1 Boring Old Man

Grassley’s Winding Road to Biederman et al
Pathoplilia
by Dr. Barbara Martin
June 11, 2008

^{…it remains unclear what led Grassley to investigate these physicians in the first place—among any number of possible targets. Grassley may have been alerted to Biederman (and thereby, his Harvard colleagues) through the death of 4-year-old Rebecca Riley. As reported by "60 Minutes" in September of last year, Rebecca Riley died on December 13, 2006, at her home in Hull, Massachusetts, due to an overdose of psychiatric drugs. The drugs — Depakote (divalproex; Abbott), Seroquel (quetiapine; AstraZeneca), and clonazepam — were prescribed by Tufts psychiatrist Kayoko Kifuji for the child’s bipolar disorder, which was diagnosed at the age of 2 years. Before her death, Rebecca had also been given an over-the-counter cold medication and at least one additional, unprescribed dose of clonazapam by her mother (and possibly more for a period of time before the child’s death).}

^{According to "60 Minutes," Dr. Kifuji’s prescribing practices were heavily influenced by the research and views of Biederman, who was interviewed for the news show. Biederman has evidently been instrumental in the trend to apply the diagnosis of bipolar disorder, in broader terms, to very young children. And with the diagnosis goes pharmaceutical treatment in the form of some drugs that have not been systematically tested in children. In a Boston Globe story, Kifuji’s lawyer stated that the Harvard psychiatrists were "by far the leading lights in terms of providing leadership in the treatment of children who have disorders such as bipolar." The paper also wrote of the extensive financial ties between pharma and Biederman, who had "received research funding from 15 drug companies and serves as a paid speaker or adviser to seven of them," including Eli Lilly (Zyprexa [olanzapine]) and Janssen (Risperdal [risperidone]). The Congressional record also reports financial ties between Biederman and BMS (Abilify [aripiprazole]), Cephalon (Vivitrol [naltraxone]), GSK, JNJ, and Pfizer…}

^{… 60 Minutes went to talk to one of the leading proponents of the diagnosis of bipolar disorder in children and whose research Dr. Kifuji has said influenced her. He is Dr. Joseph Biederman, professor at Harvard and head of child psychopharmacology at Mass General Hospital.}

^{"Previous studies that were conducted in the ’70s and ’80s determined it was very, very rare for a child to have bipolar disorder. And now you’re saying up to a million children are running around with this," Couric remarks. "Why such a sea change?" "The idea is rare if you define it in very strict ways," Dr. Biederman explains. "Our contribution has been to describe the many ways that this condition may emerge in children that may make it a little bit more diagnosable and less rare than people have thought about it."}

^{The classic adult definition for manic depression or bipolar disorder is dramatic mood swings from severe highs to severe lows, which can last for weeks or months. Dr. Biederman’s definition for children, though, is much broader. It emphasizes extreme irritability and at least four other symptoms such as recklessness, sleeplessness and hyperactivity. And while most doctors now believe that a child can be bipolar, there is no definitive medical test. Now there’s a cottage industry of bestselling books, magazine covers and Internet sites where you can test your child online. But even the top researchers can not agree on exactly what bipolar disorder looks like in children or at what age it can be diagnosed..}

^{"The average age of onset is about four," Biederman says. "It’s solidly in the preschool years." "What about those who say, ‘Oh, come on Dr. Biederman, a preschooler displaying these characteristics is often acting like a preschooler,’" Couric asks. "Absolutely not," Biederman says. "The bar to consider a diagnosis in a very young child is very high." Asked if he worries that his work is being used or applied too broadly and that too many children are being diagnosed as a result, Biederman tells Couric, "I am not so concerned if a practitioner recognizes that the symptoms have to be severe, debilitating, devastating, to consider the diagnosis"…}

^{"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."}

^{Many parents told 60 Minutes their children are so out of control and disruptive, medication is the only option. A parent who took her children to Biederman’s Mass General clinic, Maria Lamb says she depends on medication for eight-year-old Annie and nine-year-old Casey, who his mother says would rage for hours when he was just two years old. Casey was recently admitted to a psychiatric hospital when he was taken off one of his medications.}

^{"I don’t think they would be able to function. I wish they could. It was a last resort, seeing the kind of rages they would have, destroying their room, kicking the door off the hinges," Lamb says. But during one recent visit, Maria’s worried that Annie is eating incessantly. Dr. Biederman’s partner Dr. Janet Wozniak says it could be a side effect from one of Annie’s three medications and suggests another medicine may help.}

^{"Actually its most common usage has been to help people with alcohol addictions resist alcohol. But it seems to also have an effect on food cravings," Dr. Wozniak remarked. One of the biggest problems with these medications is side effects, including major weight gain, hand tremors, shakes, drooling and muscle spasms. And side effects are at the heart of the Rebecca Riley case…}

Anyone who has worked in a psychiatric clinic seeing kids knows the dilemma. There are plenty of very difficult disturbed kids. There are many parents who don’t know how to parent a rambunctious child. And there are often situations where both things are part of the problem and the differentiation between overwhelming kid, overwhelmed parent, or both is too murky to tease apart. Having been there, it’s hard to take a simple stance on these issues, to focus one’s outrage. But in the Rebecca Riley case, blame comes easily. The only innocent seems to be Rebecca. In the various accounts of this case, there’s more than enough blame to spread anywhere you look – father, mother, psychiatrist, social services. Rebecca was treated for ADHD and bipolar disorder diagnosed at age two by psychiatrist Dr. Kayoko Kifuji at Tufts, relying primarily on the mother’s narrative. The only clear fact in this case is that Rebecca Riley did not have Bipolar Disorder.

^{• What Killed Rebecca Riley?}
^{• Hull parents arrested in girl’s poisoning death}
^{• Mother convicted of second-degree murder in daughter’s drug death}
^{• Father convicted of 1st-degree murder in death of Rebecca Riley}
^{• Rebecca Riley’s estate gets $2.5 million in lawsuit settlement with psychiatrist}
^{• A timeline of the story}
^{• Spence, ousted as DSS commissioner, blames ‘nature of the work’}

I’m not naturally drawn to such nightmare cases, but this one makes the central point in the Childhood Bipolar story. Dr. Biederman and his colleagues had spent a decade broadening the diagnosis of Bipolar Disorder in childhood. If that had been all, looking for clear evidence of missed cases, there would be no complaint. But that’s not what they did. They incorporated a large group of kids under the Bipolar Umbrella that would never have gotten there on their own. ADHD kids, Conduct Disorder kids, Disruptive Behavior Disorder kids, Autistic kids, Retarded kids. Suddenly, Bipolar Disorder was comorbid with every kind of difficult to manage, difficult to treat kid in the book.

Along with the comorbidity, there were other things. One hallmark of Mania is a euphoric, grandiose, mood. Biederman’s Manic kids didn’t have that. They had "super angry/grouchy/cranky irritability" instead. Another hallmark of bipolar illness is periodicity. Biederman’s bipolar kids didn’t have that so much either. They were disturbed most of the time. And their illnesses were severe, worse than the syndrome in adults. They had a tendency to smoke and drink or use drugs as teens. The lower their SES [socioeconomic class], the worse they were. In case you’re wondering what it is about these children and adolescents that made him think that they were bipolar, I have absolutely no idea. And the treatment? From the start, he treated them with Atypical Antipsychotics. In fact, his first paper on treatment was a chart review that declared them responsive to Risperdal. So Biederman’s group essentially declared that many of the extremely hard to treat out of control kids brought to child psychiatrists were undiagnosed cases of Bipolar Disorder.

When Janssen came out with Risperdal, they had something called the Risperidone Disruptive Behavior Study Group. They clearly thought there would be a market for their drug in treating Disruptive Behavior Disorder and Conduct Disorder kids – essentially quieting difficult, aggressive children. I think that calling the kids "Bipolar" was a lot more acceptable rationale and that it was a marriage made in heaven. Janssen wanted to sell the drug as a safe alternative to the older neuroleptics for controlling these difficult children. The beleaguered parents and caretakers were a "hot market" for something like that. And Biederman’s jury-rigged Bipolar Child diagnostic criteria fit the bill – legitimizing the enterprise. The thing that makes me think that Janssen and Biederman were working on this together I’ve already said [bipolar kids: postscript, detestable?…]. Janssen revived an old 1997 Risperidone Disruptive Behavior Study Group clinical trial and had Biederman present it in 2002 and then publish it in 2006 – as if the symptoms had something to do with Bipolar Disorder. Unless Biederman is a complete idiot, he had to know what he was actively participating in – even if the whole thing was ghost-written. Joseph Biederman is not an idiot.

What does that have to do with Rebecca Riley? Rebecca was a kid whose problem was that she was born into a crazy family with a mother who drugged her kids rather than raise them, born in a time when there was a popular rationalization for using big medicines in little people. So the mother described Rebecca to the psychiatrist as fitting the Biederman criteria, got the Bipolar diagnosis, and Rebecca was treated with Depakote, Seroquel, and Clonidine in escalating doses until they killed her. The tragedy is profound. Like I said, Rebecca probably didn’t have the symptoms her mother reported. But, even if she had them, it wouldn’t have meant she was bipolar in my book. She was treated for symptoms she didn’t have, with treatments for an illness that unlikely exists, using drugs not appropriate for a small child, and died at age four.

^{"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."}