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 medications), 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.
Етіологія
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, phencyclidine, certain antidepressants) and environmental toxins (eg, lead) can exacerbate or mimic the disorder. Certain disorders (eg, thyroid disorders) can cause similar symptoms. There are also a few case reports of mania associated with asymptomatic (7) and symptomatic (8) COVID-19 infections in youths.
Довідкові матеріали загального характеру
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.
7. Meeder R, Adhikari S, Sierra-Cintron, et al: New-onset mania and psychosis in adolescents in the context of COVID-19 infection. Cureus14(4):e24322, 2022. doi: 10.7759/cureus.24322
8. Uzun O, Akpolat T, Varol A, et al: Could COVID-19 be a trigger for manic attack in an adolescent?Neurol Sci. 42(9):3521-3522, 2021. doi: 10.1007/s10072-021-05390-0
Симптоми та ознаки
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.
Діагностика
Psychiatric assessment
Diagnostic and Statistical Manual of Mental Disorders, Fifth edition, (DSM-5-TR) criteria
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.
Лікування
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.
Цінні поради та підводні камені
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Окремі лікарські препарати для лікування біполярного розладу*
Medication | 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 |
Asenapine in children>10 years | Bipolar mania | 2.5 mg twice a day sublingual | Up to 10 mg twice a day | Tongue numbness and tingling |
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 medications) because newer medications 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 and toxic epidermal necrolysis (SJS/TEN) especially in patients with HLA-B*15:02 genotype (more common in East Asian populations) and maculopapular exanthema (MPE), drug reaction with eosinophilia (DRESS) and SJS/TEN in patients with HLA-A*31:01 genotype (more common in Caucasians and Hispanics) a |
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 medications 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 medications have not been studied in children. For dosing in children under 12 years of age, see the prescribing information. | ||||
§ These medications 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 aPhillips EJ, Sukasem C, Whirl-Carrillo, et al: Clinical pharmacogenetics implementation consortium guideline for HLA genotype and use of carbamazepine and oxcarbazepine: 2017 Update. https://doi.org/10.1002/cpt.1004 | ||||
Довідкові матеріали щодо лікування
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
Прогноз
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.
Довідковий матеріал щодо прогнозу
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
Ключові моменти
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.
