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Recognition and Treatment of Pediatric Bipolar Disorder

Diagnosis, Phenomenology, Differential Diagnosis, and Comorbidity of Pediatric Bipolar Disorder

Diagnosis, Phenomenology, Differential Diagnosis, and Comorbidity of Pediatric Bipolar Disorder

Diagnosing a pediatric patient with bipolar disorder can pose a challenge for clinicians. Children typically do not present with the full criteria for a mood episode and may have symptoms of other disorders such as attention-deficit/hyperactivity disorder, oppositional defiant disorder, anxiety disorders, and other mood disorders, which may complicate the diagnostic process. By diligently interviewing parents and children about behaviors, thoroughly reviewing family histories, and systematically ruling out other disorders, clinicians can provide an accurate diagnosis for their pediatric patients.

(J Clin Psychiatry 2016;77[suppl E1]:e01)

From the Departments of Sleep Medicine and Child Psychiatry, Nationwide Children’s Hospital, The Ohio State University, Columbus.

This article is derived from the planning teleconference series "Recognition and Treatment of Pediatric Bipolar Disorder," which was held in August and September 2015 and supported by an educational grant from Forest Laboratories, Inc.

Dr Kowatch is a consultant for Forest and is a member of the speakers/advisory board for the REACH Institute.

Corresponding author: Robert A. Kowatch, MD, PhD, 700 Children’s Dr, Center for Innovation in Pediatric Practice, J West 4th Floor, Room G4-4921, Columbus, OH 43025 (Robert.kowatch@nationwidechildrens.org).

dx.doi.org/10.4088/JCP.15017su1c.01

© Copyright 2016 Physicians Postgraduate Press, Inc.

Bipolar disorder is a serious mental disorder that affects not only adults but also children. The National Comorbidity Survey Replication in adults estimated a 2.1% lifetime prevalence of threshold bipolar disorders and a 2.4% rate for subthreshold bipolar disorders.1 In adolescents (aged 13-17 years), the lifetime prevalence rates were 2.3% for threshold bipolar disorders and, depending on the scale used, 4.3% or 3.9% for subthreshold bipolar disorders.2 A meta-analysis of 12 studies that enrolled 16,222 youths aged 7 to 21 years found a 1.8% mean prevalence (point to lifetime) rate for threshold pediatric bipolar spectrum disorders, or 2.7% when only participants aged 12 years or older were included.3

Goodwin and Jamison4 noted that the majority of patients in studies from 1990 to 2006 reported onset of bipolar symptoms between the ages of 15 and 19 years.4 The next most common ages at onset were 10 to 14 years and 20 to 24 years.4 Because symptom onset can occur fairly early, clinicians treating children and adolescents should be familiar with the diagnostic criteria and phenomenology, other disorders to rule out in the differential diagnosis, and frequently comorbid conditions.

DIAGNOSIS

Diagnostic Criteria for Bipolar Disorders

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lists the following 7 diagnoses under the "Bipolar and Related Disorders" category, of which the first 4 will be discussed in this article: bipolar I disorder, bipolar II disorder, cyclothymic disorder, other specified bipolar and related disorder, substance/medication-induced bipolar and related disorder, bipolar and related disorder due to another medical condition, and unspecified bipolar and related disorder.5 The new edition of diagnostic criteria separated the bipolar disorders from the depressive disorders, and a lifetime major depressive episode is not a requirement for the bipolar I diagnosis (AV 1).5

Click figure to play

Bipolar I disorder. Bipolar I disorder is categorized by a manic episode that lasts at least 1 week, with symptoms of elevated or irritable mood or increased energy lasting most of the day. In addition, 3 or more of the following symptoms should be present and must represent a change in the patient’s usual behavior: grandiosity, decreased need for sleep, increased talkativeness, racing thoughts, distractibility, increased goal-oriented activity or psychomotor agitation, and risky behavior.5 Manic symptoms must cause marked impairment.

In my clinical experience, many parents will say their children are always moody and irritable. What I have found to be useful is to ask if there are periods of time when the children are euthymic and other periods of time (3 or 4 days) when their mood is heightened, they need less sleep, they have more projects going on, and they have inappropriate sexual behavior. I have found it unusual to see symptoms that meet criteria for a manic episode in prepubertal children; this level of symptomatology seems more likely to occur in mid-adolescence.

clinical points

  • Pediatric patients may not present with adequate symptoms to meet criteria for a bipolar I or II episode, and they may cycle through mood swings quickly.
  • Consider prevalent disorders such as anxiety disorders and ADHD in the differential diagnosis, but look for periods of mania or hypomania.
  • Screening tools, such as the Child Mania Rating Scale, can aid the diagnostic process.
  • Carefully evaluate the temporal course of symptoms to avoid a misdiagnosis of ADHD, ODD, or another disorder.

In the bipolar I disorder criteria, the manic episode may be preceded or followed by a hypomanic or major depressive episode. The DSM-5 defines hypomania as manic symptoms that last most of the time for 4 or more days (not 7 days, as with mania) and that cause a change in functioning that is recognizable to others (not marked impairment, as with mania).5 Children who are experiencing a manic episode may not be able to function properly in school or with their peers and may be on the verge of needing hospitalization. But, if children are experiencing a hypomanic episode, their parent or caregiver may notice a change in behavior (eg, not sleeping as much, acting giddy and silly, having more energy than normal).

For adolescent patients, a presentation that I often observe is a severe depressive episode followed by a manic episode, either immediately or months to years later. These patients may present with a recent onset depressive episode, sometimes with psychotic features, melancholic features, or very severe depression, and then cycle into a full manic episode.

Bipolar II disorder. Like bipolar I disorder, bipolar II disorder is classified the same way in adults and in children. The diagnosis requires 1 or more hypomanic episodes and 1 or more major depressive episodes.5 Patients must not have experienced a manic episode. For patients to be diagnosed with bipolar II disorder, they must have a major depressive episode that lasts at least 2 weeks and a hypomanic episode that lasts at least 4 days.5

Cyclothymic disorder. Cyclothymia is a disorder that is categorized by a chronic, fluctuating mood disturbance that lasts for a distinct period of time. Patients must have exhibited symptoms of hypomania and symptoms of depression that have never met the full criteria for a hypomanic, manic, or major depressive episode.5 Adults must have had these symptoms for 2 years, and pediatric patients for 1 year, and patients cannot have been without symptoms for more than 2 months.5

Other specified bipolar and related disorder. Formerly known as bipolar not otherwise specified in the previous DSM, the diagnosis of other specified bipolar and related disorder is given to pediatric patients who have bipolar symptoms that do not meet the full criteria for any of the disorders in the bipolar class but that cause distress or impairment.5 These symptoms can last 2 to 3 days each week.

With diagnoses of bipolar disorder, clinicians may also add specifiers for specific symptoms (eg, with mood-congruent or mood-incongruent psychotic features, with anxious distress, with mixed features, with rapid cycling).

Phenomenology

The pediatric literature contains estimates that children with bipolar disorder may have thousands of mood swings (or cycles) per year.6 A key distinction to make when considering mood swings in pediatric bipolar disorder is between cycles and episodes. A cycle is defined as "a pronounced shift in mood and energy from one extreme to another," while an episode is "an extended period of mood dysregulation often encompassing multiple cycles in polarity."6(p5) The term cycling as used with pediatric patients should not be confused with the term rapid cycling, which in the DSM is defined as the occurrence of 4 or more mood episodes in 1 year.5 Children and adolescents may have an almost daily mood cycle that is out of context for the child’s environment and not precipitated by any external trigger. For many pediatric patients in my practice, parents have described a cycle in which children wake up in a giddy or silly mood for no reason and have pressured speech, which is followed by a normal day at school. They then have a depressed or irritable mood once they return home, again with no reason. This phenomenology does not mean that the patients have rapid cycling bipolar disorder, because the number of distinct episodes remains small. While both children and adolescents may have daily mood cycling, mood episodes (extended periods of mood dysregulation) typically do not become evident until adolescence.

A recent meta-analysis of studies of pediatric bipolar disorder found heterogeneous presentations.7 However, the following symptoms were found in more than 70% of study participants: increased energy, irritability, mood lability, distractibility, and goal-directed activity (AV 2).7

The Course and Outcome of Bipolar Youth (COBY) study8 investigated the course of bipolar I, bipolar II, and other specified bipolar and related disorders over 4 years in 413 youths aged 7 to 17 years. This study showed that pediatric patients had symptoms 60% of the time, exhibiting numerous mood cycles and more subsyndromal than syndromal symptoms.8 Additionally, they spent more time experiencing depressive symptoms than manic or hypomanic symptoms.8

Click figure to play

Often, children under 13 years will be diagnosed with other specified bipolar and related disorder due to the lack of symptoms meeting criteria for an episode.9 These younger patients will also commonly exhibit irritability, mood lability, and a worse course of illness than patients with a later onset.8,10

Meanwhile, adolescents (compared with children) more often have symptomatology that meets bipolar I or II disorder criteria, with episodes of depression or typical manic episodes (with elation and grandiosity), as well as substance abuse and suicide attempts.9-11

Red Flag Symptoms and Features

Several signs should prompt clinicians to look for bipolar disorder in pediatric patients. One of the most common "red flag" symptoms is rage and aggression. A potential bipolar disorder should be considered if the child displays aggression several times a day for hours at a time with seemingly little provocation, leaving the parents "walking on eggshells." Many parents of these children fear a public outburst of anger because their children can become uncontrollable. Children who do not have bipolar disorder will typically display aggression for short periods of time when being told "no." Many children with bipolar disorder also display a decreased need for sleep due to a manic or hypomanic episode, which can last for several days. Meanwhile, children with other psychiatric and medical diagnoses may experience insomnia due to anxiety and will act tired and sluggish as a result.

Decreased need for sleep is also a common "red flag" symptom to be aware of. Children with bipolar disorder will have an episodic reduced need for sleep, while children with attention-deficit/hyperactivity disorder (ADHD) may instead have insomnia.12

Spontaneous mood shifts may also help to suggest a bipolar diagnosis. Children without bipolar disorder may tend to be generally moody with their parents and siblings and fine around their peers, but they usually do not have mood swings out of context of their surroundings. Additionally, adolescent patients with bipolar disorder tend to have a higher level of grandiosity than their nonbipolar peers. For example, a teenager with bipolar disorder may say, "Despite the fact that I have a 1.0 grade point average, I am going to go to Harvard," which represents a disconnect from reality.

Pediatric patients who display certain high risk behaviors may also be exhibiting bipolar symptoms if their actions are not appropriate in the context that they occur. For example, patients who engage in isolated incidents such as "senior pranks" may not be bipolar, while patients who may have bipolar disorder will engage in disruptive incidents regularly.

A higher level of suspicion for a possible bipolar diagnosis should arise when patients have a family history of mood disorders, especially bipolar disorders.5 Birmaher et al13 found that 10.6% of children of parents with bipolar disorder had bipolar spectrum disorders, compared with 0.8% of those whose parents did not have bipolar disorder. Other risk factors for or features that suggest bipolar disorder include early-onset depression,14 psychotic features, and recurring episodes of depression.15

Screening Tools

A variety of screening tools are available for pediatric mania. However, while they are sensitive, many are not specific for the disorder and are not diagnostic. The Young Mania Rating Scale (YMRS)16 was designed primarily for adult inpatients and focuses on the severity of symptoms. Other screening tools are the Mood Disorder Questionnaire (MDQ),17 the Child Behavior Checklist (CBCL), and the Conners Third Edition Parent (Conners 3-P). Patients with conduct disorder or oppositional defiant disorder, not just those with bipolar disorder, may also have positive results on these scales.

The Child Mania Rating Scale (CMRS)18 is a rating scale that is completed by parents and is useful in screening children for mania. Pavuluri and colleagues18 determined that the scale showed excellent sensitivity and specificity in detecting mania versus ADHD or no disorder. A problem that can arise with the use of this scale is that parents may ignore the fact that it asks whether symptoms occur together at a certain period of time, so clinicians should use good clinical judgement when analyzing the results.

DIFFERENTIAL DIAGNOSIS

Many pediatric patients may exhibit bipolar symptoms, but few meet the diagnostic criteria. A chart review19 investigated the prevalence of bipolar disorder among 100 consecutive patients (mean age 8 years) with mood swings. Among these 100 patients, 12% met the criteria for bipolar I, bipolar II, or other specified bipolar and related disorders.19 Many patients (39%) were diagnosed with ADHD, while 15% were diagnosed with oppositional defiant disorder (ODD) and ADHD.19 Another 15% had anxiety disorders (usually generalized anxiety disorder), and a secondary mood disorder (often fetal alcohol spectrum disorder) was found in 10%.19

Attention-Deficit/Hyperactivity Disorder

Many clinicians mistake pediatric bipolar disorder for ADHD.19 The DSM-5 defines ADHD as "a persistent pattern of inattention and hyperactivity-impulsivity that interferes with functioning or development."5(p59) Children and adolescents diagnosed with ADHD are generally hyperactive and impulsive, which are also symptoms of bipolar disorder, making a correct diagnosis challenging. How can clinicians differentiate between the two?

A study by Geller and colleagues20 sought to find the differences that exist between patients with bipolar disorder and ADHD. In a sample of 120 youths (with mean ages of 11.0 years for the bipolar disorder group and 9.6 years for the ADHD group), they found that most manic symptoms were significantly more prevalent in patients with bipolar disorder than in those with ADHD. Features that were common to both groups—and therefore not useful in differentiating the disorders—were irritability, hyperactivity, accelerated speech, and distractibility.20

Clinicians should remember that one symptom alone does not define a bipolar diagnosis but rather a cluster of symptoms. Parents of children with ADHD typically report that since their children were young, they were impulsive and hyperactive, and these symptoms have not changed much, whereas a child with bipolar disorder will often display a change in mood and behavior when an episode occurs.12

Oppositional Defiant Disorder

In the DSM-5, ODD is defined as "a pattern of angry and irritable mood, argumentative and defiant behavior, or vindictiveness lasting at least 6 months."5(p462) Patients diagnosed with ODD typically exhibit aggressive behavior and often lose their temper and act defiantly toward authority. Unlike bipolar disorder, ODD is not categorized by cycles—it is a chronic disorder that is different from a mood disorder.

Patients with ODD do not exhibit the manic symptoms (eg, euphoria, grandiosity, decreased need for sleep, pressured speech) that patients with bipolarity will present with; however, some patients have both disorders. For children with bipolar disorder, clinicians should focus first on stabilizing mood in order to determine whether or not ODD is present during euthymic periods.

Anxiety Disorders

The National Comorbidity Study-Adolescent Supplement found that nearly one-third of US adolescents have an anxiety disorder.21 Anxiety disorders may cause mood swings and irritability, and some children experience increased anxiety at the beginning of the school year. Clinicians should focus on whether or not the patient is also exhibiting signs of manic behavior, as that will be a clear indicator of bipolarity.

Fetal Alcohol Syndrome (FAS)

Fetal alcohol syndrome (FAS) or neurobehavioral disorder associated with prenatal alcohol exposure can occur in children who were exposed to alcohol in utero.5,22 No biological markers exist for this diagnosis, but patients have permanent brain damage, stunted growth, and abnormal facial features such as a flat nasal bridge and short nose, a smooth philtrum, a thin upper lip, and a small chin. Clinically, FAS is easy to diagnose using the parental history and dysmorphic signs. However, other children may have another FAS spectrum disorder known as alcohol-related neurodevelopmental disorder. For these patients, the family history is unclear—perhaps the mother used drugs while pregnant or the clinician is not sure whether she drank alcohol—and they exhibit symptoms such as poor impulse control, deficits in school performance (especially mathematics), and mood dysregulation.22,23

COMORBID DISORDERS

Comorbidity is common in patients with bipolar disorder. As many as 60%-90% of pediatric patients with bipolar disorder have been described as having ADHD.24 Reported rates of ODD among patients with bipolar disorder range from 47% to 88%.24 Studies have also found higher rates of 1 or more anxiety disorders in children with bipolar disorder than in pediatric patients without bipolar disorder.24 Additionally, patients with pediatric bipolar disorder may be at increased risk of developing a substance use disorder, which may worsen psychiatric symptoms.24,25 A study by Wilens et al26 found that adolescents with bipolar disorder were nearly 5 times more likely to have a substance use disorder than the control participants (32% vs 7%).

Recognizing Manic Symptoms in Patients With Comorbidities

Distinguishing manic symptoms from symptoms of comorbid disorders can be a difficult challenge for many clinicians. However, inquiring about the temporal course of symptoms can be a solid first step. Clinicians should examine which came first, mood symptoms or behavior symptoms, and should ask what happens when children begin having mood cycles. Typically, behavioral symptoms worsen when a bipolar episode occurs.27 That is, an adolescent patient may have a history of ADHD or ODD, and the mood disorder exacerbates their previous symptoms. It is important for clinicians to decipher when and how the symptoms occur; if they occur only periodically, they are more likely to be caused by a bipolar episode than by another disorder.5 In my clinical experience, it can be helpful to treat the mood disorder and observe whether any symptoms remain that could be caused by a comorbid disorder.

CONCLUSION

While bipolar disorder is still a clinical diagnosis, several tools have been established to aid clinicians. The parent-rated CMRS is helpful but not diagnostic. Clinicians must be diligent in interviewing parents and children about episodes of mania, hypomania, and depression. Additionally, comorbid disorders must be considered during diagnosis as they may be causing some symptoms and exacerbating others. Family history and medical history are also useful.

Disclosure of off-label usage: Dr Kowatch has determined that, to the best of his knowledge, no investigational information about pharmaceutical agents that is outside US Food and Drug Administration–approved labeling has been presented in this activity.

REFERENCES

1.Merikangas KR, Akiskal HS, Angst J, et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry. 2007;64(5):543-552. PubMed doi:10.1001/archpsyc.64.5.543

2.Kessler RC, Avenevoli S, Green J, et al. National comorbidity survey replication adolescent supplement (NCS-A), III: concordance of DSM-IV/CIDI diagnoses with clinical reassessments. J Am Acad Child Adolesc Psychiatry. 2009;48(4):386-399. PubMed doi:10.1097/CHI.0b013e31819a1cbc

3.Van Meter AR, Moreira AL, Youngstrom EA. Meta-analysis of epidemiologic studies of pediatric bipolar disorder. J Clin Psychiatry. 2011;72(9):1250-1256. PubMed doi:10.4088/JCP.10m06290

4. Goodwin FK, Jamison KR. Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression. 2nd ed. Oxford University Press; 2007.

5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition. Washington, DC: American Psychiatric Publishing; 2013.

6. Youngstrom EA, Birmaher B, Findling RL. Pediatric bipolar disorder: validity, phenomenology, and recommendations for diagnosis. Bipolar Disord. 2008;10(1 pt 2):194-214. PubMed doi:10.1111/j.1399-5618.2007.00563.x

7. Van Meter AR, Burke C, Kowatch RA, et al. Ten-year updated meta-analysis of the clinical characteristics of pediatric mania and hypomania. Bipolar Disord. 2016;18(1):19-32. PubMed doi:10.1111/bdi.12358

8. 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. PubMed doi:10.1176/appi.ajp.2009.08101569

9. 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. PubMed doi:10.1001/archpsyc.63.10.1139

10. Hunt J, Birmaher B, Leonard H, et al. Irritability without elation in a large bipolar youth sample: frequency and clinical description. J Am Acad Child Adolesc Psychiatry. 2009;48(7):730-739. PubMed doi:10.1097/CHI.0b013e3181a565db

11. Goldstein TR, Birmaher B, Axelson D, et al. History of suicide attempts in pediatric bipolar disorder: factors associated with increased risk. Bipolar Disord. 2005;7(6):525-535. PubMed doi:10.1111/j.1399-5618.2005.00263.x

12. Singh MK, Ketter T, Chang KD. Distinguishing bipolar disorder from other psychiatric disorders in children. Curr Psychiatry Rep. 2014;16(12):516. PubMed doi:10.1007/s11920-014-0516-2

13. Birmaher B, Axelson D, Monk K, et al. Lifetime psychiatric disorders in school-aged offspring of parents with bipolar disorder: the Pittsburgh Bipolar Offspring study. Arch Gen Psychiatry. 2009;66(3):287-296. PubMed doi:10.1001/archgenpsychiatry.2008.546

14. Luby JL, Navsaria N. Pediatric bipolar disorder: evidence for prodromal states and early markers. J Child Psychol Psychiatry. 2010;51(4):459-471. PubMed doi:10.1111/j.1469-7610.2010.02210.x

15. Youngstrom EA, Jenkins MM, Jensen-Doss A, et al. Evidence-based assessment strategies for pediatric bipolar disorder. Isr J Psychiatry Relat Sci. 2012;49(1):15-27. PubMed

16. Young RC, Biggs JT, Ziegler VE, et al. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978;133(5):429-435. PubMed doi:10.1192/bjp.133.5.429

17. Hirschfeld RMA. The Mood Disorder Questionnaire: a simple, patient-rated screening instrument for bipolar disorder. Prim Care Companion J Clin Psychiatry. 2002;4(1):9-11. PubMed doi:10.4088/PCC.v04n0104

18. Pavuluri MN, Henry DB, Devineni B, et al. Child mania rating scale: development, reliability, and validity. Am Acad Child Adolesc Psychiatry. 2006;45(5):550-560. PubMed doi:10.1097/01.chi.0000205700.40700.50

19. Kowatch R, Monroe E, Delgado S. Not all mood swings are bipolar disorder. Curr Psychiatry. 2011;10(2):38-52.

20. Geller B, Williams M, Zimerman B, et al. Prepubertal and early adolescent bipolarity differentiate from ADHD by manic symptoms, grandiose delusions, ultra-rapid or ultradian cycling. J Affect Disord. 1998;51(2):81-91. PubMed doi:10.1016/S0165-0327(98)00175-X

21. Merikangas KR, He JP, Burstein M, et al. Lifetime prevalence of mental disorders in US adolescents: results from the National Comorbidity Survey Replication—Adolescent Supplement (NCS-A). Am Acad Child Adolesc Psychiatry. 2010;49(10):980-989. PubMed doi:10.1016/j.jaac.2010.05.017

22. Fetal Alcohol Spectrum Disorders (FASDs). CDC Web site. http://www.cdc.gov/ncbddd/fasd/diagnosis.html. Updated June 2014.

23. Recognizing Alcohol-Related Neurodevelopmental Disorder (ARND) in primary health care of children. Rockville, MD; 2011:1-25.

24. Joshi G, Wilens T. Comorbidity in pediatric bipolar disorder. Child Adolesc Psychiatr Clin N Am. 2009;18(2):291-319, vii-viii. PubMed doi:10.1016/j.chc.2008.12.005

25. Deas D. Adolescent substance abuse and psychiatric comorbidities. J Clin Psychiatry. 2006;67(suppl 7):18-23. PubMed doi:10.4088/JCP.0706e02

26. Wilens TE, Biederman J, Kwon A, et al. Risk of substance use disorders in adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2004;43(11):1380-1386. PubMed doi:10.1097/01.chi.0000140454.89323.99

27. Geller B, Warner K, Williams M, et al. Prepubertal and young adolescent bipolarity versus ADHD: assessment and validity using the WASH-U-KSADS, CBCL and TRF. J Affect Disord. 1998;51(2):93-100. PubMed doi:10.1016/S0165-0327(98)00176-1

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