\nProzac Is No Magic Pill, but It Works<\/a><\/div>\nNew York Times<\/font><\/strong><\/div>\nby Robert Gibbons and J. John Mann<\/div>\nOctober 7, 2014<\/div>\nThe changes in treatment and attitude brought on by Prozac prompted two colliding points of view. One was that antidepressants were overprescribed and people were encouraged to turn to a pill to solve all their problems. Another viewpoint was that major depression was one of the most debilitating illnesses in the world and was mostly untreated or undertreated, and even though we were now prescribing a lot of antidepressants there were still too many people with moderate to severe depression that remained untreated.<\/p>\n
A third claim intruded into this debate, namely that the efficacy of antidepressant medications is overstated and the best evidence of effectiveness was in only the most severely ill patients. In an effort to shed light on this question, we obtained much of the world’s complete longitudinal data<\/a> on randomized controlled trials of the antidepressants fluoxetine [Prozac] and venlafaxine [Effexor] in depressed patients conducted by Lilly, Wyeth and the National Institute of Mental Health. We included studies regardless of whether they demonstrated the medications were effective in order to get the clearest picture possible of the efficacy of these widely used antidepressants. <\/p>\n
From the statistical model that synthesized these data across all studies separately for each age category, we computed estimated response and remission rates. We found an improvement in depression regardless of age in both medications relative to a placebo pill. Interestingly, the greatest benefit in terms of response and remission rates was seen in children, followed by adults, and then by more modest effects in the elderly. There was no evidence that severity of depression made a difference to how well the antidepressant medication worked. Based on these findings we concluded that antidepressants work across the lifespan, in patients with moderate or severe depression.<\/div>\n<\/blockquote>\nIn a recent blog post, I reviewed Dr. Gibbons’ most recent paper, yet another assault on the Black Box Warning, this time using commercial databases [gibbons everlasting…<\/a>] and cataloged his many previous attempts to cast doubt on the 2004 FDA Black Box Warning. He has made similar attempts to debunk the warnings on Neurontin® and Chantix® [very monotonous…<\/a>].. This recent NYT comment is based on his 2012 articles with the same intent. I had offered a strong criticism at the time of those 2012 articles [an anatomy of a deceit 1…<\/a> etc.], as did many others. But in gibbons everlasting…<\/a>, I left out something important, something mentioned by Dr. Bernard Carroll both in his comment here<\/a> and to the New York Times<\/a>. So I thought I’d just run it around again:<\/div>\n\nAntidepressant treatment and suicide attempts and self-inflicted injury in children and adolescents<\/a><\/div>\nby Gibbons RD, Coca Perraillon M, Hur K, Conti RM, Valuck RJ, and Brent DA<\/div>\nPharmacoepidemiologic Drug Safety<\/font><\/strong>. 2014 Sep 29. doi: 10.1002\/pds.3713. [Epub ahead of print] <\/div>\n<\/p>\n
PURPOSE:<\/font><\/strong><\/u> In the 2004, FDA placed a black box warning on antidepressants for risk of suicidal thoughts and behavior in children and adolescents. The purpose of this paper is to examine the risk of suicide attempt and self-inflicted injury in depressed children ages 5-17 treated with antidepressants in two large observational datasets taking account time-varying confounding.<\/div>\nMETHODS:<\/font><\/strong><\/u> We analyzed two large US medical claims databases (MarketScan and LifeLink) containing 221,028 youth (ages 5-17) with new episodes of depression, with and without antidepressant treatment during the period of 2004-2009. Subjects were followed for up to 180 days. Marginal structural models were used to adjust for time-dependent confounding.<\/div>\nRESULTS:<\/font><\/strong><\/u> For both datasets, significantly increased risk of suicide attempts and self-inflicted injury were seen during antidepressant treatment episodes in the unadjusted and simple covariate adjusted analyses.<\/font><\/strong> Marginal structural models revealed that the majority of the association is produced by dynamic confounding in the treatment selection process; estimated odds ratios were close to 1.0 consistent with the unadjusted and simple covariate adjusted association being a product of chance alone.<\/div>\nCONCLUSIONS:<\/font><\/strong><\/u> Our analysis suggests antidepressant treatment selection is a product of both static and dynamic patient characteristics. Lack of adjustment for treatment selection based on dynamic patient characteristics can lead to the appearance of an association between antidepressant treatment and suicide attempts and self-inflicted injury among youths in unadjusted and simple covariate adjusted analyses. Marginal structural models can be used to adjust for static and dynamic treatment selection processes such as that likely encountered in observational studies of associations between antidepressant treatment selection, suicide and related behaviors in youth.<\/div>\n<\/blockquote>\nIn gibbons everlasting…<\/a> I listed Dr. Gibbons previous articles on this topic since the Black Box Warning was issued by the FDA in 2004. While the FDA meta-analysis supported the case that suicidality is an uncommon but dangerous side effect of the use of SSRIs in adolescents, it was the case reports heard by the panel that lead them to append the warning. Dr. Gibbons statistical analyses have chased disproving the warning all over the map – from multi-country comparisons, the CDC statistics, proprietary databases, VAH statistics, drug company clinical trials, etc. always chasing the same hypothesis, the same one recently espoused by Lu et al [all databases are not created equal…<\/a>]:<\/div>\n\n\n
The Hypothesis<\/font><\/strong> [my version]<\/em>: <\/div>\nThe Black Box Warning is wrong. It scared doctors who prescribe fewer antidepressants to adolescents, depriving them of needed treatment, thereby increasing the incidence of suicidality. <\/font><\/em><\/div>\n<\/ul><\/div>\nIn his previous outings, over the last decade, Gibbons has stuck to attempts at using population meta-analyses to show that antidepressants don’t increase the incidence of suicidality. His articles are difficult because they can’t be vetted [not enough information] and they involve complicated statistical analyses that he describes, but does not show. They are invariable followed by media reports, The ones mentioned in the NYT above were followed by a media blitz<\/em> [the campaign…<\/a>]. Invariably he finds no evidence of suicidality in adolescence on SSRIs. There are several points to make about these papers:<\/div>\n<\/p>\n
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There is no<\/u> strong evidence that SSRIs are even effective in adolescent depression. Only Prozac was approved, and that was early on before these questions were raised. So the notion that effective treatment is being withheld is unsubstantiatable.<\/font><\/em> <\/div>\n<\/li>\n- \n
This syndrome is not common, but once you see it, you have no question of causality [at least I didn’t]. It’s not a population study<\/u> thing, it’s a case report<\/u> thing. And there are plenty of cases of completed suicides among those reports. I don’t even treat adolescents, but I personally know of several such cases. The cases are substantiatable.<\/font>
<\/em> <\/div>\n<\/li>\n<\/span><\/ol>\n
Now to the most recent paper and Dr. Carroll’s point. After a decade of trying to prove it doesn’t happen, in this new study, it seems that it does happen after all:<\/div>\n\n
"For both datasets, significantly increased risk of suicide attempts and self-inflicted injury were seen during antidepressant treatment episodes in the unadjusted and simple covariate adjusted analyses."<\/strong> <\/font><\/em><\/div>\n<\/ul>\nAnd then Dr. Gibbons undoes it with some kind of factor analysis that is opaquely described and unintelligible to any physician no matter how statistically sophisticated. Carroll<\/a> calls it "voodoo statistical hand waving<\/em>," but even that is forgiving because Gibbons’ presentation is effete and insulting to the reader. So the question really comes down to Why do these recurrent articles against the Black Box Warning keep coming?<\/em> with each study more questionable and convoluted than the last. They are presented as being in the service of child advocacy – hardly likely. One hint about their persistence is in looking at the authorship: <\/div>\n\nImpact of publicity concerning pediatric suicidality data on physician practice patterns in the United States.<\/a><\/div>\nby Nemeroff CB<\/font><\/strong>, Kalali A, Keller MB<\/font><\/strong>, Charney DS, Lenderts SE, Cascade EF, Stephenson H, and Schatzberg AF<\/font><\/strong>.<\/div>\nArchives of General Psychiatry<\/font><\/strong>. 2007 64[4]:466-72.<\/div>\n<\/blockquote>\nThree authors on Senator Grassley’s list, chairmen who lost their chairs in the following years; four customers of Sally Laden, notorious ghost-writer; and the medical director and emplyees of Quintiles, a major CRO. Then:<\/div>\n\nNews coverage of FDA warnings on pediatric antidepressant use and suicidality<\/font><\/strong><\/u><\/div>\nby Barry CL and Busch SH.<\/div>\nPediatrics<\/font><\/strong>. 2010 125[1]:88-95.<\/div>\n[full text online<\/a>]<\/div>\n<\/blockquote>\nThese studies were financed by the National Bureau of Economic Research<\/font><\/strong>, a think tank founded by a member of the Eli Lilly Board at the time [see pretty loud coi…<\/a>, the NBER study<\/a>, and tortured numbers…<\/a>]. Then there are the numerous studies of Dr. Gibbons who has testified for Pfizer in the cases involving SSRIs, Chantix, and Neurontin. Throw in the recent study by Lu et al [see all databases are not created equal…<\/a>], employed by Harvard’s Managed Care conglomerate. There are others, but nowhere among them are the expected child psychiatrists or psychologists. This is pretty much an industry effort all the way through.<\/div>\n
\n
\nThis is a strange story about an unlikely collection of people diligently pursuing the debunking of a clear, if uncommon, adverse effect of a class of medications when given to youth – a potentially fatal complication. It proposes to be advocacy for teens being denied effective treatment, yet even the evidence for its effectiveness is decidedly underwhelming. The people producing these studies are not from the community of people actively involved in treating the populations studied, and the evidence they present is at some distance removed from the actual patients [claims databases, population statistics, etc.], invariably connected with some industry [PHARMA, Managed Care, etc.], and generally accompanied by some kind of prominent media coverage like the NYT piece I started with above. The important question is Why? Why do they keep at it? Of course we can’t truly know their motives, but it’s a pretty good guess that it’s not what the articles say. And though unprovable, we can easily hypothesize for ourselves what drives this campaign. Almost anyone reading this could come up with a set of motives, but I want to say a few of them out loud: <\/div>\n<\/p>\n
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PHARMA: Depressed adolescents are common – a lucrative market for the sale of antidepressants.<\/font><\/em><\/div>\n<\/li>\n- \n
PHARMA: The suicidality Adverse Event was downplayed in the original reports – a litigation liability.<\/em><\/font><\/div>\n<\/li>\n- \n
Managed Care: The cost of delivering care other than drugs to depressed teens would be expensive<\/em><\/font>.<\/div>\n<\/li>\n- \n
Psychiatry: The KOL psychiatrists have based their reason d’etre on the effectiveness of the SSRI drugs, talking about ‘depression’ as if it’s a ‘disease entity’ and the SSRIs as the ‘treatment’ for that ‘disease entity’. They essentially define psychiatry by this disease\/treatment dyad. <\/em><\/font><\/div>\n<\/li>\n<\/span><\/ul>\n
In my mind, this is an affront to the biological psychiatrists who have given us effective treatments for the subset of depressed people who have the depressions that fit the disease model – eg Manic Depressive Illness, Melancholia. It is an affront to the psychotherapists from a variety of disciplines who work with adolescents who present with depression. It is an affront to psychiatrists who don’t subscribe to the neoKraepelinian dictum that all mental illness is biological. And it is an affront to the scientists who adhere to the scientific method and use its tools carefully – hypervigilant to the introduction of bias, including their own. But first and foremost, it is a betrayal of the trust of the depressed adolescents, their parents, and the practitioners who treat them…<\/div>\n","protected":false},"excerpt":{"rendered":"Prozac Is No Magic Pill, but It Works New York Times by Robert Gibbons and J. John Mann October 7, 2014 The changes in treatment and attitude brought on by Prozac prompted two colliding points of view. One was that antidepressants were overprescribed and people were encouraged to turn to a pill to solve all their […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_bbp_topic_count":0,"_bbp_reply_count":0,"_bbp_total_topic_count":0,"_bbp_total_reply_count":0,"_bbp_voice_count":0,"_bbp_anonymous_reply_count":0,"_bbp_topic_count_hidden":0,"_bbp_reply_count_hidden":0,"_bbp_forum_subforum_count":0,"footnotes":""},"categories":[5],"tags":[],"class_list":["post-50725","post","type-post","status-publish","format-standard","hentry","category-opinion"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/50725","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/comments?post=50725"}],"version-history":[{"count":37,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/50725\/revisions"}],"predecessor-version":[{"id":50762,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/50725\/revisions\/50762"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=50725"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=50725"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=50725"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}