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Bipolar Disorder in Children and Adolescents

By

Josephine Elia

, MD, Sidney Kimmel Medical College of Thomas Jefferson University

Last full review/revision Apr 2021| Content last modified Apr 2021
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Topic Resources

Bipolar disorder is characterized by alternating periods of mania, depression, and normal mood, each lasting for weeks to months at a time. Diagnosis is based on clinical criteria. Treatment is a combination of mood stabilizers (eg, lithium, certain anticonvulsants, antipsychotic drugs), psychotherapy, and antidepressants.

Bipolar disorder typically begins during mid-adolescence through the mid-20s. In many children, the initial manifestation is one or more episodes of depression. (See also Bipolar Disorders in adults.)

Bipolar disorder is rare in children. In the past, bipolar disorder was diagnosed in prepubertal children who were disabled by intense, unstable moods. However, because such children typically progress to a depressive rather than bipolar disorder, they are now classified as having disruptive mood dysregulation disorder.

Etiology of Bipolar Disorder

Heredity is involved and several genetic variants have been associated with bipolar disorder (1), although there are currently no markers useful for diagnosing bipolar disorder. However neuroimaging studies in youths report smaller volumes in the amygdala (2–4) and prefrontal cortex (5) as well as lack of the normal increase in volume of the amygdala (6) and anterior white matter (5) that occurs in normal controls during adolescence.

Certain drugs (eg, cocaine, amphetamines, phencyclidines, certain antidepressants) and environmental toxins (eg, lead) can exacerbate or mimic the disorder. Certain disorders (eg, thyroid disorders) can cause similar symptoms.

General references

  • 1. Craddock N, Sklar P: Genetics of bipolar disorder. Lancet 381(9878):1654-1662, 2013. doi: 10.1016/S0140-6736(13)60855-7

  • 2. Phillips ML, Swartz HA: A critical appraisal of neuroimaging studies of bipolar disorder: Toward a new conceptualization of underlying neural circuitry and a road map for future research. Am J Psychiatry 171(8):829-843, 2014. doi: 10.1176/appi.ajp.2014.13081008

  • 3. Hafeman D, Bebko G, Bertocci MA, et al: Amygdala-prefrontal cortical functional connectivity during implicit emotion processing differentiates youth with bipolar spectrum from youth with externalizing disorders. J Affect Disord 208:94-100, 2017. doi: 10.1016/j.jad.2016.09.064

  • 4. Mwangi B, Spiker D, Zunta-Soares JC, et al: Prediction of pediatric bipolar disorder using neuroanatomical signatures of the amygdala. Bipolar Disord16(7):713-721, 2104.

  • 5. Najt P, Wang F, Spencer L, et al: Anterior cortical development during adolescence in bipolar disorder. Biol Psychiatry 79(4):303-310, 2016.

  • 6. Bitter SM, Mills NP, Adler CM, et al: Progression of amygdala volumetric abnormalities in adolescents following their first manic episode. J Am Acad Child Adolesc Psychiatry 50(10):1017-1026, 2011.

Symptoms and Signs of Bipolar Disorder

Bipolar disorder is characterized by recurrent episodes of elevated mood (mania or hypomania). Manic episodes alternate with depressive episodes, which can be more frequent. During a manic episode in adolescents, mood may be very positive or hyperirritable; the 2 moods often alternate depending on social circumstances. Speech is rapid and pressured, sleep is decreased, and self-esteem is inflated. Mania may reach psychotic proportions (eg, “I have become one with God”). Judgment may be severely impaired, and adolescents may engage in risky behaviors (eg, promiscuous sex, reckless driving).

Prepubertal children may experience dramatic moods, but the duration of these moods is much shorter (often lasting only a few moments) than that in adolescents.

Onset is characteristically insidious, and children typically have a history of always being very temperamental and difficult to manage.

Diagnosis of Bipolar Disorder

  • Clinical evaluation

  • Testing for toxicologic causes

Diagnosis of bipolar disorder is based on identification of symptoms of mania as described above, plus a history of remission and relapse.

A number of medical disorders (eg, thyroid disorders, brain infections or tumors) and drug intoxication must be ruled out with appropriate medical assessment, including a toxicology screen for drugs of abuse and environmental toxins. The interviewer should also search for precipitating events, such as severe psychologic stress, including sexual abuse or incest.

Prognosis for Bipolar Disorder

Prognosis for adolescents with bipolar disorder varies but worsens with each recurrence. Factors that increase risk of recurrence include early age of onset, severity, family psychopathology, and lack of, and/or poor adherence to, treatment (1). Those who have mild to moderate symptoms, who have a good response to treatment, and who remain adherent and cooperative with treatment have an excellent prognosis. However, treatment response is often incomplete, and adolescents are notoriously nonadherent to drug regimens. For such adolescents, the long-term prognosis is not as good.

Little is known about the long-term prognosis of prepubertal children diagnosed with bipolar disorder based on highly unstable and intense moods.

Prognosis reference

  • 1. Birmaher B, Merranko JA, Gill MK: Predicting personalized risk of mood recurrences in youths and young adults with bipolar spectrum disorder. J Am Acad Child Adolesc Psychiatry 59(10):1156-1164, 2020. doi:https://doi.org/10.1016/j.jaac.2019.12.005

Treatment of Bipolar Disorder

  • Mania: 2nd-generation antipsychotics, sometimes mood stabilizers

  • Depression: 2nd-generation antipsychotics plus an SSRI, sometimes lithium

For mania, 2nd-generation antipsychotics are the first line of treatment (1–3). Agents include aripiprazole, lurasidone, olanzapine, quetiapine, risperidone, ziprasidone. Lithium or other mood stabilizers (divalproex, lamotrigine, carbamazepine) may be used for patients who fail 2 or 3 trials of antipsychotics (4).

For depression, 2nd-generation antipsychotics combined with a selective serotonin reuptake inhibitor (SSRI) are the first line of treatment. Lithium is an alternative and may also be combined with an SSRI. Compared to other mood stabilizers and antipsychotics, lithium results in decreased suicidality, less depression and better psychosocial function. These findings mimic those found in adults (5). Antidepressants should not be used alone but in combination with the antipsychotics or lithium. Antidepressants do not increase the risk of treatment-emergent mania (as was thought in the past) but may destabilize children and adolescents with a bipolar disorder (6–8). Psychotherapy is also important.

Pearls & Pitfalls

  • 2nd-generation antipsychotics are the first-line treatment for pediatric bipolar disorder.

  • Lithium can decrease suicidal ideation.

Table
icon

Selected Drugs for Bipolar Disorder*

Drug

Indication

Starting Dose†

Maintenance Dose†

Comments

Lithium

Lithium extended-release‡,§, in adolescents 12 years

Acute mania and maintenance

450–900 mg twice a day

Dose titrated to a blood level of 0.8–1.2 mEq/L (or mmol/L)

Lithium, immediate-release‡,§, in adolescents

Acute mania and maintenance

200–300 mg three times a day

300–600 mg three times a day up to 2400 mg

Maximum daily dose is 40 mg/kg

Associated with decreased suicidality, decreased depression, and better psychosocial functioning in children and adolescents with bipolar disorder¶

Antipsychotics

Aripiprazole§ in children 10 years

Acute mania

Psychosis

2–5 mg once a day

Up to 30 mg once a day

Limited experience in children

Chlorpromazine in children>5 years‡,§

Acute mania

Psychosis

0.6–1.5 mg/kg every 6 hours up to 200 mg/day

Rarely used (in children who do not respond to newer drugs) because newer drugs have a more favorable adverse effect profile

Lurasidone in children > 10 years

Bipolar depression

20 mg once a day

Up to 80 mg/day

Olanzapine in children>13 years§

Acute mania

Psychosis

2.5–5 mg once a day

Up to 10 mg twice a day

Causes weight gain, which may limit use in some patients

Olanzapine/fluoxetine fixed combination in children >10 years‡,§

Bipolar depression

3 mg/25 mg once a day

Up to 12 mg/50 mg once a day

Limited experience in children

Paliperidone in children >12 years ‡,§

Acute mania

Psychosis

3 mg once a day

Up to 3 mg twice a day

Closely related to risperidone

Very limited experience in children

Quetiapine, immediate-release, in children >10 years§

Acute mania

Psychosis

25 mg twice a day

Up to 200 mg twice a day

Causes sedation that may limit dose increases

Risperidone in children >10 years§

Acute mania

Psychosis

0.5 mg once a day

Up to 2.5 mg/day

Maintenance dose highly variable

Doses up to 6 mg/day have been studied, but they provide no additional benefit and increase risk of neurologic adverse effects

Ziprasidone in children >10 years§

Acute mania

Psychosis

20 mg once a day

Up to 40 mg twice a day

Very limited experience in children

Anticonvulsants

Carbamazepine

Acute mania and mixed episode

200 mg twice a day

Up to 600 mg twice a day

Metabolic enzyme induction, possibly requiring dose adjustments

May cause Stevens-Johnson syndrome, especially in patients with HLA-B*1502 genotype, which is most common in patients of Asian ancestry, who should probably have HLA genotyping

Divalproex

Acute mania

5 mg/kg two or three times a day

Up to 10–20 mg/kg three times a day

Dose titrated to a blood level of 50–125 mcg/mL

Lamotrigine

Maintenance

25 mg once a day

Up to 100 mg twice a day

Requires that dosing guidelines in the package insert be followed closely

* These drugs pose a small but serious risk for a wide variety of major adverse effects. Therefore, benefits must be carefully weighed against potential risks.

† Dose ranges are approximate. Interindividual variability in therapeutic response and adverse effects is considerable. This table is not a substitute for the full prescribing information.

‡ These drugs have not been studied in children. For dosing in children under 12 years of age, see the prescribing information.

§ These drugs increase the risk of weight gain, negative effects on the lipid profile, increases in glucose and prolactin levels, and QT prolongation.

Hafeman DM, Rooks B, Merranko J, et al: Lithium versus other mood-stabilizing medications in a longitudinal study of youth diagnosed with bipolar disorder. J Am Acad Child Adolesc Psychiatry 59(10):1146-1155. doi:https://doi.org/10.1016/j.jaac.2019.06.013

Treatment references

  • 1. Kendall T, Morriss R, Mayo-Wilson E, et al: Assessment and management of bipolar disorder: Summary of updated NICE guidance. BMJ 349:g5673, 2014. doi: https://doi.org/10.1136/bmj.g5673

  • 2. Yatham LN, Kennedy SH, Parikh SV, et al: Canadian Network for mood and anxiety treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: Update 2013. Bipolar Disord 15(1):1-44, 2013. doi: 10.1111/bdi.12025

  • 3. Walkup JT, Wagner KD, Miller L: Treatment of early-age mania: Outcomes for partial and nonresponders to initial treatment. J Am Acad Child Adolesc Psychiatry 54(12):10081019, 2015.

  • 4. Kowatch RA, Suppes T, Carmody TJ, et al: Effect size of lithium, divalproex sodium, and carbamazepine in children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry39(6):713-720, 2000. doi: 10.1097/00004583-200006000-00009

  • 5. Hafeman DM, Rooks B, Merranko J, et al: Lithium versus other mood-stabilizing medications in a longitudinal study of youth diagnosed with bipolar disorder. J Am Acad Child Adolesc Psychiatry 59(10):1146-1155, 2020. doi: 10.1016/j.jaac.2019.06.013

  • 6. Biederman J, Mick E, Spencer TJ, et al: Therapeutic dilemmas in the pharmacotherapy of bipolar depression in the young. J Child Adolesc Psychopharmacol 10(3):185-192, 2000. doi: 10.1089/10445460050167296

  • 7. Scheffer RE, Tripathi A, Kirkpatrick FG, et al: Guidelines for treatment-resistant mania in children with bipolar disorder. J Psychiatr Pract 17(3):186-193, 2011. doi: 10.1097/01.pra.0000398411.59491.8c

  • 8. Baumer FM, Howe M, Gallelli K, et al: A pilot study of antidepressant-induced mania in pediatric bipolar disorder: Characteristics, risk factors, and the serotonin transporter gene. Biol Psychiatry60(9):1005-1012, 2006. doi: 10.1016/j.biopsych.2006.06.010

Key Points

  • Bipolar disorder is characterized by alternating periods of mania, depression, and normal mood, each lasting for weeks to months at a time.

  • Bipolar disorder typically begins during mid-adolescence through the mid-20s; it is rare in children.

  • Typically, onset is insidious; children have a history of being very temperamental and difficult to manage.

  • In adolescents and prepubertal children, treat manic or agitated episodes with antipsychotics first since these medications work quickly, followed by mood stabilizers to prevent relapses, and SSRIs and psychotherapy to treat depressive episodes.

Drugs Mentioned In This Article

Drug Name Select Trade
No US brand name
TEGRETOL
INVEGA
ABILIFY
GEODON
RISPERDAL
LAMICTAL
LATUDA
PROZAC, SARAFEM
ZYPREXA
SEROQUEL
LITHOBID
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