simply ‘fuel the fire’…

Posted on Sunday 6 April 2014

In the Fall of 2012, having had a chance to look at the raw numbers for the first time, I sent a series of posts to the Ethics Committee of the American Academy of Child and Adolescent Psychiatry along with a request that they consider retracting their article. I had written Dr. Andres Martin the year before [letter], but he hadn’t responded. Here’s my 2012 letter:

To: The American Academy of Child and Adolescent Psychiatry Ethics Committee
Date: September 22, 2012

In 2001, the JAACAP published an article on the use of Paroxetine [Paxil] in adolescent depression, now known as Study 329:

Journal of the American Academy of Child and Adolescent Psychiatry, 2001, 40[7]:762–772.

It has been widely seen as the paradigm for a period in psychiatry when we were at our worst – an industry financed, ghost-written article that made claims of both efficacy and safety that were unsupported by its data. The article has been the centerpiece for numerous successful legal suits, the most recent being a $3 Billion settlement by GSK with the DOJ in which they admit all allegations. Calls for retraction of this article began a decade ago, but have been repeatedly rejected – at first by defending this indefensible article, then later for unclear reasons, likely political, related to a fear of embarrassing the Editor, the AACAP, and the "Authors" [many of whom remain active in the organization].

Psychiatry is in decline, largely because the increasing awareness of the extensive alliance between the pharmaceutical industry and academic psychiatry has undermined confidence in the traditional ethic of medicine. Fledgling moves to reform the extensive conflict of interest problems in our specialty, however, will have no traction if organized and academic psychiatry refuse to acknowledge the problem in need of reform. Child and Adolescent psychiatry is at the center of the growing storm of complaints about over-medication, particularly of children.

Your predecessors have refused to retract this article, saying it is factually correct, or that the Journal is not responsible for its distortions, or worse, saying nothing. It is not factually correct. It was published over the objections of peer reviewers. And saying nothing is tantamount to treating cancer by watchful waiting. It has earned its right to be retracted in courtroom proceedings and media across the land. If you’re not familiar with its history, I’ve appended a series of blog posts about it to the end of this email. Alison Bass’s Pulitzer Nominated book Side Effects is another good resource.

I urge you to familiarize yourself with this story if you don’t already know it, and implore the Ethics Committee to retract Study 329 from the literature. It’s the right thing to do and a right time to do it.

John M. Nardo MD
retired psychiatrist and psychoanalyst

I thought this letter had a chance of being well received. The 329 data was now public and I’d done my homework, The $3 B suit had just been settled by GSK. I used my long name and spell checked it several times. Looking back, rereading it, the "familiarize yourself with this story" part was a little cheesy, but otherwise not bad for a non-English Major. The letter was received warmly by the President of the AACAP, the President Elect, and the Chair of the Ethics Committee who assigned a member of the Committee to work with me, presumabely to present it at the meeting coming up in several months. We had several amicable exchanges. I sent her Alison Bass’s book. All very civilized.

The meeting came and went and I heard nothing. Somewhere down the road, I got a terse email. It was going to be handled by the editor. No action taken. It was a surprise – reading more like a second notice on an overdue water bill than the collegial  and professional emails earlier. That’s the last I heard from them. Now, in retrospect, I read this:

Tuesday, January 22, 2013 • 12:00–1:00 pm EDT/11:00 a.m. – 12:00 p.m. CDT

Conference Call Minutes

Council members in attendance: Martin J. Drell, M.D., President; Paramjit T. Joshi, M.D., President-Elect; David R. DeMaso, M.D., Secretary; Steven P. Cuffe, M.D., Treasurer; Louis J. Kraus, M.D., Assembly Chair; Laurence L. Greenhill, M.D., Steven Adelsheim, M.D., Mark Borer, M.D., Stephen Cozza, M.D., Deborah Deas, M.D., Joan Luby, M.D., Neal D. Ryan, M.D., Jennifer S. Saul, M.D., Margaret L. Stuber, M.D., Sourav Sengupta, M.D., M.P.H., Marika Wrzosek, M.D.

Council members absent: Warren Y.K. Ng, M.D., Harsh K. Trivedi, M.D.

Others participating: Andrés Martin, M.D. Staff: Heidi B. Fordi, Mary Billingsley, Jill Brafford, Larry Burner, Yoshie Davison, Colleen Dougherty, Genifer Goldsmith, Rob Grant, Earl Magee, Kristin Kroeger Ptakowski

Study 329: Andrés Martin, M.D., M.P.H

As an author of the JAACAP article, Keller et al 2001, Neal Ryan recused himself from this conversation. Dr. Martin briefly summarized the situation regarding Study 329. He and the JAACAP Action Editors [AEs] reviewed this issue over the past 6 months, and shared a letter outlining the situation, steps taken, and their determinations, with Academy leadership. In short, Study 329 and the article published in JAACAP about it, Keller et al 2001, was mentioned in a federal lawsuit against GlaxoSmithKline [GSK], but none of the criminal charges related to the article itself. This is the 4th time the Journal has conducted an inquiry into the circumstances surrounding Study 329 and Keller et al 2001 since its publication, and it has again been determined that while the article is not perfect, the ethical concerns raised by the GSK lawsuit are not substantiated. The AEs consulted with many individuals in making their determination, including several lawyers and editors of other academic journals, and have decided not to take any action against the paper. Both the Academy and the Journal received inquiries from the press about the situation and what was to be done, and Dr. Martin and the AEs believe that there is little to gain in responding and that doing so would simply ‘fuel the fire.’

hat tip to 1boringyoungman…
I don’t do moral outrage very well, but this would be a good place to practice if I wanted to learn. That report to the AACAP Council reads like they’re making a policy decision about pesky door-to-door salesmen. The Ethics Committee was  waved off from above, clearly. It’s hard to imagine him saying "but none of the criminal charges related to the article itself" and "the ethical concerns raised by the GSK lawsuit are not substantiated" with a straight face, much less to the committee. Then I remembered a peculiar episode that happened around the same time though I hadn’t connected the dots. In the fall of that year, the Chronicle of Higher Education published an article [Academic Researchers Escape Scrutiny in Glaxo Fraud Settlement] pointing out that the academics who signed on to Paxil Study 329, a prominent part of the $3 B settlement, had gotten off without a even a hand-slap [see the only enduring contract…]. In response, GSK’s lawyer wrote this letter to the Chronicle:
Chronicle of Higher Education
October 1, 2012

To the Editor:

As counsel for GlaxoSmithKline LLC in its recently concluded settlement with the United States government, I write to correct some significant factual inaccuracies in "Academic Researchers Escape Scrutiny in Glaxo Fraud Settlement" [The Chronicle, August 6]. The piece focuses on a peer-reviewed journal article published in 2001 in the Journal of the American Academy of Child and Adolescent Psychiatry reporting the results of a clinical trial sponsored by Glaxo­SmithKline [Study 329] of Paxil® [paroxetine hydrochloride] for the treatment of major depressive disorder in adolescents [the article was "Efficacy of Paroxetine in the Treatment of Adolescent Major Depression: A Randomized, Controlled Trial," by M.B. Keller et al., in the July 2001 issue]. Unfortunately, your piece incorrectly states that, as part of its government settlement, GlaxoSmithKline admitted that the journal article "was part of the fraud" and "constituted scientific fraud." In fact, GlaxoSmithKline made no such admission and vigorously disputes that the journal article was false, misleading, or fraudulent.

As part of its settlement with the government, GlaxoSmithKline pleaded guilty to a misdemeanor violation of federal law related to the marketing of Paxil for use by patients under 18, an unapproved, "off label" use for Paxil. While the law permits physicians to prescribe medications for such off-label uses, manufacturers are not permitted to market them for such purposes. The charging document filed by the United States, known as an information, contains many allegations that are either inaccurate or incomplete, that tell only part of the story, and that draw unwarranted conclusions from disputed facts. Throughout the investigation, the settlement process, and the guilty-plea proceeding, GlaxoSmithKline made clear to the government and to the court that it did not agree with all of the factual allegations made in the information. In particular, GlaxoSmithKline has consistently denied and disputed the allegations that the journal article was false or misleading. Nothing in the settlement or the guilty plea has changed Glaxo­SmithKline’s position on the journal article. Most important, Glaxo­SmithKline did not admit and has not admitted that the journal article was part of any fraud or that it was false or misleading.

Your piece also incorrectly states that the journal article "was actually written by Glaxo-hired authors to overstate the benefits and understate the risks of a highly profitable Glaxo drug." While GlaxoSmithKline did hire a medical writer to provide editorial assistance to the clinical investigators, a fact that the journal article itself acknowledged, control over the contents of the manuscript remained at all times with the clinical-investigator authors who provided substantial comments on and input into the manuscript. GlaxoSmithKline believed then and continues to believe that the journal article reflects the honestly held views of the clinical-investigator authors.

Thomas H. Lee II

Editor’s note: The federal "criminal information" document in the Paxil case repeatedly describes the journal article as "false and misleading." It also notes that GlaxoSmithKline distributed the article to its marketing department and its sales representatives, who used it to promote the use of the drug for children and adolescents. In addition, the criminal information says that a contractor hired by Glaxo­SmithKline wrote the first draft of the article and incorporated changes made in the article by researchers and another GlaxoSmithKline employee. The plea agreement between GlaxoSmithKline and the U.S. Department of Justice states that GlaxoSmithKline "expressly and unequivocally admits that it committed the crimes charged in the information, and is in fact guilty of those offenses."
If you read the settlement agreement and the government complaint, their letter doesn’t hold water. Jon Juriedini and Leeman McHenry quickly responded [‘Any Reasonable Person’ Would See Glaxo Study as Fraud][see also the only enduring contract…]. Ever since I read that letter from GSK’s lawyer, I’ve wondered why he wrote it. It just makes him look silly to anyone who reads the settlement and complaint. Unlikely any reader of the Chronicle of Higher Education would see it as anything other that humorous. But now, coming when it did, I wonder if Andrés Martin was feeling a strong pressure to finally retract Paxil Study 329, and GSK wrote that letter cover the authors and the Journal against some kind of legal action, or maybe to justify not retracting it, or to make the authors and journal not ‘thrown under the bus’ by GSK. I even wonder if one of those lawyers Martin mentions consulting wasn’t Thomas Lee, the author of the Chronicle letter.

I’m not so grandiose as to think that my letter was the impetus for all that wheeling and dealing, for the GSK Chronicle letter, for the AACAP to go silent and dig in its heels even further. Because the call for retraction was coming from everywhere at that time [and ever since]. And I have no notion of the potential legal ramifications of JAACAP retraction the article. But I do feel sorry for the members of the AACAP Ethics Committee. It must be mighty disillusioning to be preparing to debate a thorny ethical issue like this one and to essentially be taken off the case and have its domain simplified down to "the ethical concerns raised by the GSK lawsuit are not substantiated" by a decree from above. What’s an Ethics Committee for if it’s not to deal with such matters?

Whatever all of this means in the end, the American Academy of Child and Adolescent Psychiatry and it’s Journal have lost sight of the reason they exist – to take care of the needs of mentally ill kids, and to do no harm. Neither the accepting editor, Mina Dulcan, nor her successor, Andres Martin, seem to have grasped these fundamentals. They’ve had numerous opportunities to make things right, and they’ve declined those chances, even now blocking anyone else from taking a look [like their own Ethics Committee]…
    April 6, 2014 | 6:19 PM

    Check this out. In my view the kind of care detailed in this report is the direct out growth of a conceptualization of human suffering that has been promoted by JAACAP.

    April 6, 2014 | 7:41 PM

    Thanks Sandra,

    You are referring to my article just published in the Journal of Clinical Medicine. My “co-author” is a young American man who I’ve met and hold in the highest esteem. Please read his story. My commentary explores how could his story have happened.

    I cannot get the link from madinamerica to work here. The direct link to the article is – it is open access.

    Bernard Carroll
    April 6, 2014 | 10:22 PM

    This episode is of a kind with the APA sweeping the Kupfer nondisclosures under the rug: a reliable source on the APA Board of Trustees informed members that the APA attorney has declared that there is no conflict of interest, effectively preempting any action by the assembly.

    April 7, 2014 | 6:45 AM

    Dr. Parry,
    Thank you for working with this young man to get his story published. It is an important one. I am doing what I can to get psychiatrists to read it. It has implications for all of us. I urge everyone checking in here to read it and to pass it on.

    April 7, 2014 | 3:54 PM

    It’s not medicine, it’s business.

    Steve Lucas
    April 7, 2014 | 4:52 PM

    Unfortunately this type of response has become common. There is an apparent interest in order to gauge the person and the nature of the complaint. Then a dismissal of the problem and a defense of “we reviewed the situation and found no violation.”

    This is the same pattern used by my denomination in !my now boring rants with the predictable results of loss of members. Ethics and morality are lost in a reliance on some vague legal standard and the threat of legal action.

    Tho only worthwhile course of action is to seek criminal charges, in this case extending the GSK suit to include this material. We are all tired of the endless litigation that plague our society, but many will use our reluctant against us in an effort to dissuade us from taking action.

    Going away only allows those responsible for this type is action to continue with no penalty.

    Steve Lucas

    April 7, 2014 | 4:57 PM

    Interesting illustration, Sandra. Typical. It’s astounding that children are being labeled with mental illnesses without a thorough examination of family dynamics. Everything should be looked for from attachment issues, to every kind of abuse, neglect, neurotic behavior, bullying, learning difficulties, drug and alcohol abuse, neglect, and sociopathy in one or more family members.

    “Adam” was horribly abused by psychiatrists and psychiatry. Before trying to parse what led to that abuse, it is most important that psychiatrists first face the fact that they were being abusive and were doing great harm. Adam is owed an apology. The psychiatrists who labeled him without getting to know him in any meaningful way need to take responsibility for what they’ve done. “Mistakes were made” or “standard of care” isn’t going to cut it. Without the recognition of having done harm and having made terrible mistakes, the rest is kabuki and ass covering that may be normal in the context of business, but has no place in a field given the power to declare people mentally ill, rob them of their civil rights, and force medication.

    I was surprised to find that the DSM-IV discounted reaction to an antidepressant as mania, yet having a “manic” episode on an antidepressant is clearly accepted now as “unmasking” bipolar disorder. I was convinced that if I did not take my medication that I would eventually become a full-blown manic depressive because of “the kindling effect”. Which, may very well have scientific validity. It’s now being understood that schizophrenia is not inherently degenerative, is the kindling theory still in effect, or is it being challenged as well? It’s certainly been used effectively to convince people that the consequences of not being medicated would be dire.

    Regardless, bipolar disorder makes the perfect poster child for pharmaceutical companies, because any desire to stop taking medication can easily be construed as a desire to be manic. That’s supposed to be true even if the only manic episode a person had was drug induced and that experience was unlike anything they ever experienced. Bipolar disorder is so easily manipulated that being an artist is practically evidence for it now in the public mind.

    I’m also pretty sure that there used to be a warning not to conflate PTSD with bipolar disorder due to some mood lability and disregulation that is typical of PTSD. Now, drugs are routinely being prescribed for PTSD, even drugs that were developed to stop night terrors. Wha? Now, it’s assumed that PTSD is the result of an inherent malfunction in an individual’s brain— a lack of “resilience”. All this can be handily accepted with reverse inference, so that no more questions need be asked. The answer is drugs, and it’s very difficult now for veterans to get counseling for combat stress. They’re even given psychoactive drugs while on active duty in combat zones. Record rates of suicide for soldiers is a warning sign, that may be interpreted as the need for more medication, and round we go. The profundity of war and the act of becoming a killer becomes quaint.

    Retreating into legal arguments is symptomatic of a serious problem. Though I can certainly understand the difficulty of facing such a damaging revelation about oneself and one’s professional conduct, and the legal ramifications are necessarily salient, it’s morally and ethically necessary for members of this profession to stand athwart it yelling “STOP!”, which many professionals here are doing. It seems psychiatry should be the last resort, not the first thing a person thinks of when they’re feeling something they perceive to be abnormal, abberant, or simply too difficult to bear.

    April 7, 2014 | 6:32 PM

    As near as I can tell, this theory that antidepressants “unmask” underlying bipolar disorder is based on a handful of papers and has never been proven. It has, however, attained the status of a psychiatric meme.

    Here is a review article summarizing 7 models of the relationship between antidepressant treatment and “emergence” of mania (and therefore, a bipolar diagnosis):

    I personally experienced hypomania from a dose of fluoxetine that was too high for me, serotonin toxicity from a dose of escilatopram that was too high, and hypomania from coming off paroxetine — and I am the least likely candidate you could imagine for bipolar disorder of any stripe. The hypomanic adverse effects gradually faded but I’ve had autonomic dysregulation from antidepressant treatment for going on 10 years.

    On, we regularly see people who have been diagnosed with bipolar whatever after an adverse SSRI reaction, with no prior indication of bipolar symptomology, and dowsed with all kinds of drug cocktails for years. (It turns out the young man who is on 6 psychiatric drugs plus Deplin started out his career as a psychiatric case with an adverse reaction to an SSRI.)

    These people taper off the drugs and, what do you know, aside from withdrawal syndrome, they’re fine. No sign of bipolar disorder.

    It defies common sense that, as wiley noted, medicine could acknowledge that manic-type adverse reactions to SSRIs are possible
    but on another page claim that such an adverse reaction is diagnostic of a psychiatric disorder that needs to be treated strenuously with an unspecified drug cocktail (“doctor — feel free to improvise here”).

    But this isn’t about common sense, it’s about stamping out mental illness wherever it raises its ugly head, patient well-being be damned.

    April 7, 2014 | 8:24 PM

    Altostrata, I’ve gotten it from desipramine twice, and was also on desipramine and other drugs with no hypomanic effects for quite some time. It seems that I’m supposed to believe that I’m a desipramine only and only desipramine manic depressive.

    I call “bunk”. While I was buying it, but on no medication, I casually said, “You know how moody I am,” to a caregiving client. The look of shock on his face was educational. He said, “What are you talking about?! You’re always your same cheerful self!” Looking back at myself, I could see he was right and stopped doing that to myself.

    April 7, 2014 | 8:34 PM

    I just glanced at that study, Alto, and will return to read the rest; but I want to note first, “An additional point of concern that has received less attention in the literature is the question of whether SSRIs may induce mania or hypomania in children and adolescents.” It is not too much of a stretch to consider that the same may be true in adults. I understand the drive to protect children and adolescents from such a controversial diagnosis as pediatric bipolar, but waiting until they’re eighteen to induce hypomania with a drug and then diagnosing them will bipolar disorder with its hopeless prognosis and sentence to rotating cocktails for life isn’t too much less damaging, though the effects of interfering with neurological development in a still developing is particularly odious, our development never really ends and neither does the fact that the we are creatures of our environment.

    April 7, 2014 | 8:35 PM

    still developing person

    April 7, 2014 | 8:40 PM

    Ah— “…the risk of inducing mania with antidepressant medication may be especially high for children and adolescents 14 years old and younger.”

    Got it. Which also lends itself to the sudden ubiquity of pediatric bipolar disorder.

    April 7, 2014 | 9:00 PM

    Right now I’m reading Thinking Fast, and Slow, which is about the difficulty even among statisticians and researches to route out bias in their heuristic analyses. Much could be forgiven, but at some time, the obvious hampers to an evidence-based approach must be removed for the purposes of harm reduction and clarity in any field.

    April 8, 2014 | 9:02 PM

    The proof of the prospective treatment pudding is in outcomes and injuries, which need to be carefully tracked. Otherwise, it’s all hypothesis.

Sorry, the comment form is closed at this time.