Posted on Tuesday 17 March 2015

I’m old enough to have been in training when the classic version of Manic Depressive Illness was still the predominant view – a familial Illness characterized by recurrent episodes of either Mania or Severe Depression that began in adulthood. After the coming of the DSM-III, the domain of that diagnosis expanded in multiple dimensions, and at the turn of the century had been extended into the childhood, primarily by Dr. Joseph Biederman and his group at Harvard. The syndrome they described in children didn’t fit the classic intermittent pattern and had as the main symptom "super angry/grouchy/cranky irritability." The notion of the "Bipolar Child" swept through the ranks of Child Psychiatry like wildfire with much fanfare and a forty fold increase in diagnosis in a short period of time.

The topic of the "Bipolar Child" and the use of Atypical Antipsychotics in children were intimately intertwined from the outset. J&J had initially hoped to obtain an indication for its first ever Atypical Antipsychotic, Risperdal®, for behavior control in intellectually impaired children, completing a Clinical Trial in 1998 [Double-blind, placebo-controlled study of risperidone for the treatment of disruptive behaviors in children with subaverage intelligence]. But the FDA turned them down. After Biederman’s 2000 paper, Pediatric mania: a developmental subtype of bipolar disorder?, there was an explosion of interest and the Harvard group published series of clinical trials of various Atypical Antipsychotics in Bipolar children [see bipolar kids: biedermania and super angry/grouchy/cranky irritability…], including a ghost-written rewrite of that earlier disruptive behaviors paper, this time pitched towards affective symptoms [see trial 93: a bad penny…, trial 93: a very bad penny…, trial 93: a very very bad penny…]. The "Bipolar Child" epidemic seemed to take a dive when Senator Grassley’s investigations of unreported pharmaceutical income in 2008 included Dr. Biederman, and he was censured by Harvard [bipolar kids: harvard acts…][see also The False Epidemic of Childhood Bipolar Disorder].

Of all the controversies around overmedication, this one draws the most sparks – the use of antipsychotic medications in children. To some, it is seen as simply an excuse to use potent [and potentially toxic] antipsychotics to control disruptive behavior, noting that the drugs are heavily used in kids in public systems, foster care, Medicaid, etc. To others, it is a welcomed treatment of a previously untreated disease. Whatever the case, the drug use continues. There were even several attempts at name-changing. When all of this broke, the Child & Adolescent Bipolar Foundation changed its name to The Balanced Mind [see what’s in a name? that which we call a rose… ]. And the DSM-5 Task Force created a category [Disruptive Mood Dysregulation Disorder (DMDD)], specifically to "give these children a diagnostic home and ensure they get the care they need." Apparently, the scope of these prescribing practices hasn’t responded to the name changing. In a recent press release, the JAMA highlighted the problem referring to a recent article:
JAMA – Journal of the American Medical Association
March 3, 2015

With a concern about inappropriate prescribing of antipsychotic medications to children, 31 states in the U.S. have implemented prior authorization policies for atypical antipsychotic prescribing, mostly within the past 5 years, and with most states applying their policies to children younger than 7 years of age, according to a study.

Over the past two decades, antipsychotic prescribing to youth, almost exclusively comprising atypical antipsychotic medications, was estimated to have increased from 0.16 percent in 1993-1998 to 1.07 percent in 2005-2009 in office-based physician visits. Antipsychotic use is also 5-fold greater in Medicaid-insured youth than in privately insured youth, and occurs mostly for indications not approved by the U.S. Food and Drug Administration [FDA]. In light of antipsychotic treatment-emergent cardiometabolic adverse events, several government reports called for efforts to improve pediatric psychotropic medication oversight in state Medicaid agencies. Such efforts have included age ­restricted prior authorization policies, which require clinicians to obtain preapproval from Medicaid agencies to prescribe atypical antipsychotics to children younger than a certain age as a condition for coverage, according to background information in the article…

And related articles are becoming increasingly common in a variety of venues [Antipsychotics For Poor Kids Are Booming, It’s Time To Look At Prescriber Decision-Making referring to Antipsychotic Medication Prescribing in Children Enrolled in Medicaid]. In the antipsychiatry writings, it’s seen as a paradigm of medical-model thinking [The Drugging of Children in Foster Care]. Meanwhile, Dr. Biederman is still chasing the Bipolar Child disease entity [Further evidence for robust familiality of pediatric bipolar I disorder: results from a very large controlled family study of pediatric bipolar I disorder and a meta-analysis]. So with that as a background, we read this Friday in the PsychiatricNews:

March 13, 2015

The Food and Drug Administration [FDA] has approved Saphris [asenapine] as a therapy for the acute treatment of manic or mixed episodes associated with bipolar I disorder in pediatric patients. Saphris becomes the first atypical antipsychotic to be approved for children with bipolar I disorder in the last five years. The medication was initially approved in 2009 for the acute treatment of bipolar I disorder and acute/maintenance treatment of schizophrenia in adults.

The FDA approval of Saphris is based on the positive results of a clinical trial of 403 children [aged 10 to 17] examining the effects of twice daily doses of 2.5 mg, 5 mg, or 10 mg of the drug. All three dose levels were associated with improvements in both mania and overall disease severity compared with placebo. Side effects included sleepiness, dizziness, strange taste sensations, numbness of the mouth, nausea, tiredness, increased appetite, and weight gain…

To read more about the treatment of pediatric bipolar disorder, see the FOCUS article "Management of Bipolar Disorder in Children and Adolescents."

The results are posted on [NCT01244815], though I don’t think there’s a published paper, and the only thing on Drugs@FDA is the Approval letter:

Acute: Measured Values after 3 Weeks

  Placebo Asenapine
2.5 mg BID
5.0 mg BID
10.0 mg BID
Participants 79 88 87 81
Change in Y-MRS
Mean ± SD
-9.6 ± 7.8 -12.3 ± 9.0 -15.1 ± 9.5 -15.9 ± 9.1
P Value   =0.008 <0.001 <0.001

There was an Extension Study [NCT01349907] of maintenance therapy for up to 50 weeks with two groups, the Placebo group and those treated with Asenapine in the Acute 3 week study. Both groups were treated with maintenance Asenapine for up tp 50 Weeks. The primary outcome measure was the number without any adverse event:

Maintenance: After 50 Weeks of Asenapine

Acute Asenapine/Asenapine Placebo/Asenapine
Participants 241 80
With Adverse Event 197 74
Completed Study 102 38

While I think that table is right, the results database and numbering on was obscure to me. Assuming I got it right, the Maintenance phase study was a bust. The Atypical Antipsychotics have generally been approved by the FDA for adolescents like this approval for Saphris®, but not for children where they have been prescribed "off-label."

And finally, here are three guides for Pediatric Bipolar Disorder for Parents and Families from the National Institute of Mental Health, the American Academy of Child and Adolescent Psychiatry, and the Balanced Mind Parents Network respectively:

NIMH Guide: Pediatric Bipolar DisorderAACAP Guide: Pediatric Bipolar DisorderBalanced Mind Guide: Pediatric Bipolar Disorder
[click on an image to link to the guide’s content]

If this post has seemed to wander aimlessly from topic to topic without any organizing outline, that was my intent rather than a lack of direction or purpose. That’s exactly how this whole story of the Pediatric Bipolar Disorder feels to me – a confusing collage of disjointed trends that can’t seem to land on any organizing principle. It’s as if the Diagnosis actually grew to meet the arrival of a new Treatment, rather than the other way around.

Not long after the Atypical Antipsychotics came on the scene, Dr. Biederman’s group [who had been primarily focused on kids with ADHD/ADD] proposed that a subgroup of their ADHD kids [a subgroup that were prone to temper outbursts and agitation] were in fact children with Bipolar Disorder. These were "super angry/grouchy/cranky irritable" kids who did not seem to have periodic illness as the classic adult Bipolar Disorder patients – nonetheless, the hypothesis was that this is the childhood equivalent of Mania. The newly introduced Risperdal had been shown to be effective in disruptive intellectually impaired children, and in a series of studies, the Atypical Antipsychotics were found effective in the kids described by Dr. Biederman’s newly minted Bipolar Disorder. As mentioned, this Diagnosis caught on like a new cell-phone technology and there was an epidemic of Pediatric Bipolar Disorder. At the same time, there was an epidemic of the rampant use of Atypical Antipsychotics in children in Foster Care. While many were diagnosed as "Bipolar," the clear implication was that the medication was being used for behavior control.

Dr. Biederman’s fall from grace in the Grassley Investigation also threw his new version of Bipolar Illness into question. The APA even actively created a new disorder in the DSM-5, Disruptive Mood Dysregulation Disorder, designed to divert people from making the diagnosis of pediatric Bipolar Disorder. A distinguishing feature of this new category was that it was non-episodic. But pediatric Bipolar Disorder didn’t retreat back into its preBiederman infrequency. It has stayed very much on the front burner. And the makers of the Atypical Antipsychotics have applied for and been granted FDA indication approval as the drugs have come onto the market [allowing them to advertise]. In the family guides above, there’s reference to the original Biederman version [super angry/grouchy/cranky irritable kids] – a negative reference [see here]. The version described in the guides is similar to the more usual adult form of the illness. In the four or five years I volunteered in a Child and Adolescent clinic that saw primarily Medicaid kids, I never saw a case that would fit the patients mentioned in those guides, though I saw a number with that diagnosis who had been put on an Atypical Antipsychotic. I did see a lot of the Biederman version, out of control disruptive kids who were among the ranks of those who had grown up pillar to post, in and out of foster care.

This clinical trial with Saphris is typical of the Antipsychotics. One can sedate any kind of out-of-control-ness with the Atypicals [just like with the First Generation Neurpleptics], so there’s no surprise that they worked acutely. However, it’s rarely true that these drugs can be taken long-term without adverse side effects of one kind or another as seen in this trial.

All things considered, I remain concerned that the epidemic started by Dr. Biederman 15 years ago is continuing. That’s not just based on my own limited experience. It’s based on the high density of "KOLs" involved in these guides, the ongoing presence of PHARMA in this thread, and the pressure to "control" these kids. In my case, the pressure to medicate didn’t come from psychiatrists. It came from people in the system and the foster parents themselves. It’s part of the reason I no longer volunteer in that clinic. As I said, I’m afraid my opinion is that this was a Diagnosis that followed the arrival of a Treatment – that the epidemic begun by Dr. Biederman’s Group has endured by inertia and continues to be heavily colored by the PHARMA allied KOLs…
    March 17, 2015 | 2:41 PM

    the only way this issue of inappropriate prescribing for children is going to be appropriately discontinued without strong validation is for people to sue the psychiatrists, preferably considering felony charges because of the overt risk of harm.

    Let people continue to pontificate when they dance around being politically correct / respectful / maintaining supposed genuine caution to avoid under estimating real illness being underdiagnosed. When the odds are 50 50, do you basically pull out a coin and flip it in front of your patient when you’re going to suggest medication?

    I think it’s time for people to have an honest and frank debate about the use of antipsychotics in general. As long as you want to dance, be prepared not only watch your toes get stepped on but you might actually fracture an ankle! Or worse!?

    March 17, 2015 | 3:48 PM

    Dr. Biederman “fell from grace,” but he still has his job at MGH. The consequences of that fall weren’t very big.

    James O'Brien, M.D.
    March 17, 2015 | 5:20 PM

    What did you expect? The best and the brightest didn’t even come down on John Mack when he went off the rails.

    Maybe he was just ahead of his time though and he would have been right at home in the BPS.

    March 17, 2015 | 7:15 PM

    I think the reality is that most of these kids have attachment, abuse or otherwise environmentally related interpersonal emotion regulation issues (often I think this interfaces with a sensitive temperament). Psychiatrists should not be treating these kids. After organic disorders and psychosis are ruled out, they should immediately be referred to someone trained to deal with these issues. These people exist, although they are marginalized by the greater mental health community.

    As Dr. Nardo mentioned antispychotic medication will subdue any externalizing behavior profile. This is not treatment. This is chemical restraint. These children (and adolescents’) brains will continue to mature with two enduring insults 1) the toxic effects of these drugs on their brains and 2) the environment that spurred this behavior will continue to exact its toll on the child’s already overwhelmed emotional-behavioral regulation capacity with no lasting improvement in this capacity.

    Family is the real third rail in psychiatry. The last frontier in psychiatry will be recognizing the role families can play in producing psychopathology in their offspring. Interpersonal connection and all its pathologic iterations are in effect based in biology. To claim that a child’s caretaker’s or other people with a significant role in the child’s life do not play a substantial role in the development of said organisms’ emotional-behavioral schemes is to spit in the face of nature itself.

    And in effect, this is what mainstream psychiatry does. And really it does come down to the profession, to regular psychiatrists speaking out against this vociferously, otherwise, everyone is just going along for the ride with Biederman et al..

    Lastly to push back on the idea Dr. Nardo, that this is a diagnosis that followed the arrival of a treatment, gives far too much credit to the pharmaceutical industry. Psychiatry in its current form is responsible for creating an environment in which the idea that this kind of behavior in children is best conceptualized as a medical disorder treated by medication. I know you didnt have a role in that (I am a big fan) but psychiatry’s insistence that they are the apex professionals in the mental health community creates a situation where they are treating behavioral problems that in all honesty, most psychiatrists are not competent to understand or manage, whether by din of the fact they see their patients for only 15 minutes every two weeks ,or, by din of the fact that psychodynamic knowledge has been increasingly mimimized in their training. Human behavior is vast and complex, even more so in children, and absolutely not amenable to the framework within which most psychiatrists train and then choose to work.

    I recenlty met with the Harvard-affiliated Biederman-colleague psychiatrist who misdaignosed me 15 years ago ( I met him along with my therapist) and basically laid bare his thoughtless, mindless cavalier attitude toward diagnosing and medicating what were essentially attachment and trauma related issues — in the words of an adult — and he really didnt have much to say. He didnt seem sorry. He seemed slightly embarrassed, quite anxious. He really had no answer for what he had done to me and all the fall out his practice caused and I basically told him that he chose to work in this environment, no one made him see patients for 15 minnutes once a month and that such and such an excuse about the “system” is not a legitimate excuse for we he did and didn’t do. This is what the current state of psychiatry has to offer children.

    This is the system psychiatry legitimizes for itself and this is the result it gets.

    With outcomes like this I think Jeffrey Lieberman should not be sursprised that psychiatry is the only branch of medicine with an “anti” movement against it.

    Yet really,there is no “antipsychiatry” what people are against, including people who call themselves by such labels, is the PRACTICE of psychiatry. There can be many legitimate opinions about the validity and harms of different PRACTICES in this field as in any field of medicine, but as I see it, for psychiatry to truly serve those who they claim to serve, there will need to be drastic transformation in the education of psychiatrists and their role in mental health treatment at large because there are many bad practices in this field. Currently this Child Bipolar disaster strikes me as a particular egregious practice for which this profession should be ashamed and ashamed enough to change.

    March 17, 2015 | 8:19 PM

    Yes, JL. It amazes me that psychiatry can ignore child development, but it shouldn’t, environment simply doesn’t count for much anymore, which bespeaks a complete lack of understanding or what it means to be human.

    As a nanny of a child with R.A.D., or rather a child who did not bond in infancy, I can attest to the phenomenal amount of work and self-control that is required just to keep the adults in charge of the household. It’s much, much harder than chemical restraints. We used basket holds for several months to effectively stop tantrums in which she would tear up the house, and eventually, the tantrums stopped— oh happy days.

    Children also suffer from degrees of neglect that allow them to bond, but still trust problems are natural with parents who aren’t worthy of trust, and children who aren’t taught how to regulate their emotions, don’t just learn it. Aside from untold damage being done by the drugs, children are being robbed of what they need, and probably being robbed of their ability to learn. It’s institutional child abuse.

    March 17, 2015 | 8:42 PM


    Just a note of clarification. The psychiatrist that wrote this post [namely me] has taught the attachment theory, object relations, and trauma courses in our analytic Institute for thirty years.

    March 17, 2015 | 10:21 PM

    Yes Mickey, but, to the JL’s of the world, you are guilty simply because you made the egregious mistake of being a psychiatrist, which is inherently the simplest and most pathetic flaw of their reasoning which is antipsychiatry at the end of the day.

    Sorry Dr N, you tolerate too much of some of the commenters, me included sometimes. Absolute intolerance should not be trivialized or rationalized, it should be marginalized and shunned. We have fools and charlatans in our ranks in psychiatry, but they do not speak for all of us as extremists and zealots shamefully conclude.

    But, as long as we don’t police our own responsibly, well, we risk giving some ammunition to our critics, eh?

    March 18, 2015 | 1:24 AM

    The whole bipolar thing is so out of control. I really liked Whittaker’s take on all that, I do wonder if the meds probably make the symptoms more intense and cycle faster. When I was a kid, I threw a lot of chairs, did a lot of crazy stuff, but my psychiatrist never prescribed any meds, it would have been ridiculous. He was a sensible person. I’m sure I would have been hospitalized if I had grown up half a century later.

    What the hell is Asenapine anyway? Funny looking molecule, isn’t it? I guess it was developed from Mianserin, which is kind of like Remeron, which seems like one of the safer atypical antidepressants, which aren’t very good for depression, but seem to be good for something. Have I got that about right? At least my clients who were taking it didn’t grind their teeth all the time or gain 60 pounds or completely lose their sex drive. It had a pretty good rep at our clinic.

    Maybe Asinine or whatever they call it actually works for something. We’ll probably never know.

    We don’t let kids drink or smoke pot before their 21, maybe– just maybe– it’s a good idea to keep them away from psychiatric medication– I mean sort of in general, without a really compelling reason to do otherwise.

    March 18, 2015 | 1:59 AM

    Dear Dr. Nardo,

    Thank you for your clarification, but it was unecessary. As I indicated in my comment I am aware of your background as I have been reading your blog closely for years and have gained not an insignificant amount of peace and validation in my life from seeing my own thoughts about a system that so poorly treated me as a child reflected in your writing and I am very thankful for that. I apologize if the tone of my comment came across as angry or blaming which it likely did. I don’t comment a lot anymore because I dont see a place for my comments here often. But because this particular topic is one that has such important salience in my life and is one that I have extensive experience with I felt the benefits of doing so outweighed the risks. I assumed that my perspective as a patient and as someone with direct, lived experience of this terrible topic would in some way be valued , or at most tolerated. Clearly I was wrong.

    On that note, prior to making this comment I had noticed the tone of your blog has become less tolerant of criticisms made ( often the same or similar criticisms you make) by those who are not psychiatrists. The tone of some of the commenters here and yes, I am going to call people out, Dr Hassman and Dr Carroll, I would consider insensitive at best, certainly intolerant and at times veering into the realm of abusive. I believe I respect, as many commenters do who have similar experiences to mine, a diversity of opinions and view points that do not comport to my own and yet we are continually labeled “antipsychiatry” despite any objection when critizing the role this profession has had in OUR OWN LIVES.

    Lets be honest. The term “antipsychiatry” here and elsehwhere is used as an epithet to summarily invalidate the opinion of those patients or mental health professionals whose analysis of these topics makes psychiatrists feel uncomfortable and vulnerable. Somehow criticisms are most and in some cases only valid if they come from psychiatrists, but then only if they give the profession an undeserved benefit of the doubt that is rarely extended to the motivations of those patients and professionals who are taunted with the epithet “antipsychiatry”.

    I really have no place here if anything I say critical of psychiatry or the dozens of psychiatrists I’ve interacted with in my life will immediately be labeled as such and in an attacking and unpleasant manner. Guess what? What I wrote is based on my extensive experience in the system. Unbeknownst to some commenters, my general opinion that good and bad psychiatrists split 50/50 best I can tell, is just as valid as your and others opinions that there are just a few bad apples in the upper echelons. If that were the case, why the need for today’s post?

    I have no desire to lurk here like others and insist my opinion is right or most valid on every single topic upon which you post. Nor do I have the desire to label, diminish or invalidate others with less power and alternative viewpoints. And thus truly, while my last comment was not my most elegant or well constructed, I do not feel my opinion has a place here at all and I do not plan on commenting on further topics.

    One of the things I respected about you most Dr. Nardo was the sensitivity with which you treated the diversity of critical and alternative viewpoints and groups that all have a stake in the topics you write about. I think that sensitivity and even handedness toward alternative viewpoints is something lacking in your profession as a whole altogether and is one of the biggest reasons psychiatry and not opthalmology or orthopedics has such a large base of vocal, unhappy patients. It is also a sensitivity that has been lacking in the comments here, far as I can tell, for quite a while. If psychiatry was full of people like you Dr. Nardo the term “antipsychiatry” wouldn’t exist. Alas…

    To Mr Hassman specifically; you dont know me. You don’t know people “like” me. However, I have read many of your insensitive, jarring comments here and I know people like you. You are not worth engaging and I will leave it at that.

    March 18, 2015 | 2:25 AM

    JL, great post. I am sorry you won’t be commentating as sadly, it is the folks who were “treated” for bipolar disorder by Biederman doctors who need to be heard from. Unfortunately, I understand your position all too well. I hope you will write start a blog/website or write a book about your experiences because again, your story needs to be told without censorship.

    March 18, 2015 | 11:56 AM

    Reactions to comments mean a nerve has been touched, and, the blatant hypocrisy of some commenters who continually smear the entire profession of psychiatry and then disingenuously call “foul” when rebuked is just pathetic to those readers who are more unbiased and objective.

    If you are going to sling mud, deal with getting dirty. This false pious attitude may work among the Legion of psychiatry haters, but your choir can only travel with you so far.

    March 18, 2015 | 12:09 PM


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