{"id":19341,"date":"2012-02-08T11:43:56","date_gmt":"2012-02-08T16:43:56","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=19341"},"modified":"2012-02-08T13:19:00","modified_gmt":"2012-02-08T18:19:00","slug":"hope-springs-3","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2012\/02\/08\/hope-springs-3\/","title":{"rendered":"hope springs…"},"content":{"rendered":"
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Antidepressant Treatment During Pregnancy<\/font><\/strong>
Commentary<\/font><\/strong> <\/a>
by Margaret Spinelli, M.D.<\/sup>
American Journal of Psychiatry<\/font><\/strong>. 2012 169:121-124.
[full text on-line<\/font><\/strong><\/u><\/a>]<\/div>\n

<\/p>\n

A behavioral health outpatient program recently decided that psychiatrists would no longer be permitted to provide new prescriptions for antidepressants to pregnant women because the sponsoring institution had determined that the risk was too high. As a psychiatrist specializing in the treatment of women in the perinatal period, I am one of many practitioners who must frequently decide whether or not to use medication to treat depressed pregnant women.<\/p>\n

Currently, the medical literature contains studies of more than 20,000 pregnancy outcomes for women exposed to antidepressants. This literature has been helpful in identifying possible effects of this exposure on the outcome of pregnancy. The results of studies that demonstrate increased risk for adverse pregnancy or birth events are frequently publicized in the media, which has resulted in many pregnant women refusing medication. Some law firms have seized on this information to seek plaintiffs to bring lawsuits. Many clinicians hear of positive studies through the media or see advertisements from law firms, scan the medical literature for abstracts, and may conclude that the risks of medication to the mother and fetus outweigh possible benefits. However, negative studies receive minimal media attention…<\/sup><\/div>\n<\/blockquote>\n

Early in the month, I find myself perusing the journals. I’m generally looking for something specific – what I call "CRO Charts." By that I mean industry funded double blind placebo controlled clinical trials of new or old drugs that have the format of so many we’ve seen before – the ones where the placebo groups have such dramatic improvements and the drug under study does only a little bit better ["statistically separates from placebo"][a few shown below]. Over the years, we’ve seen so many of those studies – the kind that get drugs through the FDA, or support application for new indications. I’m looking for them because I want to cry "foul!" early. Way too many of those slipped under the wire over the years and became the handouts for drug Sales Reps or FDA approvals and shouldn’t have been published in the first place [hey, somebody needs to keep an eye out for such things]. I also look for modern versions of those formerly ubiquitous review articles that were such obvious infomercials. You know, those ones with titles like "the neurobiology of…" or "recent advances in…". There was one recently in the Lancet, that review by Ian Hickie of Agomelatine – Novel melatonin-based therapies: potential advances in the treatment of major depression<\/font><\/strong><\/u><\/a> [ see [of sound and fury…<\/font><\/strong><\/u><\/a>, it’s about time…<\/font><\/a><\/strong><\/u>, long overdue…<\/font><\/a><\/strong><\/u>]. It was an infomercial extraordinaire that shouldn’t have been published. <\/div>\n

I don’t have any illusions that I can single-handedly catch all the industry seeding of our literature, but it does make me feel like I’m doing my part to look for it. The years of letting those articles slide under the radar has contributed to a lot of corruption and over-medication. Then sometimes I run across Commentaries<\/font><\/em><\/strong> and I usually read them, even if the topic isn’t particularly interesting to me, just to see what they’re about. That’s how I got to reading this one. By the first paragraph, it was clear that Dr. Spinelli is in the give antidepressants to pregnant women<\/em> camp, with the usual preventive medicine outweighs the risk<\/em> arguments. I don’t particularly like those arguments. They presume that anti-depressants are specific, work well, and will halt the negative consequences of untreated depression – a simplistic and indefensible position. These articles are usually like this one – filled with hypothetical arguments, categorical statements, and very little in the way of science. This one can only be considered a strongly held opinion piece – motives unspecified. I was thinking that it’s not particularly compelling, but I guess it’s her prerogative to say what she thinks. <\/p>\n

But then I got to the last paragraph, and her first sentence pulled me out of the scanning mode and I started reading carefully: <\/div>\n
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We saw an inappropriate decline in the prescription of antidepressants for adolescents and young adults because of a Food and Drug Administration black box warning about suicidality. However, untreated depression itself has a far greater impact on suicidal behavior than the adverse effects of the antidepressants. Psychiatrists have generally used appropriate judgment in prescribing antidepressants and psychotherapies for this patient population, but other physicians did not. We now need to communicate clearly about the risks and benefits of treatment for depressed pregnant women if we wish to avoid similar adverse consequences to their well-being and the well-being of their infants.<\/sup><\/div>\n<\/blockquote>\n
To bolster her argument about risk\/benefit ratios in pregnancy, she throws in an amazing categorical statement about the "inappropriate decline in the prescription of antidepressants for adolescents and young adults because of a Food and Drug Administration black box warning about suicidality<\/font><\/strong>" – essentially accusing the FDA of being alarmist with the warnings, implying that they caused harm. That’s something I looked into back in the Fall and I sure can’t confirm anything about that statement. In fact, just the opposite. As you may recall, the antidepressant manufacturers did everything in their power to hide the suicidality in adolescents on SSRIs and worked equally hard to claim their efficacy in adolescents. They failed in both dimensions. <\/div>\n

Here are the underwhelming efficacy graphs for Prozac [2], Paxil, and Zoloft – "CRO Charts" [pretty loud coi…<\/font><\/a><\/strong><\/u>]. By the way, that’s the famous Study 329 in the lower left<\/em>:<\/p>\n

<\/p>\n

 <\/p>\n

And the claim that suicides in adolescence increased in response to the FDA warnings came from two sources. First, an article by a rogues gallery of compromised KOLs working with Quintiles, funding unspecified [see the apogee<\/font><\/strong><\/u>…<\/a>]:<\/div>\n
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Impact of Publicity Concerning Pediatric Suicidality Data on Physician Practice Patterns in the United States<\/font><\/strong><\/u><\/a>
by Charles B. Nemeroff, Amir Kalali<\/font>, Martin B. Keller, Dennis S. Charney, Susan E. Lenderts, Elisa F. Cascade, Hugo Stephenson<\/font>, and Alan F. Schatzberg<\/sup>
Archives of General Psychiatry<\/font><\/strong>. 2007 64(4):466-472.<\/div>\n<\/blockquote>\n
And second, from several articles funded by a foundation [National Bureau of Economic Research<\/font><\/strong><\/u><\/a>] established by conservative economist, Martin S. Feldstein<\/font><\/strong>, who sits on the Board of Eli Lilly [see pretty loud coi…<\/font><\/a><\/strong><\/u>, and tortured numbers…<\/font><\/a><\/strong><\/u>]. <\/div>\n

If you don’t recall these articles, take a look [the apogee<\/font><\/strong><\/u>…<\/a>, pretty loud coi…<\/font><\/a><\/strong><\/u>, tortured numbers…<\/font><\/a><\/strong><\/u>]. Within a year, three of the four non-Quintiles authors on the first study were busted for unreported personal income from industry and all four were on POGO’s list of authors using ghost-writers. Three were Department Chairmen who "stepped down" early under pressure in the coming years. None of them were Child and Adolescent Psychiatrists. I called my post "the apogee<\/font><\/strong><\/u><\/a>" because It seemed to me it was the pinnacle of the arrogance of the times. I named the other studies "tortured numbers<\/font><\/a><\/strong><\/u>" for reasons easily seen. This looked like a thinly disguised, industry-lead campaign against the FDA because<\/u> the FDA warning resulted in a fall in sales of anti-depressants. Doctors and Patients listened to the FDA! Good for them.<\/p>\n

Dr. Spinelli’s only reference for her comment was an article in the American Journal of Psychiatry<\/font><\/strong> from the same period [2007], one that I apparently overlooked last time around:<\/div>\n
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Decline in Treatment of Pediatric Depression After FDA Advisory on Risk of Suicidality With SSRIs<\/font><\/strong><\/u><\/a>
by Anne M. Libby; David A. Brent; Elaine H. Morrato; Heather D. Orton; Richard Allen; and Robert J. Valuck<\/sup>
American Journal of Psychiatry<\/font><\/strong> 2007 164:884-891.
[full text on-line<\/font><\/strong><\/u><\/a>]<\/div>\n

<\/p>\n

Objective<\/font><\/strong><\/u>: In October 2003, the U.S. Food and Drug Administration (FDA) issued a public health advisory about the risk of suicidality in pediatric patients taking selective serotonin reuptake inhibitors (SSRIs) for depression. This study used data from a large national pediatric cohort to examine patterns of diagnosis of depression, prescription of antidepressants, prescription of pharmacological alternatives to antidepressants, and use of psychosocial care before and after the FDA advisory was issued.
Method<\/font><\/strong><\/u>: A large pediatric cohort with newly diagnosed episodes of depression was created from a national integrated claims database of managed care plans from October 1998 to September 2005 (N=65,349). Time-series models were used to compare diagnosing and prescribing trends during the 2 years after the FDA advisory and the expected trends based on data from the 5-year period preceding the advisory.
Results<\/font><\/strong><\/u>: From 1999 to 2004, pediatric diagnoses of depression increased from 3 to 5 per 1,000. After the FDA advisory was issued, the national rate decreased to 1999 levels, a significant deviation from the historical trend. Pediatricians and nonpediatrician primary care physicians accounted for the largest reductions in new diagnoses. Among patients with depression, the proportion receiving no antidepressant increased to three times the rate predicted by the preadvisory trend, and SSRI prescription fills were 58% lower than predicted by the trend. There was no evidence of a significant increase in use of treatment alternatives (psychotherapy, atypical antipsychotics, and anxiolytics).
Conclusions<\/font><\/strong><\/u>: The FDA advisory was associated with significant reductions in aggregate rates of diagnosis and treatment of pediatric depression.<\/sup><\/div>\n<\/blockquote>\n
It’s another version of Nemeroff et al using data from a managed care database. Here’s the important part:<\/div>\n
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Mr. Allen, Dr. Libby, Ms. Orton, Dr. Morrato, and Dr. Valuck report an unrestricted investigator-initiated research grant from Eli Lilly and Company; Dr. Valuck also is an advisory board member for Eli Lilly. Dr. Morrato has received research support from Janssen and Pfizer. Mr. Allen has received research support from GlaxoSmithKline. Dr. Brent reports no competing interests.<\/p>\n

Supported by an investigator-initiated grant from Eli Lilly and Company to fund the access fees to the independent PharMetrics database and salary support for the investigators.<\/font><\/strong><\/sup><\/div>\n<\/blockquote>\n

and their conclusion:<\/div>\n
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Strengths of this study include the patterns of community care observed in the data, as well as implications for future policies on drug risks. The FDA’s drug safety policy has moved toward broader and more proactive communication of new safety warnings for marketed drugs. The FDA has emphasized its "aggressive development of electronic health information" to directly alert patients and providers about the risks of prescription medications. The agency has issued draft recommendations for a "Drug Watch" system to disseminate emerging drug safety information as safety signals emerge and before causality is determined<\/a>. The results of our study suggest a need for public health interventions to ease unintended but predictable changes in treatment patterns that may increase "the risk of doing nothing"<\/a>.<\/font><\/strong><\/sup><\/div>\n<\/blockquote>\n
Judging by the dates and sponsorship, this article appears to be a part of the same campaign as the ones I reported on earlier. I’ll not linger here except to say that the idea that the motive of these industry-funded studies was to make sure that pediatric depression wasn’t undertreated is laughable. First, there’s no evidence that antidepressants treat pediatric depression. Second, the suicidality of adolescents on SSRIs is beyond solid. And third, any fool can see they’re out to increase drug sales, plain and simple. <\/div>\n

So back to Dr. Spinelli’s Commentary. She declares no competing interests, and for all I know may well be passionate about using antidepressants during pregnancy for the best of motives. But if that’s the case, I’d prefer that she divert her zeal into some solid epidemiological research rather that speculating about the studies done by others. But that’s neither here nor there. My beef is that she has taken an industry campaign against the FDA Warnings about the adverse effects of SSRIs in adolescents at face value. She makes definite statements like "However, untreated depression itself has a far greater impact on suicidal behavior than the adverse effects of the antidepressants<\/font><\/strong>" without giving any references as if it’s the truth, rather than the tired party line of drug companies and their KOLs. <\/p>\n

It’s irresponsible to suggest that we should use these drugs in pregnancy based simply on someone’s opinion. And it’s suspect to use a questionable, industry driven campaign heavily tainted with blatant conflicts of interest as a template on which to hang our logic. Pregnant women represent a large market for antidepressant manufacturers, just like children and adolescents. After the last twenty-five years of stealth and deceit from that quarter, if she wants to convince anyone of her point, she’s going to have to come at it from another direction.<\/p>\n

But my main point is that those 2007 industry influenced very questionable studies made it into the literature and there they remain, now being included in a similar argument five years later as if they are the "truth." That’s the reason to fight letting these things slide into our literature. That’s the reason I scan the journals at the beginning of the month. That’s the reason I’ll probably fire off yet another letter to the AJP this afternoon for them to not publish. Hope springs eternal… <\/div>\n","protected":false},"excerpt":{"rendered":"

Antidepressant Treatment During Pregnancy Commentary by Margaret Spinelli, M.D. American Journal of Psychiatry. 2012 169:121-124. [full text on-line] A behavioral health outpatient program recently decided that psychiatrists would no longer be permitted to provide new prescriptions for antidepressants to pregnant women because the sponsoring institution had determined that the risk was too high. As a […]<\/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_forum_subforum_count":0,"footnotes":""},"categories":[2],"tags":[],"class_list":["post-19341","post","type-post","status-publish","format-standard","hentry","category-politics"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/19341","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=19341"}],"version-history":[{"count":40,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/19341\/revisions"}],"predecessor-version":[{"id":19381,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/19341\/revisions\/19381"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=19341"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=19341"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=19341"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}