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Primary Psychiatry. 2010;17(9):19-22
To the Editor:
It is with dismay that I read Kiki Chang, MD’s1 response to the argument that the increase in diagnosis of bipolar disorder in children and adolescents is because there are now drugs approved and promoted for that diagnosis. Chang minimizes this consideration, even going as close to describing it as “complete lunacy.”
The peril of accepting Dr. Chang’s dismissal at face value—since he was interviewed as an expert—is that it hinders an objective appraisal of presented information promoting the diagnosis and treatment of bipolar disorder in youths, eg, pharmaceutical company-sponsored dinners. This is especially salient for practitioners (primary care physicians and psychiatrists) who are not well versed in diagnosing and treating childhood conditions; they may not take the time or effort to review the relevant literature or use accepted criteria in diagnosing these serious conditions, thereby doing a disservice to patients.
There has been a debate in child psychiatry for many years now about the criteria used to diagnose mania and bipolar disorder. There are a large number of child psychiatrists who believe that it is not wise to relax the criteria delineated by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision.2 Though many psychiatrists, especially adult psychiatrists, loosely diagnose bipolar disorder or mania in children, this is not the standard of practice nor is it acceptable unless specific criteria are utilized in making such diagnoses.
In a well-written letter to the editor of the Journal of the American Academy of Child and Adolescent Psychiatry, Roberts and colleagues3 pointed out that long-term follow-up suggested that a 4% to 8% later diagnosis of bipolar disorder in previously identified children was prudent, ie, that the true incidence of bipolar disorder later in life was not as high as expected in children with symptoms that might be consistent with bipolar disorder. Carlson and colleagues4 pointed out that a diagnosis of mania or bipolar disorder was confirmed in only four out of 15 children admitted to an inpatient hospital setting with a preadmission diagnosis of bipolar disorder. Other sources of data suggest that ~50% of youngsters diagnosed with bipolar disorder do not persist into adulthood with that diagnosis.5 Stringaris and colleagues6 found that only 1.2% of children with “severe mood dysregulation” had hypomanic or manic episodes on follow-up compared to 62.4% with narrowly defined bipolar disorder.
In another letter to the editor, Holtmann and colleagues7 noted the United States trend in outpatient diagnosis of bipolar disorder8 in which there was a nearly 40-fold increase of bipolar disorder diagnosis from 1994–2003 in children and adolescents ≤19 years of age. Commenting from a European perspective, they noted that while there was an increase in hospitalization rates for bipolar disorder in youths in Europe, this rise was far more moderate than the 40-fold increase in the US, and the estimated underlying prevalence was much lower. Holtmann and colleagues7 pointed out that the prevalence rate in children using strict criteria for bipolar disorder was comparable with pediatric bipolar disorder rates in other countries, which was ~1% of an epidemiologic sample and ~7% in a child psychiatric clinical sample. US psychiatrists would have overdiagnosed that sample with bipolar disorder (~75% instead of 1% and 7%).
Similarly, Parry and Allison9 pointed out “the very marked rise” in bipolar disorder diagnosis in youths in the US, which appeared to be driven by reconceptualizing emotional and behavioral symptom clusters, which in turn was spearheaded by three regional academic departments; among the controversial features they noted was pharmaceutical company influence.
All these indicate that the rise in bipolar disorder rates reported in the US may be a local or regional trend, which is the “flavor of the day” that is magnified by lax diagnostic thinking and precision. One might consider what factors would promote such a fad.
I would suggest that it is more than coincidence that this increase in awareness and rates of diagnosis of bipolar disorder in youths corresponds with the increase in the more expensive pharmaceutical interventions promoted by the pharmaceutical industry. This mirrors the increase in awareness and rates of diagnosis of other conditions that have manifested in the US market in synchrony with greater marketing of branded commercial pharmaceutical agents, eg, social phobia in the 1990s and attention-deficit/hyperactivity disorder (ADHD) in children and adults.
We would be wise as clinicians in the US to be precise and conservative in the diagnosis of such a serious condition, as the lifelong or protracted use of psychotropic medications such as thymoleptics and antipsychotics exposes such children to significant long-term risks.10 It has been my clinical (anecdotal) experience that the judicious application of diagnostic criteria for bipolar disorder results in changes in diagnosis in youths from bipolar disorder to conditions such as ADHD comorbid with oppositional defiant disorder. When treated for the more benign conditions, those children had good long-term response to treatment for the new diagnosis, did not require thymoleptics, and did not manifest manic episodes with long-term follow up.
Sincerely,
Roger Z. Samuel, MD, FAPA
Dr. Samuel is medical director at the Boca Raton Psychiatric Group in Florida.
Disclosures: Dr. Samuel reports no affiliation with or financial interest in any organization that may pose a conflict of interest.
References
1. Chang K, Sussman N. In session with Kiki Chang, MD: bipolar disorder in children and adolescents. Primary Psychiatry. 2010;17(4):23-26.
2. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000.
3. Roberts N, Parker KC, Woogh C, Cripps L, Froese AP. Bipolar disorder and ADHD children growing up [letter]. J Am Acad Child Adolesc Psychiatry. 2000;39:6.
4. Carlson GA, Potegal M, Margulies D, Gutkovich Z, Basile J. Rages – What are they and who has them? J Child Adolesc Psychopharmacol. 2009;19(3):281-288.
5. Ruggero CJ, Carlson GA, Kotov R, Bromet EJ. Ten-year diagnostic consistency of bipolar disorder in first-admission sample. Bipolar Disord. 2010;12(1):21-31.
6. Stringaris A, Baroni A, Haimm C, et al. Pediatric bipolar disorder versus severe mood dysregulation: risk for manic episodes on follow-up. J Am Acad Child Adolesc Psychiatry. 2010;49(4):397-405.
7. Holtmann M, Bölte S, Poustka F. Rapid increase in rates of bipolar diagnosis in youth: “true” bipolarity or misdiagnosed severe disruptive behavior disorders? Arch Gen Psychiatry. 2008;65(4):477.
8. Moreno C, Laje G, Blanco C, Jiang H, Schmidt AB, Olfson M. National trends in the outpatient diagnosis and treatment of bipolar disorder in youth. Arch Gen Psychiatry. 2007;64(9):1032-1039.
9. Parry P, Allison S. Pre-pubertal paediatric bipolar disorder: a controversy from America. Australas Psychiatry. 2008;16(2):80-84.
10. Samuel RZ. Letters to the editor. Side effects of atypical antipsychotics in children and adolescents. Primary Psychiatry. 2005:12(10):14-15.
Response
To the Editor:
I agree with many if not most of the main points brought up by Roger Z. Samuel, MD, FAPA. The field clearly needs more education regarding the diagnosis of bipolar disorder in children and adolescents. In my clinical practice, I provide consultations on children who have presumable bipolar diagnoses, from the Bay Area in California, and beyond. Many of these children have been diagnosed with bipolar disorder (rarely classified further as I, II, or not otherwise specified [NOS]) in the community. Approximately 50% of those children I re-diagnose with another condition that better explains their symptoms (such as explosive irritability). Frequently, these diagnoses are depression (either major depressive episode, dysthymia, or depression NOS), anxiety (usually generalized anxiety disorder, or NOS), or pervasive developmental disorder (PDD; usually NOS, or Aspergers). That is, irritability is clearly a common presenting problem of children in general, and most children with irritability do not have bipolar disorder. However, the other 50% I do diagnose with a form of bipolar disorder. At Stanford, we have adopted criteria for bipolar disorder NOS, similar to that used by researchers at the University of Pittsburgh for their Course and Outcome of Bipolar Youth study.1 Thirty-eight percent of these children have been found to progress to bipolar I or II disorder within 4 years.2
However, it is easy to dismiss bipolar disorder as a “rare” disorder in children. It is not rare. However, the exact prevalence of bipolar spectrum disorders in children and adolescents is indeed unclear. One study of high schoolers in Oregon found the incidence of bipolar spectrum disorders to be .99%. Of the 18 adolescents with bipolar disorder, two had bipolar I disorder, 11 bipolar II disorder, and five cyclothymia.3 Ninety-seven were found to have a distinct period of elevated, expansive, or irritable mood, without meeting full criteria for a bipolar spectrum disorder. However, whereas a reliable semi-structured interview was used to interview adolescents, parents themselves were not interviewed. Furthermore, only adolescents in the regular public high school were assessed. Adolescents in alternate education programs (home school, special education schools, etc) were not included, which may have significantly skewed the sample away from including children with bipolar disorder, as many of them would likely have been in these alternate education placements.
A Midwest study4 indicated rates of <2% in the general population. One could also extrapolate from epidemiologic studies in adults to estimate the prevalence of bipolar disorder in children. The 2001–2003 National Comorbidity Survey Replication study5 found a prevalence of bipolar I or II disorder in the United States to be 4%. Studies6,7 assessing age of onset of bipolar disorder retrospectively in adults with bipolar disorder in the US have shown that between 15% and 28% had their onset before 13 years of age, and between 50% and 66% before 19 years of age. Thus, the prevalence of bipolar disorder (or early forms of bipolar disorder) in children <13 years of age could be as high as 1% and in children <19 years of age is 2% to 3%. Therefore, 420,000–2,072,000 US children alone could suffer from bipolar I or II disorder.8
Regarding Dr. Samuel’s concerns for my dismissal of the pharmaceutical industry’s role of increasing the diagnosis of bipolar disorder in children, I wish to clarify that I did not say it was complete lunacy, rather I stopped short of that and wrote that “Without just flat out saying that is complete lunacy... I think it is a little bit of an incorrect kind of accusation.”9 It is possible that industry-sponsored dinners, in which the diagnosis of bipolar disorder in children were discussed, may have led to community practitioners being more aware of this diagnosis in children and then feeling more comfortable to use this “label,” even in children who did not meet the criteria. There is no real way of knowing the level of impact these dinners may have had. However, to me, these practitioners would have gotten the information from any number of other sources, as they would for any condition, and would be free to distort or misinterpret the information regardless. Children with explosive irritability, who may or may not have bipolar disorder, are nonetheless very ill, and their doctors and parents are searching for solutions. Very often they are prescribed antipsychotics or mood stabilizers, whether they are diagnosed with bipolar disorder or not, often in desperation. The recent proposal from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition,10 committee to include “Temper Dysregulation Disorder with Dysphoria”11 in the DSM-5 came from a desire to better categorize these types of children and take away their bipolar diagnoses. However, this may be another misguided attempt to solve the situation by creating another category, this one not studied at all, in which children will be lumped into and probably treated with the same psychotropic medications anyway. What we need are better studies parsing children with explosive and chronic irritability into different etiologies (eg, anxiety, depression, mood dysregulation, PDD, bipolar disorder) and examining response to varying treatments (including behavioral and psychosocial ones).
Regardless, Dr. Samuel does not present any actual data supporting his claim that industry is responsible for the growth in bipolar disorder diagnosis among youths. It is his opinion that this is the case, an opinion that is difficult to prove or refute given the absence of empirical data. However, my opinion is that the pharmaceutical industry influence on the rise of pediatric bipolar disorder diagnoses in the community has been small, and more a symptom of the problem than a cause. Such dinners, or other educational events, could be used to better educate practitioners regarding the subtleties of diagnosing bipolar disorder in children, leading to more accurate community-based diagnoses. However, as of 2010 in the US, there is little to no marketing of psychotropic medications to treat children <18 years of age with bipolar disorder. I believe this is due to fear of a media and public opinion backlash and fear of legal actions from consumer groups such as class action lawsuits. In this way, it is possible that children are actually losing out due to the pharmaceutical industry not supporting such dinners anymore.
I would also like to clarify some of the studies that Dr. Samuel references. Dr. Samuel states that “Other sources of data suggest that ~50% of youngsters diagnosed with bipolar disorder do not persist into adulthood with that diagnosis,” citing Ruggero and colleagues.12 This is an erroneous interpretation of the study, as the Ruggero and colleagues study consisted of subjects 15–60 years of age, who were diagnosed at some point over 10 years with bipolar disorder. Approximately half of all the subjects diagnosed at some point with bipolar disorder did not carry this diagnosis consistently. Examples included a college graduate with psychosis who was first diagnosed with bipolar disorder and then later felt to have schizophrenia, and a patient with ADHD and psychosis as a youth who was at some point diagnosed with bipolar disorder, but later felt to have schizoaffective disorder at follow-up. Clearly, these are important issues, but not relevant to Dr. Samuel’s assertion.
The Carlson and colleagues13 study cited by Dr. Samuel is not relevant either, as it simply supports the notion that many children are being diagnosed incorrectly with bipolar disorder in the community, and that when they are subject to more rigorous interviews in the hospital, many are re-diagnosed with a different condition. The other letters to the editors cited by Dr. Samuel also are not based on data, but simply continue to support this point. One letter14 is simply a review of the controversy in the US and briefly mentions that the media has had concerns of pharmaceutical company influence. There was not any stated link of pharma to three academic centers in the US. Regardless, many, but not all, academic researchers do have pharma ties—this in itself does not mean that pharma is responsible for the increase in pediatric bipolar disorder diagnoses!
I am not an apologist for pharmaceutical companies, although I do work with a few. I find it mostly a good situation, in which companies can benefit from the expertise of academic researchers to better design their studies and conduct studies they otherwise would not be required to do by the Food and Drug Administration. However, I do believe that the industry’s effect on psychiatry has been strong and not always positive. It is just my opinion that the current overdiagnosis of pediatric bipolar disorder in the US is not largely due to pharma’s influence—that is simply my opinion, and in the absence of any evidence to the contrary it appears reasonable to me that other forces have been at work to lead to this point. The answer is not blaming pharma, but educating community physicians better and supporting more research in the field to discover biological markers that will ultimately aid in better diagnosis and parsing this disorder to more meaningful subtypes.
Overall, Dr Samuel and I appear to agree that careful diagnosis is required to separate out children with bipolar disorder from children with other disorders, such as ADHD, anxiety, and depression. Better education to community practitioners may aid in this cause, but ultimately, better methods of diagnosis, using biological markers such as genetics or brain imaging, may eventually be brought from the research bench to clinical practice.
In the midst of this discussion, please let us not forget that there are real children out there with real bipolar disorder who are suffering and require thoughtful treatment to prevent lifelong morbidity and early mortality.
Sincerely,
Kiki Chang, MD
Dr. Chang is associate professor of Psychiatry and Behavioral Sciences in the Division of Child Psychiatry at the Stanford University School of Medicine in California.
Disclosures: Dr. Chang is consultant to Bristol-Myers Squibb, Eli Lilly, and GlaxoSmithKline; is on the speaker’s bureau Merck; and receives research support from GlaxoSmithKline, the National Alliance for Research on Schizophrenia and Depression, and the National Institute of Mental Health.
References
1. Axelson D, Birmaher B, Strober M, et al. Phenomenology of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006;63(10):1139-1148.
2. Birmaher B, Axelson D, Goldstein B, et al. Four-year longitudinal course of children and adolescents with bipolar spectrum disorders: the Course and Outcome of Bipolar Youth (COBY) study. Am J Psychiatry. 2009;166(7):795-804.
3. Lewinsohn PM, Klein DN, Seeley JR. Bipolar disorder during adolescence and young adulthood in a community sample. Bipolar Disord. 2000;2(3 pt 2):281-293.
4. Carlson GA, Kashani JH. Manic symptoms in a non-referred adolescent population. J Affect Disord. 1988;15(3):219-226.
5. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):593-602.
6. Leverich GS, Post RM, Keck PE Jr, et al. The poor prognosis of childhood-onset bipolar disorder. J Pediatr. 2007;150(5):485-490.
7. Perlis RH, Miyahara S, Marangell LB, et al. Long-term implications of early onset in bipolar disorder: data from the first 1000 participants in the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry. 2004;55(9):875-881.
8. Post RM, Kowatch RA. The health care crisis of childhood-onset bipolar illness: some recommendations for its amelioration. J Clin Psychiatry. 2006;67(1):115-125.
9. Chang K, Sussman N. In session with Kiki Chang, MD: bipolar disorder in children and adolescents. Primary Psychiatry. 2010;17(4):23-26.
10. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association. In press.
11. American Psychiatric Association. DSM-5 Development. Temper Dysregulation Disorder with Dysphoria. Available at: www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=397. Accessed August 10, 2010.
12. Ruggero CJ, Carlson GA, Kotov R, Bromet EJ. Ten-year diagnostic consistency of bipolar disorder in first-admission sample. Bipolar Disord. 2010;12(1):21-31.
13. Carlson GA, Potegal M, Margulies D, Gutkovich Z, Basile J. Rages – What are they and who has them? J Child Adolesc Psychopharmacol. 2009;19(3):281-288.
14. Parry P, Allison S. Pre-pubertal paediatric bipolar disorder: a controversy from America. Australas Psychiatry. 2008;16(2):80-84.
Please send letters to the editor to Primary Psychiatry, c/o Norman Sussman, MD, 333 Hudson St., 7th Floor, New York, NY 10013; via the Web: http://mc.manuscriptcentral.com/primarypsy.
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