The recent publication of the Treatment of Early Age Mania (TEAM) studies provides vivid illustrations of the many flaws of current research on bipolar disorder in children (Geller, B. et al. A randomized controlled trial of risperidone, lithium or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. Arch Gen Psychiatry. 2012 69: 515-528; 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. 2012: 51: 867-878). The shortcomings of the studies were difficult to overlook; they led to a critical editorial in the Journal of the American Academy of Child and Adolescent Psychiatry and a letter to the editor of the same journal (Stringaris, A. What we can all learn from the treatment of early age mania (TEAM) trial. J Am Acad Child Adolesc Psychiatry. 2012:51:861-863; Blader, J. Another look at the Treatment of Early-Age Mania (TEAM) trial. J Am Acad Child Adolesc Psychiatry. 2013: 52: 205-206).
Similar to many investigations of bipolar disorder in children, the study was funded by the National Institute of Mental Health, five prestigious universities served as sites for the studies, and leaders in the field of child psychiatry served as authors of the studies. The prestige of the studies’ authors, their universities, and the National Institute of Mental Health might seem intimidating for many who would consider challenging the studies. The public and the profession of child psychiatry should be particularly grateful for the thoughtful critiques provided by Stringaris and Blader noted above.
In this post, the characteristics of the research subjects will be critically reviewed. In a subsequent post, the conduct of the study will be considered.
The purpose of the TEAM study was to develop evidence for the best psychopharmacological treatment of children and early adolescents diagnosed with bipolar I disorder. 279 children and adolescents with an average age of 10.1 years and an age range from 6 years to 15 years were given one of three medications: risperidone lithium and valproate for eight weeks in a double blind study. Risperidone worked best.
The Geller et al report begins by noting that only children and adolescents who met the criteria for bipolar I disorder were eligible for admission to the study. There are many reasons to question whether the children and adolescents met DSM IV criteria for that diagnosis. For example, 90% of the sample was reported to have been grandiose. Grandiosity is a symptom of mania and must be present to an extreme degree to support a diagnosis of mania. The authors gave two examples of behaviors that were considered grandiose and used to support a diagnosis of bipolar disorder. The first was a 6 year old child who took his parents’ beer and tried to sell it to neighbors. The second was a 9 year old child who went to see the school principal to have his teacher fired. These seem to be at most mildly aberrant behaviors that might merit some passing attention from neighbors and school officials but would not count toward the diagnosis of a major psychiatric illness such as bipolar disorder. As stated, 90% of the sample was regarded as grandiose.
92.8% had ADHD. Dr Stringaris, an English child psychiatrist and research scientist, in his editorial called this amount of ADHD in the research subjects “staggering.” The mania episodes were largely characterized by “daily rapid cycling,” for a minimum of four hours per day. ”Rapid cycling” seems to have meant periods of intense irritability and agitation interspersed with other symptoms of bipolar disorder such as elation and grandiosity. The patients were understood by the authors to be rapidly cycling between mania and depression. 99.3% had daily rapid cycling. Stringaris regards this finding as “surprising.” Stringaris, with admirable restraint, seems to use the word “surprising” to describe a reported finding that may not be believable.
Dr. Stringaris was also “surprised” by the length of the manic episodes. The episodes lasted 4.9 years. On average, they began at 5.2 years of age. The average number of episodes for each subject was one. This description of manic episodes and their length is distinctly different from the characterization of manic episodes found in adult bipolar disorder patients. Stringaris notes that the average length of a manic episode in an adult patient is weeks.
I note that a major criterion for the DSM IV diagnosis of bipolar disorder is that the patient in a manic episode must be distinctly different from his or her usual self. It would be difficult to characterize young children as different from usual when their episode has lasted 5 years, which for many is a full half of their lives. They would not be recognized as different from their usual selves. Their usual selves were rapid cycling states. They did not meet this necessary criterion for the diagnosis of DSM IV bipolar disorder.
97% of the subjects were diagnosed as having a mixed manic state. A mixed manic state is one in which patients have to simultaneously meet full DSM IV criteria for a manic episode and full DSM IV criteria for a major depressive episode. In an earlier post it has been noted that Dr. Ellen Frank, an authority on adult bipolar disorder, disclosed that she had never seen an adult patient with a mixed manic state http://www.psychologytoday.com/blog/your-child-does-not-have-bipolar-disorder/201212/small-unicornsupdate-dsm-5-bipolar-disorder--0. Improbably, investigators in the TEAM study regularly encountered this phenomenon in children and young adolescents.
The presentation of this work at a scientific meeting is briefly described here http://www.psychologytoday.com/blog/your-child-does-not-have-bipolar-disorder/201201/the-world-series-child-bipolar-disorder. In the next post the conduct of the study will be reviewed.
Copyright 2013, Stuart L. Kaplan, M.D. http://notchildbipolardisorder.com