let the circle be unbroken…

Posted on Wednesday 19 December 2012

I’m sympathetic to the dilemma of the Child Psychiatrists and parents when they are presented with the a chronically out-of-control kid. I have seen some myself and they are diagnostic and management problems of the first order, particularly in an era where there’s no inpatient back-up for evaluation. We’ve all have heard the debate about the Bipolar Child, persistent for the last several decades – Dr. Biederman’s super angry grouchy cranky irritable kids [bipolar kids: biedermania and super angry/grouchy/cranky irritability…]. The DSM-5 is approaching the confusion by adding a new diagnostic category – Disruptive Mood Dysregulation Disorder. So I took a look at the Field Trials to see how that category fared:
DSM-5 Field Trials in the United States and Canada, Part II: Test-Retest Reliability of Selected Categorical Diagnoses and Analytic Approaches
by Darrel A. Regier, William E. Narrow, Diana E. Clarke, Helena C. Kraemer, S. Janet Kuramoto, Emily A. Kuhl, and David J. Kupfer
American Journal of Psychiatry. 2012 October 30, AJP in Advance

[modified to fit]
The group below were considered unsuccessful because the 95% confidence limits were unacceptably broad [Bipolar being one of them]:

[modified to fit]
This is the commentary about the Disruptive Mood Dysregulation Disorder results from the article:
"Disruptive mood dysregulation disorder. This condition was proposed to differentiate patients with pediatric bipolar disorder and those with some similar symptoms who did not progress to adult bipolar disorder. However, the field trial data present a challenging case in which one site, the one with the largest number of patients [predominantly from the inpatient service], produced a good level kappa of 0.49 [95% CI=0.33–0.66], whereas two other sites that obtained patients primarily from outpatient settings produced unacceptable kappas. Since the major distinction between this disorder and oppositional defiant disorder or intermittent explosive disorder is the presence of persistent irritability and anger mood states between frequent rage reactions, it appears that this disorder is more reliably diagnosed in its more severe form and with longitudinal assessment associated with inpatient hospitalization. This is consistent with the “severe mood dysregulation” disorder, which has been differentiated from pediatric bipolar disorder in the NIMH studies that provided the research basis for this proposal."
What a mega-wad of confusion! Conduct Disorder? Oppositional Defiant Disorder?, Bipolar Disorder? Intermittent Explosive Disorder? Disruptive Mood Dysregulation Disorder? And the distinction in the text doesn’t help very much in that the inpatient versus outpatient parameter may well reflect availability of services rather than severity. This is obviously a work in progress, and I can’t envision how the DMDD diagnosis is going to contribute much to that progress. But this is not the beginning of the Disruptive Mood Dysregulation Disorder narrative. It’s already in its second decade. Here’s what I wrote in June 2011, trying to summarize the high points and sleuth it out [trial 93: a bad penny…, trial 93: a very bad penny…, trial 93: a very very bad penny…]:
Finding out that Janssen had tried and failed to get Risperdal approved for disruptive kids through the FDA sometime after 1998 got that all stirred up in my mind again. Here is the timeline that keeps rolling around in my mind…

  • Risperdal was approved by the FDA in 1993, Zyprexa in 1996.
  • In 1995, Biederman’s Group started looking at bipolar mania in children.
  • At some point around 1995, Janssen asked Dr. Biederman to submit a request to study Risperdal in children. He submitted it and was turned down.
  • In 1998, Janssen finished a trial of Risperdal in disruptive children and submitted it for approval to the FDA. They were turned down.
  • In 1999, Biederman and Janssen had a contentious relationship. Yet that same year, Biederman’s group published a positive retrospective study of Risperdal in the treatment of childhood mania.
  • In 2001 Biederman published a positive trial of Zyprexa in bipolar kids supported by Lilly.
  • In 2002, Biederman published a inconclusive study of Depakote in bipolar kids sopported by Abbott.
  • In 2002, Janssen funded Biederman’s J&J Center for the Study of Pediatric Psychopathology and Biederman became an author of record on the 1998 Janssen trial for a ghost-wriiten AACAP presentation, later publishing that study again in 2006.
I now know that Janssen wanted to get Risperdal approved for disruptive kids early on. The FDA turned them down. Dr. Biederman had been approaching Janssen to fund a Center at MGH. After Biederman published a positive study of Zyprexa for bipolar kids, Janssen did fund Biederman’s Center and Biederman began to focus on Risperdal. The broad facts are that:

  • Janssen wanted approval for Risperdal in the treatment of disruptive kids.
  • Biederman led a charge for diagnosing disruptive kids as being bipolar with a wide range of other diagnoses being comorbid.
  • Biederman and Janssen revived their older disruptive retarded kids study and reframed it as evidence that Risperdal was effective in treating bipolar symptoms.

So I can’t shake the suspicion that the inclusion of so many kids in the bipolar category was simply a way to rationalize treating them with Atypical Antipsychotics. I feel pretty confident that was a Janssen motivator. I suspect Biederman’s group of being a part of that too, but it’s mostly a nagging hunch that just won’t go away. The circumstantial evidence is the timeline, the oddness of the expansion of the diagnostic criteria for childhood bipolar disorder, the slimness of the scientific evidence for that expansion, the inclusion of an old Janssen study of disruptive retarded kids in the ‘bipolar child’ literature, and the jury-rigging of that study’s clinicaltrial.gov information.
So that’s just the bare bones of a story that began with the Janssen Risperidone Disruptive Behavior Study Group shortly after Risperdal was introduced in 1993 with the goal of getting an FDA indication in disruptive children. Failing at that when the FDA said no dice, the trial was later revived and launched Dr. Biederman’s Bipolar Child craze with an Excerptia Medica ghost-written article in 2002. But after a period of what I call Biedermania in which the diagnosis of Bipolar Child increased 40 fold and the use of Atypical Antipsychotics in children soared, people began to increasingly question the diagnosis, Senator Grassley included Dr. Biederman on his unreported pharmaceutical income list, and Doctor Biederman found himself on the witness stand being challenged [2009] and began to sing a different tune:

Likewise, in his interview on 60 Minutes about the death of Rebecca Riley [in tears and despair…] he said:
    "Does it disturb you or worry you that many of these medications, most of these medications are being used off-label, and have not been tested in children?" Couric asks Biederman. "Yes. I recognize the fact that we have a gap in knowledge," Biederman says. "But the patients that come to me, and the families in tears and despair with these type of problems, I in good faith cannot tell them, ‘Come back in ten years until we have all the data in hand.’ I still need to use medicines that I am assuming that if they work in adults, with appropriate care and supervision, may also work in children."

So in July 2011, Dr. Biederman was censured by Harvard [bipolar kids: harvard acts…], and the diagnosis of the Bipolar Child has begun to smell more and more like three day old fish. But in spite of the odor, the use of Atypical Antipsychotics in children continues to be a problem.

Somewhere along the path from then to now, the DSM-5 Task Force takes on the problem of the overmedication of children and the epidemic of diagnosing out-of-control children as being Bipolar, and comes up with the solution of creating a new group – the Disruptive Mood Dysregulation Disorder [This condition was proposed to differentiate patients with pediatric bipolar disorder and those with some similar symptoms who did not progress to adult bipolar disorder.]. And in spite of an outcry, the diagnosis made it to the Field Trials [see above] where it more or less bombed except at a site where most of the subjects were in-patients. Note: The worry about over-medicating these kids with these drugs is largely an out-patient issue – office practice, foster kids.

If you’ve made it this far, there’s something incredibly circular about this story:
  • 1993: Risperdal comes on the market approved for Schizophrenia. Jannsen forms the Risperidone Disruptive Behavior Study Group aiming towards extending the approved indications to disruptive behavior in children.
  • 1995: Janssen asks Dr. Biederman to submit a grant request to study Risperdal in kids [Bipolar kids?], but when he does, they turn him down. He’s plenty pissed off.
  • 1998: Janssen completes the trial in disruptive children and tries for FDA approval, but is turned down. Part of the reason given is that the request was for a behavior [disruptiveness] rather than for a Disorder [a diagnosis].
  • 1999 & 2001: Dr. Biederman publishes Clinical Trials for non-Janssen drugs in Bipolar children [Zyprexa and Depakote].
  • 2002: Janssen woos Dr. Biederman back into the fold by funding a Center at Harvard. Dr. Biederman then signs on to an Exceprta Medica article [ghost-written] that is a re-write of the 1998 Trial in Disruptive children presented at the AACAP meeting [2002] and later published [2006].
  • ~2002 to ~2008: The Biedermania Era. There is a 40 fold increase in the diagnosis of childhood Bipolar Disorder. The journals fill with articles and it’s a hot topic at conferences. There is a frenzy of off-label prescribing [see “sunlight is the best disinfectant”…].
  • 2008: Senator Grassley’s investigation of unreported pharmaceutical income includes Dr. Biederman who first denies the charge, the admits to ~$1 M worth of unreported income.
  • 2009: 60 Minutes does a program about Bipolar Children focusing on Rebecca Riley, a four year old who died from over-medication.
  • 2011: Harvard censures Dr. Biederman and restricts him from doing industry funded studies for two years.
  • Meanwhile, the DSM-5 Task Force begins to consider adding a diagnosis – Disruptive Mood Dysregulation Disorder – specifically planned to decrease the diagnosis of distruptive kids as Bipolar, specifically hoping it would decrease the overmedication of children. It started life as Temper Dysregulation Disorder with Dysphoria but the name got changed along the way.
  • 2012: The DSM-5 Field Trials are released with kappas of 0.06, 0.49, and 0.11. Explained away as above.
  • 2013: Presumably, will be an official APA Disorder when the DSM-5 is released in May 2013.
So twenty years ago, a pharmaceutical company set out to get a drug approved for disruptive behavior in children. The plan didn’t work at first because it wasn’t a diagnosis. So the they found Dr. Biederman who provided a diagnosis [The Bipolar Child] that legitimized and supported the use of the drugs. While there wasn’t FDA Approval, there were official Guidelines [not much solid ground…] "sponsored by the Child and Adolescent Bipolar Foundation and supported by unrestricted educational grants from Abbott Laboratories, AstraZeneca Pharmaceuticals, Eli Lilly and Company, Forest Pharmaceuticals, Janssen Pharmaceutical, Novartis, and Pfizer." When his diagnosis fell into disrepute, the DSM-5 Task Force decided to add yet another diagnosis to offset the Bipolar Child diagnosis. They called it the Disruptive Mood Dysregulation Disorder which is exactly what Janssen set out to do in the first place in 1993! We’re back where we started! It’s like those ads for the 1950 extravaganza movies – twenty years in the making! cast of thousands!

So what used to be a behavior is now a Disorder, and we’re supposed to believe that will decrease the prescribing of antipsychotics to kids? Not in a million years. In the modern world of first-line office-practice psychopharmacologic treatment, that diagnosis is sure to be treated just like the Bipolar Child has been treated – with Atypical Antipsychotics. The irony is that the drugs have all just about gone off of patent, so their twenty year old marketing scheme is now about to finally have a solid home in our diagnostic manual in perpetuity. Whether this is intentional misbehavior, unintended consequences, or just plain dumb as hell doesn’t even really matter. The outcome is the same.

And it points up one thing wrong with our descriptive diagnostic system. We call the categories Disorders, but act like they’re Diseases. The Disruptive Mood Dysregulation Disorder doesn’t describe a unitary group with some unifying cause or even a unique syndrome. It can’t even be reliably diagnosed [0.06, 0.49, 0.11]. Atypical Antipsychotics actually work on the target symptoms at times, but the risk/benefit profile can be quite problematic, particularly long term. The DSM-5 Task Force is taking a big problem and institutionalizing it. The fact that the Child Psychiatrists and parents are between a rock and a hard place with these kids is a reality – a difficult reality. But defining a Disorder that will legitimize and routinize over-riding the known toxicity of medications is hardly a solution. It’s already a problem, and this move by the DSM-5 Task Force makes it worse…
    Evelyn Pringle
    December 19, 2012 | 10:34 PM

    When I was putting together a timeline on the path to child drugging in the US I also noticed the “coincidences” you so aptly point out above involving the long history of attempts to get Risperdal prescribed for various disorders that did not even exist. Now it looks like one does exist and yes it sounds eerily similar to the disorder they started out trying to establish in the first place.

    Not at all surprised.

    Evelyn Pringle
    December 19, 2012 | 10:35 PM

    BTW: Thanks for all you do and I hope you keep up the good work!

    December 20, 2012 | 1:29 AM

    “The fact that the Child Psychiatrists and parents are between a rock and a hard place with these kids is a reality – a difficult reality. But defining a Disorder that will legitimize and routinize over-riding the known toxicity of medications is hardly a solution. It’s already a problem, and this move by the DSM-5 Task Force makes it worse…”

    Then, let’s warn parents to – by all means – reject this new ‘diagnosis’ (so-called).

    And, Mickey, this is an important post you’ve written. What I feel needs more emphasis is the fact, that: teaching certain kids self-control may require professional help, but it is not rocket science. I.e., there are pros who are good at it; unfortunately, most Child Psychiatrists (I see you are fond of capitalizing that title) are prescribers, firstly; and, so, their attempts at ‘medicating symptoms’ away are short-term, palliative ‘solutions’ for ‘ill’ behavior, at best – which will create, in the long run, iatrogenic disease.

    May I suggest the following Youtube:


    12 year old Testifies in U S Senate Hearing

    (Note: At minute 12:30, one piece of advice from 12-year-old Ke’onte Cook… “That meds aren’t gonna help a child with their problems. It’s just gonna sedate them, make them tired, make them forget it for a while, and then it comes back, it happens again. What I learned in therapy is that, when you’re taking therapy, you talk about the deepest thing, it hurts, then it comes back, but you can handle it better.”)


    P.S. — Evelyn, you’ve done great work reporting on these issues.

    The few lines I offer below are excerpted from your 2007 article, “World Experts Demand End to Child Drugging in the US–Part 1” (apropos of Mickey’s post):

    …neurologist Dr Fred Baughman, a recognized authority on psychotropic drugs and author of “The ADHD Fraud,” stated: “Psychiatry and the pharmaceutical industry married and launched the joint market strategy of calling all emotional and behavioral problems ‘brain diseases’, due to ‘chemical imbalances’, needing ‘chemical balancers’ – pills.”

    “Every time parents are [led] to believe that their child’s emotional or behavioral problems are a ‘disease’ due to an abnormality in the brain,” Dr Baughman says, “they are lied to.”

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