Bipolar disorder is characterized by alternating periods of mania, depression, and normal mood, each lasting for weeks to months at a time. The label “bipolar” has also been applied to prepubertal children disabled by intense, unstable moods. However, in these young children, the mood states last from moments to days. In both cases, diagnosis is by history and mental status examination. Treatment is a combination of mood stabilizers (eg, lithium, certain anticonvulsants and 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; about ¹/₃ of children who have an episode of severe depression before puberty convert to bipolar disorder during their adolescent or early adult years. The term “bipolar” has been applied to prepubertal children with unstable, intense moods, but typically, the moods last only a short time. Thus, whether this condition constitutes bipolar disorder is unclear; research in this area is ongoing.

Etiology

Etiology is unknown, but heredity is involved. Dysregulation of serotonin and norepinephrineSome Trade Names
LEVOPHED
Click for Drug Monograph
may be involved, as may a stressful life event. 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.

Symptoms and Signs

The hallmark of bipolar disorder is the manic episode. Manic episodes alternate with depressive episodes, which can be more frequent.

During a manic episode in adolescents, mood may be very positive or hyperirritable and often alternates between the 2 moods 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

• Clinical evaluation
• Testing for toxicologic causes

Diagnosis is based on history and mental status examination. 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

Prognosis for adolescents with bipolar disorder varies. 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.

Treatment

• Mood stabilizers and antidepressants
• Psychotherapy

For adolescents and prepubertal children, mood stabilizers are used to treat manic or agitated episodes, and psychotherapy and antidepressants treat the depressive episodes.

Mood stabilizers (see Table 2: Mental Disorders in Children and Adolescents: Selected Drugs for Bipolar Disorder*) roughly fall into 3 categories:

• Mood-stabilizing anticonvulsants
• Mood-stabilizing antipsychotics
• LithiumSome Trade Names
  ESKALITH
  LITHOBID
  LITHONATE
  Click for Drug Monograph
  

All mood stabilizers have a potential for troubling and even dangerous adverse effects. Thus, treatment must be individualized. Furthermore, drugs that are highly successful during initial stabilization may be unacceptable for maintenance because of adverse effects, most notably weight gain.

Antidepressants may trigger a switch from depression to mania; therefore, they are usually used with a mood stabilizer.

Table 2
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Selected Drugs for Bipolar Disorder* Drug Indication Starting Dose† Maintenance Dose† Comments LithiumSome Trade Names ESKALITH LITHOBID LITHONATE Click for Drug Monograph LithiumSome Trade Names ESKALITH LITHOBID LITHONATE Click for Drug Monograph extended-release‡ Acute mania and maintenance 300 mg bid 300–1200 mg bid Dose titrated to a blood level of 0.8–1.2 mEq/L Antipsychotics AripiprazoleSome Trade Names ABILIFY Click for Drug Monograph Acute mania 2.5–5 mg once/day Up to 30 mg once/day Very limited experience in children ChlorpromazineSome Trade Names THORAZINE Click for Drug Monograph ‡ Acute mania 10 mg once/day 50–300 bid Rarely used because newer drugs have a more favorable adverse effect profile OlanzapineSome Trade Names ZYPREXA Click for Drug Monograph Acute mania 2.5–5 mg once/day Up to 10 mg bid Causes weight gain, which may limit use in some patients Paliperidone‡ Acute mania 3 mg once/day Up to 3 mg bid Closely related to risperidoneSome Trade Names RISPERDAL Click for Drug Monograph Very limited experience in children RisperidoneSome Trade Names RISPERDAL Click for Drug Monograph Acute mania 0.5 mg once/day Up to 2.5 mg/day in divided doses (eg, 0.5 mg tid) Maintenance dose highly variable In high doses, increased risk of neurologic adverse effects QuetiapineSome Trade Names SEROQUEL Click for Drug Monograph Acute mania 25 mg bid Up to 200 mg bid Causes sedation that may limit dose increases OlanzapineSome Trade Names ZYPREXA Click for Drug Monograph /fluoxetineSome Trade Names PROZAC SARAFEM Click for Drug Monograph fixed combination‡ Bipolar depression 6 mg/25 mg once/day Up to 12 mg/50 mg once/day Limited experience in children ZiprasidoneSome Trade Names GEODON Click for Drug Monograph Acute mania 20 mg bid Up to 80 mg bid Very limited experience in children Anticonvulsants CarbamazepineSome Trade Names TEGRETOL Click for Drug Monograph Acute mania and mixed episode 200 mg bid Up to 600 mg bid Metabolic enzyme induction, possibly requiring dose adjustments DivalproexSome Trade Names DEPAKOTE Click for Drug Monograph Acute mania 250 mg bid Up to 30 mg/kg bid in divided doses Dose titrated to a blood level of 50–125 μg/mL LamotrigineSome Trade Names LAMICTAL Click for Drug Monograph Maintenance 25 mg once/day Up to 100 mg bid 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. Selected Drugs for Bipolar Disorder* Drug Indication Starting Dose† Maintenance Dose† Comments LithiumSome Trade Names ESKALITH LITHOBID LITHONATE Click for Drug Monograph LithiumSome Trade Names ESKALITH LITHOBID LITHONATE Click for Drug Monograph extended-release‡ Acute mania and maintenance 300 mg bid 300–1200 mg bid Dose titrated to a blood level of 0.8–1.2 mEq/L Antipsychotics AripiprazoleSome Trade Names ABILIFY Click for Drug Monograph Acute mania 2.5–5 mg once/day Up to 30 mg once/day Very limited experience in children ChlorpromazineSome Trade Names THORAZINE Click for Drug Monograph ‡ Acute mania 10 mg once/day 50–300 bid Rarely used because newer drugs have a more favorable adverse effect profile OlanzapineSome Trade Names ZYPREXA Click for Drug Monograph Acute mania 2.5–5 mg once/day Up to 10 mg bid Causes weight gain, which may limit use in some patients Paliperidone‡ Acute mania 3 mg once/day Up to 3 mg bid Closely related to risperidoneSome Trade Names RISPERDAL Click for Drug Monograph Very limited experience in children RisperidoneSome Trade Names RISPERDAL Click for Drug Monograph Acute mania 0.5 mg once/day Up to 2.5 mg/day in divided doses (eg, 0.5 mg tid) Maintenance dose highly variable In high doses, increased risk of neurologic adverse effects QuetiapineSome Trade Names SEROQUEL Click for Drug Monograph Acute mania 25 mg bid Up to 200 mg bid Causes sedation that may limit dose increases OlanzapineSome Trade Names ZYPREXA Click for Drug Monograph /fluoxetineSome Trade Names PROZAC SARAFEM Click for Drug Monograph fixed combination‡ Bipolar depression 6 mg/25 mg once/day Up to 12 mg/50 mg once/day Limited experience in children ZiprasidoneSome Trade Names GEODON Click for Drug Monograph Acute mania 20 mg bid Up to 80 mg bid Very limited experience in children Anticonvulsants CarbamazepineSome Trade Names TEGRETOL Click for Drug Monograph Acute mania and mixed episode 200 mg bid Up to 600 mg bid Metabolic enzyme induction, possibly requiring dose adjustments DivalproexSome Trade Names DEPAKOTE Click for Drug Monograph Acute mania 250 mg bid Up to 30 mg/kg bid in divided doses Dose titrated to a blood level of 50–125 μg/mL LamotrigineSome Trade Names LAMICTAL Click for Drug Monograph Maintenance 25 mg once/day Up to 100 mg bid 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.

Last full review/revision April 2009 by Hugh F. Johnston, MD

Content last modified February 2012