Let me start by explaining that the creation of TDD does NOT deny the existence of classic bipolar disorder in childhood. That is, although extremely rare, bipolar disorder can occur in children and adolescents, and it looks very much like adult bipolar.  Instead, TDD was created to capture a valid syndrome with characteristics and outcomes that are different than those of bipolar disorder. The available scientific data supports the position that the TDD syndrome is NOT simply the manifestation of bipolar disorder in childhood. This means that thousands of children that have been diagnosed with childhood bipolar disorder may not have bipolar and instead have a completely different syndrome now called Temper Dysregulation Disorder with Dysphoria.

So what is TDD?

Here is the proposed criteria for TDD:

A. The disorder is characterized by severe recurrent temper outbursts in response to common stressors.

1.  The temper outbursts are manifest verbally and/or behaviorally, such as in the form of verbal rages, or physical aggression towards people or property.

2.  The reaction is grossly out of proportion in intensity or duration to the situation or provocation.

3.  The responses are inconsistent with developmental level.

B. Frequency: The temper outbursts occur, on average, three or more times per week.

C. Mood between temper outbursts:

1.  Nearly every day, the mood between temper outbursts is persistently negative (irritable, angry, and/or sad).

2.  The negative mood is observable by others (e.g., parents, teachers, peers).

D. Duration: Criteria A-C have been present for at least 12 months.  Throughout that time, the person has never been without the symptoms of Criteria A-C for more than 3 months at a time.

E. The temper outbursts and/or negative mood are present in at least two settings (at home, at school, or with peers) and must be severe in at least in one setting.

F.  Chronological age is at least 6 years (or equivalent developmental level).

G. The onset is before age 10 years.

H. In the past year, there has never been a distinct period lasting more than one day during which abnormally elevated or expansive mood was present most of the day for most days, and the abnormally elevated or expansive mood was accompanied by the onset, or worsening, of three of the “B” criteria of mania (i.e., grandiosity or inflated self esteem, decreased need for sleep, pressured speech, flight of ideas, distractibility, increase in goal directed activity, or excessive involvement in activities with a high potential for painful consequences; see pp. XX). Abnormally elevated mood should be differentiated from developmentally appropriate mood elevation, such as occurs in the context of a highly positive event or its anticipation.

I.  The behaviors do not occur exclusively during the course of a Psychotic or Mood Disorder (e.g., Major Depressive Disorder, Dysthymic Disorder, Bipolar Disorder) and are not better accounted for by another mental disorder (e.g., Pervasive Developmental Disorder, post-traumatic stress disorder, separation anxiety disorder). (Note: This diagnosis can co-exist with Oppositional Defiant Disorder, ADHD, Conduct Disorder, and Substance Use Disorders.) The symptoms are not due to the direct physiological effects of a drug of abuse, or to a general medical or neurological condition.

The syndrome captured by section A-C (frequent and intense temper outbursts, happening several times per week in the context of negative emotionality) is the core of the symptoms that has been incorrectly interpreted as indicative of childhood bipolar disorder.  Section H is very interesting. It states that this diagnosis is not appropriate if the person has experienced classic mania (e.g., bnormally elevated or expansive mood), as in such a case the diagnosis of bipolar is likely more accurate.

So why did the DSM-V decide that this syndrome is not simply bipolar disorder of childhood?

1. Lack of continuity to bipolar.

If TDD is simply the expression of bipolar disorder during childhood, then children diagnosed with this condition would eventually develop symptoms of classic bipolar disorder as they reach adulthood. The data do not support this hypothesis. That is, children who display the TDD syndrome in childhood (and are often incorrectly diagnosed as bipolar) are not more likely to develop classic bipolar disorder later in life as their peers (see Brotman et al., 2006; Leibenluft et al, 2006; Stringaris et al, 2009).  Instead, these children are more likely to develop depression, not bipolar!

2. Different Biological Markets.

Youth who are diagnosed with classic bipolar differ significantly from those who have a TDD-like syndrome (see Brotman et al, 2010; Guyer et al, 2007; Rich et al, 2008).  If TDD is simply bipolar, then the biomarkers of TDD should be similar to those of bipolar, but this is not the case.

3. Different Demographic Factors.

If TDD is simply bipolar, then the gender distribution of TDD should be similar to that of bipolar. This does not appear to be the case. Specifically, there is no gender differences in the rate of classic bipolar; male and females are equally likely to develop the condition. However, the TDD-like syndrome is disproportionately observed in boys rather than girls.

4. A need for a new category that would impact treatment and research.

In theory, the presence of TDD will educate clinicians, researchers, and the public that this syndrome is not simply a version of bipolar disorder. This would facilitate research on the causes, features, and treatments for this condition. This has major implications for treatment. For example, the standard treatment for bipolar disorder does NOT seem to work in children that have the TDD syndrome (Dickstein et al, 2009). By explicitly stating that TDD is not bipolar, researchers would be less likely to approach the search for treatments from a “bipolar framework”, which would potentially facilitate the discovery of more effective interventions.

I am actually glad about this change as it will have a clear impact on clinical practice and research that will most likely benefit the children affected with this condition.

References:

Brotman MA, Schmajuk M, Rich BA, Dickstein DP, Guyer AE, Costello EJ, Egger HL, Angold A, Pine DS, & Leibenluft E (2006). Prevalence, clinical correlates, and longitudinal course of severe mood dysregulation in children. Biological psychiatry, 60 (9), 991-7 PMID: 17056393

Dickstein DP, Towbin KE, Van Der Veen JW, Rich BA, Brotman MA, Knopf L, Onelio L, Pine DS, Leibenluft E (2009): Randomized double-blind placebo-controlled trial of lithium in youth with severe mood dysregulation. J Child Adolesc Psychopharm 19: 61-73

Guyer AE, McClure EB, Adler AD, Brotman MA, Rich BA, Kimes AS, Pine DS, Ernst M, Leibenluft E (2007): Specificity of face emotion labeling deficits in childhood psychopathology. Journal of Child Psychiatry and Psychology, 48:863-71

Leibenluft E, Charney DS, Towbin KE, Bhangoo RK, Pine DS (2003): Defining clinical phenotypes of juvenile mania. Am J Psychiatry 160: 430-437

Rich BA, Grimley ME, Schmajuk M, Blair KS, Blair RJR, Leibenluft E (2008): Face emotion labeling deficits in children with bipolar disorder and severe mood dysregulation. Development and Psychopathology 20: 529-546

Stringaris A, Cohen P, Pine DS, Leibenluft E (2009): Adult outcomes of adolescent irritabilty: A 20-year community follow-up. Am J Psychiatry 166: 1048-54

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New placebo-controlled clinical study examines the effectiveness of Divalproex Extended Release for the treatment of childhood-onset bipolar disorder.

A review of: Wagner, Karen, Redden, Laura, Kowatch, Robert, Wilens, Timothy, Segal, Scott, Chang, Kiki, Wozniak, Patricia, Vigna, Namita, Abi-Saab, Walid, & Saltarelli, Mario (2009). A Double-Blind, Randomized, Placebo-Controlled Trial of Divalproex Extended-Release in the Treatment of Bipolar Disorder in Children and Adolescents. Journal of the American Academy of Child & Adolescent Psychiatry DOI: 10.1097/CHI.0b013e31819c55ec NOTE: the DOI provided by the JACCAP can not be found by DOI.org.

In an upcoming issue of the Journal of the American Academy of Child and
Adolescent Psychiatry Dr. Karen Dinnen Wagner from the Department of Psychiatry at University of Texas and her colleagues report the findings of a randomized, placebo-controlled study of the effectiveness and safety of Divalproex Extended Release for the treatment of bipolar disorder in children and adolescents.

Although there are a number of differences between adult and child bi-polar disorder, and the dramatic increases in diagnoses of bipolar disorder in children is a highly controversial and debated topic, in general terms children with bipolar disorder show frequent and rapid changes between periods of depression and periods of mania. The periods of depression and mania are usually very severe, so that the diagnosis of bipolar does not apply to simply “very moody” or irritable kids. True childhood-onset bipolar disorder is a very serious condition that, if untreated, is associated with several negative outcomes including high risk of suicidal behaviors.

Currently, Divalproex is often used “off-label” (without FDA approval) for the treatment of bipolar in children. This practice reflects findings from a few ‘open label’ studies (studies in which the patients know that they are taking the medication and often no placebo group is included). Unfortunately, open label studies do not tell us whether the observed positive effects of the drug is truly due to the drug or to the expectation that the drug will work (“the placebo effect”). Therefore, to properly assess for the effectiveness of this drug in children and adolescents, the authors randomly assigned 151 children with bipolar (age 11 to 17) disorder to receive Divalproex or to receive a placebo (e.g., a sugar pill). The patients did not know whether they were taking the placebo or the actual drug.

The authors found that after 28 days, the effect of Divalproex was not different than the effect of the placebo drug. Both treatments resulted in equal reductions of symptoms.

There was also a modest reduction of symptoms after 6 months, but this did not include the placebo drug. Therefore, given the findings of the 28-day trial, the reduction in symptoms observed at after six months is likely due to the placebo effect and not to the drug. The authors conclude:

This is the first report of a multicenter double-blind, randomized, placebo-controlled trial of divalproex ER in the treatment of bipolar I disorder, mixed or manic, in children and adolescents (aged 10Y17 years). There was no statistically significant difference between the divalproex ERYtreated patients and the placebo-treated patients on the primary efficacy measure or secondary measures. At the present time, based on the results of this study, there is not evidence to support the use of divalproex ER in the treatment of youths with bipolar I disorder, manic or mixed state. Because this is the only reported double-blind placebo-controlled trial of divalproex ER in youths with bipolar disorder, it would be reasonable to conduct another controlled trial to confirm or refute the findings from this study.

Please do not make any changes to your child’s medication regime without consulting with your health care provider.

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