{"id":42456,"date":"2013-12-20T07:00:49","date_gmt":"2013-12-20T12:00:49","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=42456"},"modified":"2013-12-20T07:04:23","modified_gmt":"2013-12-20T12:04:23","slug":"lost-years","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2013\/12\/20\/lost-years\/","title":{"rendered":"lost years…"},"content":{"rendered":"
2003 was a long time ago for me. It was the year I retired from practice, sold my house in Atlanta, and moved to the mountains. It was also the year Jon Jureidini first wrote the JAACAP about the Paxil® Study 329 article, but I didn’t know about that then. I did, however, know about Paxil®. I was on the clinical faculty at Emory, far from any association with Dr. Nemeroff’s department of psychiatry, but it wasn’t possible to be in proximity without hearing about Paxil®. I knew Dr. Nemeroff talked about it a lot, and one of his researchers, Dr. Zach Stowe, a specialist in depression in women, was recommending its use in pregnancy. That didn’t sound right to me. How could anyone know that? Though I had never prescribed Paxil®, I’d used SSRIs enough to know that they weren’t that essential. They helped sometimes, but they weren’t helpful enough to warrant taking risks, particularly in pregnancy. I remember wondering if he worked for whoever it was that made<\/em> Paxil®. In retrospect, my naivet\u00e9 back then is embarrassing, but that’s the first real inkling I recall – the tip of a conflict of interest iceberg.  Some years later, I ran across this from those days:<\/div>\n
<\/div>\n
He’s letting someone at GSK know that his study to prove that Paxil® didn’t get into the amniotic fluid didn’t work out. He was disappointed. He goes on to complain about getting stiffed for one drug talk and inquired about another "gig in Miami." Note his remark, "I will have the manuscript to you for review…<\/em>" That document came out in 2009 when this story broke:<\/div>\n
\n
Emory Psychiatrist Cited in Conflicts of Interest<\/a><\/div>\n
WSJ<\/font><\/strong><\/div>\n
By DAVID ARMSTRONG<\/div>\n
June 10, 2009<\/div>\n

Emory University has disciplined a prominent psychiatrist who was being paid by an antidepressant maker at the same time he was conducting federal research about the use of such drugs in pregnant women.<\/font><\/strong> The university said its medical school dean issued a letter of reprimand on April 30 to psychiatrist Zachary Stowe related to his "external relationships." Dr. Stowe was instructed to immediately eliminate conflicts related to current federal grants and was barred from having any conflicts for the next two years.<\/p>\n

Dr. Stowe, the director of the Women’s Mental Health Program at Emory, is considered a leading expert on the use of antidepressants in pregnant women. He is listed as the primary investigator on at least three National Institutes of Health grants, beginning in 2003 and continuing through last year, that involve antidepressant use in pregnant women and the effects on children delivered by those women…<\/font><\/strong><\/p>\n

In a letter earlier this month to Emory, Sen. Charles Grassley (R., Iowa) said he learned the school had informed the NIH last summer that Dr. Stowe had financial conflicts of interest. The senator said records he obtained from GlaxoSmithKline PLC, the maker of the antidepressant Paxil, indicated Dr. Stowe was paid $154,400 by the drug company in 2007 and $99,300 during the first 10 months of 2008. The totals included payments for at least 95 promotional talks on behalf of the company. A Glaxo spokesman was unavailable for immediate comment…<\/div>\n<\/blockquote>\n
The resulting article [American Journal of Psychiatry<\/font>. 2006 163:145-147.<\/a>] is not preferential among the various drugs [though it differs from the email in reporting only 2\/28 subjects on Paxil®, none on 60mg?]. The point is that his "Damnit", his sending his manuscript to GSK for review, and his paid speaking "gigs" suggest more than COI, they spell bias. What I now know is that there was a back story like this to much of the psychiatric literature in those days – and we didn’t know it [at least I didn’t]. It came onto our radar when Drs. Carroll and Rubin exposed several of Dr. Nemeroff’s misadventures, and it was Senator Grassley’s investigations that moved it to the foreground in 2008-2009.<\/div>\n

We didn’t always think of experts as Key Opinion Leaders [KOLs]. Medical experts were physicians, usually academics, who devoted their interests and research to a particular aspect of the medical world. We went to their presentations and followed their writing and recommendations because they were the ones "in the know<\/em>." Their centrality in medical opinion was earned at the bench and at the bedside. I have no idea when they became a commodity and went on the block. These days, the pharmaceutical companies have KOL managers that have meetings and journals. Zach Stowe was such a KOL – getting paid by drug companies to speak around the country. In fact, 5\/7 authors on the paper were on multiple speaker’s bureaus. And the study was funded by the NIMH and two pharmaceutical companies.<\/p>\n

So here we are ten years later. This next paper came out in the NEJM yesterday. It’s a large Danish registry study that found no definitive evidence of as association of Autism with SSRIs in pregnancy. Several earlier studies, including another Danish registry study did find such an association:<\/div>\n
\n
Use of Selective Serotonin Reuptake Inhibitors during Pregnancy and Risk of Autism<\/a><\/div>\n
by Anders Hviid, Mads Melbye, and Björn Pasternak<\/div>\n
New England Journal of Medicine<\/font><\/strong>. 2013 369:2406-2415.<\/div>\n

<\/p>\n

Background<\/u>:<\/font><\/strong> Studies have raised concern about an association between the use of selective serotonin reuptake inhibitors [SSRIs] during pregnancy and an increased risk of autism spectrum disorders in the offspring.<\/div>\n
Methods<\/u>:<\/font><\/strong> We conducted a cohort study of all singleton live births in Denmark from 1996 through 2005 [626,875 births], with follow-up through 2009. Using Danish population registries, we linked information on maternal use of SSRIs before and during pregnancy, autism spectrum disorders diagnosed in the offspring, and a range of potential confounders. We used a survival analysis of the time to diagnosis in the offspring with Poisson regression to estimate rate ratios of autism spectrum disorders according to maternal use of SSRIs.<\/div>\n
Results<\/u>:<\/font><\/strong> During 5,057,282 person-years of follow-up, we identified 3892 cases of autism spectrum disorder [incidence rate, 77.0 per 100,000 person-years]. A total of 52 cases during 42,400 person-years of follow-up involved offspring of women who were exposed to SSRIs during their pregnancy [incidence rate, 122.6 per 100,000 person-years]. As compared with no use of SSRIs both before and during pregnancy, use during pregnancy was not associated with a significantly increased risk of autism spectrum disorders [fully adjusted rate ratio, 1.20; 95% confidence interval [CI], 0.90 to 1.61]. Among women who received SSRIs before pregnancy but not during pregnancy, the corresponding fully adjusted rate ratio was 1.46 [95% CI, 1.17 to 1.81].<\/div>\n
Conclusions<\/u>:<\/font><\/strong> We did not detect a significant association between maternal use of SSRIs during pregnancy and autism spectrum disorder in the offspring. On the basis of the upper boundary of the confidence interval, our study could not rule out a relative risk up to 1.61, and therefore the association warrants further study.<\/div>\n
[Funded by the Danish Health and Medicines Authority]<\/div>\n<\/blockquote>\n
And here’s a pretty interesting editorial by an expert discussing and critiquing these studies [which appear to be outside the COI\/bias sphere, as is the discussant]. It’s an interesting discussion, and the comments are part of what’s interesting:<\/div>\n
\n
The Op-Ed: Antidepressants, Pregnancy & Autism: A Potent Mix<\/a><\/div>\n
Pharmalot<\/font><\/strong><\/div>\n
by Ed Silverman<\/div>\n
12\/19\/2013<\/div>\n
[full text on-line<\/a>]<\/div>\n

<\/p>\n

Earlier this year, a study reported a link between antidepressants and autism, the second time in two years that such a relationship has been suggested. This week, a study in The New England Journal of Medicine found that children of women using SSRIs during pregnancy were not at increased risk of autism when compared with other children, although at the same time, the incidence of autism spectrum disorders in children born to women who used the drugs before pregnancy and then stopped was 46 percent than in other children. These results have fueled intensified debate over the extent to which there is cause-and-effect link. In the latest Pharmalot op-ed, Adam Urato, an assistant professor in the obstetrics and gynecology department at the School of Medicine at Tufts University, argues there is reason to be concerned that serotonin use that can alter the brains of developing babies…<\/div>\n<\/blockquote>\n
I must’ve known that the recommendations from experts ten years ago were suspect, because there’s never been a time when I’d give much of any medication to a pregnant patient, certainly not in the first trimester, certainly not a drug that alters some important body process. On the few occasions I was involved in the treatment of depression in pregnancy, I referred the patients to a female obstetrician\/psychiatrist colleague that I trust – even though Emory’s program was only a mile or so away.<\/div>\n

I think this post tells a big story. These are good articles presenting an as yet unresolved issue – antidepressant use in pregnancy. Their sources are clean in so far as I can tell – addressing the medical issue rather than some drug company’s attempt at indication sprawl. They didn’t change my mind. I’m not going to be prescribing antidepressants or much of anything else to unborn babies, There are plenty of other ways to help depressed pregnant women. But my point is that this whole KOL era of the last several decades left us with the same questions it proposed to address, complicated by the biased literature of the period. The only way I found to negotiate those years was to be skeptical and conservative – relying on my own experience and that of colleagues I trusted. The usual resource of the literature at large had to be suspect and that was a difficult loss to deal with. That’s the way I see it – psychiatry’s lost years.<\/p>\n

I’m currently following a patient whose child has the Fetal Valproic Acid [Depakote®] Syndrome<\/a>. She was taking Depakote® as prophylaxis for a diagnosis of Bipolar Disorder – something she doesn’t have in my opinion. The impact on her life, her child’s future, and her relationship with the father of the child has been devastating. She was referred to me after being hospitalized for a Conversion Reaction, something we don’t see a lot of these days. It was in part due to her situation with this child. At the time her baby was born, I’m not even sure the syndrome had yet been described. There’s been a lot more lost in those years than just our access to the literature…<\/div>\n","protected":false},"excerpt":{"rendered":"

2003 was a long time ago for me. It was the year I retired from practice, sold my house in Atlanta, and moved to the mountains. It was also the year Jon Jureidini first wrote the JAACAP about the Paxil® Study 329 article, but I didn’t know about that then. I did, however, know about […]<\/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-42456","post","type-post","status-publish","format-standard","hentry","category-politics"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/42456","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=42456"}],"version-history":[{"count":21,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/42456\/revisions"}],"predecessor-version":[{"id":42477,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/42456\/revisions\/42477"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=42456"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=42456"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=42456"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}