Collaborative Role of the Pediatrician in the Diagnosis and Management of Bipolar Disorder in Adolescents - American Academy of Pediatrics
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FROM THE AMERICAN ACADEMY OF PEDIATRICS
Guidance for the Clinician in
Rendering Pediatric Care
CLINICAL REPORT
Collaborative Role of the Pediatrician in the Diagnosis
and Management of Bipolar Disorder in Adolescents
Benjamin N. Shain, MD, PhD and COMMITTEE ON
ADOLESCENCE abstract
KEY WORDS Despite the complexity of diagnosis and management, pediatricians
adolescent bipolar disorder, interview guidelines, psychiatric
diagnosis, psychotropic medication, collaboration
have an important collaborative role in referring and partnering in
the management of adolescents with bipolar disorder. This report
ABBREVIATIONS
ADHD—attention-deficit/hyperactivity disorder presents the classification of bipolar disorder as well as interviewing
DSM-IV-TR—Diagnostic and Statistical Manual of Mental Disor- and diagnostic guidelines. Treatment options are described, particu-
ders, Fourth Edition, Text Revision larly focusing on medication management and rationale for the com-
FDA—US Food and Drug Administration
OCD—obsessive-compulsive disorder mon practice of multiple, simultaneous medications. Medication
SMD—severe mood dysregulation adverse effects may be problematic and better managed with collab-
This document is copyrighted and is property of the American oration between mental health professionals and pediatricians. Case
Academy of Pediatrics and its Board of Directors. All authors examples illustrate a number of common diagnostic and management
have filed conflict of interest statements with the American
issues. Pediatrics 2012;130:e1725–e1742
Academy of Pediatrics. Any conflicts have been resolved through
a process approved by the Board of Directors. The American
Academy of Pediatrics has neither solicited nor accepted any
commercial involvement in the development of the content of
this publication.
Pediatricians are faced with increasing numbers of patients diagnosed
with bipolar disorder and taking multiple psychotropic medications. In
The guidance in this report does not indicate an exclusive
course of treatment or serve as a standard of medical care. addition, pediatricians may be seeing these patients long before they are
Variations, taking into account individual circumstances, may be diagnosed and treated by a child and adolescent psychiatrist or other
appropriate. mental health professional. Pediatric bipolar disorder, once thought to
be rare in adolescents and nearly nonexistent in younger children, has
been diagnosed increasingly over the past decade.1–3 In 2004, bipolar
disorder accounted for 26% of primary discharge diagnoses among
psychiatrically hospitalized adolescents in the United States.3 Bipolar
spectrum disorders,4 encompassing the several types of bipolar dis-
order, have an estimated prevalence of 4% of children and adolescents
in the general population.5 The diagnosis remains controversial, and
there has been a shift in how the diagnosis has been defined in youth.1
Associated impairments may include severe depression, high risk of
www.pediatrics.org/cgi/doi/10.1542/peds.2012-2756
suicide, psychosis, impulsive and dangerous behaviors, social and
doi:10.1542/peds.2012-2756
cognitive deficits, and frequent comorbidity with other psychiatric
All clinical reports from the American Academy of Pediatrics disorders, including substance use disorders, attention-deficit/
automatically expire 5 years after publication unless reaffirmed,
revised, or retired at or before that time. hyperactivity disorder (ADHD), anxiety disorders, oppositional de-
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
fiant disorder, and conduct disorder. Insight is frequently diminished,
with youth vehemently blaming others for their difficulties and having
Copyright © 2012 by the American Academy of Pediatrics
little recognition of their own disruptive symptoms.1 Management of
these youth is additionally complicated by medication limitations,
including troublesome adverse effects, lack of full response and the
resultant common prescription of multiple medications, and in-
complete prevention of relapse.1 Not surprisingly, poor adherence to
prescribed dosing is common.6
PEDIATRICS Volume 130, Number 6, December 2012 e1725
Downloaded from www.aappublications.org/news by guest on October 29, 2021This report is not expected to give TABLE 1 Diagnostic Criteria for a Manic TABLE 2 Diagnostic Criteria for a Hypomanic
Episode Episode
general pediatricians the tools neces-
sary to diagnose and manage these A. A distinct period of abnormally and persistently A. A distinct period of persistently elevated,
complex cases independently. Some elevated, expansive, or irritable mood, lasting expansive, or irritable mood, lasting throughout
at least 1 wk (or for any duration if at least 4 d, that is clearly different from the
specific techniques are described with hospitalization is necessary) usual nondepressed mood
the intent of facilitating partnerships B. During the period of mood disturbance, 3 (or B. Same as manic episode “B” (Table 1)
between pediatricians and child and more) of the following symptoms have C. The episode is associated with an unequivocal
persisted (4 if the mood is only irritable) and change in functioning that is uncharacteristic
adolescent psychiatrists and other
have been present to a significant degree of the person when not symptomatic
mental health professionals. Additional 1. Inflated self-esteem or grandiosity D. The disturbance in mood and the change in
goals include improved understanding 2. Decreased need for sleep (eg, feels rested functioning are observable by others
of diagnosis and treatment; earlier after only 3 h) E. The episode is not severe enough to cause
3. More talkative than usual or pressure to marked impairment in social or occupational
referral of new, suspected cases, and keep talking functioning or to necessitate hospitalization,
patients with symptom relapse or 4. Flight of ideas or subjective experience that and there are no psychotic features
worsening; and assistance in recog- thoughts are racing F. Same as manic episode “E” (Table 1)
5. Distractibility (ie, attention too easily drawn
nizing and managing medication ad- to unimportant or irrelevant external
verse effects. stimuli)
DSM-IV-TR asks for specification of
6. Increase in goal-directed activity (either
The focus of this report is diagnosis certain patterns, including longitudinal
socially, at work or school, or sexually) or
and management of adolescents with psychomotor agitation course as with or without full inter-
bipolar disorder. Children are men- 7. Excessive involvement in pleasurable episode recovery and/or rapid cycling.
tioned as well when the subject matter activities that have a high potential for
painful consequences (eg, engaging in Rapid cycling is defined as more than 4
applies to them. unrestrained buying sprees, sexual mood changes in a year. Researchers
indiscretions, or foolish business have defined patterns that commonly
investments)
CLASSIFICATION apply to pediatric bipolar disorder, in-
C. The symptoms do not meet criteria for a mixed
The Diagnostic and Statistical Manual episode cluding ultrarapid cycling, episodes
of Mental Disorders, Fourth Edition, D. The mood disturbance is sufficiently severe to lasting a few days to a few weeks, and
cause marked impairment in occupational
Text Revision (DSM-IV-TR)7 describes 4 ultradian cycling, variation occurring
functioning or in usual social activities or
types of bipolar disorders, all without relationships with others or to necessitate within a 24-hour period.8,9
hospitalization to prevent harm to self or
age limitations: bipolar I disorder, bi-
others, or there are psychotic features Bipolar II Disorder
polar II disorder, cyclothymic disorder, E. The symptoms are not due to the direct
and bipolar disorder not otherwise physiologic effects of a substance (eg, a drug of Depression typically is the major
specified. Manic symptoms are the abuse, a medication, or other treatment) or problem in bipolar II disorder. A current
a general medical condition (eg,
key feature of these diagnoses; Tables hyperthyroidism) or at least 1 past major depressive
1, 2, and 3 provide criteria for mania, Reprinted with permission from American Psychiatric episode is required, and the patient
hypomania, and mixed episodes.7 A Association. Diagnostic and Statistical Manual of Mental must have a current or past episode of
Disorders, Fourth Edition, Text Revision (DSM-IV-TR).
key criterion is duration: the mini- Washington, DC: American Psychiatric Association; 2000.
hypomania with no manic or mixed
mum duration for mania and mixed episodes at any time. That is, currently
episodes is 7 days and for hypomania or historically, a patient with bipolar I
is 4 days. still meet this criterion. History of disorder has big “ups” (mania) and
a depressive episode is common but may or may not have “downs” (de-
Bipolar I Disorder not required. Other criteria are that pression). A patient with bipolar II
Bipolar I disorder is the “classic” form the mood symptoms cause significant disorder has little “ups” (hypomania)
of the disorder and requires a current distress or impaired functioning; are plus big “downs” (major depression).
or past manic or mixed episode. At not better accounted for by schizo-
any given time, the patient may be in affective disorder or superimposed on Cyclothymic Disorder
a manic, hypomanic, mixed, or major schizophrenia, schizophreniform dis- Cyclothymic disorder is characterized
depressive episode or may have fully order, delusional disorder, or psychotic by relatively mild but chronic symptoms
or partially recovered from the last disorder not otherwise specified; and (hypomanic and depressive symptoms)
mood episode. Notably, this is a his- are not the effect of a substance (in- that last at least 2 years (1 year with
torical diagnosis because the patient cluding medications) or general medi- children and adolescents) before any
may be in any current mood state and cal condition. full manic, mixed, or major depressive
e1726 FROM THE AMERICAN ACADEMY OF PEDIATRICS
Downloaded from www.aappublications.org/news by guest on October 29, 2021FROM THE AMERICAN ACADEMY OF PEDIATRICS
TABLE 3 Diagnostic Criteria for a Mixed (Tables 4, 5, and 6). These criteria are was irritable rather than euphoric.
Episode
included in this report to illustrate This phenotype still includes mood
A. The criteria are met for both a manic episode important features of diagnosis that cycling as a required feature. Broad
and a major depressive episode (except for are not present in DSM-IV-TR; they phenotype refers to a disorder char-
duration) nearly every day during at least a 1-
wk period
should not be construed as generally acterized by chronic irritability and
B. Same as manic episode “D” (Table 1) accepted by physicians or research- hyperarousal and does not include
C. Same as manic episode “E” (Table 1) ers. Narrow phenotype refers to mood cycling. Compared with their
a disorder in which, for at least 1 peers, children and adolescents who
episode, full DSM-IV-TR criteria are have the broad phenotype show
episodes. These patients have little met, including duration criteria, and markedly increased reactivity to neg-
“ups” (hypomania) and little “downs” elation and/or grandiosity also is ative emotional stimuli. The broad
(dysthymia), but the disorder is chronic. present. Elation and grandiosity were phenotype has been referred to as
argued by Geller et al9 to be core bi- severe mood dysregulation (SMD).
Bipolar Disorder Not Otherwise polar features. Intermediate pheno-
Specified SMD among children 9 to 19 years of
type refers to patients with episodes
age has a lifetime prevalence of 3.3%,
DSM-IV-TR describes the category of that met full DSM-IV-TR criteria but
with most affected children having
bipolar disorder not otherwise speci- lacked duration criteria (episodes too
comorbid psychiatric disorders, most
fied as including, “disorders with bi- short) or had mania/hypomania that
frequently disruptive behavior dis-
polar features that do not meet
orders (ADHD, conduct disorder, and
criteria for any specific bipolar disor-
oppositional defiant disorder).15 Chil-
der.”7 The American Academy of Child TABLE 4 Research Criteria for the Narrow
Phenotype of Juvenile Mania
dren with SMD were 7 times more
and Adolescent Psychiatry recom-
likely to develop depression as young
mends using this diagnosis for youth A. Modification to the DSM-IV-TR criteria for manic adults compared with those without
with manic symptoms lasting hours to episode
a. The child must exhibit either elevated/ SMD. Compared with children with
days or for those with chronic manic-
expansive mood or grandiosity while also narrow phenotype bipolar disorder,
like symptoms.1 These youth may be meeting the other DSM-IV-TR criteria for subjects with SMD had different psy-
significantly impaired and constitute a (hypo)manic episode
B. Guidelines for applying the DSM-IV-TR criteria
chopathological measures and were
the majority of those referred to
a. Episodes must meet the full duration criteria less likely to have parents with bi-
mental health professionals.10 Emerg- (ie, at least 7 d for mania and at least 4 d for polar disorder,16 suggesting that SMD
ing evidence suggests that this disor- hypomania) and be demarcated by switches is a disorder distinct from narrow
der is on a continuum with bipolar I from other mood states (depression, mixed
state, euthymic). phenotype bipolar disorder.
disorder,11,12 and 45% of patients con-
b. Episodes are characterized by a change from
verted to bipolar I or bipolar II disor- baseline in the patient’s mood and, Mood diagnoses continue to evolve.
der at follow-up an average of 5 years simultaneously, by the presence of the The development web site for the
later, particularly patients with a fam- associated symptoms. forthcoming Diagnostic and Statisti-
c. Decreased need for sleep should be
ily history of bipolar disorder.13 distinguished from insomnia.
cal Manual of Mental Disorders, Fifth
d. Poor judgment is not a diagnostic criterion Edition, lists an additional proposed
unless it is in the context of “increased goal- mood diagnosis of “disruptive mood
Beyond DSM-IV-TR directed activity” or “excessive involvement dysregulation disorder,”17 character-
in pleasurable activities that have a high
Akiskal and Pinto described a bipolar ized by severe recurrent temper out-
potential for painful consequences.”
spectrum in adults, ranging from bipolar bursts in response to common
I disorder to hyperthymic tempera- stressors and similar to the broad
ment.4 The disorders and conditions on phenotype. Characteristics for this
TABLE 5 Research Criteria for the
the spectrum share symptom charac- Intermediate Phenotypes of diagnosis as well as others on the
teristics that generally responded bet- Juvenile Mania development Web site have been
ter to mood-stabilizing medication than A. The child meets the criteria for the narrow changing in response to public feed-
to antidepressant medication. phenotype except: back. The Diagnostic and Statistical
Leibenluft et al suggested research a. (Hypo)manic episodes are 1to 3 d in duration Manual of Mental Disorders, Fifth
OR
diagnostic criteria for 3 clinical phe- b. The (hypo)manic episodes include exclusively Edition, is expected to be published in
notypes of pediatric bipolar disorder: irritable, not elevated or expansive, mood, May 2013. Because the final version
narrow, intermediate, and broad14 and DSM-IV-TR duration criteria are met may be fairly different, this report
PEDIATRICS Volume 130, Number 6, December 2012 e1727
Downloaded from www.aappublications.org/news by guest on October 29, 2021TABLE 6 Research Criteria for Broad cally, depressive symptoms are also attempt initiation of treatment in newly
Phenotype of Juvenile Mania:
Severe Mood and Behavioral
present at some point in the illness diagnosed cases. The goal for the
Dysregulation and may be the major concern, but pediatrician in identification, there-
depression is not required to be fore, should be reasonable suspicion
A. Inclusion criteria
a. Age 7–17 y, with onset of symptoms before present either currently or historically rather than diagnosis, followed by
age 12 for a bipolar diagnosis. Depressed referral or seeking an appropriate
b. Abnormal mood present at least half of the patients with bipolar disorder, par- mental health professional as partner.
day most days and of sufficient severity to be
noticeable by people in the child’s
ticularly those with the narrow or in- The balance of this section discusses
environment termediate phenotype, may require several historical symptoms that may
c. Hyperarousal, as defined by at least 3 of the different medication from those with be considered red flags for the di-
following symptoms: insomnia, agitation,
depression alone, so it is important for agnosis. The clear presence of any of
distractibility, racing thoughts or flight of
ideas, pressured speech, intrusiveness the pediatrician or mental health these should be considered sufficient
d. Compared with his/her peers, the child professional to attempt to make this for reasonable suspicion.
exhibits markedly increased reactivity to differentiation before initiating phar-
negative emotional stimuli that is manifest
verbally or behaviorally macotherapy.
Red Flag Symptoms
e. The symptoms noted in the previous 3 items
are currently present and have been present Rage Outbursts or Verbal or Physical
for at least 12 mo without any symptom-free Challenges in Diagnosing Mania
periods exceeding 2 mo in duration
Aggression
f. The symptoms are severe in at least 1 setting At a minimum, a full psychiatric evalu- Rage is not a bipolar symptom per se
and at least mild symptoms in a second ation should be performed to determine but is common with adolescents ex-
setting diagnosis.1 A significant problem is that
B. Exclusion criteria periencing episodic irritable mania or
a. The individual exhibits any of the cardinal the diagnosis of mania typically is his- chronic severe mood dysregulation. In
bipolar symptoms: elevated or expansive torical. Even with a patient who dem- both cases, the adolescent is edgy and
mood, grandiosity or inflated self-esteem, onstrates manic symptoms during the
episodically decreased need for sleep easily frustrated and provoked. Ques-
b. The symptoms occur in distinct periods
interview, the interviewer still needs to tions the interviewer may ask include,
lasting more than 4 d determine that the symptoms represent “Do you lose your temper?” If so, the
c. The individual meets criteria for a change, interfere with functioning, and adolescent should be asked about
schizophrenia, schizoaffective illness,
are associated with less evident manic frequency, duration, what happens,
pervasive developmental disorder, or
posttraumatic stress disorder symptoms. Much more often, however, and what the triggers are (see Table 7
d. The individual has met the criteria for the patient presents as depressed or for a summary of examples of in-
substance abuse disorder in the past 3 mo euthymic, leaving it for the interviewer
e. IQFROM THE AMERICAN ACADEMY OF PEDIATRICS
TABLE 7 Examples of Interview Questions very edgy or much more happy or
Symptom Question examples angry than is typical for you?”
Rage outbursts “Do you lose your temper?” If so, ask about Any or all of these symptoms may be
frequency, duration, what happens, what the
present currently, recently, or in the
triggers are.
Episodes of requiring little sleep “Do you ever have nights when you have lots of more distant past.
energy, do not need to sleep much, and do lots of
things?” If so, “Are you tired the next day?”
Spontaneous mood shifts “Do you find yourself suddenly angry or extremely TREATMENT
happy for no apparent reason?” If so, ask about
frequency and duration of the moods. Psychotherapy
Running away, sneaking out at night, spending “Have you even run away or snuck out of the house
Psychotherapeutic interventions are
money, hypersexuality at night?” “Do you have time when you spend a lot
of money or when you feel that you cannot an important component of an overall
control your sexual urges?” treatment plan.1 Interventions should
Grandiosity “Do you have times when you feel that nothing can be targeted to the following areas.
happen to you?” “Do you have times when you
greatly overestimate your talents or abilities?”
Agitation or mania with antidepressant “Have you ever taken medication for depression?” If Psychoeducation
so, “Did you have any side effects?” “Did you ever
Information is provided to patient and
become very edgy or much more happy or angry
than is typical for you?” family on the illness, treatment options,
impact on functioning, and heritability.
Relapse prevention typically is an im-
Spontaneous Mood Shifts Grandiosity portant issue. Education is provided
The adolescent experiences sudden Grandiosity is a grossly inflated belief regarding importance of treatment
mood shifts between euthymic, giddy, in oneself having special talents or adherence, avoidance of precipitating
depressed, or angry, with no evident abilities, such as never being in danger factors, and early recognition of
circumstantial trigger. The giddy, de- regardless of the activity or being the symptoms. The illness may result in
pressed, or angry mood state should best at a certain sport, or endless talk a dramatic tendency to blame others
significantly interfere with functioning, about a real talent. This must be and minimize one’s own symptoms and
such as making concentration in a change from baseline and does not limitations, making engagement in the
school or appropriate behavior with include a consistent picture of boast- treatment plan difficult. For some
friends much more difficult. A mood fulness or failure to appreciate con- individuals and families, education re-
shift may happen multiple times per sequences. Questions include, “Do you garding relapse prevention is the key
day. Questions include, “Do you find have times when you feel that nothing intervention.
yourself suddenly angry or extremely can happen to you?” “Do you have
happy for no apparent reason?” If so, times when you greatly overestimate Individual Psychotherapy
ask about frequency and duration of your talents or abilities?” Cognitive-behavioral psychotherapy and
the moods. interpersonal therapy support emo-
Agitation or Mania With tional and cognitive development, cop-
Running Away, Sneaking Out at Night, Antidepressant ing, and symptom monitoring.
Spending Money, Hypersexuality Adverse effects for a patient under the
These activities may be categorized as influence of antidepressant medica- Social and Family Functioning
“excessive involvement in pleasurable tion may be edginess, agitation, or less Interventions aimed at communication
activities that have a high potential for commonly, frank mania. By definition, and problem solving are needed to
painful consequences” (Table 1).7 Run- a cluster of manic symptoms resulting address disruptions in family and so-
ning away also may be an example of from a medication or substance is not cial relationships.
an impulsive activity related to severe mania. It is, however, a risk factor for
irritability. Questions include, “Have mania either continuing once the Academic and Occupational
you ever run away or snuck out of the medication is withdrawn or mania at Functioning
house at night?” “Do you have times another time. Questions include, “Have Educational planning, specialized ed-
when you spend a lot of money or you ever taken medication for de- ucational programs, and occupational
when you feel that you cannot control pression?” If so, “Did you have any training and support may be needed to
your sexual urges?” side effects?” “Did you ever become address disruption of functioning in
PEDIATRICS Volume 130, Number 6, December 2012 e1729
Downloaded from www.aappublications.org/news by guest on October 29, 2021school or work from ongoing or in- cause of the high unpredictability of information is available from the
termittent symptoms. the behavior of afflicted individuals as American Academy of Child and Ado-
well as difficulty with treatment ad- lescent practice parameters.1,22–25
Treatment of Comorbidities herence at a time when vigorous The American Academy of Child and
Psychosocial interventions should be treatment is indicated. Adolescent Psychiatry1 recommends
aimed at treatment of pre- or coex- Partial hospitalization20 or hospital basing the medication choice on the
isting substance abuse disorders, be- day treatment is used as a less re- following: evidence of efficacy, phase
havioral disorders, anxiety disorders, strictive, step-down treatment from of illness, type of presentation (eg,
learning problems, and confounding inpatient care or as step-up treatment with psychotic symptoms), safety and
social issues. from mental health office services. adverse effect profile, history of
Partial hospitalization does not afford medication response, and patient or
Inpatient Psychiatric the 24-hour monitoring and harm family preference. Medication combi-
Hospitalization prevention provided with inpatient nations are common, with some
services but is less disruptive to the patients on 5 or more drugs. See
Inpatient care typically is aimed at
patient’s life, less expensive, and gives Kowatch et al5 for a suggested pre-
preventing imminent harm to self and
the patient and family more re- scribing algorithm.
others as well as allowing for treat-
sponsibility for the patient’s care
ment that could not be accomplished
while still providing intensive psycho-
in a less restrictive setting.19 A com- Efficacy Studies
therapeutic and medical management.
mon reason for admission is suicid- Currently, lithium, aripiprazole, risper-
ality, including suicidal ideation or Residential treatment21 is longer-term,
idone, olanzapine, and quetiapine are
a recent attempt. To be at high risk of 24-hour-a-day care in a less intensive,
approved by the US Food and Drug Ad-
suicide, the patient need not be typically nonhospital setting, and may
ministration (FDA) for use in adolescents
thinking of suicide at the time of be a month to a year or more in du-
with bipolar disorder (Table 8).26 In ad-
admission. Mood and behavior may ration. Residential care is designed
dition, divalproex, lamotrigine, carba-
have considerable day-to-day or even for patients who cannot be safely
mazepine, oxcarbazepine, gabapentin,
minute-to-minute variation; therefore, managed otherwise despite adequate
and topiramate have nonmental health
judgment as to safety should be based treatment or who have symptoms
pediatric indications, and divalproex,
on recent thoughts, moods, and that require long-term behavioral in-
lamotrigine, ziprasidone, and asena-
behaviors rather than just the current tervention to effect improvement.
pine have indications for treatment of
ones and on near-future projection adults with bipolar disorder. Pub-
on the basis of possible and sudden Psychopharmacology lished studies have had mixed results
occurrence of common adolescent Medication management is an impor- (Tables 9, 10, and 11). Not all studies
stressors. For example, in an adoles- tant component of treatment of youth are available, because pharmaceutical
cent with recent suicidal behavior and with bipolar disorder and is the companies are not required to publish
a history of grossly overreacting to primary treatment in cases of well- their studies even when submitted
negative circumstances, a romantic defined mania.1,5 The primary medi- to the FDA as part of an application
breakup could be lethal. cations used to treat patients with for an indication. Lithium, aripipra-
Other common reasons for psychiatric bipolar disorder are mood stabilizers, zole, and olanzapine showed efficacy
hospitalization for harm prevention such as lithium; certain anticonvul- in published, double-blind, placebo-
are recent episodes of severe rage, sant medications, including divalproex, controlled studies, with open-label,
agitation, or aggression attributable to lamotrigine, carbamazepine, oxcarba- chart review, and comparison studies
mood symptoms or manic symptoms zepine, gabapentin, and topiramate; giving support for use of divalproex,
accompanied by severe impulsivity in and atypical antipsychotics, including lamotrigine, clozapine, risperidone,
areas that could inadvertently result in aripiprazole, olanzapine, quetiapine, quetiapine, and carbamazepine. Nota-
self-harm, such as running away or risperidone, ziprasidone, paliperidone, bly, divalproex and oxcarbazepine each
sexual activity with multiple partners. clozapine, asenapine, and iloperidone. failed to show efficacy in a double-blind,
Patients with florid mania or acute Adjunctive medications include anti- placebo-controlled study, but given the
psychosis typically require hospitali- depressant medications and “typical” heterogeneity of this disorder, 1 nega-
zation even in the absence of overtly antipsychotics, as well as medications tive study is not conclusive. Divalproex,
dangerous behaviors or ideation be- for ADHD, anxiety, and insomnia; more lamotrigine, lithium, aripiprazole,
e1730 FROM THE AMERICAN ACADEMY OF PEDIATRICS
Downloaded from www.aappublications.org/news by guest on October 29, 2021FROM THE AMERICAN ACADEMY OF PEDIATRICS
and resistant depression (in combination with fluoxetine)
quetiapine, risperidone, and top-
Schizophrenia, bipolar manic and mixed episodes, bipolar
Schizophrenia, bipolar manic and mixed episodes, bipolar
iramate have shown efficacy in med-
ication combination studies. Kowatch
Bipolar mania, schizophrenia, adjunctive for major
Schizophrenia, bipolar manic and mixed episodes
Schizophrenia, bipolar manic and mixed episodes
Schizophrenia, bipolar mania, bipolar depression
et al27 found a medication combina-
tion response rate of 80% among
All adult mental health
Schizophrenia, schizoaffective disorder
Schizophrenia, schizoaffective disorder
patients who did not respond to
monotherapy with a mood stabilizer.
Adverse Effects
Mood stabilizer (Table 12)5 and atypi-
Bipolar maintenance
cal antipsychotic (Table 13)28,29 medi-
maintenance
cations have a variety of adverse
Schizophrenia
Schizophrenia
depression
effects, interactions, and safety con-
Mania
Mania
cerns. Pediatricians probably need
to be most aware of weight gain
and metabolic effects common with
the atypical antipsychotics, although
trigeminal neuralgia
Seizures, ages 0–17;
Seizures, ages 0–17
Seizures, ages 2–17
Seizures, ages 2–17
Seizures, ages 3–17
Seizures, ages 2–17
Nonmental health
weight gain is also commonly associ-
ated with valproate and, to a lesser
extent, lithium. Prescription of atypi-
cal antipsychotics in youth for bipolar
disorder as well as for psychosis,
disruptive behavior disorders, and
other mood disorders has increased
Irritability associated with autism
drastically in recent years.30 Children
and adolescents may be more vul-
nerable than adults to weight gain
TABLE 8 FDA Indications for Oral Formulations of Mood Stabilizers and Atypical Antipsychotics
from these medications and, thus,
likely to be at higher risk of glucose
Ages 6–17
Ages 5–16
and lipid abnormalities.31 Weight man-
agement potentially can be addressed
with suggestions of diet and exercise
as well as changing the dose and/or
Ages 13–17
Ages 13–17
Ages 13–17
Ages 13–17
Schizophrenia
type of medication. Use of metformin
may be of some help.32,33 Stable
patients should be seen by their pe-
diatrician every 4 to 6 months, with
more frequent visits when there are
episodes, ages 10–17
episodes, ages 10–17
episodes, ages 13–17
Mania, ages 12–17
Bipolar disorder
active adverse effects, interactions, or
Manic and mixed
Manic and mixed
Manic and mixed
Manic episodes,
safety issues.
ages 10–17
The American Diabetes Association34
published a protocol for use in mon-
itoring for weight gain and metabolic
changes in adults treated with atypi-
Carbamazepine (Tegretol)
cal antipsychotics, including obtaining
Oxcarbazepine (Trileptal)
Risperidone (Risperdal)
Gabapentin (Neurontin)
Lamotrigine (Lamictal)
Topiramate (Topamax)
Divalproex (Depakote)
Quetiapine (Seroquel)
Ziprasidone (Geodon)
Paliperidone (Invega)
personal and family history of related
Olanzapine (Zyprexa)
Aripiprazole (Abilify)
Iloperidone (Fanapt)
Asenapine (Saphris)
Atypical antipsychotics
Lurasidone (Latuda)
Clozapine (Clozaril)
Lithium (Eskalith)
Medication
disorders, determining weight and
Mood stabilizer
height, determining waist circum-
ference, taking blood pressure, and
measuring fasting plasma glucose
and fasting lipid profile. Weight should
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TABLE 9 Published Studies of Efficacy of Mood Stabilizers With Pediatric Bipolar Disordera
Medication Study Ages Type Results Comments
Divalproex Wagner et al (2002)41 7–19; n = 40 Open-label trial Response rate 61% with manic Manic, mixed, or hypomanic
symptoms
Divalproex Henry et al (2003)42 4–18; n = 15 Records review Response rate 53% after 1 y Divalproex alone and as add-on
Divalproex Wagner et al (2009)43 10–17; n = 150 Double-blind No significant difference from Manic or mixed
placebo
Lamotrigine Chang et al (2006)44 12–17; n = 20 Open-label trial Significant decreases in depression, Lamotrigine alone and in combination with
mania, and aggression other medication
FROM THE AMERICAN ACADEMY OF PEDIATRICS
Lamotrigine Pavuluri et al (2009)45 8–18; n = 46 Open-label trial Response rate 72% with manic Monotherapy
symptoms and 82% with depressive
symptoms
Lithium Strober et al (1990)46 13–17, n = 37 Naturalistic prospective Relapse rate 3 times higher when Lithium alone and in combination with
follow-up lithium discontinued other medication
Lithium Geller et al (1998)47 12–18; n = 25 Double-blind Significant response rate difference, Bipolar disorder with secondary
46% versus 8% of placebo group substance dependence
Lithium Kafantaris et al (2003)48 12–18; n = 100 Open-label trial Response rate 63% with manic Acute mania
symptoms
Lithium Kafantaris, et al (2004)49 12–18; n = 40 Double-blind No significant difference from Mania with or without psychosis or
discontinuation placebo aggression
Lithium Patel et al (2006)50 12–18; n = 27 Open-label trial Response rate 48% with depressive Acute bipolar depression
symptoms
Oxcarbazepine Wagner et al (2006)51 7–18; n = 116 Double-blind No significant difference from Manic or mixed
placebo
Topiramate Del Bello et al (2002)52 5–20; n = 26 Chart review Response rate 73% for mania and Outpatient with acute manic, mixed, or
62% for overall illness depressive episode; adjunctive or
monotherapy
Topiramate Barzman et al (2005)53 7–20; n = 25 Chart review Response rate 64% Hospitalized with acute manic, mixed,
or depressive episode; adjunctive or
monotherapy
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Topiramate DelBello, et al (2005)54 6–17; n = 56 Double-blind Mixed results Inconclusive; study stopped early when
early adult studies failed to show
efficacy
a
Includes only the most recent studies of divalproex and lithium.TABLE 10 Published Studies of Efficacy of Atypical Antipsychotics for Pediatric Bipolar Disorder
Medication Study Ages Type Results Comments
Aripiprazole Barzman et al (2004)55 5–19; n = 30 Chart review Response rate 67% Bipolar or schizoaffective; adjunctive or monotherapy
Aripiprazole Biederman et al (2005)56 4–17; n = 41 Records review 71% improvement of manic symptoms Aripiprazole alone and as add-on
Aripiprazole Biederman et al (2007)57 6–17; n = 19 Open-label trial Significant improvement Mania
Aripiprazole Tramontina et al (2007)58 8–17; n = 10 Open-label trial Significant improvement Comorbid bipolar and ADHD; improved both mania
and ADHD symptoms
Aripiprazole Findling et al (2009)59 10–17; n = 296 Double-blind Significant response rate difference, 44% (10 mg), Manic or mixed
64% (30 mg), 26% (placebo)
Aripiprazole Tramontina et al (2009)60 8–17; n = 43 Double-blind Significant response rate difference, 89% vs 52% of Manic or mixed comorbid with ADHD
placebo group
Clozapine Masi et al (2002)61 12–17; n = 10 Open-label trial Significant improvement Severe treatment-resistant manic or mixed
Olanzapine Frazier et al (2001)62 5–14; n = 23 Open-label trial Response rate 61% Acute mania
Olanzapine Tohen et al (2007)63 13–17; n = 161 Double-blind Significant response rate difference, 45% vs 19% of Acute manic or mixed
placebo group
PEDIATRICS Volume 130, Number 6, December 2012
Olanzapine Joshi et al (2010)64 4–17; n = 52 Open-label trial; secondary Significantly less antimanic response with comorbid Bipolar disorder
analysis of 2 trials OCD
Quetiapine Del Bello et al (2007)65 12–18; n = 20 Single-blind, open label Response rate 87% with mood symptoms Patients at high risk for bipolar I
Quetiapine Del Bello et al (2009)66 12–18; n = 32 Double-blind No significant difference from placebo Bipolar depression
Quetiapine Scheffer et al (2010)67 6–16; n = 75 Open-label trial 94% much improved at 8 wk; rapid loading tolerated Bipolar disorder
well
Risperidone Frazier et al (1999)68 4–17; n = 28 Records review Response rate 82% with manic and aggressive Mixed or hypomanic
symptoms
Risperidone Biederman et al (2005)69 6–17; n = 30 Open-label trial Response rate 70% with manic symptoms Manic, mixed, or hypomanic
Risperidone Haas et al (2009)70 10–17; n = 169 Double-blind Significant response rate difference, 59% (0.5–2.5 Acute manic or mixed
mg), 63% (3–6 mg), 26% (placebo)
Risperidone Carlson et al (2010)71 5–12; n = 151 Chart review Reduced duration or rages Hospitalized children with possible bipolar disorder
Risperidone Krieger et al (2011)72 7–17; n = 21 Open-label trial Significant reduction of irritability, depression, ADHD Severe mood dysregulation
symptoms, and global functioning
Ziprasidone Biederman et al (2007)73 6–17; n = 21 Open-label trial Response rate 71% with manic symptoms Mania
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verse effects.
sufficient response.
Other Medication Caution
rently for children and adolescents.28
by the psychiatrist. The pediatrician
sant to the mix only if there is in-
practice is to start with a mood sta-
for treatment. Antidepressant in-
common reason for the initial referral
polar disorder usually includes de-
are commonly prescribed, because bi-
use of mood stabilizers and atypical
than once thought,35 but common
crease mood cycling (Table 14).18 In
used with care because they may in-
scribing physician in monitoring for
signs, height, weight, and waist size,
monitors the patient’s weight and
When medications are prescribed by
and then quarterly. Lipids and fasting
months. There is no a protocol cur-
be reassessed monthly for 3 months
should collaborate with the pre-
cation may be a matter of practicality.
a physician other than the pediatri-
ter 3 months and then every 6
plasma glucose may be measured af-
antipsychotics with pediatric bipolar
Few studies have addressed the
duction of mania may be less frequent
pression, and depression is the most
physically intrusive when obtained
ally does not have a nurse on staff. In
with the proper equipment and usu-
office, because it typically is not set up
difficult to obtain in a psychiatrist’s
a pediatrician’s office but much more
are easily and routinely obtained in
Certain measurements, such as vital
cian, the decision of which physician
bilizer or atypical antipsychotic (or
and managing these medication ad-
perceive these measurements to be
addition, at times, the patients may
metabolic consequences of the medi-
e1733
depression. Lithium and lamotrigine
combination) and add an antidepres-
particular, antidepressant medications
A number of medications should be
FROM THE AMERICAN ACADEMY OF PEDIATRICSStabilized on lithium plus divalproex and then compared
have shown efficacy in open-label trials
No significant wt gain in either group; better retention
Manic or mixed; compared quetiapine and divalproex
(Table 9) and quetiapine was not sig-
maintenance monotherapy with one or the other
Manic or mixed; divalproex plus quetiapine versus
nificantly better than placebo (Table 10).
Medication Combinations
of subjects in risperidone group
Adolescents with bipolar disorder may
Comments
More wt gain with risperidone
have a range of symptoms within the
divalproex plus placebo
disorder, including symptoms of mania
or hypomania, depression, and psy-
chosis, and commonly have comorbid-
Manic or mixed
Manic or mixed
ities with a variety of other psychiatric
disorders, including ADHD, generalized
anxiety disorder, obsessive-compulsive
disorder (OCD), posttraumatic stress
disorder, and others.5 These comor-
Large effect size for all 3 medications; response rate with
difference in amount of improvement but significantly
manic symptoms of divalproex 53%, lithium 38%, and
Risperidone group showed significantly faster decrease
Response rate 80% for risperidone plus divalproex and
Significant improvement in both groups; no significant
bidities can lead to a complexity of
More rapid improvement in risperidone group but no
Significant response rate difference, 87% vs 53% of
symptoms and often difficult choices
TABLE 11 Published Comparison Studies of Efficacy of Mood Stabilizers and Atypical Antipsychotics With Pediatric Bipolar Disorder
for medication management. As a re-
No significant difference between the groups
faster improvement in quetiapine group
sult, use of multiple medications is
of symptoms than divalproex group
common in treating adolescents with
82% for risperidone plus lithium
bipolar disorder, who often are pre-
Results
scribed 2 to 5, or more, simultaneous
difference in final scores
medications. Even in a research setting
carbamazepine 38%
using algorithms designed to limit the
placebo group
number of medications, only 28% of
patients were able to remain on mon-
otherapy for >6 months.36
Reasons for combining medications
include the following:
placebo group
placebo group
placebo group
Partial response. A group of symp-
Double-blind; no
Double-blind, no
Double-blind, no
Records review
Open-label trial
Open-label trial
Double-blind
Type
toms, such as expansive mood,
grandiosity, and pleasure-seeking
behaviors, may have improved
with a particular medication (with
6–18; n = 42
12–18; n = 30
5–18; n = 37
5–17; n = 60
12–18; n = 50
5–14; n = 28
8–18; n = 66
adequate dose and time), but
Ages
symptoms continue sufficiently to
cause distress and/or impairment
of functioning. A second (or some-
MacMillan et al (2008)79
Del Bello et al (2002)75
Del Bello et al (2006)78
times third) medication is then
(2000)74
Pavuluri et al (2004)76
Pavuluri et al (2010)80
Findling et al (2005)77
added as an “augmentation agent”
Study
to improve response. Another type
Kowatch et al
of partial response is when some
symptoms improve and others do
not (eg, symptoms of mania im-
prove but the patient still suffers
Risperidone, Divalproex
Risperidone, Divalproex
Quetiapine, Divalproex
Quetiapine, Divalproex
Risperidone, Lithium,
from intermittent or persistent de-
Lithium, Divalproex,
Lithium, Divalproex
Carbamazepine
Medication
pression).
Divalproex
Target specific symptom. There may
be a particular troublesome and/or
easily treated symptom, such as
e1734 FROM THE AMERICAN ACADEMY OF PEDIATRICS
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TABLE 12 Adverse Effects and Possible Monitoring of Mood Stabilizers pital. The way to decrease the like-
Medication Summary of adverse effects Suggested monitoring lihood of relapse and treat current
Lithium Reduced renal function, hypothyroidism, Baseline: serum electrolytes, creatinine, symptoms more quickly is to
nausea, diarrhea, abdominal distress, BUN, calcium, CBC count, TFTs, EKG,
sedation, tremor, polyuria, wt gain, pregnancy test (sexually active
“cross-taper,” for example, starting
acne, cardiac conduction problems, female patients) the second medication with the
hypoparathyroidism full dose of the first medication,
Wt gain may be additive when combined Ongoing: lithium level, renal function,
with an atypical antipsychotic28 thyroid function, calcium and then, if the second medication
Toxic levels may produce confusion, is tolerated and appears to be
ataxia, dysarthria, seizures, coma,
death adding incremental benefit, the
Divalproex Polycystic ovaries, nausea, increased Baseline: height and wt, pregnancy second medication gradually is in-
appetite, wt gain, sedation, test (sexually active female patients),
creased while the first medication
thrombocytopenia, hair loss, tremor, liver function tests, CBC
vomiting, rare pancreatitis or liver is decreased.
failure
Wt gain may be additive when combined Every 6 mo: divalproex level, liver
Treat comorbid disorders. Addi-
with an atypical antipsychotic28 function tests, CBC tional medications may be used
Carbamazepine Multiple medication interactions Baseline: CBC to treat symptoms of comorbid dis-
(decrease or increase the other Every 6 mo: carbamazepine level, CBC orders, such as inattentiveness
medication levels including oral
contraceptive failure), sedation, ataxia, with ADHD or worrying with an
dizziness, blurred vision, nausea, anxiety disorder.
vomiting, aplastic anemia,
hyponatremia, Stevens-Johnson
Lamotrigine Severe cutaneous reactions (risk 3 times Baseline: CBC and liver function tests PRESCRIBING GUIDELINES
greaterTABLE 13 Adverse Effects and Possible Monitoring of Atypical Antipsychotics
Adverse effect Time course Suggested monitoring Medications most likely to cause
Anticholinergic Early Clozapine, olanzapine
Acute parkinsonism Early During titration, at 3 mo and Paliperidone, risperidone
annually
Akathisia Early/intermediate During titration, at 3 mo and Aripiprazole
annually
Cardiovascular events Not known EKG at baseline if taking
ziprasidone or clozapine and
during titration if taking
ziprasidone
Diabetes Late Fasting blood glucose at 3 mo and Clozapine, olanzapine (but problem
then every 6 mo for all)
Increased lipids Early? Lipids at 3 mo and then every 6 mo Clozapine, olanzapine (but problem
for all)
Neutropenia Most likely within first 6 mo Clozapine registry recommended Clozapine
CBC monitoring
Orthostasis Early Orthostatic blood pressure and Clozapine, olanzapine, quetiapine
pulse if symptomatic; blood
pressure and pulse at 3 mo and
annually
Increased prolactin and sexual Early Sexual history during titration and Paliperidone, risperidone,
dysfunction then every 3 mo; prolactin level olanzapine
only if symptomatic
Decreased prolactin Early Prolactin level only if symptomatic Aripiprazole
Increased QTc interval Not known EKG at baseline if taking Ziprasidone
ziprasidone or clozapine and
during titration if taking
ziprasidone
Sedation Early Each visit Clozapine, olanzapine, quetiapine
(but problem for all)
Seizures During titration Clozapine
Tardive dyskinesia Late At 3 mo and annually (abnormal Lower risk compared with first
involuntary movement scale) generation antipsychotics
Withdrawal dyskinesia Early during fast switch During titration Aripiprazole, paliperidone
Wt gain First 3–6 mo Height, wt, BMI percentile, BMI z All, but clozapine and olanzapine
score each visit highest and aripiprazole and
ziprasidone least
Other laboratories Electrolytes, CBC, renal function
test annually, and liver function
tests at 3 mo and annually
TABLE 14 Medications That May Increase
Mood Cycling in Children and nia or acute psychosis, it must be best for any particular group of
Adolescents addressed first. symptoms but has the potential
Antidepressants Treat the Most Troublesome to treat ≥2 groups of symptoms.
Tricyclic antidepressants
Selective serotonin reuptake inhibitors
Symptoms First. A more common Manage an Adverse Effect.
Serotonin-norepinephrine reuptake inhibitors situation is that there is no group Depending on the urgency of the
Aminophylline of symptoms that is overwhelming. need for clinical effect and the trou-
Oral or intravenous corticosteroids In that case, first treat the group of blesomeness of the adverse effect,
Sympathomimetic amines (eg, pseudoephedrine)
Antibiotics (eg, clarithromycin, erythromycin, and symptoms that is causing the most an adverse effect may temporarily
amoxicillin) distress or impairment. For exam- halt the search for an effective reg-
ple, moderate depression is trea- imen until it can be resolved or re-
adverse effects of medications in ted before mild to moderate duced to an acceptable level.
a particular combination. inattentiveness. Treat a “Lynchpin” Symptom. At
Important Cluster of Symptoms. Opportunity to Reduce the Num- times, a symptom seems to be the
When a group of symptoms is ber of Medications That Eventu- basis for other symptoms, for ex-
causing severe impairment and ally Will Be Needed. A medication ample, an anxious and inattentive
distress, such as full-fledged ma- may be used that may not be the adolescent who goes into a rage
e1736 FROM THE AMERICAN ACADEMY OF PEDIATRICS
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attempting to complete homework. or its treatment, (2) conditions that Case 1
As an alternative to using a medi- mimic mania, (3) conditions that oc- Mary is a 16-year-old girl who presents
cation that works to reduce rage, cur more commonly in patients with for admission to psychiatry inpatient
using a medication to reduce anx- bipolar disorder that appear un- after sudden onset 1 week previously of
iety or to increase attentiveness related to its treatment, and (4) con- euphoric and giddy mood, talking rap-
may be at least as effective (of ditions related to risk behaviors idly and jumping from topic to topic,
course, the prescriber may choose associated with bipolar disorder. The and little sleep with almost none over
to do both to potentially increase authors noted that little has been the past 3 days. She has spent most of
the effect). published specifically with regard to her time since then at her health club
Preference for a Medication pediatric bipolar disorder and con- trying to “pick up” male patrons, a be-
That Works Quickly. At times, current medical conditions, but a num- havior very out of character for her.
a medication is chosen over an- ber of reports that focused on adults Before age 14, she was high achieving
other one for a particular effect included pediatric subjects. and well adjusted, earning mostly A’s in
because it works quickly. The Tables 12 and 13 summarize medical school, socially active, and described
thinking is that if it then does not adverse effects from medications by her parents as a “model daughter.”
work, less time is lost in pursuing commonly used to treat bipolar dis- At age 14, she broke up with a boy-
the other medication, thus increas- order. Pediatricians should familiarize friend and became severely depressed,
ing the chance of finding an effec- themselves with these and monitor responding after 2 months to a combi-
tive medication in a given period of for them. Lithium treatment can result nation of sertraline and psychotherapy.
time. in hypothyroidism and, regardless of She discontinued both treatments 4
An example that illustrates the use of the cause, hypothyroidism can make months later because she had been
several of these guidelines is a patient bipolar disorder more difficult to doing well. She continued to do well
with insomnia in the context of de- treat.37 Elevated prolactin levels, typi- until 1 year ago, when she developed
pression. Choices for the first medi- cally from certain atypical antipsy- an episode similar to the current one,
cation(s) include (1) a mood agent chotics, are associated with low bone but her behavior was controlled, and
to treat the depression (the more mass for chronologic age, sexual she was managed outside the hospital,
impairing symptom) while waiting for dysfunction, menstrual irregularities, responding after 2 weeks to a combi-
the insomnia to resolve as the de- gynecomastia, galactorrhea, and ret- nation of lithium and psychotherapy.
pression improves, (2) a hypnotic to rograde ejaculation. Cardiovascular She had difficulty with moodiness and
treat the insomnia because the re- disease38 and type 2 diabetes melli- functioning in school for the next 6
sponse is likely to be quick and the tus39 may be associated with the ill- months and again stopped the treat-
patient’s mood may improve once he ness itself. Conditions that may mimic ments. She then continued about the
or she no longer is sleep deprived, mania are listed in Table 15.5,37 Un- same until this current episode.
(3) combination of a hypnotic with an related conditions more common in
patients with bipolar disorder37 in- Mary is diagnosed with bipolar I dis-
optimal mood agent for this patient,
clude migraine headaches, epilepsy, order, current episode manic, severe,
or (4) a sedating mood agent that
and at least in 1 large family, auto- and without psychotic features. She
may treat both the depression and
somal dominant medullary cystic kid- has the narrow phenotype. She is
the insomnia. For a particular pa-
ney disease. Conditions associated restarted on lithium and also is started
tient, these may all be reasonable
with bipolar risk behaviors37 include on quetiapine for sleeping, calming,
options, or there may be other fac-
complications of substance use and and additional mood stabilization.
tors, such as treatment history, that
abuse, sexually transmitted diseases, Lithium is chosen because of her past
favor one option over others.
and traumatic brain injury. response to this medication. Her psy-
chiatrist decides to combine this with
quetiapine immediately, despite treat-
CONCURRENT MEDICAL CASE VIGNETTES ment algorithms suggesting starting
CONDITIONS The following fictitious cases are with monotherapy,5,18 for 2 reasons: (1)
Scheffer and Linden37 divided medical conglomerates based on the authors’ previous treatment with lithium yielded
conditions concurrent with pediatric clinical experience and are designed a good acute response but only a par-
bipolar disorder into 4 types: (1) to illustrate common diagnostic and tial response long-term, even before
conditions related to bipolar disorder treatment issues. she stopped the medication and (2)
PEDIATRICS Volume 130, Number 6, December 2012 e1737
Downloaded from www.aappublications.org/news by guest on October 29, 2021TABLE 15 Medical Conditions That May Additional questions reveal that de- cases the first mood episode in pedi-
Mimic Mania
pression probably existed on and off for atric bipolar disorder is depression.40
Hyperthyroidism quite some time before the divorce.
Closed or open head injury Furthermore, the depression is not
Temporal lobe epilepsy
Case 3
Multiple sclerosis continuous. Even over the past week, he
Dan is a 17-year-old boy who presents
Systemic lupus erythematosus reports having 1 or 2 days at a time of
for psychiatric inpatient admission af-
Fetal alcohol spectrum disorder/alcohol-related feeling great and “energized,” spending
neurodevelopmental disorder ter damaging his father’s car with
most of the night playing an online
Wilson disease a crow bar and threatening to kill his
HIV game with little fatigue the next day,
parents and then himself after parents
Lyme disease talking more, having racing thoughts,
Dementia took away his cell phone. The patient
and having a more difficult time focus-
Fibromyalgia reports having had difficulty with
Niemann-Pick disease ing on school work. He has other times,
temper outbursts for years. This is the
Familial leukoencephalopathy up to 2 days at a time, of being easily worst such episode, but the patient
angered, punching a wall at times, ru- commonly yells or leaves the house
lithium can easily take 1 week or more minating about slights from peers and when upset and tends to overreact to
to be effective, and Mary needs some- parents, and generally feeling “edgy.” his parents’ attempts to set limits. Both
thing with more immediate effect for Charles is diagnosed with bipolar patient and parents report that he
calming and sleeping. disorder not otherwise specified and does “fine” most of the time and just
Mary is in a relatively consistent (ab- the intermediate phenotype. He does overreacts to frustration. He was di-
normal) mood state. The primary not meet duration criteria for mania (7 agnosed with ADHD in the third grade
treatment goals are, therefore, to help days) or hypomania (4 days). Key and has been on and off treatment for
her out of this state, return her to features are the spontaneous and that (currently off). He has had mild to
a euthymic mood, and prevent the next frequent changes of mood symptoms, moderate depression at times but not
mood episode. If her current mood unrelated or only very loosely related recently. On interview, the patient
state were depression instead of ma- to environmental circumstances, and reports that the incident with the car
nia, mood-stabilizing medication would the lack of distinct, continuous manic was “not a big deal” and says that he
still be the first choice, but often, an- or hypomanic states for even 4 days. currently feels “fine,” although he
tidepressant medication is cautiously Medication management for Charles is appears quite edgy and becomes
added should the depression prove similar to that for Mary in case 1; the frustrated with the interviewer for
resistant to the mood stabilizing primary initial objective is mood sta- “asking too many questions.”
medication alone. The caution is re- bilization with ≥1 mood stabilizers The patient is diagnosed with mood
lated to the possibility that the anti- and/or atypical antipsychotics. A dif- disorder not otherwise specified and
depressant could make it easier for ference is that Charles’s mood symp- meets criteria for bipolar spectrum
her to go into a manic episode, even toms are not stable. He only has to broad phenotype or severe mood
when combined with the mood- wait a few days or less to switch to dysregulation. He shows no evidence
stabilizing medication. In addition, a different group of symptoms. Despite for mood cycling, except for the history
during the time she is in a manic state, depression being the primary concern, of depression, but his mood changes
an antidepressant is generally not antidepressants may make his condi- quickly with minor provocation, and he
recommended. tion worse by increasing the frequency is highly sensitive to frustrating cir-
or intensity of mood changes or cumstances.
Case 2 undermining the effects of the mood- Common practice is to treat the rage
Charles is a 15-year-old boy who stabilizing medication. Even for treat- symptoms and edginess with mood
presents to the psychiatrist’s office ing the depression symptoms, the stabilizers and/or atypical antipsy-
for his first mental health visit with preference is typically to find more chotics. Treatment of rage and edginess
the complaint of increasing, severe effective mood stabilizing medication in this population has been poorly
depression over the past month. He rather than add an antidepressant. studied, but risperidone and aripipra-
feels that the depression started 3 Exceptions are common, however, with zole are approved by the FDA for the
years ago when his parents divorced the treatment of bipolar illness. treatment of irritability associated with
and he moved with his mother and Cases 1 and 2 illustrate the findings of autism (Table 8). With some patients,
siblings to a new city and new school. a recent study showing that in 90% of these symptoms may respond to ≥1
e1738 FROM THE AMERICAN ACADEMY OF PEDIATRICS
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