/strong>:<\/div>\n
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Varenicline, Smoking Cessation, and Neuropsychiatric Adverse Events <\/a><\/div>\n
by Robert D. Gibbons<\/font> and J. John Mann<\/font><\/div>\n
American Journal of Psychiatry<\/font><\/strong>. 2013<\/font><\/strong> Sep 13. [Epub ahead of print]<\/div>\n

<\/p>\n

Objective<\/font><\/strong>: In 2009, the U.S. Food and Drug Administration issued a black box warning for varenicline regarding neuropsychiatric events. The authors used data from randomized controlled trials and from a large Department of Defense [DOD] observational study to assess the efficacy and safety of varenicline. <\/p>\n
<\/div>\n

C<\/font><\/strong>onclusions<\/font><\/strong>: This analysis revealed no evidence that varenicline is associated with adverse neuropsychiatric events. The evidence supports the superior efficacy of varenicline relative to both placebo and bupropion, indicating considerable benefit without evidence of risk of serious neuropsychiatric adverse events, in individuals with and without a recent history of a psychiatric disorder.<\/div>\n<\/blockquote>\n

Like I said, it looks familiar. We have been here before with Drs. Gibbons and Mann:<\/div>\n
\n
Gabapentin and Suicide Attempts<\/a><\/div>\n
by Robert D. Gibbons<\/font>, Kwan Hur, C. Hendricks Brown, and J. John Mann<\/font><\/div>\n
Pharmacoepidemiologic Drug Safety<\/font><\/strong>. 2010<\/font><\/strong> 19[12]:1241–1247.<\/div>\n
[full text on-line<\/a>]  <\/div>\n

<\/p>\n

Purpose<\/font><\/strong>: On December 16, 2008 FDA issued a class warning for antiepileptic drugs and suicidal thoughts and behavior. The purpose of this study was to determine if the antiepileptic drug gabapentin increases risk of suicide attempt in patients to which it was prescribed for various indications.<\/div>\n
<\/div>\n
Conclusions<\/font><\/strong>: This study finds that gabapentin does not increase risk of suicide attempts in non-psychiatric populations and is associated with a reduction in suicide attempt risk in patients with psychiatric disorders.<\/div>\n<\/blockquote>\n
\n
Suicidal Thoughts and Behavior With Antidepressant Treatment: Reanalysis of the Randomized Placebo-Controlled Studies of Fluoxetine and Venlafaxine<\/a><\/div>\n
by Robert D. Gibbons<\/font>, C. Hendricks Brown, Kwan Hur, John M. Davis, and J. John Mann<\/font><\/div>\n
Archives of General Psychiatry<\/font><\/strong>. Published online February 6, 2012<\/font><\/strong>.<\/div>\n

<\/p>\n

Context<\/font><\/strong>: The US Food and Drug Administration issued a black box warning for antidepressants and suicidal thoughts and behavior in children and young adults.<\/div>\n
<\/div>\n
Conclusions<\/font><\/strong>: Fluoxetine and venlafaxine decreased suicidal thoughts and behavior for adult and geriatric patients. This protective effect is mediated by decreases in depressive symptoms with treatment. For youths, no significant effects of treatment on suicidal thoughts and behavior were found, although depression responded to treatment. No evidence of increased suicide risk was observed in youths receiving active medication…<\/div>\n<\/blockquote>\n
It would appear that Dr. Gibbons and Dr. Mann never met an FDA Black Box Warning<\/font><\/strong> 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:<\/div>\n