BIPOLAR DISORDER IN YOUTH
From Day of Discovery Conference on Youth Psychiatric Issues: Disruptive Behavior, Disrupted Lives, presented by the
Medical University of South Carolina
Matthew Koval, MD, Associate Professor, Department of Psychiatry and Behavioral Sciences, Youth Division, Medical
University of South Carolina, Charleston
| Introduction: mania and hypomania may be difficult to diagnose in young people; features generally agreed on include
1) chronicity with long episodes (sometimes ≥2 yr), 2) mostly mixed episodes and/or rapid cycling, 3) predominantly
irritable mood, 4) high rate of comorbid attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders,
and 5) family history helpful in making diagnosis
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| Bipolar disorder in youth: generally agreed that it exists in children who meet Diagnostic and Statistical Manual of
Mental Disorders, Fourth Edition (DSM-IV) criteria, but what about children who do not meet full criteria? in
children—4-day duration of hypomania or 7-day duration of mania sometimes not seen; irritable mood far more common
than elevated mood; sleep sometimes not significantly disturbed; adult symptoms of grandiosity, excessive spending,
and hypersexuality not easily defined in children (depends on child’s age) and must be assessed on individual
basis; clear episodicity sometimes not present; in addition, symptoms not described in adult criteria have been attributed
to juvenile mania (including chronic mania or baseline manic-like state), ultrarapid cycling (5-364 cycles/yr), ultradian
cycling (>365 cycles/yr), and affective storm; debate further confused by fact that symptoms of mania and
hypomania overlap with other psychiatric disorders, and in young patients, comorbidity is rule, not exception; symptoms
often overlap with symptoms of other psychiatric disorders
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| What is unique to bipolar disorder? grandiosity and elevated mood most useful for distinguishing bipolar disorder
from ADHD in youth; other features include flight of ideas, decreased need for sleep, hypersexuality, and increased goal-
directed activity; grandiosity may be difficult to detect in children (may be braggarts about “what they want to be when
they grow up,” without realizing those occupations may be unrealistic or unattainable); hypersexuality even more difficult
to detect in younger children, who have no experience of sexuality, and in teenagers, who usually have intense interest in
sexuality
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| Media fuel for debate: rate of bipolar disorder in young people increasing; news-reporting media exploit and sensationalize
these statistics; one news magazine depicted child with bipolar disorder as monster waiting to erupt into violence;
media promote treatment for children with bipolar disorder, but also question if those children are being
overmedicated
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| How to resolve debate? adolescent bipolar disorder similar to adult form of illness, and data suggest diagnostic continuity;
suggested that prepubertal bipolar disorder can present as “narrow,” “intermediate 1,” “intermediate 2,” and
“broad” phenotypes; narrow phenotype—defined as meeting DSM-IV criteria for mania or hypomania, including duration
and hallmark symptoms of elevated mood and grandiosity; intermediate 1 phenotype—defined as hallmark
symptoms of short duration (1-3 days; categorized in DSM-IV as mania or hypomania not otherwise specified [NOS]);
intermediate 2 phenotype—defined as episodic irritable mania or hypomania that meets duration criterion but without
elation; broad phenotype—defined as nonepisodic irritability and hyperarousal without hallmark symptoms
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 | Problems with phenotypes: intermediate and broad phenotypes should be termed bipolar disorder NOS; broad phenotype
represents most referrals to mental health care providers, but no evidence that patients with intermediate or
broad phenotypes go on to have adult bipolar disorder (narrow phenotype shows most continuity with adult bipolar
disorder); most treatment recommendations in literature based on narrow phenotype
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| Continuity of mania: high rates of “mania” described in clinical samples of children with ADHD, but follow-up
studies did not show increased bipolar disorder when these patients reached adulthood
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| Continuity of bipolar disorder NOS: subsyndromal cases of bipolar disorder showed increased psychopathology
and increase in adverse outcomes, but no increase in diagnoses of “classic” bipolar types I or II; at follow-up, when
youth with subsyndromal cases compared with youth that had full syndrome, both groups had increased risk for symptoms
of antisocial and borderline personality disorders
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| Misbehavior vs bipolar behavior: bipolar disorder has known course, prognosis, “aura” with providers, and stigma
with public, raising question of whether diagnosis of bipolar diagnosis NOS should be given when not known if broad
phenotype really is bipolar disorder; does label of “NOS” make patients vulnerable to aggressive pharmacotherapy
with little supporting data? does diagnosis of bipolar disorder provide parents and youth with excuse for problematic or
criminal behavior? is there negative impact on person who has been given NOS label? diagnosis of bipolar disorder
NOS common, and patients have significant emotional and behavioral dysregulation, often comorbid with other serious
psychiatric disorders; these patients go on to display significant impairment as adults, and they need and deserve
treatment
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| Assessment measures: recent study compared 6 screening instruments for bipolar disorder; found that when parents
used Parent Version of Young Mania Rating Scale (P-YMRS) or Parent General Behavior Inventory (PGBI), they outperformed
teachers and patients themselves in identifying bipolar disorder in children; no benefit seen in combining
screening instruments
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| Comorbidity: juvenile bipolar disorder more often than not accompanied by other Axis I and Axis II diagnoses; most
common comorbidities include ADHD, oppositional-defiant disorder/conduct disorder (ODD/CD), and anxiety disorders;
in younger children, ADHD seen most often; in adolescents, substance abuse most common; pervasive developmental
disorders (PDDs), primarily Asperger’s syndrome, also seen
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| Prevention: screen patients with family history of affective disorder; evidence suggests that youth often have ≥1 depressive
episodes before first manic or hypomanic episode; factors that predict development of mania—depression with
rapid onset, psychomotor retardation, or psychosis; family history of affective disorders, especially bipolar disorder; history
of hypomania or mania when treated with antidepressant
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| Practice parameter for assessment and treatment of children and adolescents with bipolar disorder:
from American Academy of Child and Adolescent Psychiatry (AACAP); clinical presentation of juvenile mania includes
child being frequently psychotic, mood being markedly labile or mixed, disorder being chronic and refractory
to treatment, and prognosis being similar to or worse than that of adults; reports of very early onset of bipolar disorder
in children raise questions about appropriateness of applying adult criteria to toddlers; validity of diagnosing bipolar
disorder in preschool children has not been established, and caution should be exercised in making diagnosis in
anyone ≤6 yr of age
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| Recommendations: screening—1) psychiatric assessment of children and adolescents should include screening questions
for bipolar disorder and questions about family history; context of emotional and behavioral dysregulation should
be ascertained; assessment—2) use DSM-IV-TR (Text Revision) criteria when diagnosing mania or hypomania in
children and adolescents; 3) use diagnosis of bipolar disorder NOS to describe youth with manic symptoms that last ≤4
days and for those with chronic mania-like symptoms that represent their baseline level of functioning; scant evidence
base from which to extrapolate treatment recommendations; remember high comorbidity with ADHD, disruptive behavior
disorders, posttraumatic stress disorder (PTSD) and other anxiety disorders, and developmental delay; 4) those
with suspected bipolar disorder must be carefully evaluated for associated problems, including suicidality, comorbid
disorders (including substance abuse), psychosocial stressors, and medical problems; rates of suicide and substance
abuse high in this population; 5) diagnostic validity of bipolar disorder in young children not established; exercise caution
in applying this diagnosis to preschool children; be mindful of stigma of bipolar disorder and of tendency for aggressive
administration of pharmacotherapy in youth with this diagnosis
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| Treatment recommendations: based on adult data; likely more appropriate in narrow phenotype or adolescent presentation;
goals of treatment—ameliorate symptoms; provide education to patient and family; promote treatment adherence
to prevent relapse; reduce long-term morbidity; promote normal growth and development
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| Treatment considerations: no medications except lithium approved by Food and Drug Administration (FDA) in
children and adolescents; lithium approved only for children ≥12 yr of age, and approval was “grandfathered in” when
lithium approved for adults; few drug studies in youth (most were open label, and most required “rescue medications”
for aggression, psychosis, and sleep disturbances); data suggest that manic switching can be induced by antidepressants
in youth (as in adults); results conflicting whether administration of stimulants worsens mania; in juvenile bipolar
disorder, atypical antipsychotics helpful when used alone or in combination with traditional agents; traditional mood
stabilizers were not promising for maintenance therapy, and no published studies looked at combination therapy for
maintenance; few studies looked at comorbidities other than ADHD
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| Somatic treatments: pharmacotherapy primary treatment for mania in well-defined bipolar disorder type I; multiple
agents may be required, but unnecessary polypharmacy should be avoided; begin with FDA-approved treatment for adults
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| Medication recommendations: lithium effective in acute mania and maintenance; valproic acid (Depakote), risperidone
(Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geoden), and aripiprazole (Abilify) effective
in acute mania; lamotrigine (Lamictral) and Zyprexa effective in maintenance; carbamazepine (eg, Tegretol) effective
in acute mania and mixed states; olanzapine and fluoxetine combination (Symbyax) effective in bipolar depression
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| Controlled studies: have not found gabapentin (Neurontin) or topiramate (Topamax) useful in adults; no evidence that
other agents, such as tiagabine (Gabitril), oxcarbazepine (Trileptal), or zonisamide (Zonegran) effective in bipolar
disorder; benzodiazepines useful in adults as adjunctive treatment, but monitor carefully for disinhibition in young
people; antidepressants in combination with mood stabilizer useful for depressive symptoms in adults, but be aware
of warnings related to use of antidepressants in youth; stimulants may be useful in young people once mood symptoms
controlled by mood stabilizer
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| More recommendations: most youth with bipolar disordertype I require ongoing pharmacotherapy to prevent relapse;
some need lifelong treatment; maintain medication regimen for 12 to 24 mo; if medications tapered in stable patient,
monitor closely and educate patient and family about signs and symptoms of relapse; resume treatment quickly if
necessary
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| Psychopharmacologic interventions: require baseline and follow-up monitoring of symptoms, side effects (including
weight gain), and laboratory tests as indicated; drug trials should last 6 to 8 wk at adequate dose; lithium—initially
check blood counts, thyroid function, urinalysis, and metabolic panel, and give pregnancy test; check lithium level,
renal function, thyroid function, and urinalysis every 3 to 6 mo; lithium known teratogenic; Depakote—initially
check liver function and blood counts, and give pregnancy test; follow valproate level, liver function, and blood
counts; valproate known teratogenic; Tegretol—initially check liver function, blood counts, and sodium, and give
pregnancy test; check carbamazepine level, liver function, and sodium levels every 3 to 6 mo
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| Atypical antipsychotics: cause weight gain; initially check liver function, blood counts, and American Dietetic Association
recommendations for managing weight gain (which include initial baseline body mass index [BMI] waist circumference,
blood pressure [BP], fasting glucose, and fasting lipid panel; give pregnancy test; check BMI monthly for
3 mo, then quarterly; recheck BP, fasting glucose, and fasting lipid panel in 3 mo, then yearly thereafter)
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| Other treatments: Lamictal—good mood stabilizer, but not included in AACAP recommendations; most useful for patients
with more depressive symptoms than mania or hypomania; can cause rash that may progress to Stevens-Johnson
syndrome, so titrate up slowly; best to avoid lamotrigine in patients with history of rash from other medications; electroconvulsive
therapy (ECT)—consider in patients who are pregnant, catatonic, or have condition that contraindicates medications;
not indicated in patients with intermediate or broad phenotypes; psychotherapy—psychoeducation indicated in
all patients; other psychotherapies may be helpful
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| Bipolar disorder NOS: AACAP recommendations say pharmacotherapy and behavioral interventions indicated; dialectic
behavioral therapy may help; no good double-blind controlled studies looking at mood stabilizers or antipsychotics,
only open-label trials; in general, open-label trials support use of mood stabilizers and antipsychotics in this
population, although treatment outcomes remain in question; these medications may help with aggression and impulsiveness
seen in bipolar disorder
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Suggested Reading
Barzman DH et al: The efficacy and tolerability of quetiapine versus divalproex for the treatment of impulsivity and
reactive aggression in adolescents with co-occurring bipolar disorder and disruptive behavior disorder(s). J Child Adolesc
Psychopharmacol 16:665, 2006; Blader JC, Kafantaris V: Pharmacological treatment of bipolar disorder among
children and adolescents. Expert Rev Neurother 7:259, 2007; Delbello MP et al: A double-blind, randomized, placebo-controlled
study of quetiapine as adjunctive treatment for adolescent mania. J Am Acad Child Adolesc Psychiatry
41:1216, 2002; Findling RL et al: Double-blind 18-month trial of lithium versus divalproex maintenance treatment in
pediatric bipolar disorder. J Am Acad Child Adolesc Psychiatry 44:409, 2005; Findling RL et al: Use of antipsychotics
in children and adolescents. J Clin Psychiatry 66(Suppl 7):29, 2005; Findling RL: Update on the treatment of bipolar
disorder in children and adolescents. Eur Psychiatry 20:87, 2005; Geller B et al: Double-blind and placebo-
controlled study of lithium for adolescent bipolar disorders with secondary substance dependency. J Am Acad Child Adolesc
Psychiatry 37:171, 1998; Geller B et al: DSM-IV mania symptoms in a prepubertal and early adolescent bipolar
disorder phenotype compared to attention-deficit hyperactive and normal controls. J Child Adolesc Psychopharmacol
12:11, 2002; Geller B et al: Phenomenology of prepubertal and early adolescent bipolar disorder: examples of elated
mood, grandiose behaviors, decreased need for sleep, racing thoughts and hypersexuality. J Child Adolesc Psychopharmacol
12:3, 2002; Geller B, Luby J: Child and adolescent bipolar disorder: a review of the past 10 years. J Am Acad
Child Adolesc Psychiatry 36:1168, 1997; Hazell PL et al: Manic symptoms in young males with ADHD predict functioning
but not diagnosis after 6 years. J Am Acad Child Adolesc Psychiatry 42:552, 2003; Hellander I: A review of
data on the U.S. health sector fall 2002. Int J Health Serv 33:173, 2003; Kafantaris V et al: Lithium treatment of acute
mania in adolescents: a placebo-controlled discontinuation study. J Am Acad Child Adolesc Psychiatry 43:984, 2004;
Kuehn BM: Scientists probe child bipolar disorder. JAMA 297:1181, 2007; Kunwar A et al: Treating common psychiatric
disorders associated with attention-deficit/hyperactivity disorder. Expert Opin Pharmacother 8:555, 2007;
Leibenluft E et al: Defining clinical phenotypes of juvenile mania. Am J Psychiatry 160:430, 2003; Lewinsohn PM
et al: Clinical implications of “subthreshold” depressive symptoms. J Abnorm Psychol 109:345, 2000; Lewinsohn
PM et al: Natural course of adolescent major depressive disorder in a community sample: predictors of recurrence in
young adults. Am J Psychiatry 157:1584, 2000; Lewinsohn PM et al: Bipolar disorders in a community sample of
older adolescents: prevalence, phenomenology, comorbidity, and course. J Am Acad Child Adolesc Psychiatry 34:454,
1995; McClellan J et al: Work Group on Quality Issues. Practice parameter for the assessment and treatment of children
and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 46:107, 2007; Orvaschel Het al:
Continuity of psychopathology in a community sample of adolescents. J Am Acad Child Adolesc Psychiatry 34:1525,
1995; Pavuluri MN et al: Pediatric bipolar disorder: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry
44:846, 2005; Rende R et al: Childhood-onset bipolar disorder: Evidence for increased familial loading of psychiatric
illness. J Am Acad Child Adolesc Psychiatry 46:197, 2007; Roberts RE et al: Symptoms of DSM-III-R major
depression in adolescence: evidence from an epidemiological survey. J Am Acad Child Adolesc Psychiatry 34:1608,
1995; West AE et al: Maintenance model of integrated psychosocial treatment in pediatric bipolar disorder: A pilot feasibility
study. J Am Acad Child Adolesc Psychiatry 46:205, 2007; Youngstrom EA et al: Comparing the diagnostic
accuracy of six potential screening instruments for bipolar disorder in youths aged 5 to 17 years. J Am Acad Child Adolesc
Psychiatry 43:847, 2004.
Educational Objectives
| The goal of this program is to improve the diagnosis and treatment of bipolar disorder in children and adolescents.
After hearing and assimilating this program, the clinician will be better able to:
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| 1. Differentiate manifestations of bipolar disorder in youth from those in adults.
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| 2. Debate the pros and cons of the assigned phenotypes for bipolar disorder in youth.
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| 3. Discuss the continuity of juvenile bipolar disorder into adulthood.
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| 4. Assess bipolar disorder in children and adolescents.
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| 5. Select the best treatments for bipolar disorder in children and adolescents.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, the Audio-Digest Foundation requires all faculty members
to disclose relevant financial relationships within the past 12 months that might create any personal conflict of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care education
and not a proprietary business or commercial interest. For this program, Dr. Koval indicated nothing to disclose. Dr.
Koval discussed off-label use of medications.
Acknowledgements
Dr. Koval was recorded at Day of Discovery on Youth Psychiatric Issues: Disruptive Behavior, Disrupted Lives, held
January 11, 2007, in Charleston, SC, and sponsored by the Medical University of South Carolina. The Audio-Digest
Foundation thanks Dr. Koval and MUSC for their cooperation in the production of this program.
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