a blast from the past…

Posted on Monday 27 June 2016

I’ve been called out at times for focusing on these older Clinical Trials like Paxil Study 329 or the Citalopram CIT-MD-18 study. I’m kind of tired of talking about them myself. However, there are substantial reasons for dwelling on these trials. For one thing, we’re finally getting to see the back story – the raw data in Paxil Study 329 and the internal emails from the Citalopram CIT-MD-18 study. For another, these trials were very much in Dr. Karen Dineen Wagner‘s memory at the recent APA Meeting in Atlanta:
by Aaron Levin
June 16, 2016

Children are not just small adults, and clinical practice and the overall health care system need to take notice of that reality, said speakers at APA’s 2016 Annual Meeting in Atlanta in a session on child and adolescent psychiatry in the 21st century….

In the clinic, managing mental illness in young people requires subtle but significant shifts in thinking, said Karen Dineen Wagner, M.D., Ph.D., a professor and chair of psychiatry and behavioral sciences at the University of Texas Medical Branch, Galveston…

As for treatment, only two drugs are approved for use in youth by the Food and Drug Administration [FDA]: fluoxetine for ages 8 to 17 and escitalopram for ages 12 to 17, said Wagner. “The youngest age in the clinical trials determines the lower end of the approved age range. So what do you do if an 11-year-old doesn’t respond to fluoxetine?”

One looks at other trials, she said, even if the FDA has not approved the drugs for pediatric use. For instance, one clinical trial found positive results for citalopram in ages 7 to 17, while two pooled trials of sertraline did so for ages 6 to 17. Another issue with pediatric clinical trials is that 61 percent of youth respond to the drugs, but 50 percent respond to placebo, compared with 30 percent among adults, making it hard to separate effects.

When parents express anxiety about using SSRIs and ask for psychotherapy, Wagner explains that cognitive-behavioral therapy [CBT] takes time to work and that a faster response can be obtained by combining an antidepressant with CBT. CBT can teach social skills and problem-solving techniques as well. Wagner counsels patience once an SSRI is prescribed.

A 36-week trial of a drug is too brief, she said. “The clock starts when the child is well, usually around six months. Go for one year and then taper off to observe the effect.” Wagner suggested using an algorithm to plot treatment, beginning with an SSRI, then trying an alternative SSRI if that doesn’t work, then switching to a different class of antidepressants, and finally trying newer drugs.

“We need to become much more systematic in treating depression,” she concluded.
Not many days after Dr. Wagner’s lecture, we read a meta-analysis of antidepressants in youth by Cipriani et al in the Lancet [Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis] that included the reports listed in Wagner’s presentation that reached a very different conclusion:
When considering the risk–benefit profile of antidepressants in the acute treatment of major depressive disorder, these drugs do not seem to offer a clear advantage for children and adolescents. Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated.
On the other hand, Wagner speaks of antidepressants as a first line treatment and suggests prescribing off-label based  on the RCTs that are well over a decade old, even including younger children in her recommendation. There’s no mention of the Black Box Warning or anything else that’s happened since then. Hers is an anachronistic presentation, one that might have been given over ten years ago when hopes were higher for the antidepressant drugs in kids.

But thinking further, that didn’t really capture the thrust of this presentation. Then it hit me, it was even older than that. The emphasis on coming on strong, using a sequence of drugs until you hit one that worked, treating for a long time, an algorithm [all without an evidence-base] – those things sounded like the catechism of John Rush and Madhukar Trivedi in their STAR*D Protocol. And STAR*D came directly from TMAP [Texas Medical Algorithm Project] – the industry seeded treatment scheme derived from Expert Opinion that required State Physicians to use on-patent drugs rather than Generics until it was finally exposed as corrupt by Allen Jones in 2004.

And finally I remembered that there was a similar program for kids – TCMAP [Texas Childrens Medical Algorithm Project] and guess who were on the expert panel? Graham Emslie and Karen Dineen Wagner. Here’s what I said previously [the answers to those questions…]:
Perhaps the biggest pharmaceutical scam to date was TMAP [Texas Medical Algorithm Project]. Before it was stopped, it had nearly bankrupted the Texas Mental Health system, had spread to 17 other States, and was on its way to Washington. It should make us all shudder when we hear the word "Guidelines." It was shepherded into being by John Rush and Madhukar Trivedi in Dallas. Basically, they controlled guidelines for the huge Mental Health system in Texas. It had a child piece [TCMAP] and Karen Dineen Wagner and Graham Emslie  were both involved in setting the Algorithms. The TMAP program was exposed in 2004 largely through the work of one man, Allen Jones, an Inspector for the Pennsylvania OIG [who was fired for his work] but who never gave up. Below is just a snippet from a report he published on the Internet in 2004 with the bare bones of Dr. Wagner’s involvement [A more complete version about her goes from pages 10-14, and tells quite a story]:
    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…
After the first year, they published periodic updates in the JAACAP:
    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.

    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]…
Only fluoxetine was a published paper [paroxetine was an abstract of Study 329 posted at the 1998 APA]. There was a consensus meeting recorded in 1998, with no details [wayback machine]. 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.
No wonder I kept thinking this was an anachronistic presentation. It is literally a blast from the past, almost twenty years ago. The fact that it has been reincarnated at the 2016 APA meeting in spite of all the intervening evidence and dialog to the contrary is remarkable. I guess she thought we would forget [and I almost did!]…
    June 27, 2016 | 3:44 PM

    Maybe spend some time on the federal Murphy Bill and it’s numerous negative impacts on mental care that should be obvious to see by now. Besides, who the hell is writing for Paxil/paroxetine now anyway? !

    I could tell you about patients who are so grossly mistreated by idiot colleagues who think they are still practicing in the 1990s the way they prescribe still! But, who seems to care?

    Not most of the administration folks running these clinics.

    Oh well, I guess these posts get you the traffic you want. …

    June 30, 2016 | 10:30 AM

    I don’t know if this is the best summary of problems with Tim Murphy’s bill, as the link is over 6 months old, but could not find a newer critique to forward:


    Again, folks here don’t think legislative onslaughts like this won’t force even more MEDS interventions to create havoc that the Paxil/Risperdal/Celexa issues pale in comparison?

    Just trying to point out potential issues that should be noted now, not later.

    Allen Jones
    July 1, 2016 | 4:33 PM

    Hey Mickey – a trip to Apalachicola would do wonders for your memory!

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