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Director’s Update
September 3, 2007

NIMH Perspective on Diagnosing and Treating Bipolar Disorder in Children

A recently published research paper (September 2007, Archives of General Psychiatry) reported a 40-fold increase in the rate of diagnosing bipolar disorder in youth over the past decade. This paper raises several important questions:

It is unclear exactly what is causing this increase, but current evidence suggests a combination of each of these and possibly other factors. The following is intended to discuss the paper's findings within the broader context of what we know about the diagnosis and treatment of bipolar disorder in children and adolescents.

It is important to note that the paper's findings were based on data from a survey conducted annually by the National Center for Health Statistics. The survey comprises a one-page form that asks a nationally representative sample of private practice doctors to describe certain characteristics of each patient visit, including children and adults, over a one-week period. Neither the survey nor the paper provides information regarding:

The survey recorded the number of office visits instead of the number of individual patients, so some people may have been counted more than once. Because the survey was conducted only over one week, it was not possible to study the length and progress of treatment. In addition, information on the doses of some medications was not available. Finally, while a 40-fold increase seems large, the base rate (25 bipolar diagnoses per 100,000 people) suggests that the diagnosis was rarely used in 1994-1995. The recent rate of 1,003 bipolar diagnoses per 100,000 people is indeed much higher than the 1994-1995 rate, but still well below the rate of bipolar disorder for adults (1,679 bipolar diagnoses per 100,000 people).

How do physicians currently diagnose bipolar disorder in children? The current edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) lists criteria to define bipolar disorder in children. These criteria are based on how the disorder typically appears in adults and have not changed over the past decade.1 Research indicates that there are children whose symptoms clearly meet these criteria, as well as a much larger group of children who show some but not all symptoms. It is in this latter group, who frequently show excessive irritability and impulsivity, where there is disagreement as to whether these are symptoms of bipolar disorder or of a broader spectrum of mood disturbances. Such mood disturbances may have been diagnosed differently or may not have come to a physician's attention a decade ago.

Co-occurring disorders can also make diagnosis more difficult. As many as 60 percent of children diagnosed with bipolar disorder in most studies also have attention deficit hyperactivity disorder (ADHD),2,3 raising questions about whether the current diagnostic criteria are specific enough to distinguish symptoms of bipolar disorder from symptoms of other related illnesses in children.

Recent research has demonstrated that many adult mental disorders begin in childhood. The NIMH-funded Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) trial found that about 65 percent of adults with bipolar disorder describe the onset of symptoms before age 19,4 suggesting that the disorder may have been insufficiently recognized in the past. It is not yet clear, however, that all of the children currently diagnosed with bipolar disorder will grow up to be adults with bipolar disorder.

A current NIMH supported study is following a group of children and adolescents diagnosed with bipolar disorder to determine the course of their symptoms over time. In this and other research studies for which having bipolar disorder is a requirement, only a small fraction of children referred for participation actually meet criteria for the disorder. It seems likely therefore, that many of the children and adolescents in the community diagnosed as having bipolar disorder do not have the same illness as adults with bipolar disorder. In this sense, the diagnosis may be over-used or mis-used in children. This is not to say that these children and their families are not in distress. While these children may not all have bipolar disorder, it appears that physicians are reporting a true increase in the number of children and adolescents presenting with severe behavioral problems, including irritability, aggression, and erratic moods.

NIMH is committed to the development of biological tests that can help validate the diagnosis of bipolar disorder in children. Recent research advances showed that electroencephalograms (EEGs) and magnetic resonance imaging (MRI) studies of the brain can reveal differences between bipolar disorder and related behavioral syndromes which cause some of the same symptoms in children as bipolar disorder causes. In addition, recent studies have identified novel candidate genes that may increase risk for adults with bipolar disorder.5,6 NIMH researchers also recently found that parents of children diagnosed with bipolar disorder appear more likely to themselves have bipolar disorder, compared with the parents of children with severe irritability but without the classic mood episodes of bipolar disorder. This suggests that genetics should ultimately prove helpful for validating bipolar diagnoses in children.

Whatever the issues are in diagnosis, the Archives paper also described widespread prescribing of medications not FDA-approved for children diagnosed with bipolar disorder. Currently, there are no antidepressants approved by the FDA for treating bipolar disorder in children and adolescents, and only one approved atypical antipsychotic, risperidone (Risperdal).

More research is needed to determine the safety and effectiveness of the many medications currently used to treat bipolar disorder in youth, as well as to identify other types of appropriate treatment. Several NIMH-funded clinical trials seek to accomplish this goal, including the Treatment of Early Age Mania study, involving children (ages 6-15) who have mania, which is comparing the effectiveness of three medications commonly used to treat bipolar disorder in adults. An additional study is focusing on teens (ages 13-17) diagnosed with bipolar disorder to examine the effectiveness of family-focused therapy (FFT) in conjunction with medication treatment. Another promising area of study lies in the ongoing trials of early diagnosis and interventions for children at risk for developing bipolar disorder because of a strong family history.

The apparent inaccurate use of the bipolar diagnosis and questions about the safety and effectiveness of medications being prescribed to young children raise real concerns. These concerns need to be balanced by recognizing that psychiatric illnesses can cause disabling and sometimes dangerous symptoms during a critical period of physical and cognitive development, with many potential long-term effects for a child's future. Parents and physicians concerned about the risk of treatment need to consider the risks of not treating children who may have impulsive behaviors that can threaten themselves or others and make it difficult or impossible for the child to function well at home, at school or with peers. Children currently in treatment should not discontinue medication without consulting a physician.

Information on current trends in mental health care can help to highlight specific areas for further research and to assess ongoing efforts. Clearly, more studies are needed to determine the best ways to define, diagnose, treat, and perhaps someday even prevent, the range of mood disorders that affect children and adolescents. By supporting a broad range of rigorous research in this area, NIMH seeks to ensure that concerns about under-diagnosis or over-diagnosis can be resolved with valid diagnostic methods and safe, effective treatments.

Press Release: Rates of Bipolar Diagnosis in Youth Rapidly Climbing, Treatment Patterns Similar to Adults

References

1 McClellan J, Kowatch R, Findling RL. Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2007 Jan;46(1):107-25.

2 Scheffer RE, Kowatch RA, Carmody T, Rush AJ. Randomized, Placebo-Controlled Trial of Mixed Amphetamine Salts for Symptoms of Comorbid ADHD in Pediatric Bipolar Disorder After Mood Stabilization With Divalproex Sodium. Am J Psychiatry. 2005 Jan;162(1):58-64.

3 Dickstein DP, Nelson EE, McClure EB, Grimley ME, Knopf L, Brotman MA, Rich BA, Pine DS, Leibenluft E. Cognitive flexibility in phenotypes of pediatric bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2007 Mar;46(3):341-55.

4 Perlis RH, Miyahara S, Marangell LB, Wisniewski SR, Ostacher M, DelBello MP, Bowden CL, Sachs GS, Nierenberg AA; STEP-BD Investigators. 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 May 1;55(9):875-81.

5 Baum AE, Akula N, Cabanero M, Cardona I, Corona W, Klemens B, Schulze TG, Cichon S, Rietschel M, Nothen MM, Georgi A, Schumacher J, Schwarz M, Abou Jamra R, Hofels S, Propping P, Satagopan J, Detera-Wadleigh SD, Hardy J, McMahon FJ. A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry. 2007 May 8; [Epub ahead of print] *Click to see NIMH press release*

6 Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007 Jun 7;447(7145):661-78.