Pediatric Bipolar Disorder (PDF)

Barry University Library Access Provided by: Current Diagnosis & Treatment: Psychiatry, 4th Edition Chapter 48: Pediatric Bipolar Disorder Rasim Diler; Benjamin I....

Barry University Library Access Provided by: Current Diagnosis & Treatment: Psychiatry, 4th Edition Chapter 48: Pediatric Bipolar Disorder Rasim Diler; Benjamin I. Goldstein; Boris Birmaher INTRODUCTION International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD­10) Diagnostic Criteria In the ICD­10, bipolar disorder (BP) is included under mood (affective) disorders, conditions in which the fundamental disturbance is a change in affect or mood to depression (with or without associated anxiety) or to elation. The mood change is usually accompanied by a change in the overall level of activity; most of the other symptoms are either secondary to, or easily understood in the context of, the change in mood and activity. Most of these disorders tend to be recurrent and the onset of individual episodes can often be related to stressful events or situations. F30 Manic Episode All the subdivisions of this category should be used only for a single episode. Hypomanic or manic episodes in individuals who have had one or more previous affective episodes (depressive, hypomanic, manic, or mixed) should be coded as bipolar affective disorder (F31.). F30.0 Hypomania A disorder characterized by a persistent mild elevation of mood, increased energy and activity, and usually marked feelings of well­being and both physical and mental efficiency. Increased sociability, talkativeness, over­familiarity, increased sexual energy, and a decreased need for sleep are often present but not to the extent that they lead to severe disruption of work or result in social rejection. Irritability, conceit, and boorish behavior may take the place of the more usual euphoric sociability. The disturbances of mood and behavior are not accompanied by hallucinations or delusions. F30.1 Mania Without Psychotic Symptoms Mood is elevated out of keeping with the patient’s circumstances and may vary from carefree joviality to almost uncontrollable excitement. Elation is accompanied by increased energy, resulting in overactivity, pressure of speech, and a decreased need for sleep. Attention cannot be sustained, and there is often marked distractibility. Self­esteem is often inflated with grandiose ideas and overconfidence. Loss of normal social inhibitions may result in behavior that is reckless, foolhardy, or inappropriate to the circumstances, and out of character. F30.2 Mania with Psychotic Symptoms In addition to the clinical picture described in F30.1, delusions (usually grandiose) or hallucinations (usually of voices speaking directly to the patient) are present, or the excitement, excessive motor activity, and flight of ideas are so extreme that the subject is incomprehensible or inaccessible to ordinary communication. Subtypes: 1) mood­congruent psychotic symptoms, 2) mood­incongruent psychotic symptoms, and 3) manic stupor. F30.8 Other Manic Episodes F30.9 Manic Episode, Unspecified (Mania NOS) Bipolar Affective Disorder (F31) A disorder characterized by two or more episodes in which the patient’s mood and activity levels are significantly disturbed. One episode of these disturbances must be an elevation of mood and increased energy and activity (hypomania or mania) and the others are often (but not required to be) a lowering of mood and decreased energy and activity (depression). Repeated episodes of hypomania or mania only are classified as bipolar manic depression; manic­depressive (illness, psychosis, reaction): Excl.: bipolar disorder, single manic episode (F30), cyclothymia (F34.0). F31.0 Bipolar Affective Disorder, Current Episode Hypomanic The patient is currently hypomanic and has had at least one other affective episode (hypomanic, manic, depressive, or mixed) in the past. Downloaded 2025­2­16 5:19 P Your IP is Chapter 48: Pediatric F31.1 Bipolar Bipolar Affective Disorder, Disorder, Rasim Current Diler;Manic Episode Benjamin I. Goldstein; Without Psychotic Boris Birmaher Symptoms Page 1 / 28 ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility The patient is currently manic, without psychotic symptoms (as in F30.1), and has had at least one other affective episode (hypomanic, manic, depressive, or mixed) in the past.  disturbances must be an elevation of mood and increased energy and activity (hypomania or mania) and the others are often (but not required to Barry University Library be) a lowering of mood and decreased energy and activity (depression). Repeated episodes of hypomania or mania only are classified as bipolar Access Provided by: manic depression; manic­depressive (illness, psychosis, reaction): Excl.: bipolar disorder, single manic episode (F30), cyclothymia (F34.0). F31.0 Bipolar Affective Disorder, Current Episode Hypomanic The patient is currently hypomanic and has had at least one other affective episode (hypomanic, manic, depressive, or mixed) in the past. F31.1 Bipolar Affective Disorder, Current Episode Manic Without Psychotic Symptoms The patient is currently manic, without psychotic symptoms (as in F30.1), and has had at least one other affective episode (hypomanic, manic, depressive, or mixed) in the past. F31.2 Bipolar Affective Disorder, Current Episode Manic with Psychotic Symptoms The patient is currently manic, with psychotic symptoms (as in F30.2), and has had at least one other affective episode (hypomanic, manic, depressive, or mixed) in the past. F31.3 Bipolar Affective Disorder, Current Episode Mild or Moderate Depression The patient is currently depressed, as in a depressive episode of either mild or moderate severity (F32.0 or F32.1), and has had at least one authenticated hypomanic, manic, or mixed affective episode in the past. F31.4 Bipolar Affective Disorder, Current Episode Severe Depression Without Psychotic Symptoms The patient is currently depressed, as in severe depressive episode without psychotic symptoms (F32.2), and has had at least one authenticated hypomanic, manic, or mixed affective episode in the past. F31.5 Bipolar Affective Disorder, Current Episode Severe Depression with Psychotic Symptoms The patient is currently depressed, as in severe depressive episode with psychotic symptoms (F32.3), and has had at least one authenticated hypomanic, manic, or mixed affective episode in the past. F31.6 Bipolar Affective Disorder, Current Episode Mixed The patient has had at least one authenticated hypomanic, manic, depressive, or mixed affective episode in the past and currently exhibits either a mixture or a rapid alteration of manic and depressive symptoms. Excl.: single mixed affective episode (F38.0). F31.7 Bipolar Affective Disorder, Currently in Remission The patient has had at least one authenticated hypomanic, manic, or mixed affective episode in the past, and at least one other affective episode (hypomanic, manic, depressive, or mixed) in addition, but is not currently suffering from any significant mood disturbance, and has not done so for several months. Periods of remission during prophylactic treatment should be coded here. F31.8 Other Bipolar Affective Disorders Bipolar II disorder, Recurrent manic episodes NOS F31.9 Bipolar Affective Disorder, Unspecified In contrast to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM­5) nomenclature for BP and related disorders that require one manic episode to make the diagnosis, the ICD­10 criteria require at least two mood episodes, one of which should be manic or mixed (e.g., either a mixture or a rapid alteration of manic and depressive symptoms) episode and the other could be depressive, hypomanic, manic, or mixed episode, to make the BP affective disorder diagnosis. Duration for hypomanic and manic episodes has similar duration criteria (4 and 7 days, respectively) in both nomenclatures. However, BP­II disorder in DSM­5 (presence of hypomanic episode plus at least one major depressive episode) is categorized as “other bipolar affective disorders” in ICD­10. The ICD­10 criteria also do not mention ‘impairment’ but require that patient’s mood and activity levels are significantly disturbed. Several changes were made in DSM­5, in comparison to DSM­IV, for BP and related disorders such as: excluding mixed episodes, introducing the new specifier of “mixed features (presence of 3 or more depressive symptoms during the course of an manic episode),” introducing the new specifier of “anxiety features (presence of anxiety symptoms specifically during the course of an manic episode),” and the new requirement of “increased energy or goal­directed activity” as the main symptom criteria (in addition to “elated mood or irritability”) Downloaded 2025­2­16 for diagnosis 5:19 Pepisode. of a manic Your IP is Chapter 48: Pediatric Bipolar Disorder, Rasim Diler; Benjamin I. Goldstein; Boris Birmaher Page 2 / 28 ©2025 McGraw Reproduced Hill. with All Rightsfrom permission Reserved. TermsStatistical International of Use Privacy Policyof Notice Classification Accessibility Diseases and Related Health Problems 10th Revision (ICD­10) Version for 2010. Geneva: World Health Organization; 2010.  excluding mixed episodes, Barry University Library introducing the new specifier of “mixed features (presence of 3 or more depressive symptoms during the course of an manic episode),” Access Provided by: introducing the new specifier of “anxiety features (presence of anxiety symptoms specifically during the course of an manic episode),” and the new requirement of “increased energy or goal­directed activity” as the main symptom criteria (in addition to “elated mood or irritability”) for diagnosis of a manic episode. Reproduced with permission from International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD­10) Version for 2010. Geneva: World Health Organization; 2010. ESSENTIALS OF DIAGNOSIS BP is a familial illness characterized by episodes of abnormally elevated mood that are above and beyond the child’s developmental stage (Birmaher 2016; Birmaher et al, 2007; Diler & Birmaher, 2012). According to the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM­5, American Psychiatric Association [APA], 2013), when accompanied by other symptoms of increased cognitive and physical activity and by major functional impairment, and lasting 7 days or longer (or requires inpatient treatment), these episodes are labeled “manic episodes.” If the manic symptoms are milder and/or briefer (e.g., 4 days or longer with functional change), the episodes are labeled as “hypomanic episodes.” In addition, to diagnose a youth with BP, the symptoms of mania or hypomania need to appear in clusters, be recurrent, and not be better accounted for by other psychiatric and medical conditions. Although not necessary for the diagnosis of BP­I, youth with this disorder often experience recurrent episodes of major depression (APA, 2013; Birmaher et al, 2009a). BP is usually subdivided into several subtypes: BP type I (BP­I), BP type II (BP­II), cyclothymia, and unspecified/other­specified Bipolar and Related Disorder (in the past referred to as BP not otherwise specified, BP­NOS) (APA, 2004, 2013; Birmaher et al, 2009a; Goodwin et al, 2007). These subtypes are usually grouped under the label “BP Spectrum Disorders.” BP­I can also be subdivided into manic, mixed (e.g., mixed features as in DSM­5), depressed, rapid cycling, and psychotic (Table 48–1). Each one of these subtypes is important because they have prognostic as well as treatment implications. Table 48–1 Subtypes of Bipolar (BP) Disorders BP­Subtype Clinical Characteristics BP­Type I (BP­I) Mixed* Recurrent episodes of mania and often episodes of major depression. episode (per DSM­IV) Concurrent symptoms of mania and depression* Rapid cycling ≥4 episodes/year of mania, hypomania, mixed or major depression Psychotic Presence of delusions and/or hallucinations BP­Type II (BP­II) Episodes of hypomania and at least one major depressive episode Cyclothymia For at least 2 years (*one year in children), the presence of numerous periods with hypomanic symptoms and numerous periods with depressive symptoms that do not meet criteria for a major depressive episode BP Disorder Episodes of mania and depression that meet symptom threshold criteria, but not minimal 7 days duration for mania, 4 Unspecified/other­ days for hypomania, or 2 weeks major depression and cause functional impairment specified Episodes of mania or hypomania that not have the meet symptom threshold criteria and cause functional impairment Recurrent hypomanic episodes without depression DSM, Diagnostic and Statistical Manual of Mental Disorders. *In DSM­5, instead of mixed episode, “mixed” is used as a specifier for an episode of mania, hypomania, or major depression. Our discussion includes the revisions in DSM­5, but it is important to note that all studies included in this chapter were carried out using the DSM­IV criteria for BP (APA, 2004, 2013). Downloaded 2025­2­16 5:19 P Your IP is Chapter 48: Pediatric Bipolar Disorder, Rasim Diler; Benjamin I. Goldstein; Boris Birmaher Page 3 / 28 GENERAL CONSIDERATIONS ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Epidemiology  DSM, Diagnostic and Statistical Manual of Mental Disorders. Barry University Library Access Provided by: *In DSM­5, instead of mixed episode, “mixed” is used as a specifier for an episode of mania, hypomania, or major depression. Our discussion includes the revisions in DSM­5, but it is important to note that all studies included in this chapter were carried out using the DSM­IV criteria for BP (APA, 2004, 2013). GENERAL CONSIDERATIONS Epidemiology A meta­analysis of 12 epidemiological studies across the world and a recent epidemiological study in Canada and the United States of America reported a lifetime prevalence of 1–2% for BP­I/II and around 3–6% for subsyndromal manic symptomatology (Kozloff et al, 2010; Merikangas et al, 2012; Van Meter et al, 2011). There were no significant differences between the studies carried out within versus outside the USA for BP­I, but there were differences for BP­NOS indicating that subsyndromal BP is more prevalent in the USA than in other countries (Van Meter et al, 2011). These results may account, at least in part, for the relative increase in the diagnosis of unspecified BP observed in recent years in the USA and other countries (Holtmann et al, 2010; Moreno et al, 2007; Stringaris and Youngstrom, 2014). The results, together with the fact that several studies in adults with BP carried out by different investigators across the world have consistently reported that up to 60% had the onset of their mood symptoms before the age of 25 years, give further validation to the observation that BP usually starts during adolescence (Chengappa et al, 2003; Goldstein and Levitt, 2006; Kozloff et al, 2010; Lish et al, 1994; Perlis et al, 2004; Van Meter et al, 2011). However, the foregoing figures need to be interpreted with caution because of the difficulties and controversies regarding the diagnosis of pediatric BP and the overlap of its symptoms with other psychiatric disorders. In clinical populations the prevalence of BP has been reported to be between 0.6% and 20%, depending on the setting, the referral source, and the methodology used to ascertain and interpret the symptoms of BP (Pavuluri et al, 2005). ETIOLOGY 1. Twin and adoption studies Twin and adoption studies have demonstrated that BP in most part (~80%) is explained by genetic factors (Axelson et al, 2015; Birmaher et al, 2009b; Goodwin et al, 2007; Wozniak et al, 2012). However, identification of the genes associated with BP has been elusive because it seems that several genes and epigenetic factors are relevant to the manifestation of this illness. In addition, other factors, including variation in ascertainment, phenotype definition, control selection, and limited power, have led to inconsistent results. 2. High­risk family studies Studies evaluating the risk for BP in offspring of parents with BP and in first­degree relatives of youth with BP have provided further evidence that BP specifically (i.e., to a meaningfully greater extent than non­BP disorders) runs in families (Birmaher et al, 2007; Birmaher et al, 2009b; Goodwin et al, 2007). In fact, offspring of parents with BP has up to 25­fold greater rates of BP when compared with offspring of control parents (Birmaher et al, 2009b; DelBello & Geller, 2001; Duffy, 2012; Mesman et al, 2013). Importantly, a large prospective high­risk BP study, the Pittsburgh Bipolar Offspring Study, suggested that offspring with mood lability, depression/anxiety, and particularly those with subsyndromal manic symptoms and whose parents had early­onset BP were at 50% risk to develop BP (Hafeman et al, 2016). However, it is important to note that children of parents with BP not only are at high risk to develop BP but also are at risk to develop depression, anxiety, attention­deficit/hyperactivity disorder (ADHD), and behavioral problems as well (Birmaher et al, 2009b). In the same vein, there is a significant increased risk for BP and depression in first­degree relatives of children and adolescents with BP when compared with relatives of adolescents with other disorders (Biederman et al, 2013; Geller et al, 2006; Wozniak et al, 2010), further indicating that BP runs in families. 3. Psychosocial factors Very few studies have evaluated the effects of psychosocial factors on the onset and maintenance of BP in youth. The few studies that have evaluated the effects of psychosocial factors on the onset and continuity of BP in youth have suggested that low socioeconomic status (SES), exposure to negative events, and high “expressed­emotion” (EE) in the family are associated with poor prognosis (Birmaher et al, 2009a; Bella et al, 2011; DelBello et al, 2007b; Geller et al, 2008; Miklowitz et al, 1988). Downloaded 2025­2­16 5:19 P Your IP is Chapter American48: PediatricAssociation Psychiatric Bipolar Disorder, Rasim Diler; (APA). Diagnostic andBenjamin I. Manual Statistical Goldstein; Boris Birmaher of Mental Page 4 / 28 Disorders. 5th ed. Washington, DC: American Psychiatric ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Association; 2013. 3. Psychosocial factors Barry University Library Very few studies have evaluated the effects of psychosocial factors on the onset and maintenance of BP in youth. The few studiesAccess thatProvided have evaluated by: the effects of psychosocial factors on the onset and continuity of BP in youth have suggested that low socioeconomic status (SES), exposure to negative events, and high “expressed­emotion” (EE) in the family are associated with poor prognosis (Birmaher et al, 2009a; Bella et al, 2011; DelBello et al, 2007b; Geller et al, 2008; Miklowitz et al, 1988). American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013. American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 2004. Axelson D, Goldstein B, Goldstein T, et al. Diagnostic precursors to bipolar disorder in offspring of parents with bipolar disorder: a longitudinal study. Am J Psychiatry. 2015;172(7):638–646. [PubMed: 25734353] Bella T, Goldstein T, Axelson D, et al. Psychosocial functioning in offspring of parents with bipolar disorder. J Affect Disord. 2011;133(1–2):204–211. [PubMed: 21463899] Biederman J, Faraone SV, Petty C, et al. Further evidence that pediatric­onset bipolar disorder comorbid with ADHD represents a distinct subtype: results from a large controlled family study. J Psychiatr Res. 2013;47(1):15–22. [PubMed: 22979994] Birmaher B. Pediatric bipolar disorder: epidemiology, pathogenesis, clinical manifestations and course. UpToDate. Accessed January 2016. Birmaher B, Axelson D, Goldstein B, et al. Four­year longitudinal course of children and adolescents with bipolar spectrum disorders: the Course and Outcome of Bipolar Youth (COBY) study. Am J Psychiatry. 2009a;166(7):795–804. [PubMed: 19448190] Birmaher B, Axelson D, Monk K, et al. Lifetime psychiatric disorders in school­aged offspring of parents with bipolar disorder: the Pittsburgh Bipolar Offspring study. Arch Gen Psychiatry. 2009b;66(3):287–296. [PubMed: 19255378] Birmaher B, Axelson D, Pavaluri M. Bipolar disorder. In: Martin A, Volkmar FR, Lewis M, eds. Lewis’ Child and Adolescent Psychiatry: A Comprehensive Textbook. 4th ed. London: Lippincott Williams & Wilkins; 2007. Chengappa KN, Kupfer DJ, Frank E, et al. Relationship of birth cohort and early age at onset of illness in a bipolar disorder case registry. Am J Psychiatry. 2003;160(9):1636–1642. [PubMed: 12944339] DelBello MP, Geller B. Review of studies of child and adolescent offspring of bipolar parents. Bipolar Disord. 2001;3(6):325–334. [PubMed: 11843782] DelBello MP, Hanseman D, Adler CM, et al. Twelve­month outcome of adolescents with bipolar disorder following first hospitalization for a manic or mixed episode. Am J Psychiatry. 2007b;164(4):582–590. [PubMed: 17403971] Diler RS, Birmaher B. Bipolar disorder in children and adolescents. In: Rey JM, ed. IACAPAP e­Textbook of Child and Adolescent Mental Health. Geneva: International Association for Child and Adolescent Psychiatry and Allied Professions; 2012. Duffy A. The nature of the association between childhood ADHD and the development of bipolar disorder: a review of prospective high­risk studies. Am J Psychiatry. 2012;169(12):1247–1255. [PubMed: 23212056] Geller B, Tillman R, Bolhofner K, Zimerman B. Child bipolar I disorder: prospective continuity with adult bipolar I disorder; characteristics of second and third episodes; predictors of 8­year outcome. Arch Gen Psychiatry. 2008;65(10):1125–1133. [PubMed: 18838629] Geller B, Tillman R, Bolhofner K, et al. Controlled, blindly rated, direct­interview family study of a prepubertal and early­adolescent bipolar I disorder phenotype: morbid risk, age at onset, and comorbidity. Arch Gen Psychiatry. 2006;63(10):1130–1138. [PubMed: 17015815] Goldstein B, Levitt AJ. Further evidence for a developmental subtype of bipolar disorder defined by age at onset: results from the national epidemiologic survey on alcohol and related conditions. Am J Psychiatry. 2006;163(9):1633–1636. [PubMed: 16946191] Goodwin FK, Jamison KR, Ghaemi SN. Manic­Depressive Illness: Bipolar Disorders and Recurrent Depression. New York: Oxford University Press; Downloaded 2007. 2025­2­16 5:19 P Your IP is Chapter 48: Pediatric Bipolar Disorder, Rasim Diler; Benjamin I. Goldstein; Boris Birmaher Page 5 / 28 ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Hafeman DM, Merranko J, Axelson D, et al. Toward the definition of a bipolar prodrome: dimensional predictors of bipolar spectrum disorders in at­ risk youth. Am J Psychiatry. 2016;173(7):695–704. [PubMed: 26892940] phenotype: morbid risk, age at onset, and comorbidity. Arch Gen Psychiatry. 2006;63(10):1130–1138. [PubMed: 17015815] Barry University Library Access Provided by: Goldstein B, Levitt AJ. Further evidence for a developmental subtype of bipolar disorder defined by age at onset: results from the national epidemiologic survey on alcohol and related conditions. Am J Psychiatry. 2006;163(9):1633–1636. [PubMed: 16946191] Goodwin FK, Jamison KR, Ghaemi SN. Manic­Depressive Illness: Bipolar Disorders and Recurrent Depression. New York: Oxford University Press; 2007. Hafeman DM, Merranko J, Axelson D, et al. Toward the definition of a bipolar prodrome: dimensional predictors of bipolar spectrum disorders in at­ risk youth. Am J Psychiatry. 2016;173(7):695–704. [PubMed: 26892940] Holtmann M, Duketis E, Poustka L, et al. Bipolar disorder in children and adolescents in Germany: national trends in the rates of inpatients, 2000– 2007. Bipolar Disord. 2010;12(2):155–163. [PubMed: 20402708] Kozloff N, Cheung AH, Schaffer A, et al. Bipolar disorder among adolescents and young adults: results from an epidemiological sample. J Affect Disord. 2010;125(1–3):350–354. [PubMed: 20226535] Lish J, Dime­Meenan S, Whybrow P, et al. The National Depressive and Manic­depressive Association (DMDA) survey of bipolar members. J Affect Disord. 1994;31:281–294. [PubMed: 7989643] Merikangas KR, Cui L, Kattan G, et al. Mania with and without depression in a community sample of US adolescents. Arch Gen Psychiatry. 2012;69(9):943–951. [PubMed: 22566563] Mesman E, Nolen WA, Reichart CG, et al. The Dutch Bipolar Offspring Study: 12­year follow­up. Am J Psychiatry. 2013;170(5):542–549. [PubMed: 23429906] Miklowitz DJ, Goldstein MJ, Nuechterlein KH, et al. Family factors and the course of bipolar affective disorder. Arch Gen Psychiatry. 1988;45:225–231. [PubMed: 3341878] Moreno C, Laje G, Blanco C, et al. National trends in the outpatient diagnosis and treatment of bipolar disorder in youth. Arch Gen Psychiatry. 2007;64(9):1032–1039. [PubMed: 17768268] Pavuluri MN, Birmaher B, Naylor MW. Pediatric bipolar disorder: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry. 2005;44(9):846– 871. [PubMed: 16113615] Perlis RH, Miyahara S, Marangell LB, et al. Investigators S­B. Long­term implications of early onset in bipolar disorder: data from the first 1000 participants in the systematic treatment enhancement program for bipolar disorder (STEP­BD). Biol Psychiatry. 2004;55(9):875–881. [PubMed: 15110730] Stringaris A, Youngstrom E. Unpacking the differences in US/UK rates of clinical diagnoses of early­onset bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2014;53(6):609–611. [PubMed: 24839878] Van Meter AR, Moreira AL, Youngstrom EA. Meta­analysis of epidemiologic studies of pediatric bipolar disorder. J Clin Psychiatry. 2011;72(9):1250– 1256. [PubMed: 21672501] Wozniak J, Faraone SV, Martelon M, et al. Further evidence for robust familiality of pediatric bipolar I disorder: results from a very large controlled family study of pediatric bipolar I disorder and a meta­analysis. J Clin Psychiatry. 2012;73(10):1328–1334. [PubMed: 23140652] Wozniak J, Faraone SV, Mick E, et al. A controlled family study of children with DSM­IV bipolar­I disorder and psychiatric co­morbidity. Psychol Med. 2010;40(7):1079–1088. [PubMed: 19891803] CLINICAL FINDINGS A. Signs & Symptoms The literature has consistently shown that some children and adolescents meet the full DSM­5 criteria for BP (Axelson et al, 2006; Diler & Birmaher, Downloaded 2025­2­16 5:19 P Your IP is 2012; Leibenluft Chapter & Rich,Bipolar 48: Pediatric 2008). However, Disorder, as discussed Rasim Diler;here, there I.was Benjamin controversy Goldstein; regarding Boris Birmahersome of the symptoms by which mania manifests Pagein 6youth, / 28 particularly ©2025 the symptoms McGraw of elation, Hill. All Rights irritability, Reserved. Terms andofgrandiosity, andPolicy Use Privacy whether BP may Notice be nonepisodic among youth. Also, it is important to note that Accessibility there are developmental differences in the way that the symptoms of mania, hypomania, or depression manifest between children, adolescents, and adults (Birmaher et al, 2009c; Holtzman et al, 2015). Symptoms are often more difficult to ascertain and differentiate from symptoms of other  Barry University Library CLINICAL FINDINGS Access Provided by: A. Signs & Symptoms The literature has consistently shown that some children and adolescents meet the full DSM­5 criteria for BP (Axelson et al, 2006; Diler & Birmaher, 2012; Leibenluft & Rich, 2008). However, as discussed here, there was controversy regarding some of the symptoms by which mania manifests in youth, particularly the symptoms of elation, irritability, and grandiosity, and whether BP may be nonepisodic among youth. Also, it is important to note that there are developmental differences in the way that the symptoms of mania, hypomania, or depression manifest between children, adolescents, and adults (Birmaher et al, 2009c; Holtzman et al, 2015). Symptoms are often more difficult to ascertain and differentiate from symptoms of other psychiatric disorders (especially ADHD) or normal behaviors in children. Additionally, there are more rapid changes in polarity and more mixed states, further challenging accurate diagnosis. In contrast, both the manic/hypomanic and depressive symptoms among adolescents are more similar to those of adults (Birmaher et al, 2009c). 1. Mania According to the DSM­IV, a manic episode is defined as a discrete period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if the manic episode caused admission the hospital). Recently, the DSM­5 added to these symptoms the criterion of “increased energy/activity as a core symptom” of mania. During the period of excessive mood elevation or irritability as well as increased energy/activity, at least three or more of the manic symptoms (e.g., increased self­esteem, decreased need for sleep, more talkative/pressured speech, flight of ideas/racing thoughts, distractibility, increased goal­directed activity/psychomotor agitation, and excessive involvement in pleasurable activities) need to be present. These symptoms exist as a collection of concurrent symptoms and behaviors (i.e., “cluster together”), and most investigators agree that the symptoms need to occur episodically (Axelson et al, 2011a; Birmaher et al, 2007; Diler & Birmaher, 2012; Leibenluft & Rich, 2008). Also, some investigators have suggested that mania among youth is manifested more by irritability than elation (Wozniak, 2005). However, it appears that this finding was due to methodological issues with the ascertainment of manic symptoms and that, as in adults, most youth with BP have both elation and irritability, with a small proportion having irritability or elation only (Hunt et al, 2009, 2013). In these last cases, elation or irritability is not the only symptoms required to diagnose mania, but other symptoms such as grandiosity, increased energy/activity, or lack of need for sleep are required. Also, to make the diagnosis, the manic episodes must impair the youth’s functioning, and the symptoms must not be mainly accounted for by the use of medications, use of substances, or medical illness. A recent meta­analysis of 20 published studies (N = 2226) evaluated the weighted rates of manic symptoms in youth (average age: 11.5 years, 64% male, mainly Caucasian) with BP­I and BP­NOS (Van Meter et al, 2016). The most common symptoms across BP subtypes included increased energy, irritability and mood lability, distractibility, and goal­directed activity (all approximately 75%), whereas hypersexuality, hallucinations, and delusions were the least frequent (all approximately 26%). Grandiosity and hypersexuality were the most specific symptoms, but they were less common (57% and 32%, respectively). As expected, youth with BP­I had more severe and greater number of symptoms than those with BP­NOS. The findings were similar to the meta­analysis published in 2005 (Kowatch et al, 2005b). However, because of methodological issues and probably also the way investigators conceptualize symptoms, there was significant variability in the prevalence of individual symptoms among the studies (Axelson et al, 2006; Diler, 2007; Kowatch et al, 2005; Van Meter et al, 2016). Some symptoms, such as not feeling tired or sleepy the day after having slept 3–4 hours during the night, or having inappropriate sexual behaviors not explained by exposure to sexual behaviors, should raise suspicion with regard to the diagnosis of BP. Perhaps due to the complexity of assessing psychosis in youth (particularly in children), the weighted rates of psychosis were unexpectedly high (31% hallucinations and 24% delusions) in the recent meta­analysis (Van Meter et al, 2016). Though it is not a symptom of mania per se and though schizophrenia is rare in children, the presence of psychosis (hallucinations and/or delusions) should also raise the question of whether the child has BP. 2. Hypomania According to the DSM­5, hypomania refers to an episode of at least 4 days of less severe manic symptoms. Hypomania usually causes functional changes, but it is not associated with marked functional impairment or hospitalization. Moreover, sometimes hypomanic youth can improve their functioning, become more creative and “sharp,” work many hours, and become more social and outgoing. The identification of hypomania may be difficult not only because the youth can function better but also because the symptoms need to be differentiated from normal moods and behaviors usually observed in youth. 3. Major depression Downloaded To be diagnosed 2025­2­16 5:19major with DSM­5 P Your IP is depression, a youth needs to have at least five depressive symptoms, and at least one of the symptoms must be Chapter 48: Pediatric Bipolar Disorder, Rasim Diler; Benjamin I. Goldstein; Boris Birmaher Page 7 / 28 either depressive/irritable mood or loss of interest (anhedonia) (APA, 2013). The symptoms should be present daily or for most of the day, or nearly ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility daily for at least 2 weeks, and must be accompanied by impairment of functioning. Similar to the symptoms of mania or hypomania, they cannot be mainly caused by medications, drug abuse, or a medical condition (e.g., hypothyroidism) and should not be accounted for by other psychiatric The identification of hypomania may be difficult not only because the youth can function better but also because the symptomsBarry need University to be Library differentiated from normal moods and behaviors usually observed in youth. Access Provided by: 3. Major depression To be diagnosed with DSM­5 major depression, a youth needs to have at least five depressive symptoms, and at least one of the symptoms must be either depressive/irritable mood or loss of interest (anhedonia) (APA, 2013). The symptoms should be present daily or for most of the day, or nearly daily for at least 2 weeks, and must be accompanied by impairment of functioning. Similar to the symptoms of mania or hypomania, they cannot be mainly caused by medications, drug abuse, or a medical condition (e.g., hypothyroidism) and should not be accounted for by other psychiatric disorders. Depressive symptoms are noted to be prominent features in most phenomenological studies of pediatric BP, and BP adults frequently recall having significant depressive symptoms in childhood or adolescence (Chengappa et al, 2003; Diler, 2007; Duffy, 2012; Egeland et al, 2000; Goodwin et al, 2007; Uchida et al, 2015). Episodes of major depression usually precede the onset of mania/hypomania so that some youth who appear to have only symptoms of depression may actually have BP with depression as their initial presentation. Mild or transient manic symptomatology that does not meet the diagnostic threshold for mania or hypomania may also precede an episode of depression (Axelson et al, 2011b, 2015). All of these factors highlight the need to carefully probe for a history of manic symptoms in youth presenting with depression, particularly in the context of a family history of BP. 4. Subtypes of BP­I disorders Mixed episodes—The majority of youth with BP have symptoms of depression interspersed in some manner with manic symptoms (Birmaher et al, 2007; Diler & Birmaher, 2012). However, only when there are enough symptoms of depression to fulfill the criteria for major depressive episode and at the same time the youth has symptoms of mania (e.g., agitation, expansiveness, and even euphoria) is the diagnosis of a “mixed episode” warranted as per DSM­IV. In DSM­5, “manic episode with mixed features” replaced mixed episodes and require co­occurring three or more depressive symptoms during the course of a manic episode. Youth with mixed presentations may be very irritable, confused, anxious, labile, agitated, depressed, suicidal, and sometimes psychotic. It appears that youth tend to have more mixed presentations than the adults (Birmaher et al, 2009a). This is important because the diagnosis and treatment of mixed BP are more complicated than for episodes of only mania or depression. Rapid cycling—Rapid cycling is defined as four or more distinct mood episodes per year (APA, 2013). Similar to the mixed presentations, rapid cycling is associated with early onset and poor prognosis. Some studies have documented that BP youth have more frequent mood polarity changes than adults with BP (Birmaher et al, 2009a). However, it seems that these studies are not referring to the DSM definition of rapid cycling, but rather rapid mood changes within any given episode (Birmaher et al, 2007). For example, a single manic episode with mixed features could include numerous polarity changes or “cycles.” Similar to the mixed presentations, the frequent variations in mood in youth make the diagnosis and treatment of BP more complex. Subsyndromal mania/hypomania—A large proportion of youth do not fulfill the criteria for mania or hypomania because they do not have the time requirements of 7 days for mania or 4 days for hypomania noted in the DSM­IV and ­5 (Axelson et al, 2011b). These youth usually are diagnosed with BP­NOS or currently labeled in the DSM­5 as unspecified/other specified bipolar and related disorders. Youth with unspecified/other specified BP are younger and have more chronic course, irritability, mixed presentations with less euphoric mania than BP­I, but otherwise phenomenologically in continuum with BD­I (Axelson et al, 2011b; Birmaher et al, 2009; Hirneth et al, 2015). Moreover, youth with unspecified/other specified BP have similar psychosocial impairment, risk to develop substance abuse and suicidal behaviors, rates of comorbid disorders, and family history for mood disorders when compared with youth with BP­I (Axelson et al, 2011b; Birmaher et al, 2007). As described later, youth with unspecified/other specified BP are at high risk to convert into BP­I, especially if they have a family history of BP (Axelson et al, 2011b; Hafeman et al, 2016). Psychosis—Sometimes during an episode of mania or depression, youth may experience delusions or hallucinations (Birmaher et al, 2009c; Kowatch et al, 2005a; Van Meter et al, 2016). For example, during an episode of mania, a child may have grandiose delusions and believe he/she has superpowers and act on these ideas. Also, a youth may be paranoid or, while depressed, have exaggerated guilty feelings. Hallucinations are usually of the auditory type, and youth may hear positive comments or derogatory and negative comments during mood episodes. B. Assessments The assessment of symptoms of mania, hypomania, and depression in youth requires careful probing and, in most cases, longitudinal assessments. In addition to the specific manic/hypomanic and depressive symptoms, it is important to ascertain the frequency, intensity, number, and duration (FIND) of the depressive and manic/hypomanic episodes (Diler & Birmaher, 2012; Kowatch et al, 2005a). Also, given that lack of insight can be associated with Downloaded 2025­2­16 mania or hypomania, it is5:19 P YourtoIPobtain imperative is information from caregivers or other significant adults who know the child well in order to accurately Chapter 48: Pediatric Bipolar Disorder, Rasim Diler; Benjamin I. Goldstein; Boris Birmaher Page 8 / 28 assess ©2025symptoms andAll McGraw Hill. potential change in functioning. Rights Reserved. Importantly, Terms of Use Privacy when Policyassessing Notice the levels of functional impairment or improvement, it is necessary Accessibility to take into account the child’s chronological age and intellectual capabilities and environmental factors.  Barry University Library B. Assessments Access Provided by: The assessment of symptoms of mania, hypomania, and depression in youth requires careful probing and, in most cases, longitudinal assessments. In addition to the specific manic/hypomanic and depressive symptoms, it is important to ascertain the frequency, intensity, number, and duration (FIND) of the depressive and manic/hypomanic episodes (Diler & Birmaher, 2012; Kowatch et al, 2005a). Also, given that lack of insight can be associated with mania or hypomania, it is imperative to obtain information from caregivers or other significant adults who know the child well in order to accurately assess symptoms and potential change in functioning. Importantly, when assessing the levels of functional impairment or improvement, it is necessary to take into account the child’s chronological age and intellectual capabilities and environmental factors. The assessment of mood (and other psychiatric symptoms) can be facilitated by the use of psychiatric interviews and rating scales. These rating scales do not provide diagnoses but help to uncover symptoms that may alert clinicians to further asses for the presence of BP disorder. 1. Psychiatric interviews There are several structured and semistructured interviews that can be used for the diagnosis of BP, including the Kiddie Schedule for Affective Disorders and Schizophrenia for school­age children—Present and Lifetime version (K­SADS­PL) (Kaufman et al, 1997). However, these interviews are lengthy and time­consuming and are mainly used for research purposes. Thus, symptom checklists based on the DSM criteria for BP as well as depressive disorders are also useful screens. 2. Clinician­based rating scales Two clinician­based rating scales are currently used for the assessment of manic symptoms and their severity in youth, the Young Mania Rating Scale (YMRS) and the KSADS Mania Rating Scale that was derived from the KSADS­P mania module (KSADS­MRS) (Axelson et al, 2003; Youngstrom et al, 2005). However, further studies to evaluate the validity of these rating scales are necessary. 3. Youth, parent, and teacher rating scales It appears that parental reports are more effective in identifying mania than youth or teacher reports (Youngstrom et al, 2005, 2015). The General Behavior Inventory (GBI), the parent version of the YMRS (P­YMRS), and more recently the Child Mania Rating Scale for Parents about their children (CMRS­P) (Youngstrom et al, 2005; Pavuluri et al, 2006) have been shown to have at least adequate psychometric properties and to be useful for the screening of BP symptoms in youth. However, further studies to evaluate the specificity of these instruments for BP are warranted. The Children Behavior Checklist (CBCL), a parent­report instrument used to assess general psychopathology, has also been used to screen for BP in youth (Diler et al, 2008; Youngstrom et al, 2005). However, this instrument is not specific to assess mania (Diler et al, 2009). 4. Mood time lines or diaries Mood time lines or diaries, using school years, birthdays, and holidays as anchors, are very helpful in the assessment of the onset and course of mood disorders. These instruments use a simple scale showing daily changes in mood. For example, they can include a scatter line in which 0 is being very sad, 10 exaggeratedly happy, and 5 is normal mood. Alternatively, depression can be measured from −1 to −10 and mania from +1 to +10 in a continuum scale along with the changes in energy levels from −10 to +10 (a.k.a. mood and energy thermometer) (Diler & Birmaher, 2012). The mood diary can include dosages of medications, sleep schedule, and stressors. As noted before, it is important to evaluate for the presence of other psychiatric (e.g., anxiety, ADHD, and substance abuse) and medical conditions, suicidal and homicidal ideations, psychosocial functioning, presence of family psychopathology, and ongoing negative life events (e.g., family conflicts, abuse). Sometimes, if the child has learning problems, psychoeducational testing is necessary. It is worth noting, however, that cognitive dysfunction is commonly associated with BP, even in the absence of antecedent learning disorders. Finally, the appropriate intensity and restrictiveness of care (e.g., hospitalization) need to be evaluated. The need for hospitalization will depend on the severity of mood symptoms, presence of suicidal and/or homicidal symptoms, psychosis, substance abuse, agitation, child’s and parents’ adherence to treatment, parental psychopathology, and family environment (Diler & Birmaher, 2012). 5. Psychological testing None of the existing psychological tests help to diagnose BP. However, these tests may help to determine the IQ and the presence of comorbid learning and/or language problems that may worsen the prognosis of BP and need to be addressed. Psychological testing may also provide some clues to the potential underlying cognitive deficits associated with BP. Several investigations have found Downloaded 2025­2­16 5:19 P Your IP is several cognitive Chapter deficits, 48: Pediatric such Disorder, Bipolar as difficulties Rasimin attentional set­shifting, Diler; Benjamin visuospatial I. Goldstein; Boris memory, Birmaherverbal memory, and executive function in BP youth Page 9 / 28 ©2025 McGraw (Joseph Hill.that et al, 2008) All Rights Reserved. may persist Terms of Use during follow­up Privacy (Pavuluri et al,Policy 2009). There Notice Accessibility is also widespread agreement that cognitive functioning independently and robustly predicts later functional outcomes in BP (Lee et al, 2013). However, a careful history­taking, ideally including school records, in order to help determine whether cognitive dysfunction predates BP, is secondary to BP, is secondary to comorbidities such as ADHD or 5. Psychological testing Barry University Library Access Provided by: None of the existing psychological tests help to diagnose BP. However, these tests may help to determine the IQ and the presence of comorbid learning and/or language problems that may worsen the prognosis of BP and need to be addressed. Psychological testing may also provide some clues to the potential underlying cognitive deficits associated with BP. Several investigations have found several cognitive deficits, such as difficulties in attentional set­shifting, visuospatial memory, verbal memory, and executive function in BP youth (Joseph et al, 2008) that may persist during follow­up (Pavuluri et al, 2009). There is also widespread agreement that cognitive functioning independently and robustly predicts later functional outcomes in BP (Lee et al, 2013). However, a careful history­taking, ideally including school records, in order to help determine whether cognitive dysfunction predates BP, is secondary to BP, is secondary to comorbidities such as ADHD or anxiety, is secondary to the pharmacological treatments use to manage the symptoms of BP, or involves some combination of these factors. 6. Laboratory testing To date, there are no laboratory, electroencephalography, or neuroimaging tests that can help with the diagnosis of BP (APA, 2013). These tests are requested, when indicated, to rule out medical or neurologic illness that may be accounting for the manic or hypomanic symptomatology. Neuroimaging is also used as research tool to evaluate potential neural circuits associated with the etiopathogenesis of BP (Diler et al, 2013a). Current structural, functional, and connectivity brain imaging studies have suggested that several brain networks related to the cognitive (e.g., dorsolateral prefrontal cortex), emotional (e.g., amygdala, ventrolateral prefrontal cortex—vlPFC), and reward (e.g., striatum) functioning of the brain are affected in individuals with BP and at risk to develop BP (Phillips et al, 2008; Schneider et al, 2012). BP is conceptualized as parallel dysfunction in bilateral prefrontal cortical (especially vlPFC)–hippocampal–amygdala emotion processing and emotion regulation neural circuitries, together with an “overactive” left­sided ventral striatal–vlPFC–orbitofrontal cortex reward processing circuitry, which results in the characteristic behavioral abnormalities associated with BP: emotional dysregulation, heightened reward sensitivity, and predisposition to mania (Phillips & Swartz, 2014). However, further studies regarding specificity and predictive validity and whether the changes are trait or state characteristics are warranted. American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013. Axelson DA, Birmaher B, Brent D, et al. A preliminary study of the Kiddie Schedule for Affective Disorders and Schizophrenia for School­Age Children Mania Rating Scale for Children and Adolescents. J Child Adolesc Psychopharmacol. 2003;13(4):463–470. [PubMed: 14977459] Axelson DA, Birmaher B, Findling RL, et al. Concerns regarding the inclusion of temper dysregulation disorder with dysphoria in the Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition. J Clin Psychiatry. 2011a;72(9):1257–1262. [PubMed: 21672494] Axelson DA, Birmaher B, Strober M, et al. Phenomenology of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006;63(10):1139–1148. [PubMed: 17015816] Axelson DA, Birmaher B, Strober MA, et al. Course of subthreshold bipolar disorder in youth: diagnostic progression from bipolar disorder not otherwise specified. J Am Acad Child Adolesc Psychiatry. 2011b;50(10):1001–1016 e3. [PubMed: 21961775] Axelson D, Goldstein B, Goldstein T, et al. Diagnostic precursors to bipolar disorder in offspring of parents with bipolar disorder: a longitudinal study. Am J Psychiatry. 2015;172 (7):638–646. [PubMed: 25734353] Birmaher B, Axelson D, Goldstein B, et al. Four­year longitudinal course of children and adolescents with bipolar spectrum disorders: the Course and Outcome of Bipolar Youth (COBY) study. Am J Psychiatry. 2009a;166(7):795–804. [PubMed: 19448190] Birmaher B, Axelson D, Pavuluri M. Bipolar disorder. In: Martin A, Volkmar FR, Lewis M, eds. Lewis’ Child and Adolescent Psychiatry: A Comprehensive Textbook. 4th ed. London: Lippincott Williams & Wilkins; 2007. Birmaher B, Axelson D, Strober M, et al. Comparison of manic and depressive symptoms between children and adolescents with bipolar spectrum disorders. Bipolar Disord. 2009c;11(1):52–62. [PubMed: 19133966] Chengappa KN, Kupfer DJ, Frank E, et al. Relationship of birth cohort and early age at onset of illness in a bipolar disorder case registry. Am J Psychiatry. 2003;160(9):1636–1642. [PubMed: 12944339] Diler, R.S. Pediatric Bipolar Disorder: A Global Perspective. New York: Nova Science Publishers; 2007a. Downloaded 2025­2­16 5:19 P Your IP is Chapter 48: Pediatric Bipolar Disorder, Rasim Diler; Benjamin I. Goldstein; Boris Birmaher Page 10 / 28 Diler RS, ©2025 Birmaher McGraw Hill.B.All Bipolar Rightsdisorder in children Reserved. Termsand adolescents. of Use Privacy In: Rey JM, Policy ed. IACAPAP Notice e­Textbook of Child and Adolescent Mental Health. Accessibility Geneva: International Association for Child and Adolescent Psychiatry and Allied Professions; 2012. disorders. Bipolar Disord. 2009c;11(1):52–62. [PubMed: 19133966] Barry University Library Access Provided by: Chengappa KN, Kupfer DJ, Frank E, et al. Relationship of birth cohort and early age at onset of illness in a bipolar disorder case registry. Am J Psychiatry. 2003;160(9):1636–1642. [PubMed: 12944339] Diler, R.S. Pediatric Bipolar Disorder: A Global Perspective. New York: Nova Science Publishers; 2007a. Diler RS, Birmaher B. Bipolar disorder in children and adolescents. In: Rey JM, ed. IACAPAP e­Textbook of Child and Adolescent Mental Health. Geneva: International Association for Child and Adolescent Psychiatry and Allied Professions; 2012. Diler RS, Birmaher B, Axelson D, et al. The Child Behavior Checklist (CBCL) and the CBCL­bipolar phenotype are not useful in diagnosing pediatric bipolar disorder. J Child Adolesc Psychopharmacol. 2009;19(1):23–30. [PubMed: 19232020] Diler RS, de Almeida JR, Ladouceur C, et al. Neural activity to intense positive versus negative stimuli can help differentiate bipolar disorder from unipolar major depressive disorder in depressed adolescents: a pilot fMRI study. Psychiatry Res. 2013a;214(3):277–284. [PubMed: 24080517] Diler RS, Uguz S, Seydaoglu G, et al. Mania profile in a community sample of prepubertal children in Turkey. Bipolar Disord. 2008;10(4):546–553. [PubMed: 18452451] Duffy A. The nature of the association between childhood ADHD and the development of bipolar disorder: a review of prospective high­risk studies. Am J Psychiatry. 2012;169(12):1247–1255. [PubMed: 23212056] Egeland JA, Hostetter AM, Pauls DL, Sussex JN. Prodromal symptoms before onset of manic­depressive disorder suggested by first hospital admission histories. J Am Acad Child Adolesc Psychiatry. 2000;39(10):1245–1252. [PubMed: 11026178] Goodwin FK, Jamison KR, Ghaemi SN. Manic­Depressive Illness: Bipolar Disorders and Recurrent Depression. New York: Oxford University Press; 2007. Hafeman DM, Merranko J, Axelson D, et al. Toward the definition of a bipolar prodrome: dimensional predictors of bipolar spectrum disorders in at­ risk youth. Am J Psychiatry. 2016;173(7):695–704. [PubMed: 26892940] Hirneth SJ, Hazell PL, Hanstock TL, et al. Bipolar disorder subtypes in children and adolescents: demographic and clinical characteristics from an Australian sample. J Affect Disord. 2015;175:98–107. [PubMed: 25601309] Holtzman JN, Miller S, Hooshmand F, et al. Childhood­compared to adolescent­onset bipolar disorder has more statistically significant clinical correlates. J Affect Disord. 2015;79:114–120. 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: 19465878] Hunt JI, Case BG, Birmaher B, et al. Irritability and elation in a large bipolar youth sample: relative symptom severity and clinical outcomes over 4 years. J Clin Psychiatry. 2013;74(1):e110–e117. Joseph MF, Frazier TW, Youngstrom EA, et al. A quantitative and qualitative review of neurocognitive performance in pediatric bipolar disorder. J Child Adolesc Psychopharmacol. 2008;18(6):595–605. [PubMed: 19108664] Kaufman J, Birmaher B, Brent D, et al. Schedule for Affective Disorders and Schizophrenia for School­Age Children­Present and Lifetime Version (K­ SADS­PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997;36:980–988. [PubMed: 9204677] Kowatch RA, Fristad M, Birmaher B, et al. Treatment guidelines for children and adolescents with bipolar disorder: child psychiatric workgroup on bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2005a;44:213–255. [PubMed: 15725966] Kowatch RA, Youngstrom EA, Danielyan A, Findling RL. Review and meta­analysis of the phenomenology and clinical characteristics of mania in children and adolescents. Bipolar Disord. 2005b;7:483–496. [PubMed: 16403174] Lee J, Altshuler L, Glahn DC, et al. Social and nonsocial cognition in bipolar disorder and schizophrenia: relative levels of impairment. Am J Psychiatry. 2013;170(3):334–341. [PubMed: 23450289] Downloaded 2025­2­16 5:19 P Your IP is Chapter 48:E,Pediatric Leibenluft Rich BA. Bipolar Disorder, Pediatric Rasim Diler; bipolar disorder. AnnuBenjamin I. Goldstein; Rev Clin Psychol Boris Birmaher. 2008;4:163–187. [PubMed: 17716034] Page 11 / 28 ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Pavuluri MN, Henry DB, Devineni B, et al. Child mania rating scale: development, reliability, and validity. J Am Acad Child Adolesc Psychiatry.  Barry University Kowatch RA, Youngstrom EA, Danielyan A, Findling RL. Review and meta­analysis of the phenomenology and clinical characteristics of mania inLibrary Access Provided by: children and adolescents. Bipolar Disord. 2005b;7:483–496. [PubMed: 16403174] Lee J, Altshuler L, Glahn DC, et al. Social and nonsocial cognition in bipolar disorder and schizophrenia: relative levels of impairment. Am J Psychiatry. 2013;170(3):334–341. [PubMed: 23450289] Leibenluft E, Rich BA. Pediatric bipolar disorder. Annu Rev Clin Psychol. 2008;4:163–187. [PubMed: 17716034] Pavuluri MN, Henry DB, Devineni B, et al. Child mania rating scale: development, reliability, and validity. J Am Acad Child Adolesc Psychiatry. 2006;45(5):550–560. [PubMed: 16601399] Pavuluri MN, West A, Hill SK. Neurocognitive function in pediatric bipolar disorder: 3­year follow­up shows cognitive development lagging behind healthy youth. J Am Acad Child Adolesc Psychiatry. 2009;48(3):299–307. [PubMed: 19182689] Phillips ML, Ladouceur CD, Drevets WC. A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Mol Psychiatry. 2008;13(9):829. [PubMed: 18574483] 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. 2014; 171(8):829–843. [PubMed: 24626773] Schneider MR, DelBello MP, McNamara RK, et al. Neuroprogression in bipolar disorder. Bipolar Disord. 2012;14(4):356–374. [PubMed: 22631620] Uchida M, Serra G, Zayas L, et al. Can unipolar and bipolar pediatric major depression be differentiated from each other? A systematic review of cross­sectional studies examining differences in unipolar and bipolar depression. J Affect Disord. 2015;176:1–7. [PubMed: 25682377] Van Meter AR, Burke C, Kowatch RA, et al. Ten­year update meta­analysis of the clinical characteristics of pediatric mania and hypomania. Bipolar Disord. 2016;18(1):19–32. [PubMed: 26748678] Wozniak J. Recognizing and managing bipolar disorder in children. J Clin Psychiatry. 2005;66(Suppl 1):18–23. [PubMed: 15693748] Youngstrom E, Meyers O, Demeter C, et al. Comparing diagnostic checklists for pediatric bipolar disorder in academic and community mental health settings. Bipolar Disord. 2005;7(6):507–517. [PubMed: 16403176] Youngstrom EA, Egerton GA, Van Meter AR. Multivariate meta­analysis of the discriminative validity of caregiver, youth and teacher rating scales for pediatric bipolar disorder: mother knows best about mania. Arch Scien Psychology. 2015;3:112–137. COURSE OF ILLNESS Several prospective naturalistic studies have consistently shown that 70– 100% of children and adolescents with BP will recover (e.g., no significant symptoms for 2 months) from their index episode (Birmaher, 2007; Birmaher et al, 2009a, 2014; DelBello et al, 2007b; Geller et al, 2008). However, of those who recover, up to 80% will experience one or more recurrences in a period of 2–5 years. These studies have shown high rates of hospitalization and health service utilization, psychosis, suicide attempts and completion, switch from BP­NOS to BP­I or II and from BP­II to BP­I, substance abuse, unemployment, legal problems, and poor academic and psychosocial functioning (Birmaher et al, 2009a; Geller et al, 2008; Goldstein et al, 2009a, 2012, 2013). The persistent BP symptoms also have a negative impact on family, marital, and sibling relationships, as well as on family economics. The considerable impairment in psychosocial functioning reported in these studies is not only specific to the fact that most of the BP youth studies have been carried out in clinical samples, because similar findings have been reported in BP adolescents never referred for treatment (Lewinsohn et al, 2000). Recent studies have shown that BP is not only manifested by recovery and recurrences but also by ongoing fluctuating syndromal and subsyndromal symptomatology (Birmaher et al, 2009a; DelBello et al, 2007b). In general, BP youth have syndromal and subsyndromal BP symptoms, particularly depressive and mixed symptoms, in about 60% of the follow­up time (Birmaher et al, 2009a). In addition, within each episode, youth manifest more fluctuations in mood than adults with BP (Birmaher et al, 2009a). This may explain, at least in part, the difficulties encountered diagnosing and treating BP symptoms in youth. A recent study evaluated a more individualized course during a 9­year period using latent growth class analyses (Birmaher et al, 2014). Four longitudinal mood trajectories were found: “predominantly euthymic” course (24.0%), “moderately euthymic” course (34.6%), “ill with improving course” Downloaded (19.1%), 2025­2­16 and 5:19 P “predominantly Your IP is ill” course (22.3%). Within each group, youth were euthymic on average 84.4%, 47.3%, 42.8%, and Chapter 11.5% of 48: Pediatric Bipolar the follow­up Disorder, Rasim time, respectively. Diler; The fact thatBenjamin I. Goldstein; a substantial Boris have group of youth Birmaher PageBP good course gives youth and their families hope that 12 / 28 ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility disorder does not necessarily convey poor prognosis (Birmaher et al, 2014). Nonetheless, continued syndromal and subsyndromal mood symptoms in all four classes underscore the need to optimize treatment (Birmaher, 2016). symptomatology (Birmaher et al, 2009a; DelBello et al, 2007b). In general, BP youth have syndromal and subsyndromal BP symptoms, particularly Barry University Library depressive and mixed symptoms, in about 60% of the follow­up time (Birmaher et al, 2009a). In addition, within each episode, youth manifest more Access Provided by: fluctuations in mood than adults with BP (Birmaher et al, 2009a). This may explain, at least in part, the difficulties encountered diagnosing and treating BP symptoms in youth. A recent study evaluated a more individualized course during a 9­year period using latent growth class analyses (Birmaher et al, 2014). Four longitudinal mood trajectories were found: “predominantly euthymic” course (24.0%), “moderately euthymic” course (34.6%), “ill with improving course” (19.1%), and “predominantly ill” course (22.3%). Within each group, youth were euthymic on average 84.4%, 47.3%, 42.8%, and 11.5% of the follow­up time, respectively. The fact that a substantial group of youth have good course gives youth and their families hope that BP disorder does not necessarily convey poor prognosis (Birmaher et al, 2014). Nonetheless, continued syndromal and subsyndromal mood symptoms in all four classes underscore the need to optimize treatment (Birmaher, 2016). Overall, across the extant studies, early age of onset, long duration, low SES, mixed or rapid cycling episodes, psychosis, subsyndromal symptoms, comorbid disorders, exposure to negative life events, and family psychopathology are associated with worse course and outcome (Birmaher et al, 2009a, 2014; DelBello et al, 2007b; Geller et al, 2008). When followed prospectively for approximately 5 years, about 50% of the youth diagnosed with BP­NOS convert into BP­I or ­II (Axelson et al, 2011b). The main predictor of conversion is the presence of a family history of mania in first­ or second­degree relatives. In a different study with offspring of BP parents, those with mood lability, depression/anxiety, and subsyndromal manic symptoms, and early­onset parental BP were at 50% risk to develop BP (Hafeman et al, 2016). DIFFERENTIAL DIAGNOSIS A. Comorbid Disorders The most common disorders found in youth with BP are ADHD, oppositional defiant disorder (ODD), conduct disorder (CD), and anxiety disorders (Axelson et al, 2006; Birmaher, 2016; Birmaher et al, 2007; Kowatch et al, 2005b; Miller et al, 2013). The prevalence of these disorders varies depending on the population studied and the methods used to ascertain them, but in general the rates fluctuate between 20% and 80%. Beginning in adolescence, the rate of comorbid substance abuse progressively increases (Goldstein et al, 2008, 2013; Wilens et al, 2004). The presence of these disorders affects the youth’s response to treatment and prognosis, indicating the need to identify and treat them effectively. In addition to the psychiatric comorbidity, the presence of medical illnesses is a major concern in BP. There are not many studies in youth, but cardiovascular disease in BP adults is both exceedingly prevalent and premature, leading to excessive cardiovascular mortality (Goldstein et al, 2009b). Although psychiatric medications are associated with metabolic disturbances, the association between BP and cardiovascular disease was observed before the advent of modern medications. In youth, BP may also incur increased risk of medical comorbidities, with 28–36% suffering from multiple medical conditions, whereas this is true for only 8% of youth with other psychiatric disorders combined (Evans­Lacko et al, 2009; Jerrell et al, 2010). Obesity, hypertension, and diabetes are highly prevalent and often precede BP, and use of specialty cardiology services is doubled. Migraine, asthma, and neurological conditions such as epilepsy may also co­occur disproportionately with BP (Evans­Lacko et al, 2009; Jerrell et al, 2010). Clinicians should pay particular attention to these medical complications when assessing and following youth with BP spectrum disorders. B. Difficulties Diagnosing Youth with BP The following factors make the diagnosis of BP in youth challenging: (1) the inherent variability in the clinical presentation of BP—youth with BP can present clinically with different degrees of severity, various subtypes (e.g., BP­I or II), and phases of the illness (e.g., depression, manic, mixed); (2) the effects of development in symptom expression; (3) children’s problems communicating their symptoms, in particular elation and grandiosity; (4) the presence of comorbid conditions, especially those whose symptoms overlap with the symptoms of mania (e.g., ADHD) manifested with symptoms of mania or hypomania; (5) the environmental context where BP is developing (e.g., family conflicts, parental symptomatology, parental viewpoints regarding symptoms); and (6) if the youth is on medications, their potential effects on the child’s mood. Regarding the effects of development (item 2), it is crucial to evaluate whether the mood symptoms are abnormal or clearly different from the child’s usual mood and behavior given the context and developmental level. For instance, elevated mood, high activity level, and rapid speech would not be considered evidence of mania symptoms in a child who is very happy during his birthday party or in an amusement park. Also, it is common for young children to believe that they are the best players, dancers, and so forth. However, children usually do not perform extreme risky behaviors when they are acting out their fantasies (e.g., trying to fly from the third floor of a building because they think that they are Superman). Also, a school­age child is not likely to perform risky business ventures, drive recklessly, go on spending sprees, or have sexual relations with multiple partners. However, they can exhibit inappropriate sexual behavior (e.g., without having history of exposure to sex, they can touch others inappropriately, frequently masturbate, or draw sexually provocative pictures). Concerning the presence of comorbid disorders (item 3), the main psychiatric conditions that can be difficult to differentiate from youth with BP are Downloaded 2025­2­16 ADHD, disruptive 5:19 disorders P Your (ODD IP isthe new DSM­5 Disruptive Mood Dysregulation Disorder (DMDD) (most of these children also meet criteria and CD), Chapter 48: Pediatric Bipolar Disorder, for ODD and/or ADHD), unipolar depression,Rasim Diler; Benjamin pervasive I. Goldstein; developmental Boris disorders Birmaher (PDD), Page 13 / 28 schizophrenia, substance use disorders, and, although its use ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility in youth below the age of 18 years is controversial, borderline personality disorder. Medical and neurological illnesses (e.g., head trauma, brain tumors, hyperthyroidism), and side effects of medications (e.g., corticosteroids, antidepressants, and stimulants) may be accompanied by mood are acting out their fantasies (e.g., trying to fly from the third floor of a building because they think that they are Superman). Also, a school­age child is Barry University Library not likely to perform risky business ventures, drive recklessly, go on spending sprees, or have sexual relations with multiple partners. However, they Access Provided by: can exhibit inappropriate sexual behavior (e.g., without having history of exposure to sex, they can touch others inappropriately, frequently masturbate, or draw sexually provocative pictures). Concerning the presence of comorbid disorders (item 3), the main psychiatric conditions that can be difficult to differentiate from youth with BP are ADHD, disruptive disorders (ODD and CD), the new DSM­5 Disruptive Mood Dysregulation Disorder (DMDD) (most of these children also meet criteria for ODD and/or ADHD), unipolar depression, pervasive developmental disorders (PDD), schizophrenia, substance use disorders, and, although its use in youth below the age of 18 years is controversial, borderline personality disorder. Medical and neurological illnesses (e.g., head trauma, brain tumors, hyperthyroidism), and side effects of medications (e.g., corticosteroids, antidepressants, and stimulants) may be accompanied by mood fluctuations that may mimic BP. Also, normal mood variability sometimes may be misinterpreted as symptoms of hypomania. Because the disruptive behavioral disorders and ADHD are the most frequent conditions that may be confused with BP, they deserve detailed assessment (Birmaher, 2004). There are some symptoms that mainly occur in BP youth and may help to differentiate between BP and these disorders, such as clinically relevant euphoria, grandiosity, decreased need for sleep, hypersexuality (without history of sexual abuse or exposure to sex), and hallucinations. The course of the symptoms over time is one of the more important factors helping differentiate BP from these disorders. Family history of BP may help, but offspring of parents with BP may suffer from other disorders such as ADHD and ODD. In general, chronic symptoms such as hyperactivity or distractibility generally should not be considered evidence of mania unless they clearly intensify with the onset of abnormal mood. Prolonged presentations of nonspecific manic­like symptoms that do not change in overall intensity should raise the possibility of an alternative psychiatric diagnosis. Most depressed youth seen in psychiatric clinics are experiencing their first episode of depression (Birmaher et al, 2007, 2009a). The presence of psychosis, family history of BP, and pharmacologically induced mania/hypomania may indicate susceptibility to develop BP (Geller et al, 1994; Strober & Carlson, 1982; Uchida et al, 2014). However, the clinical picture of depression is not sufficiently specific to help differentiate between depressed youth with BP and those with unipolar depression. Thus, it is important to continue to follow these youth longitudinally and continue to evaluate for the presence of manic or hypomanic symptoms. Due to the controversy regarding irritability as a key symptom for the diagnosis of pediatric BP, the DSM­5 included a new disorder in the category of mood disorders entitled Disruptive Mood Dysregulation Disorder (DMDD). This disorder is characterized by frequent, severe, recurrent temper outbursts and chronically irritable and/or angry mood, both of which must be present for at least a year and cannot be accounted by other mood disorders (and cannot be diagnosed if the child meets criteria for BP diagnosis). Moreover, perhaps with the exception of severely irritable youth with positive family history of mania, longitudinal data indicate that youth with severe mood dysregulation (SMD), the condition from which DMDD was derived, are not at high risk to develop BD as they age (Towbin et al, 2013). Schizophrenia is very rare in children. Thus, if a youth presents with symptoms of psychosis, mood disorders need to be ruled out. Youth with subsyndromal symptoms of autism spectrum disorders (a.k.a. PDD) including Asperger disorder (or mild autism) may have mood lability, aggression, and agitation and may be misdiagnosed as having BP. Substance abuse may also induce severe mood changes that may be difficult to differentiate from BP. Moreover, youth with mood disorders are at higher risk for using illicit drugs or alcohol for a number of reasons including self­medication, impulsivity, and reward seeking. The use of medications such as the antidepressants may unmask or precipitate a manic or hypomanic episode in a susceptible individual (Martin et al, 2004). However, not every child who becomes agitated or giddy and excited with these or other medications has BP. Family history and the severity, length, and quality of manic symptomatology may help to differentiate between BP or agitation induced by these or other medications (Birmaher et al, 2007; Pavuluri et al, 2005). In the DSM­5, a new “medication/substance induced bipolar and related disorders” diagnosis is introduced for those who develop a manic episode during medication or substance use (APA, 2013). Finally, although there is controversy about the validity of borderline personality disorder in youth, some BP teens, particularly those with BP­II, may be misdiagnosed as having this condition. Even in the absence of a full diagnosis, borderline personality­spectrum symptoms are common and associated with increased burden of psychiatric symptoms and impairment (Fonseka et al, 2015; Yen et al, 2015). American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013. Axelson DA, Birmaher B, Strober M, et al. Phenomenology of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006;63(10):1139–1148. [PubMed: 17015816] Axelson DA, Birmaher B, Strober MA, et al. Course of subthreshold bipolar disorder in youth: diagnostic progression from bipolar disorder not otherwise specified. J Am Acad Child Adolesc Psychiatry. 2011b;50(10):1001–1016 e3. [PubMed: 21961775] Downloaded 2025­2­16 5:19 P Your IP is Birmaher B. New Hope for Children and Teens with Bipolar Disorder. New York: Three Rivers Press; 2004. Chapter 48: Pediatric Bipolar Disorder, Rasim Diler; Benjamin I. Goldstein; Boris Birmaher Page 14 / 28 ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Birmaher B. Longitudinal course of pediatric bipolar disorder. Am J Psychiatry. 2007;164(4):537–539. [PubMed: 17403961] Axelson DA, Birmaher B, Strober M, et al. Phenomenology of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006;63(10):1139–1148. [PubMed: 17015816] Barry University Library Access Provided by: Axelson DA, Birmaher B, Strober MA, et al. Course of subthreshold bipolar disorder in youth: diagnostic progression from bipolar disorder not otherwise specified. J Am Acad Child Adolesc Psychiatry. 2011b;50(10):1001–1016 e3. [PubMed: 21961775] Birmaher B. New Hope for Children and Teens with Bipolar Disorder. New York: Three Rivers Press; 2004. Birmaher B. Longitudinal course of pediatric bipolar disorder. Am J Psychiatry. 2007;164(4):537–539. [PubMed: 17403961] Birmaher B. Pediatric bipolar disorder: epidemiology, pathogenesis, clinical manifestations and course. UpToDate. Accessed January 2016. Birmaher B, Axelson D, Goldstein B, et al. Four­year longitudinal course of children and adolescents with bipolar spectrum disorders: the Course and Outcome of Bipolar Youth (COBY) study. Am J Psychiatry. 2009a;166(7):795–804. [PubMed: 19448190] Birmaher B, Gill MK, Axelson D, et al. Longitudinal trajectories and associated baseline predictors in youth with bipolar spectrum disorders. Am J Psychiatry. 2014;171(9):990–999. [PubMed: 24874203] DelBello MP, Hanseman D, Adler CM, et al. Twelve­month outcome of adolescents with bipolar disorder following first hospitalization for a manic or mixed episode. Am J Psychiatry. 2007b;164(4):582–590. [PubMed: 17403971] Diler RS, Birmaher B. Bipolar disorder in children and adolescents. In: Rey JM, ed. IACAPAP e­Textbook of Child and Adolescent Mental Health. Geneva: International Association for Child and Adolescent Psychiatry and Allied Professions; 2012. Evans­Lacko SE, Zeber JE, Gonzalez JM, Olvera RL. Medical comorbidity among youth diagnosed with bipolar disorder in the United States. J Clin Psychiatry. 2009;70(10):1461–1466. [PubMed: 19744408] Fonseka TM, Swampillai B, Timmins V, et al. Significance of borderline personality­spectrum symptoms among adolescents with bipolar disorder. J Affect Disord. 2015;170:39–45. [PubMed: 25233237] Geller B, Fox LW, Clark KA. Rate and predictors of prepubertal bipolarity during follow­up of 6­ to 12­year­old depressed children. J Am Acad Child Adolesc Psychiatry. 1994;33(4):461–468. [PubMed: 8005898] Geller B, Tillman R, Bolhofner K, Zimerman B. Child bipolar I disorder: prospective continuity with adult bipolar I disorder; characteristics of second and third episodes; predictors of 8­year outcome. Arch Gen Psychiatry. 2008;65(10):1125–1133. [PubMed: 18838629] Goldstein BI, Fagiolini A, Houck P, Kupfer DJ. Cardiovascular disease and hypertension among adults with bipolar I disorder in the United States. Bipolar Disord. 2009b;11(6):657–662. [PubMed: 19689508] Goldstein BI, Strober M, Axelson D, et al. Predictors of first­onset substance use disorders during the prospective course of bipolar spectrum disorders in adolescents. J Am Acad Child Adolesc Psychiatry. 2013;52(10):1026–1037. [PubMed: 24074469] Goldstein BI, Strober MA, Birmaher B, et al. Substance use disorders among adolescents with bipolar spectrum disorders. Bipolar Disord. 2008;10(4):469–478. [PubMed: 18452443] Goldstein T, Ha W, Axelson DA, et al. Predictors of prospectively examined suicide attempts among youth with bipolar disorder. Arch Gen Psychiatry. 2012;69(11):1113–1122. [PubMed: 22752079] Goldstein TR, Birmaher B, Axelson D, et al. Psychosocial functioning among bipolar youth. J Affect Disord. 2009a;114(1–3):174–183. [PubMed: 18715651] Hafeman DM, Merranko J, Axelson D, et al. Toward the definition of a bipolar prodrome: dimensional predictors of bipolar spectrum disorders in at­ risk youth. Am J Psychiatry. 2016;173(7):695–704. [PubMed: 26892940] Jerrell JM, McIntyre RS, Tripathi A. A cohort study of the prevalence and impact of comorbid medical conditions in pediatric bipolar disorder. J Clin Psychiatry. 2010;71(11):161–168. Kowatch RA, 2025­2­16 Downloaded Youngstrom5:19 EA,PDanielyan A, Findling RL. Review and meta­analysis of the phenomenology and clinical characteristics of mania in Your IP is children 48: Chapter andPediatric adolescents. Bipolar Bipolar DisordRasim Disorder,. 2005b;7:483–496. [PubMed: Diler; Benjamin 16403174] I. Goldstein; Boris Birmaher Page 15 / 28 ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Lewinsohn PM, Klein DN, Seeley JR. Bipolar disorder during adolescence and young adulthood in a community sample. Bipolar Disord. 2000;2:281– 293. [PubMed: 11249806] risk youth. Am J Psychiatry. 2016;173(7):695–704. [PubMed: 26892940] Barry University Library Access Provided by: Jerrell JM, McIntyre RS, Tripathi A. A cohort study of the prevalence and impact of comorbid medical conditions in pediatric bipolar disorder. J Clin Psychiatry. 2010;71(11):161–168. Kowatch RA, Youngstrom EA, Danielyan A, Findling RL. Review and meta­analysis of the phenomenology and clinical characteristics of mania in children and adolescents. Bipolar Disord. 2005b;7:483–496. [PubMed: 16403174] Lewinsohn PM, Klein DN, Seeley JR. Bipolar disorder during adolescence and young adulthood in a community sample. Bipolar Disord. 2000;2:281– 293. [PubMed: 11249806] Martin A, Young C, Leckman JF, et al. Age effects on antidepressant­induced manic conversion. Arch Pediatr Adolesc Med. 2004;158(8):773–780. [PubMed: 15289250] Miller S, Chang KD, Ketter TA. Bipolar disorder and attention­deficit/hyperactivity disorder comorbidity in children and adolescents: evidence based approach to diagnosis and treatment. J Clin Psychiatry. 2013;74(6):628–629. [PubMed: 23842014] Pavuluri MN, Birmaher B, Naylor MW. Pediatric bipolar disorder: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry. 2005;44(9):846– 871. [PubMed: 16113615] Strober M, Carlson G. Bipolar illness in adolescents with major depression: clinical, genetic, and psychopharmacologic predictors in a three­ to four­ year prospective follow­up investigation. Arch Gen Psychiatry. 1982;39(5):549–555. [PubMed: 7092488] Towbin K, Axelson D, Leibenluft E, et al. Differentiating bipolar disorder­not otherwise specified and severe mood dysregulation J Am Acad Child Adolesc Psychiatry. 2013;52(5):466–481. [PubMed: 23622848] 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: 15502597] Yen S, Frazier E, Hower H, et al. Borderline personality disorder in transition age group in youth with bipolar disorder. Acta Psychiatr Scand. 2015;132(4):270–280. [PubMed: 25865120] TREATMENT A. General Considerations The treatment of BP is subdivided into acute and maintenance phases. The main aim of the acute treatment is to stop the acute mood symptoms and related functional decline. The maintenance phase aims to prevent relapses and recurrences (new episodes). In each one of these phases, the treatment may change according to the polarity of the episode (mania, hypomania, mixed, rapid cycling, psychosis, and depression). In addition, the type, dosage, and length of treatment depend of the age of the child, presence of comorbid psychiatric and medical illness, and tolerance to the side effects induced by these treatments. All types of treatments require comprehensive education for the parents and the youth and other people such as teachers about the nature of the illness and consequences if it remains untreated. In addition, the education should encompass a review of the existent psychosocial and pharmacological treatments with their positive and potential negative consequences and need to adhere to the treatment to avoid relapses and further recurrences. The vast majority of randomized controlled trials (RCT) for youth with BP pertain to the acute treatment of youth with BP­I with manic or mixed presentations (Liu et al, 2011). There are no controlled studies for youth with BP­II, and there are limited studies focusing on maintenance and prevention (recurrences). Thus, until further studies become available, the management of these conditions is strongly informed by the adult literature. However, it is important to note that not all the treatments that seem to work or are well tolerated in adults will be appropriate for the treatment of youth. When medications are employed, the minimum clinically effective dose with the fewest side effects should be used. Unless there are significant side effects, in the presence of ongoing symptoms, the medications should be increased to the maximum tolerated dose found to be safe in youth to Downloaded determine the2025­2­16 5:19 full efficacy P Your of the IP is This process of dose optimization should be undertaken before adding another medication. Ongoing medication. Chapter 48: Pediatric Bipolar Disorder, Rasim Diler; evaluation of adherence and barriers to adherence, Benjamin including I. effects side Goldstein; Boris (which could reduce adherence), is warranted (Diler & Birmaher,Page Birmaher 2012;16 / 28 ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Kowatch et al, 2005a). It is important to assess the risk of overdose, whether accidental or purposeful. If necessary, regardless of the youth’s age, a responsible adult should prevention (recurrences). Thus, until further studies become available, the management of these conditions is strongly informed by the adult Barry University Library literature. However, it is important to note that not all the treatments that seem to work or are well tolerated in adults will be appropriate for the Access Provided by: treatment of youth. When medications are employed, the minimum clinically effective dose with the fewest side effects should be used. Unless there are significant side effects, in the presence of ongoing symptoms, the medications should be increased to the maximum tolerated dose found to be safe in youth to determine the full efficacy of the medication. This process of dose optimization should be undertaken before adding another medication. Ongoing evaluation of adherence and barriers to adherence, including side effects (which could reduce adherence), is warranted (Diler & Birmaher, 2012; Kowatch et al, 2005a). It is important to assess the risk of overdose, whether accidental or purposeful. If necessary, regardless of the youth’s age, a responsible adult should manage the medications. This is also true for cases where diversion of medication (stimulants and benzodiazepines in particular) might be an issue. Providing a limited supply of the medication or changing to another medication may be necessary in these cases. B. Psychopharmacologic Interventions 1. Acute treatment phase BP­I manic or mixed episodes—Monotherapy with traditional mood stabilizers (lithium, valproate, and carbamazepine) and second­generation antipsychotics (SGAs) (e.g., risperidone, olanzapine, aripiprazole, quetiapine, and asenapine) is indicated for the acute treatment of BP­I manic or mixed episode without psychosis (Correll et al, 2010; DelBello et al, 2005, 2007a, 2008; Findling et al, 2009, 2013, 2015a, 2015b; Geller et al, 2012; Haas et al, 2009; Liu et al, 2011; Pathak et al, 2013; Tohen et al, 2007; Wagner et al, 2006, 2009). Of these medications, most acute RCTs have shown that the SGAs (response: 50–68%) are more effective than the traditional mood stabilizers (response: 23–55%) and yield a quicker response (Correll et al, 2010; Findling et al, 2013, 2015a, 2015b; Fraguas et al, 2011; Kowatch et al, 2000; Meduri et al, 2016). However, as noted later, it is not yet well known whether the SGAs are also useful and safe for the prevention of further mood recurrences in youth with BP. Lithium was approved for youth 12 years and older with BP­I before any RCT in youth, and the recent RCT with lithium in youth aged from 7 to 17 years old with mixed or manic episodes suggested that 47% of youth responded to lithium (very much/much improved on Clinical Global Impression) compared to 21% of those to placebo (Findling et al, 2015b). Open treatment with carbamazepine indicates that this medication appears to be effective and safe for BP youth, but RCTs are needed to confirm this (Findling et al, 2014). An RCT for oxcarbazepine was negative (Wagner et al, 2006). Further validation for the acute efficacy of the SGAs was given by a recent large controlled, randomized 8­week parallel comparison of risperidone, lithium carbonate, and valproate (Geller et al, 2012). Youth responded significantly better to risperidone (68.5%) than to lithium (35.6%) or valproate (24%) However, there were site differences, with some sites also showing good respond to lithium. As expected, risperidone was associated with more metabolic side effects. The dosages for each of the foregoing medications are noted in Table 48–2. It is important to emphasize that the dosages of lithium, valproate, and carbamazepine depend o