1 Boring Old Man

In deeply troubling…, I started in 2001 with the publication of the Paxil Study 329 paper looking at Karen Dineen Wagner’s history, but perhaps I should’ve started a couple of years earlier with the now infamous TMAP project. And then there was an appearance at a SmithKline Beechum Neuroscience Division meeting that bears mentioning…

TMAP/TCMAP

In 1997-98, TMAP, with pharmaceutical industry funding, began working on the Texas  Children’s Medication Algorithm Project [TCMAP]. An "Expert Consensus" panel was assembled to determine which drugs would be best for the treatment of mental and emotional problems in children and adolescents. The panel consisted almost exclusively of persons already involved in TMAP or associated with TMAP officials. A survey was not necessary. These persons simply met and decided that the identical drugs being used on adults should also be used on children. There were no studies or clinical trial results whatsoever to support this consensus…

One of the members of the children’s "expert consensus panel" was Graham J. Emslie,M.D., Professor and Chair, Division of Child and Adolescent Psychiatry. University of Texas Southwestern Medical Center, [a TMAP site] and Director. Bob Smith Center for Research in Pediatric Psychiatry, Dallas, TX…

The panel also included Dr. Karen Dineen Wagner…

In 1998, without any published trial data and based on the "consensus opinion" of Emslie, Wagner and others, TCMAP began widespread usage of these SSRIs and other drugs on children within the Texas state Juvenile Justice system and state Foster Care System…

Between 1998 and 2003, state doctors following the TCMAP guidelines routinely and regularly prescribed these antidepressant drugs to children in accordance with the TCMAP algorithm requirements…

The Texas Children’s Medication Algorithm Project: Report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder

by CARROLL W. HUGHES, GRAHAM J. EMSLIE, M. LYNN CRISMON, KAREN DINEEN WAGNER, BORIS BIRMAHER, BARBARA GELLER, STEVEN R. PLISZKA, NEAL D. RYAN, MICHAEL STROBER, MADHUKAR H. TRIVED, MARCIA G. TOPRAC, ANDREW SEDILLO, MARIA E. LLANA, MOLLY LOPEZ, A. JOHN RUSH, AND THE TEXAS CONSENSUS CONFERENCE PANEL ON MEDICATION TREATMENT OF CHILDHOOD MAJOR DEPRESSIVE DISORDER

Journal of the American Academy of Child and Adolescent Psychiatry, 1999 38[11]:1442-1454.

The consensus panel agreed on categorizing 3 levels of "data" hierarchically in formulating stages and differential branching of the treatment algorithm. Level A data consist of both child and adult randomized controlled clinical trials, level B data consist of open trials and retrospective analyses, and level C data are based on case reports and panel consensus as to recommended current clinical practices. Level A takes precedence over level B, and B over C…

The recommended monotherapy antidepressant for stage 1 are SSRIs [fluoxetine, paroxetine, or sertraline]. [Fluvoxamine and citalopram may be added to the list at a future date with additional research and experience]…

SSRIs are deemed first-line treatments because of supporting efficacy data for fluoxetine in children and adolescents and paroxetine in adolescents [level A], open trials of sertraline [level B], and clinical experience [level C]. Information extrapolated from adults further supports the initial use of SSRIs given the minimal need for dosage titration [level A in adults and level C in children/adolescents] and favorable side effect profiles [levels A and C]…

With the coming of Jones’ whistle blower suit and the mounting awareness of adverse effects that lead to the Black Box Warning, TCMAP just disappeared. TCMAP was never adjudicated, and the only specific TMAP suit I know of was the settlement in Allen Jones and the State of Texas v. J&J.

Paxil in Pediatric Depression and «The Launch»

We all know about the famous Paxil Study 329, published in July 2001 in the JAACAP with 24 authors [Karen Dineen Wagner among them]. The Acute phase of Study 329 ran from 04/1994 until 03/1997 [blind broken]. In October 1998, this internal memo went out:

The draft of the paper came from ghost writer Sally Laden to First Author Martin Keller in February 1999, and by August 1999, he had submitted the paper to the JAMA. It was turned down there in November 1999. In December 1999 and again April 2000, there were emails saying that they were rethinking it, planning to go for the AJP. But in June 2000  [?], it was at the JAACAP where it was accepted in January 2001 and published in their July 2001 issue.

"As many of you know, SB is preparing an indication for adolescent depression for Paxil next year! SB’s clinical study demonstrating the success of Paxil in treating depression among adolescents will be published in a peer reviewed journal during first quarter 2000…"

"Dr. Wagner said the window of opportunity is before SB. Several other competing SSRls and other compounds have studies ongoing. But Paxil and Prozac are the only two SSRIs that have any published data to date and many physicians have already found success in treating adolescent patients with Paxil…"

"The paroxetine study measured treatment of adolescent depression. It is the largest study to date, involving 275 adolescents at 12 sites for eight weeks. In the study, one of three treatments was possible: imipramine, paroxetine, or placebo. Results:

• 66% of paroxetine group improved
• 52% imipramine improved
• 48% of placebo improved."

"As a result of this large study," Dr. Wagner said, "We can say that paroxetine has both efficacy and safety data for treating depression in adolescents."

At the time she gave this presentation, that first paragraph  simply wasn’t true. SB had long before decided not to go for an indication for Paxil in adolescents. The paper had just been rejected by the JAMA – with no publication in sight. The JAMA reviewers pointed to the low HAM-D cut-off, the effect of supportive care, the high Placebo response, the small or absent differences in rating scales, the significant incidence of Serious Side Effects with Paroxetine, and the inappropriate dosing of Imipramine. For that matter. I have no clue where those results came from, not from the paper or the CSR.

A look at the work of one medical school researcher, Dr. Karen Dineen Wagner, shows the challenges and possible pitfalls such research can entail. For example, from 1998 to 2001, university records show, Dr. Wagner was one of several academic researchers participating in more than a dozen industry-financed pediatric trials of antidepressants and other types of drugs. While some of the results were published, many were not. 

I ran across this 2004 article from the New York Times by Barry Meier [Contracts Keep Drug Research Out of Reach]. An excellent article, it prominently mentions Dr. Wagner and reminds us that this was the heyday of industry-funded Clinical Trials and that Dr. Wagner was one of a handful of Academic Child Psychiatrists who were involved with almost every study published – people who were and who remain prominent figures in the American Academy of Child and Adolescent Psychiatry, the organization Dr. Wagner was just elected to lead.

This is hard for me to personally understand. Dr. Wagner has essentially made her career advocating the use of psychophatmacologic agents in the treatment of children – having covered the gamut of conditions, drugs, and worked with many of the front-running drug companies who make and profit from these drugs. Surely the broad membership of the AACAP knows that, and knows about the dark side of her work – ghost-writing, financial COI, withheld negative studies, TMAP, training sessions for PHARMA. At a time when such things are moving closer and closer to the front burner, why would the AACAP membership choose her as President? Are her colleagues unaware of her history? Is that possible? Is this a sign that her position represents the consensus of the members? For that matter, why would she even run for that office instead of lowering her profile? It’s similar to the questions asked when people like Drs. Alan Schatzberg or Jeffrey Lieberman have been elected to the APA Presidency.