Evidence-Based Reviews

Pediatric bipolar disorder: Mood swings, irritability are cues to this diagnosis

Current Psychiatry. 2003 March;2(3):40-48

References

1. Lewinsohn PM, Klein DN, Seeley JR. Bipolar disorders in a community sample of older adolescents: prevalence, phenomenology, comorbidity, and course. J Am Acad Child Adolesc Psychiatry 1995;34:454-63.

2. Nottelmann E. National Institute of Mental Health Research Roundtable on Prepubertal Bipolar Disorder. J Am Acad Child Adolesc Psychiatry 2001;40:871-8.

3. Wozniak J, Biederman J, Kiely K, et al. Mania-like symptoms suggestive of childhood-onset bipolar disorder in clinically referred children. J Am Acad Child Adolesc Psychiatry 1995;34(7):867-76.

4. Isaac G. Misdiagnosed bipolar disorder in adolescents in a special educational school and treatment program. J Clin Psychiatry 1992;53(4):133-6.

5. Lish JD, Dime-Meenan S, et al. The National Depressive and Manic-depressive Association (DMDA) survey of bipolar members. J Affect Disord 1994;31(4):281-94.

6. Egeland JA, Hostetter AM, Pauls DL, Sussex JN. Prodromal symptoms before onset of manic-depressive disorder suggested by first hospital admission histories. J Am Acad Child Adolesc Psychiatry 2000;39(Oct):1245-52.

7. Geller B, Sun K, Zimerman B, Luby J, Frazier J, Williams M. Complex and rapid-cycling in bipolar children and adolescents: a preliminary study. J Affect Disord 1995;34:259-68.

8. Geller B, Zimerman B, Williams M, et al. Diagnostic characteristics of 93 cases of a prepubertal and early adolescent bipolar disorder phenotype by gender, puberty and comorbid attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 2000;10:157-64.

9. Findling RL, Gracious BL, McNamara NK, et al. Rapid, continuous cycling and psychiatric co-morbidity in pediatric bipolar I disorder. Bipolar Disord 2001;3:202-10.

10. Wozniak J, Biederman J. Childhood mania: insights into diagnostic and treatment issues. J Assoc Acad Minor Phys 1997;8(4):78-84.

11. West SA, McElroy SL, Strakowski SM, et al. Attention-deficit/hyperactivity disorder in adolescent mania. Am J Psychiatry 1995;152(2):271-3.

12. Kovacs M, Pollock M. Bipolar disorder and comorbid conduct disorder in childhood and adolescence. J Am Acad Child Adolesc Psychiatry 1995;34(6):715-23.

13. Geller B, Cooper TB, Sun K, et al. Double-blind and placebo-controlled study of lithium for adolescent bipolar disorders with secondary substance dependency. J Am Acad Child Adolesc Psychiatry 1998;37(2):171-8.

14. Strober M, Schmidt-Lackner S, Freeman R, Bower S, Lampert C, DeAntonio M. Recovery and relapse in adolescents with bipolar affective illness: a five-year naturalistic, prospective follow-up. J Am Acad Child Adolesc Psychiatry 1995;34(6):724-31.

15. Geller B, Craney JL, Bolhofner K, Nickelsburg MJ, Williams M, Zimerman B. Two-year prospective follow-up of children with a prepubertal and early adolescent bipolar disorder phenotype. Am J Psychiatry 2002;159(6):927-33.

16. DelBello M, Schwiers M, Rosenberg H, Strakowski S. Quetiapine as adjunctive treatment for adolescent mania associated with bipolar disorder. J Amer Acad Child Adolesc Psychiatry 2002;41(10):1216-23.

17. Strober M, Morrell W, Lampert C, Burroughs J. Relapse following discontinuation of lithium maintenance therapy in adolescents with bipolar I illness: a naturalistic study. Am J Psychiatry 1990;147(4):457-61.

18. Kowatch RA, Suppes T, Carmody TJ, et al. Effect size of lithium, divalproex sodium and carbamazepine in children and adolescents with bipolar disorder. J Amer Acad Child Adolesc Psychiatry 2000;39(6):713-20.

19. Youngerman J, Canino IA. Lithium carbonate use in children and adolescents. A survey of the literature. Arch Gen Psychiatry 1978;35(2):216-24.

20. Strober M. Mixed mania associated with tricyclic antidepressant therapy in prepubertal delusional depression: three cases. J Child Adolesc Psychopharmacol 1998;8:181-5.

21. Wagner KD, Weller E, Biederman J, et al. An open-label trial of divalproex in children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 2002;41(10):1224-30.

22. West SA, Keck PE, Jr, McElroy SL, et al. Open trial of valproate in the treatment of adolescent mania. J Child Adolesc Psychopharmacol 1994;4:263-7.

23. Papatheodorou G, Kutcher SP, Katic M, Szalai JP. The efficacy and safety of divalproex sodium in the treatment of acute mania in adolescents and young adults: an open clinical trial. J Clin Psychopharmacol 1995;15(2):110-6.

24. Evans RW, Clay TH, Gualtieri CT. Carbamazepine in pediatric psychiatry. J Am Acad Child Adolesc Psychiatry 1987;26(1):2-8.

25. Puente RM. The use of carbamazepine in the treatment of behavioural disorders in children. In: Birkmayer W (ed). Epileptic seizures - behaviour - pain. Baltimore: University Park Press, 1975;243-52.

26. Isojarvi JI, Laatikainen TJ, Pakarinen AJ, Juntunen KT, Myllyla VV. Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med 1993;329(19):1383-8.

27. Rasgon NL, Altshuler LL, et al. Medication status and polycystic ovary syndrome in women with bipolar disorder: a preliminary report. J Clin Psychiatry 2000;61:173-8.

28. O'Donovan C, Kusumakar V, Graves GR, Bird DC. Menstrual abnormalities and polycystic ovary syndrome in women taking valproate for bipolar mood disorder. J Clin Psychiatry 2002;63:322-30.

29. Kowatch RA, Suppes T, Gilfillan SK, et al. Clozapine treatment of children and adolescents with bipolar disorder and schizophrenia: a clinical case series. J Child Adolesc Psychopharmacol 1995;5(4):241-53.

30. Frazier J, Meyer M, et al. Risperidone treatment for juvenile bipolar disorder: a retrospective chart review. J Am Acad Child Adolesc Psychiatry 1999;38:960-5.

31. Soutullo C, Sorter M, Foster K, et al. Olanzapine in the treatment of adolescent acute mania: a report of seven cases. J Affect Disord. 1999;53:279-83.

32. Khouzam H, El-Gabalawi F. Treatment of bipolar I disorder in an adolescent with olanzapine. J Child Adolesc Psychopharmacol 2000;10:147-51.

33. Chang K, Ketter T. Mood stabilizer augmentation with olanzapine in acutely manic children. J Child Adolesc Psychopharmacol 2000;10:45-9.

34. Ratzoni G, Gothelf D, Brand-Gothelf A, et al. Weight gain associated with olanzapine and risperidone in adolescent patients: a comparative prospective study. J Am Acad Child Adolesc Psychiatry 2002;41:337-43.

35. Kafantaris V, Dicker R, et al. Adjunctive antipsychotic treatment is necessary for adolescents with psychotic mania. J Child Adolesc Psychopharmacol 2001;11:409-13.

36. Biederman J, Mick E, Prince J, et al. Systematic chart review of the pharmacologic treatment of comorbid attention deficit hyperactivity disorder in youth with bipolar disorder. J Child Adolesc Psychopharmacol 1999;9(4):247-56.

37. Fristad MA, Goldberg-Arnold JS. Working with families of children with early-onset bipolar disorder. In: Geller B, DelBello M (eds). Child and early adolescent bipolar disorder: Theory, assessment, and treatment. New York: Guilford Publications, 2002.

five types of episodes (manic, hypomanic, mixed, depressed, unspecified)
four severity levels (mild, moderate, severe without psychosis, severe with psychosis)
and three course specifiers (with or without inter-episode recovery, seasonal pattern, rapid cycling).

Table 2

PEDIATRIC BIPOLAR DISORDER SUBTYPES: DIAGNOSTIC CHARACTERISTICS AND ASSOCIATED FEATURES

DSM-IV subtype	Minimum duration of manic symptoms	Depression symptoms	Cardinal features
Bipolar I	Pure mixed or manic 1 week (or hospitalization needed)	Major depressive disorder presentation of bipolar may be the first disorder, particularly in adolescents	Multiple daily mood swings with severe irritability (mood lability) Short periods of euphoria Decreased need for sleep Hypersexuality Grandiosity Racing thoughts Pressured speech
Bipolar II	Hypomania 4 days	One or more prior episodes of major depressive disorder required, each with a duration of 2 weeks	Noticeable manic symptoms that do not cause significant dysfunction or lead to hospitalization
Cyclothymia	Hypomania cycling with depressive symptoms 1 year	Hypomania cycling with depressive symptoms, without manic, mixed, or major depressive episodes (1 year, with symptom-free intervals <2 months)	Chronic, low-level mood cycling
Bipolar NOS	< 4 days of bipolar symptoms	Rapid alternation (within days) between manic depressive symptoms without full manic, mixed, or major depressive episodes	May include hypomanic and episodes (but <4 days) without intercurrent depression May also be diagnosed when clinician determines bipolar disorder is present but cannot determine whether it is primary, due to a general medical condition, or substance-induced, such as severe mood lability secondary to fetal alcohol syndrome or alcohol-related neurodevelopmental disorder
NOS: not otherwise specified

Table 3

COMPLICATING FACTORS IN PEDIATRIC BIPOLAR DISORDER

Medical conditions that may mimic bipolar mania
Temporal lobe epilepsy
Hyperthyroidism
Closed or open head injury
Multiple sclerosis
Systemic lupus erythematosus
Alcohol-related neurodevelopmental disorder
Wilson’s disease (rare progressive disease caused by defective copper metabolism)
Medications that may increase mood cycling
Tricyclic antidepressants
Selective serotonin reuptake inhibitors
Serotonin and norepinephrine reuptake inhibitors
Aminophylline
Corticosteroids
Sympathomimetic amines, such as pseudoephedrine

DSM-IV criteria for mania—which were developed from data on adults with bipolar disorders—do not take into account developmental differences between bipolar adults and bipolar children and adolescents.

Diagnostic characteristics of the pediatric bipolar disorder subtypes are compared in Table 2. Generally:

Pediatric patients with bipolar I disorder have multiple daily mood swings, a “mixed” type of episode with short periods of euphoria and longer periods of irritability, and comorbidities such as ADHD, oppositional defiant disorder, or conduct disorder.^3,11,12
Bipolar II disorder presents more typically in adolescence and is usually noticed clinically as a major depressive episode. Past episodes of hypomania may have been missed unless a careful history was taken.
Cyclothymia is difficult to diagnose because the hypomania and depressive symptoms are not as severe as in bipolar types I or II. Prospective mood charting can help the clinician diagnose cyclothymia (see “Related Resources”).
Bipolar disorder NOS represents the largest group of patients with bipolar symptoms. This diagnosis is made when bipolar symptoms are present but not of sufficient severity or duration to warrant a diagnosis of bipolar I, II or cyclothymia. Bipolar NOS also can be diagnosed when a bipolar disorder is secondary to a general medical condition, such as fetal alcohol syndrome or alcohol-related neurodevelopmental disorder.

Differential diagnosis. Medications and medical disorders may exacerbate or mimic pediatric bipolar symptoms (Table 3), so it is important to assess these potential confounds before initiating treatment. Psychiatric comorbidities also frequently complicate the presentation of pediatric bipolar disorder and its response to treatment (Table 4). ADHD is the most common comorbidity, with rates as high as 98% in bipolar children.^3,13

Outcomes

Long-term outcomes of children and adolescents with bipolar disorders have not been well studied. In the only prospective follow-up investigation of adolescent inpatients with mania, Strober et al found that most of 54 patients (96%) recovered from an index affective episode, but nearly one-half (44%) experienced one or more relapses within 5 years.¹⁴ The rate of recovery varied according to the index episode’s polarity. Recovery was faster in patients with pure mania or mixed states, and multiple relapses occurred more frequently in those with mixed or cycling episodes. Twenty percent of the patients attempted suicide.

Recently, Geller et al reported the results of the first large, prospective, follow-up study of children with bipolar disorder.¹⁵ In 89 outpatients (mean age 11) with bipolar I disorder, comprehensive assessments at baseline and at 6, 12, 18, and 24 months showed that 65% recovered from mania but 55% relapsed after recovery. Mean time to recovery was 36 weeks, and relapse occurred after a mean of 28.6 weeks. Children living with their intact biological families were twice as likely to recover as those in other living arrangements.

The poor outcomes of these bipolar children highlight the need for earlier recognition and more effective treatments.

Treating acute mania

Many psychotropic medications used to treat adults with bipolar disorders are also used for children and adolescents. To date, only two double-blind, placebo-controlled studies^13,16 and one uncontrolled maintenance treatment study¹⁷ have examined treatment of acute mania in pediatric bipolar disorder.