Reading the just published Treatment of Early Age Mania (TEAM) studies of medication in child bipolar disorder is like jumping down the rabbit hole with Lewis Carrol’s Alice (Vitiello, B. et al. Treatment moderators and predictors of outcome in the treatment of early age mania (TEAM) study. J Am Acad Child Adolesc Psychiatry. September 2012;51:867-878; Geller, B. et al. A randomized controlled trail of risperidone, lithium, or divalproex sodium for initial treatment of bipolar disorder, manic or mixed phase, in children and adolescents. Arch Gen Psychiatry. May 2012;69:515-528).  Familiar terms in the language of bipolar disorder take on new and unfamiliar meanings; time seems to change, and familiar symptoms and behaviors are measured differently from the same phenomena in other studies of bipolar disorder.  The effect is unsettling; the concepts are familiar, but nothing is recognizable.

The greatest distortion is the redefinition of “episode” in bipolar disorder.  An episode is the length of time of a period of mania or depression in bipolar illness.   The average length of an episode is about 4.2 months (Goodwin and Jameson, Manic Depressive Illness, Oxford University Press, 2007, p. 133).  In the TEAM study, episodes lasted 4.9 +/- 2.5 years and, for 99.3 % of the patients, this one long episode was the only episode ever experienced. The bizarre meaning of this redefinition becomes more clear with the knowledge that this is a study of children and young  adolescents with an average age of  10.1 years +/- 2.8 years).  The single manic episode encompassed much of their lifetimes. 

Outside of wonderland, episodes in bipolar disorder are temporary states distinctly different from patients’ usual selves. In TEAM, the peculiar use of “episode” distorts the meaning of the word beyond recognition.

The most important criterion for diagnosing a psychiatric illness in DSM IV is the A. criterion.  The A criterion for mania or bipolar disorder is that the elevated expansive or irritable mood is a “distinct” state ( DSM- IV-TR, American Psychiatric Association, May 2000 p.362)  The patient must be recognized as different from his or her usual self.  As the children in the TEAM study had been manic for years - a large portion of their lives - they did not meet the DSM IV criteria for mania or bipolar disorder.  They did not have the diagnosis required by the TEAM research study despite being presented as if they did. 

In adults, cycles and episodes have the same meaning.  On average, an adult bipolar patient has less than one cycle or episode a year (Goodwin and Jameson, Manic Depressive Illness, Oxford University Press, 2007, p128.).  A subgroup of bipolar patients called rapid cycling patients have up to four cycles per year.  The TEAM study claims there is a group of bipolar children who have one or more cycles per day and over 360 cycles per year.  These high frequency cycles are called “ultraradian.”  This use of the concept of “cycles” greatly distorts the original meaning of the word.  These children are not having cycles or mood swings; they are simply having tantrums or irritable outbursts.  They are not having the major shift in personal organization that is a required characteristic of a bipolar mood swing or cycle (Liebenluft, E. et al. Defining clinical phenotypes of juvenile mania.  Am J. Psychiatry. 2003;160: 430).

The TEAM study itself was a clinical trial to learn which of three medications worked best in the initial treatment of bipolar children and adolescents.  Three different medications used in adult bipolar disorder were compared: risperidone, an antipsychotic; valproex, an anticonvulsant; and, lithium, a salt. The children only took one of the medications and the study lasted eight weeks. 

In some ways, a clinical trial is like a contest or race between the three medications to learn which one will help illness the most.  It is not like the race of the dodo bird in Alice in Wonderland in which all win and all receive prizes.  In this comparative clinical trial there was an expectation that there would be a winner. 

In this study, risperidone  won;  valproex and lithium were not as effective.  With further analysis, it  became clear that the trial had another flaw worthy of the imagination of Lewis Carroll. It was as if the medications did not begin the contest from the same starting line.  The study was done at five locations or sites, but at one location risperidone did five times better than it did at others. Although the risperidone effect overall was greater than the effect of the site, drug effects are not supposed to differ greatly by site; the purpose of the study is to measure the effect of the medications not the effect of sites. 

In an accompanying editorial this flawed study is praised effusively (Stringaris, A. What we can all learn from the treatment of early age mania (TEAM ) trial. September 2012;51:861-863).

Copyright 2012, Stuart L. Kaplan, M.D.

Stuart L. Kaplan, M.D., is the author of Your Child Does Not Have Bipolar Disorder: How Bad Science and Good Public Relations Created the Diagnosis, available on


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Your Child Does Not Have Bipolar Disorder