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]
[modified to fit]
"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."
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 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.
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  and later published .
~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 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.