Childhood-onset mania generally went unrecognized over the first part of this century, despite
Kraepelin's (1921) observations that mania occurred rarely in children and that the onset of first
episodes increased significantly after puberty. Anthony and Scott (1960) reached similar
conclusions by using criteria derived from the adult literature to review reported cases of manic-
depressive psychosis in children. They established a basis for further research by separating
childhood onset from that during adolescence and by applying a criterion-based diagnostic
schema to youth (Carlson, 1990).
The clinical biases that mania did not occur in adolescents persisted until large-scale studies of
bipolar adults indicated that approximately one fifth of cases presented prior to age 19 (Carlson et
al., 1977; Winokur et al., 1969). Subsequent studies have confirmed these findings (Joyce, 1984;
Loranger and Levine, 1978).
Another previously held clinical bias, that schizophrenia was more common in youth, was
complicated by the fact that manic adolescents frequently present with psychotic symptoms
(McGlashan et al., 1988). Carlson and Strober (1978) reported on six bipolar adolescents
originally misdiagnosed as schizophrenic, a diagnostic tendency further noted in subsequent
studies (Bashir et al., 1987; Joyce, 1984; McClellan et al., 1993; Werry et al., 1991). Although
clinicians have become increasingly aware of the confusion between early-onset bipolar disorder
and schizophrenia, bipolar disorder in youth continues to be underrecognized and misdiagnosed
(Carlson et al., 1994).
Historically considered rare, childhood-onset bipolar disorder is now being reported more often,
although its frequency remains an area of some controversy (Carlson, 1990). Further research is
needed to establish the specificity of symptoms distinguishing childhood mania from behavior
disorders. Furthermore, if severity and duration are not included in the diagnostic criteria,
estimated lifetime prevalence rates are greatly increased (Carlson and Kashani, 1988). This is an
important issue when reviewing the literature since DSM-III-R (APA, 1987) removed the 7-day
duration requirement specified in DSM-III (APA, 1980). Thus, studies reporting on early-onset
mania using DSM-III-R (APA, 1987) criteria may have overdiagnosed mania. With DSM-IV (APA,
1994b) the 7-day duration criterion has been reinstituted, and a severity requirement has been
The existing research examining early-onset bipolar disorder is limited. Methodological problems
include small sample sizes, lack of comparison groups, retrospective designs, and tack of
standardized measures. More research is clearly needed in all aspects of this disorder but
especially in examining the efficacy of various modes of treatment, longitudinal course, and
diagnostic issues. Given these limitations, some of the information presented in this review had to
be drawn from the adult literature. When discussing aspects of the disorder in relation to age of
onset, we refer to early onset as prior to 18 years of age and very early onset as prior to 13 years
of age. The literature has referred to the latter group as prepubescent but often on the basis of
age rather than actual physiological development.
Children and adolescents are diagnosed with bipolar disorder based onthe same criteria used for
adults as outlined in DSM-IV (American Psychiatric Association [APA], 1994b). The existing data
are sufficient to suggest that bipolar disorder with onset before the age of 18 years is essentially
the same disorder as that in adults, but further studies are needed to clarify the long-term course
and outcome of the early-onset forms, especially for those with very early onset. The following
definitions should be used:
I. Manic Episode. A manic episode, the hallmark feature of this disorder, is described by
the following DSM-IV (APA, 1994b) criteria:
A. A distinct period of abnormally and persistently elevated, expansive, and/or
irritable mood. This represents a significant change in the patient's baseline
mental status, and must last for at least 1 week (or any duration if hospitalization
B. During the period of mood disturbance, the patient must display at least three
(four if the mood is only irritable) of the following symptoms: grandiosity,
decreased sleep, pressured speech, racing thoughts, distractibility, increased
goal-directed activity, and/or excessive involvement in reckless activities.
C. The mood disturbance is not part of a mixed manic-depressive episode, which is
D. The mood disturbance must cause marked impairment in occupational/social
functioning. This may include the need for hospitalization or the presence of
E. The symptoms are not due to the direct effects of a substance (e.g., drug abuse,
antidepressant medications) or to a general medical condition.
II. Mixed Episode. A mixed episode is diagnosed when the patient meets criteria for both a
manic episode and a major depressive episode over at least a 1-week period. The
requirement for significant impairment and the exclusion of organic causes are the same
as for a manic episode.
III. Hypomanic Episode. A hypomanic episode has similar symptoms as a manic episode but
differs in the severity and duration criteria. The symptoms must be present for at least 4
days and must produce an unequivocal change in the patient's functioning that is
observable by others. However, by definition, there is no marked deterioration in
functioning, need for hospitalization, or psychotic symptoms; otherwise, a manic episode
DSM-IV (APA, 1994b) has outlined several subtypes of bipolar disorder, including:
1. Bipolar I Disorder. To have bipolar I disorder, the patient must have experienced at least
one manic or mixed episode.
2. Bipolar II Disorder. Patients with bipolar II disorder have had one or more episodes of
both major depression and hypomania, but no manic or mixed episodes.
3. Cyclothymic Disorder. For children and adolescents, cyclothymia is described as periods
of 1 year or more (2 years or more for adults) where there are numerous hypomanic and
depressive symptoms that do not meet full criteria for either a major depressive disorder,
manic episode, or mixed episode. Symptoms must be present for much of the defined
period (no more than 2 consecutive months symptom-free) and must cause clinically
significant distress or impairment of functioning.
Whether there is either a seasonal pattern or rapid cycling should be specified for both bipolar I
and II. A seasonal pattern represents a course of illness where the major depressive episodes
occur consistently at a particular time of year. Rapid cycling is diagnosed when the patient has at
least four episodes of a mood disturbance (major depression, mania, mixed, or hypomania) over
a 12-month period.
None of the above three disorders is diagnosed if the symptoms are either better accounted for,
or superimposed on, schizoaffective disorder, schizophrenia, schizophreniform disorder,
delusional disorder, or a psychotic disorder not otherwise specified.
The diagnostic assessment needs to incorporate both current and past history regarding
symptomatic presentation, treatment response, and psychosocial stressors. Cross-cultural issues
may influence the expression or interpretation of symptoms and/or treatment response; therefore,
they must be assessed (APA, 1994a). It is helpful to organize the clinical information using a life
chart to characterize the course of illness, patterns of episodes, severity, and treatment response
(APA, 1994a). Using such a longitudinal perspective to conceptualize the disorder helps with
diagnostic accuracy, since the presenting symptoms during the acute phases often can be
confused with other disorders.
Similarly, it is important to recognize the various phases and patterns of episodes associated with
bipolar disorder. Youth may first present with either manic or depressive episodes. Twenty to
thirty percent of youth with major depressions go on to have manic episodes (Geller et al., 1994;
Rao et al., 1995; Strober and Carlson, 1982). Risk factors predicting eventual mania include: (1) a
depressive episode characterized by rapid onset, psychomotor retardation, and psychotic
features; (2) a family history of affective disorders, especially bipolar disorder; and (3) a history of
mania or hypomania after treatment with antidepressants (Strober and Carlson, 1982). The same
risk factors are also noted in the adult literature (Goodwin and Jamison, 1990). Similarly,
psychotic depression, a family history of bipolar disorder, and a history of attention-deficit
hyperactive disorder (ADHD) with associated affective instability are factors associated with youth
switching to mania on antidepressant therapy (Venkataraman et al., 1992). In children with major
depressive disorder, Geller et al. (1994) found that 31.7% (n = 25) went on to develop either
mania or hypomania; 80 percent of them were 12 years old or younger (mean age 11.1 years) at
the time of onset. Neither exposure to antidepressants, nor atypical features, were predictive in
In studies of adults, characteristic stages of mania have been described: stage I includes
euphoria, increased psychomotor activity, and mood lability. This evolves into stage II, with
symptoms of irritability, racing thoughts, dysphoria, and disorganization. Finally, in stage III, the
patient's cognitive status deteriorates, with significant confusion and florid psychosis (Carlson and
Goodwin, 1973). Significant depressive symptoms may either precede, occur conjointly (mixed
episodes), and/or follow those of mania within the same episode. Depressive episodes in bipolar
disorder are typically characterized by psychomotor retardation and hypersomnia, significant
suicide attempts, and often psychotic symptoms (Goodwin and Jamison, 1990). Severe cases
may progress to catatonia.
Children with mania frequently present with symptoms that are considered a typical (Bowring and
Kovacs, 1992). The changes noted in mood, level of psychomotor agitation, and mental
excitement are often markedly labile and erratic, rather than persistent. Irritability, belligerence,
and mixed manic-depressive features are more common than euphoria. The types of reckless
behaviors seen are constrained by the child's developmental and social boundaries, and thereby
limited to typical childhood behavior problems, such as school failure, fighting, dangerous play,
and inappropriate sexualized activity. Thus, hallmark manic symptoms, such as grandiosity,
psychomotor agitation, and reckless behavior, must be differentiated from those of other more
common childhood disorders, as well as from the normal childhood phenomena of boasting,
imaginary play, overactivity, and youthful indiscretions.
The incidence and validity of the diagnosis in children remains controversial (Carlson, 1990).
Dating back to Kraepelin (1921), large surveys have found that onset prior to age 10 occurs in
only 0.3% to 0.5% of bipolar patients (Goodwin and Jamison, 1990; Kraepelin, 1921; Loranger
and Levine, 1978). Since the estimated lifetime prevalence in the general population is 0.8%
(APA, 1994a), it has generally been accepted that childhood-onset bipolar disorder is rare.
However, more recent case reports question these estimates, noting that many seriously
emotionally disturbed children meet criteria for mania by virtue of their problems with irritability,
emotional lability, increased energy and reckless/dangerous behaviors (Weller et al., 1986b;
Wozniak et al., 1995). These symptoms, which often have a chronic and, at times, rapidly
fluctuating course, may represent the child's baseline state, rather than a marked change in
functioning (Wozniak et al., 1995). Such presentations differ from the episodic course classically
ascribed to the illness and are more typical of childhood behavioral disorders (Bowring and
Kovacs, 1992). Further research is needed to clarify whether these reflect "true cases" of mania,
or are, rather, a nonspecific collection of behavioral and emotional difficulties. Of particular
importance will be longitudinal studies following these youth into adolescence/adulthood to
determine if their symptoms evolve into the more typical presentation of the disorder (Goodwin
and Jamison, 1990).
Adolescents with mania frequently have complicated presentations, including: (1) psychotic
symptoms, including mood-incongruent hallucinations, paranoia, and marked thought disorder;
(2) markedly labile moods, with mixed manic and depressive features; and (3) severe
deterioration in their behavior (Akiskal et al., 1985; Goodwin and Jamison, 1990). These varying
presentations have led to underdiagnosis of bipolar disorder in teenagers (Carlson et al., 1994),
including very high rates of misdiagnosis as schizophrenia (Carlson, 1990; McClellan et al., 1993;
Werry et al., 1991). Although the early course of bipolar disorder in adolescents is often more
chronic and refractory to treatment, the long-term prognosis is probably similar to that of adults
(Carlson, 1990; McClellan et al., 1993; McGlashan, 1988; Werry et al., 1991).
A diagnosis of bipolar disorder should be considered for any youth with a marked deterioration in
functioning associated with either mood or psychotic symptoms. Since diagnostic accuracy does
improve if DSM criteria are reliably applied (Carlson et al., 1994), using the available structured
and semistructured diagnostic interviews may be warranted. However, even with these
instruments, there is still a risk of overdiagnosis in youth with conduct disorder and ADHD (Weller
et al., 1995). The Mania Rating Scale (Fristad et al., 1992) and subscales on the Child Behavior
Checklist (Achenbach and Edelbrock, 1983; Biederman et al., 1995) have been used to
distinguish manic children from those with ADHD.
Youth presenting with symptoms suggestive of bipolar disorder need to have a thorough
psychiatric evaluation, including any necessary pediatric and neurological assessments. In this
section, we highlight the most pertinent diagnostic conditions that need to be considered.
Schizophrenia. Early-onset bipolar disorder is frequently misdiagnosed (rates of 50% or more) as
schizophrenia, especially in patients with onset during adolescence (Carlson, 1990; McClellan et
al., 1993; Werry et al., 1991). Adolescents with mania more often have "schizophrenic-like"
symptoms (i.e., hallucinations and delusions), and are more likely to be diagnosed as having
schizophrenia or schizoaffective disorder than patients with adult-onset bipolar disorder (Bashir et
al., 1987; McGlashan, 1988). Using standardized diagnostic techniques improves accuracy,
although differentiation can still be problematic (Carlson et al., 1994).
Schizoaffective Disorder. The diagnosis of schizoaffective disorder requires a period of illness in
which the patient has both a significant mood disorder (either major depression, mania, or a
mixed episode) and psychotic symptoms fulfilling the requirements for schizophrenia (APA,
1994b). During the same period of illness, there also must be at least a 2-week period where
hallucinations and delusions persist in the absence of predominant mood symptoms. Finally, the
mood symptoms must be present for a substantial portion of the overall illness.
Schizoaffective disorder has not been well defined in youth. Eggers (1989) found that 28% of
patients with early-onset schizophrenia had schizoaffective psychoses at follow-up. This is an
ICD-9 diagnosis that overlaps with DSM-III-R (APA, 1987) diagnoses of bipolar disorder and
schizoaffective disorder. Other follow-up studies of psychotic youth have found that the diagnosis
of schizoaffective disorder was made infrequently, was associated with the most severe
impairment, and was somewhat unreliable (McClellan et al., 1993; Werry et al., 1991).
Agitated Depression. An agitated depression may be confused with a mixed episode due to
symptoms of increased psychomotor activity and anxiety. Ratings of manic symptoms have been
used to differentiate the two conditions in adults (Swann et al., 1993). Conversely, patients with
agitated depressions may eventually develop bipolar disorder.
Posttraumatic Stress Disorder. Youth with significant histories of trauma, including childhood
maltreatment, often present with mood instability, hypervigilance, irritability, dissociative
symptoms, and sleep disturbances. These symptoms may be confused with mania/mixed
episodes. Some youth will have both disorders (Borchardt and Bernstein, 1995).
Borderline Personality Disorder. The affective instability, poor impulse control, and erratic
behaviors associated with borderline personality disorder may be misdiagnosed as bipolar
disorder. To differentiate, the traits of a personality disorder should be pervasive and persistent,
whereas the symptoms of bipolar disorder represent a marked change in the patient's baseline
mental status and global functioning. However, patients with bipolar disorder may have chronic
symptoms of irritability, cyclothymia, and/or dysthymia, and are, therefore, at risk of being
misdiagnosed as borderline (Akiskal, 1981). Some youth may have both (Kutcher et al., 1990).
An additional problem is that a diagnosis of borderline personality disorder in adolescents may
lack specificity (Garnet et al., 1994).
Childhood Disruptive Behavioral Disorders. The impulsivity, hyperactivity and irritability of ADHD
or the antisocial and provocative behaviors of conduct disorder may all be confused with mania.
Many of the symptoms overlap, including aggression, school failure, psychomotor agitation,
restless sleep, distractibility, and sexually inappropriate behaviors. Although historically, mania
was undoubtedly underdiagnosed in youth felt to be behaviorally disordered, the increased
recognition of the phenomenon may now be leading to overdiagnosis, especially in
preadolescents. Adding to this confusion is the fact that many youth with bipolar disorder have
comorbid ADHD and/or conduct disorder (Carlson, 1990). However, the reverse does [not (bpso
ed.)] seem to be true, since longitudinal follow-up studies of ADHD have not shown an increased
ncidence of bipolar disorder (Gittelman et al., 1985). Finally, Wozniak et al. (1994) found that first-
degree relatives of children who meet DSM-III-R (APA, 1987) criteria for mania (94% also had
ADHD) had high rates of both ADHD and bipolar disorder, and relatives of children with only
ADHD had high rates of ADHD but not bipolar disorder.
Differentiating between these conditions can usually be done via history and mental status
examination (Bowring and Kovacs, 1992). Both ADHD and conduct disorder are chronic
persistent disorders of impulse control and behavioral regulation, and they represent stable
patterns of functioning. ADHD begins before age 7 and may evolve into conduct disorder during
late childhood or early adolescence. Bipolar disorder is usually episodic, with onset usually after
age 12. It is a disorder of affect regulation characterized by abnormal mood and mental
excitement usually presenting as a marked change in a youth's baseline functioning.
Cross-Cultural Issues and Culture-Bound Syndromes. Ethnic minorities and individuals from
lower socioeconomic settings have had a greater risk of misdiagnosis of schizophrenia (Goodwin
and Jamison, 1990). Ki1gus et al. (1995) found that psychiatrically hospitalized African-American
adolescents were more often diagnosed with organic/psychotic disorders and less often
diagnosed with affective/anxiety disorders than Caucasian teenagers.
Culture-bound syndromes represent recurrent patterns of maladaptive behaviors and/or troubling
experiences specifically associated with different cultures or localities (APA, 1994b). Clinicians
should refer to DSM-IV for a glossary of the best-studied culture-bound syndromes (APA, 1994b).
These syndromes may be confused with bipolar disorder, and in many cases, the clinician will
need to obtain consultation from a professional familiar with the particular cultural issues involved.
Mood Disorder Due to a Medical Condition. Symptoms of mania can be produced by a variety of
different medical conditions (Cummings, 1985), including: (1) neurological disorders, such as
brain tumors and CNS infections, including human immunodeficiency virus (HIV), multiple
sclerosis, temporal lobe seizures, and Klein-Levin syndrome; (2) systemic conditions, such as
hyperthyroidism, uremia, Wilson's disease, and porphyra; (3) prescribed medications, including
antidepressant agents, sympathomimetics, bromocriptine, stimulants, and steroids; and (4)
substances of abuse, including amphetamines, cocaine, phencyclidine, inhalants, and
methylenedioxymethamphetamine (ecstasy). Youth presenting with manic symptoms need to
have a thorough physical evaluation. Decisions regarding more extensive laboratory and
neuroimaging studies should be made based on the clinical findings of the psychiatric, pediatric,
and neurological examinations.
ASSOCIATED CLINICAL FEATURES
Although the number of studies examining early-onset bipolar disorder is limited, the data are
sufficient to outline some of the associated features of the disorder:
Prevalence and Age of Onset. Epidemiological surveys of childhood psychiatric disorders have
generally not addressed bipolar disorder (Costello, 1989a). A community school survey of older
adolescents (14 to 18 years of age) found the lifetime prevalence rate to be approximately 1%
(Lewinsohn et al., 1995). Most of the patients identified had bipolar II disorder. An additional 5.7%
had subthreshold symptomatology. Carlson and Kashani (1988), in an epidemiological survey of
14- to 16-year-old youth, found that the estimated lifetime prevalence of mania varied from 0.6%
to 13.3%, depending on whether duration and severity criteria were applied; for comparison, the
lifetime prevalence in adults is estimated to be 0.8% (APA, 1994a). The incidence appears to
increase after onset of puberty. Despite anecdotal reports of onset prior to 6 years of age, further
research is needed to establish whether such cases represent true bipolar disorder.
Subtypes of Bipolar Disorder. Manic symptoms in youth frequently do not persist long enough to
meet the 1-week duration criteria required by DSM-IV (APA, 1994b) for a manic episode (Akiskal,
1995; Akiskal et al., 1985; Carlson and Kashani, 1988;Lewinsohn et al., 1995). This is especially
true for children. Therefore, youth are more likely to have a diagnosis of either bipolar II or
cyclothymic disorder, rather than bipolar I disorder. Children and adolescents may also be more
likely than adults to present with rapid-cycling episodes. Geller et al. (1995) found that in 26
patients with early-onset bipolar disorder (ages 7 to 18 years), 81% had a rapid-cycling course.
Gender Ratio. 0verall, bipolar disorder affects both sexes equally. However, in studies of early-
onset cases, males seem to be more often affected, especially in those with onset before the age
of 13 years. Females are more likely overall to have depressive disorders, although for children
younger than 12 years of age, boys again appear to be at greater risk (Costello, 1989b).
Rapidity of Onset. Studies of the rapidity of onset have found that the majority of youth have
either an acute (less than 2 weeks) or subacute (less than 3 months) prodromal course
(McClellan et al., 1993; Werry et al., 1991).
Premorbid Functioning. Many youth with bipolar disorder have normal premorbid histories.
However, preexisting behavioral problems, including ADHD and/or conduct disorder, are also
found in a significant number (Carlson, 1990; McClellan et al., 1993; Werry et al., 1991).
Premorbid anxiety and emotional problems are also common, including among those whose first
affective episode is a depressive disorder. Dysthymic, cyclothymic, or hyperthymic (irritable,
driven) temperaments may presage eventual bipolar disorder (Akiskal, 1995).
Intellectual Functioning. Studies have generally reported that over 90% of youth with bipolar
disorder have normal IQs (Geller et al., 1994; McClellan et al., 1993; Werry et al., 1991).
However, bipolar disorder, including rapid cycling, has been reported in patients with moderate to
severe mental retardation, autism, and trisomy 21 (Carlson, 1990).
Family History. Bipolar disorder definitely has been shown to be a familial disorder (Rice et al.,
1987; Strober, 1992b). The degree of familiarity is increased in early-onset cases, with reported
lifetime rates of bipolar disorder of approximately 15% in first-degree relatives (Strober, 1992b;
Todd et al., 1993, 1994).
Comorbid Conditions. A significant number of youth displays comorbid ADHD and/or conduct
disorder (Borchardt and Bernstein, 1995; Carlson, 1990; Kovacs and Pollock, 1995; West et at.,
1995). High rates of substance abuse are also noted in some samples (Borchardt and Bernstein,
1995; Carlson, 1990; McClellan et al., 1993). The presence of comorbid behavioral disorders and/
or substance abuse negatively influences prognosis and treatment response (Carlson, 1990;
Kovacs and Pollock, 1995; Strober, 1992a).
Course and Prognosis. In adults, bipolar disorder is generally an episodic disorder with a variable
course (APA, 1994a). The majority of patients will have multiple episodes, usually 10 or more in
untreated patients (Goodwin and Jamison, 1990). Episodes tend to come more frequently over
time, until the cycle length stabilizes after the fourth or fifth episode (Goodwin and Jamison,
In a 5-year naturalistic prospective follow-up study of 54 adolescents with bipolar disorder, two
patients never achieved complete remission (Strober et al., 1995). Of the remaining patients, 44%
had a relapsing course (either major depression or mania), and 21% had two or more further
episodes (Strober et al., 1995). Recovery from the index episode took longer for patients with
depression (median time to recovery, 26 weeks) than for either mania or mixed episodes (median
time, 9 and 11 weeks, respectively) (Strober et al., 1995).
Compared with adults, adolescents with bipolar disorder may have a more prolonged early
course and less responsiveness to treatment (McGlashan, 1988; Strober et al., 1995). This may
be due to the fact that adolescents with bipolar disorder frequently present with either mixed
features, psychotic symptoms, and/or comorbid behavior/substance abuse problems, all of which
predict a more refractory response to lithium therapy. However, the few available studies suggest
that the long-term prognosis of early-onset bipolar disorder is similar to that of adult onset; with
approximately one half of patients showing significant functional impairment compared with their
premorbid state (McClellan et al., 1993; McGlashan, 1988; Werry et al., 1991). Premorbid
characteristics, including intellectual functioning, also strongly influence outcome (Werry et al.,
1992). Further research is needed to examine how bipolar disorder affects evolving
developmental processes, given the disruptive impact of the episodes on academic, social, and
Adolescents with bipolar disorder are at increased risk for completed suicides (Brent et al., 1988,
1993, 1994; Welner et al., 1979). Strober et al. (1995) found that 20% of their adolescent patients
made at least one medically significant suicide attempt. In the adult literature, a large review of
studies examining depressive and manic depressive disorders found the mean rate of completed
suicides to be 19% (Goodwin and Jamison, 1990). Patients who are male or who are in the
depressed phase of their illness are at the highest risk.
A multimodal treatment plan, combining medications with psychotherapeutic interventions, is
needed to address the symptomatology and confounding psychosocial factors in children and
adolescents with bipolar disorder. Cultural issues must be appropriately incorporated into the
treatment plan. The goal of therapy is to ameliorate symptoms and prevent relapse, while also
reducing long-term morbidity and promoting normal growth and development.
This guideline will focus primarily on the treatment of mania and mixed episodes. The treatment
of bipolar depression will be more thoroughly addressed in a practice parameter that is being
developed for the assessment and treatment of depression in children and adolescents.
Psychopharmacological intervention is necessary to effectively treat early-onset bipolar disorder.
The literature regarding medication treatment for children and adolescents with bipolar disorder is
limited. Many of the current recommendations are, therefore, based on studies of adults.
Pharmacotherapy is usually instituted to address manic (or mixed) symptoms and depressive
symptoms or to prevent relapse of the disorder.
Regardless of medication choice, the procedures that need to be followed when initiating
Informed Consent. Informed consent (addressing the rationale for treatment, as well as the
potential risks and benefits of the therapy) should be obtained from both the youth and the youth's
parents/guardians. If the mental status of the patient precludes this or if therapy is refused,
invoking the relevant statutory mechanisms for involuntary treatment may become necessary. For
patients under the legal age of consent, basic information regarding treatment should be provided
in a developmentally appropriate manner.
Examinations. Prior to medication therapy, a thorough psychiatric evaluation is needed. The
symptoms for which treatment is targeted should be documented. A thorough physical
examination is also necessary, including any clinically indicated laboratory and/or neuroimaging
studies to evaluate potential organic etiologies and to provide baseline assessments for
monitoring specific medications.
Phase of the Illness. The clinician must assess which phase of the patient's illness (i.e., manic,
depressed, mixed, or in remission) to effectively intervene. As patients are effectively treated for
mania, they will frequently progress through the stages of the disorder. Thus, they may appear to
be worsening when, in fact, they are undergoing a natural progression of symptoms. Some
patients with mania will have a depressive phase before their mood returns to its baseline state.
Similarly, mania often progresses from a euphoric/hyperexcited condition to a more disorganized
state before showing clinical improvement. Recognition of these changes is important when
considering the addition of other medications or a change in the primary antimanic agent.
Length of Treatment. Short-term, an antimanic agent needs to be given at an adequate dose for
at least 4 to 6 weeks before its efficacy can be determined. Clinicians should avoid multiple
medication changes/additions, since doing so frequently confuses the clinical picture and
generally does not improve efficacy.
Long-term, the evidence to date shows that the relapse rate is quite high for early-onset bipolar
disorder. Strober et al. (1990) prospectively followed 37 adolescents with bipolar disorder over 18
months and found that more than 90% of those who were noncompliant with their lithium
treatment relapsed (12 of 13 cases). The relapse rate for those compliant with treatment was
37.5%. This study suggests that prophylactic therapy is needed for at least 18 months. However,
further research is needed.
In the adult literature, over 80% of patients with a manic episode will have at least one episode of
relapse (APA, 1994a). Withdrawal of maintenance lithium therapy has been associated with an
increased risk of relapse, especially within the 6-month period following lithium discontinuation
(APA, 1994a). In addition, there are reports of patients whose symptoms were well managed
long-term on lithium, but after the lithium was discontinued, the patients relapsed and no longer
responded adequately to lithium therapy (Post et al., 1992). The indications for, and the overall
duration of, long-term maintenance therapy need further study. Clinically, however, some
individuals may need lifelong prophylaxis.
Since no definitive studies address the long-term treatment of early-onset bipolar disorder, the
clinician must balance the potential deleterious impact of relapse versus that of the side effects of
the medications. Any attempts to taper prophylactic therapy must be closely monitored for
symptoms of relapse. Further, patients and families must be thoroughly educated as to the signs
and symptoms of relapse to provide for resumption of treatment as soon as possible, if
necessary. Finally, the patient's diagnostic status must be reassessed over time, given the high
rate of misdiagnosis in youth, to ensure that the course of medication therapy is appropriate.
Medication Choice. The choice of medication(s) should be made based on: (1) evidence of
efficacy, (2) the phase of illness (see above), (3) the presence of confounding presentations (e.g.,
rapid-cycling mood swings, psychotic symptoms), (4) the agent's side effect spectrum, (5) the
patient's history of medication response, and (6) the preferences of family/patients. In addition,
different ethnic groups may vary in their pharmacokinetic response to lithium, antidepressants,
and the other psychotropic agents, with a potential impact on side effects, blood levels, and
efficacy (Lin et al., 1995). ultiple agents are often required, but care should be taken to avoid
unnecessary polypharmacy. A discussion of the individual agents follows.
Lithium, traditionally the agent of first choice in the treatment of bipolar disorder, has the largest
database supporting its efficacy (APA, 1994a). In adults, lithium has been shown to be effective
for: (1) the treatment of acute manic and depressive episodes, (2) prevention of recurrent manic
and depressive episodes, and (3) reduction of mood instability between episodes (Goodwin and
Jamison, 1990). Approximately 80% of patients with bipolar disorder respond to lithium, both for
acute mania and depression (APA, 1994a). However, the response rate for mania is quicker (2
weeks versus 6 to 8 weeks for depression). Lithium also helps recurrent episodes of both mania
and major depression. Discontinuation of long-term lithium therapy increases the risk of relapse,
at least in the short term (APA, 1994a). Some patients may develop a more treatment-resistant
form of the illness after previously effective lithium prophylaxis has been discontinued (Post et al.,
A paucity of data examines the efficacy of lithium for early-onset bipolar disorder (Alessi et al.,
1994; Kafantaris, 1995; Strober, 1992a; Viesselman et al., 1993). The few double-blind placebo-
controlled studies are limited by either small sample size and/or mixed diagnostic status,
including more broadly defined psychotic disorders and/or the combination of manic symptoms
and disruptive behavior disorders (Carlson et al., 1992; Delong and Aldershof, 1987; Gram and
Rafaelsen, 1972; McKnew et al., 1981). These studies, plus case series and individual case
reports, have found lithium to be effective (Alessi et al., 1994; Carlson and Strober, 1978;
Hassanyeh and Davison, 1980; Horowitz, 1977; Hsu and Starzynski, 1986; Strober et al., 1988),
with greater evidence published for those with adolescent onset (Alessi et al., 1994). However,
the overall response may be less than that for adults, possibly because youth, especially
adolescents, with mania often have either mixed manic-depressive syndromes and/or a
predominance of psychotic symptoms, both of which are generally more refractory to treatment.
1. Pharmacology. Lithium, an alkali metal similar to sodium, is prescribed as one of two salt
preparations, lithium carbonate or citrate (Viesselman et al., 1993). It has multiple complex
neurochemical effects, with impact on ion channels, serotonin, dopamine, and norepinephrine
neurotransmitter systems, as well as on second messenger systems (e.g., adenylate cyclase)
(Alessi et al., 1994). How these neurochemical effects influence mania is not clearly understood
(Viesselman et al., 1993).
Lithium is excreted almost entirely by the kidneys without undergoing hepatic metabolism
(Viesselman et al., 1993). Serum levels increase linearly with dose, and steady-state levels are
usually reached after approximately 1 week of administration. Since children generally have a
higher glomerular filtration rate than adults, the required dose to weight ratio is usually higher for
this age group (Viesselman et al., 1993).
2. Blood Levels. As in adults, the recommended therapeutic serum levels for the acute phase
range from 0.6 to 1.2 mEq/ L (Viesselman et al., 1993). However, if manic symptoms persist, the
serum levels may be carefully increased beyond this range, as long as the side effects are
tolerated. In adults, maintenance serum levels generally have been in the range of 0.6 to 0.8
mEq/L, although this has not been adequately studied (APA, 1994a). Patients maintained on
lower prophylactic levels (0.4 to 0.6 mEq/L) have fewer side effects but higher rates of relapse
than those maintained on higher dosages (0.8 to 1.0 mEq/L) (Gelenberg et al., 1989). For some
patients, the necessary acute phase and maintenance phase serum levels will be the same (APA,
To achieve therapeutic levels, clinicians may choose to initiate a reasonable starting dose and
monitor blood levels over time. Lithium levels are often needed at least weekly when starting
treatment. Serum levels are assessed 12 hours after the last dose. Generally, starting dosages
range from 300 mg to 900 mg per day, depending on the size of the child. Weller et al. (1986a)
found that, for children, a starting dose of 900 mg/m2 (approximately 30 mg/kg daily) generally
produced a therapeutic serum level within 5 days, although some children may develop levels
greater than 1.4 mEq/L (Alessi et al., 1994). Also, published nomograms used to calculate
dosages based on blood levels after single test doses (Alessi et al., 1994; Geller and Fetner,
1989) may be helpful in avoiding excessive dosages in children who are slow metabolizers and
may permit more rapid dosage adjustments.
Several studies have examined the possibility of using saliva levels in children to avoid blood
draws. However, methodological problems have limited the utility of this technique. Saliva levels
are more variable than serum, and to establish an accurate serum-saliva ratio for a given patient,
several blood draws are needed (Alessi et al., 1994). Therefore, serum levels remain the
standard of care.
3. Side Effects. Youth generally tolerate lithium well and may have fewer side effects than adults
(Alessi et al., 1994). Younger children may be more prone to side effects than older children
(Campbell et al., 1991). Commonly reported adverse reactions include nausea, diarrhea,
vomiting, tremor, weight gain, headache, polyuria, polydipsia, enuresis, fatigue, and ataxia (Alessi
et al., 1994; Silva et al., 1992; Viesselman et al., 1993). Although the spectrum of lithium side
effects in youth is similar to that in adults, there are few studies regarding its long-term effects in
youth. Therefore, the potential side effects outlined below are primarily derived from the literature
Endocrine. Lithium has been associated with the development of hypothyroidism, goiters, and
thyroid autoantibodies, including reported cases in children (Alessi et al., 1994). Thyroid
stimulating hormone is elevated in lithium-induced hypothyroidism and, therefore, conducting the
laboratory test for its level is useful in monitoring lithium therapy.
Renal. Lithium inhibits the action of antidiuretic hormone on the distal tubules and collecting
ducts, leading to the common side effects of polyuria and polydipsia. This may evolve into
diabetes insipidus, which is usually reversible if the lithium is discontinued (Gelenberg and
In adults, structural changes in the kidney, including focal glomerular atrophy, interstitial fibrosis,
and impaired tubular functioning, have been reported with long-term lithium therapy (Gelenberg
and Schoonover, 1991). However, the risk of significant glomerular damage with long-term lithium
therapy appears to be minimal (Gelenberg and Schoonover, 1991; Hetmar, 1991; Meyers, 1989).
Other reported renal problems include nephrotic syndrome, proteinuria, and renal failure with
acute intoxication (Alessi etal., 1994; Gelenberg and Schoonover, 1991).
Cardiovascular. Lithium can have significant effects on cardiac conduction, including first-degree
atrioventricular block, irregular sinus rhythms, and increased premature ventricular contractions.
However, serious adverse reactions are rare (Gelenberg and Schoonover, 1991). In children,
reversible conduction abnormalities have been reported (Campbell et al., 1972).
Hematological. Benign mild leukocytosis is commonly noted (Viesselman et al., 1993).
Dermatological. Lithium can induce or exacerbate dermatological problems, including acne, which
may be a significant concern to adolescent patients (Viesselman et al., 1993).
Neurological. Lithium may produce a variety of neurological effects, including muscle weakness,
tremor (which can be treated with propranolol), lethargy, cognitive blunting, and headaches
(Gelenberg and Schoonover, 1991; Viesselman et al., 1993). These are often time-limited and
remit quickly. Serious neurotoxicity may develop with higher blood levels, including ataxia,
dysarthria, nystagmus, and confusion. With blood levels above 3.0 mEq/L, patients may develop
more devastating neurological impairments, including seizures, coma, and death (Gelenberg and
In children, lithium has been reported to alter EEG patterns and to decrease performance on
cognitive testing (Portteus Mazes test) (Alessi et al., 1994). However, at therapeutic blood levels,
the impact on overall cognitive functioning does not appear to be significant (Viesselman et al.,
Osseous. Given lithium's interaction with calcium metabolism, it theoretically might cause long-
term problems with skeletal growth. However, it does not seem to increase the risk for
osteoporosis in adults (Viesselman et al., 1993). How lithium potentially interacts with the
developmental maturation of a child needs to be further researched.
Teratogenic. In utero exposure to lithium has been associated with various congenital
abnormalities, especially cardiac anomalies (Ebstein's anomaly) (Jacobson et al., 1992).
However, when examined prospectively in a multicenter study, women who used lithium during
the first trimester of pregnancy had no greater risk of mania or congenital malformations in their
offspring than controls (one out of 148 cases with in utero exposure to lithium developed
Ebstein's anomaly) (Jacobson et al., 1992). It is generally recommended that lithium be avoided
during pregnancy, especially during the first trimester (Green, 1995). If lithium is used, adequate
monitoring for fetal congenital anomalies, including ultrasound and fetal echocardiography, is
needed (Jacobson et al., 1992). Adolescent females should be evaluated for unsuspected
pregnancies prior to making medication decisions.
Drug-Drug Interactions. Lithium is commonly used with antipsychotic agents without significant
problems. However, there are reports of patients developing an encephalopathic syndrome or
neuroleptic malignant syndrome with concomitant use of lithium and neuroleptics (Green, 1995).
This may be dose-related. Many agents influence lithium levels. For example, carbamazepine,
nonsteroidal antiinflammatory agents, some antibiotics (tetracycline), and thiazide diuretics all
may raise lithium levels (Green, 1995).
4. General Medical Evaluation. Prior to initiating lithium therapy, a thorough psychiatric and
pediatric evaluation is warranted, including inquiring about any history of renal, endocrine, and/or
cardiovascular problems. Whether or not the patient is on a low-salt diet or diuretic therapy
should also be noted, since these will influence lithium levels.
Baseline laboratory assessment should include: blood counts, thyroid functions, urinalysis, blood
urea nitrogen, creatinine, and a pregnancy test in adolescent females (Rosenberg et al., 1994).
When clinically indicated, an electrocardiogram and a 24-hour creatinine clearance should also
be obtained. Once a stable lithium dose is obtained, lithium levels, renal and thyroid functions,
and urinalyses need to be regularly monitored (every 3 to 6 months) (Rosenberg et al., 1994).
ANTICONVULSANT MOOD STABILIZERS
In the adult literature, both open and controlled studies have supported the efficacy of the
anticonvulsants carbamazepine and valproate for the acute treatment of bipolar disorder (APA,
1994a; McElroy et al., 1992). Greater evidence supports the use of valproate, which was recently
approved as a treatment for mania by the U.S. Food and Drug Administration. Some patients who
do not respond to, or are intolerant of, lithium, may respond to the anticonvulsants. These agents
have been used by themselves, together, or in combination with lithium. Indications for their use
include rapid cycling and dysphoric (or mixed) mania (both of which are associated with poor
response to lithium) (APA, 1994a; McElroy et al., 1992). Some evidence supports their use as
prophylactic agents during the maintenance phase of therapy, but controlled studies are lacking
(APA, 1994a). The anticonvulsants are probably less effective for acute depressive symptoms
than lithium, although valproate has been reported beneficial for the depressive phases of bipolar
II disorder (Puzynski and Klosiewicz, 1984).
Only a few case reports examine the efficacy of anticonvulsant agents for early-onset bipolar
disorder, but none is placebo-controlled (Pataki and Carlson, 1992; Viesselman et al., 1993).
Therefore, the justification for their use is derived primarily from the adult literature. Valproate has
been reported to be effective for treating mania in adolescents (West et al., 1994). However, the
patients in these reports were also receiving adjunctive psychotropic agents (primarily
neuroleptics). Carbamazepine has been reported to be effective in manic adolescents
nonresponsive to lithium (Hsu, 1986). Since these agents have been widely used in children and
adolescents with seizure disorders, there is considerable information regarding side effects in
youth (Carpenter and Vining, 1993).
Valproate. Valproate, a commonly used anticonvulsant in youth, is effective for a wide variety of
seizure disorders (Carpenter and Vining, 1993). Its antiepileptic effects are believed to be due to
its increasing brain levels of (-aminobutyric acid (GABA) (Viesselman et al., 1993). It is hepatically
metabolized and highly protein-bound (APA, 1994a). Valproate tends to inhibit the metabolism of
other agents and, therefore, may cause an increase in the plasma levels of concurrent
medications (APA, 1994a; Viesselman et al., 1993).
The relationship between valproate serum levels and its effectiveness for mania has not been
adequately defined (APA, 1994a). Thus, the recommended therapeutic levels are the same as for
treating seizure disorders -– 50 to 100 (g/mL (Viesselman et al., 1993). The usual dose for
children is 10 to 60 mg/kg daily, and for adolescents, 1,000 to 3,000 mg daily (Pedley et al.,
Most youth tolerate valproate well. Common side effects include sedation, nausea, and vomiting
(Viesselman et al., 1993). Although rare, potentially serious side effects are reported. Valproate
has been associated with fatal hepatic toxicity. Those at highest risk are very young children (less
than 2 years old) during the first 6 months of therapy, especially those on multiple
anticonvulsants: and/or with severe seizure disorders/organic impairment (PDR, 1994).
Hematological side effects have been noted, including reported cases of coagulopathies,
thrombocytopenia, neutropenia, pancytopenia, and/or aplastic anemia (PDR, 1994; Viesselman
et al., 1993). Increased rates of polycystic ovary disease in adult women with seizure disorders
have also been reported (Isojarvi,et al., 1993). Finally, valproate has been associated with neural
tube defects when exposure occurred during the first trimester (PDR, 1994).
Prior to treatment, baseline liver functions, blood cell counts, and coagulation tests are
recommended (Visselman et al., 1993). Once a stable therapeutic valproate level is obtained,
serum valproate levels, plus hepatic and hematological measures, should then be periodically
monitored every 3 to 6 months (Papatheodorou and Kutcher, 1993). However, periodic
monitoring does not ensure that abnormalities will be identified; it is also important to advise
patients and families about presenting symptoms of these side effects.
Carbamazapine. Carbamazapine is chemically related to tricyclic antidepressants. Its dosing
kinetics are linear. However, it causes induction of hepatic metabolic enzymes, which accelerates
its own metabolism, as well as that of other hepatically metabolized agents. This autoinduction
often results in decreased blood levels over time without any change in dosage. Similar to
valproate, the therapeutic range for serum levels has not been established for treating mania. The
recommended range is the same as that used for seizure disorders–4 to 12 (g/mL (Rosenberg et
al., 1994). The dosage for children generally is 10 to 20 mg/kg daily (200 to 600 mg per day), and
for adolescents, dosages may go as high as 1,200 mg per day or more (Pedley et al., 1995;
Viesselman et al., 1993). When initiating a trial of Carbamazapine, starting dosages begin at 100
to 300 mg per day and are increased as tolerated while monitoring blood levels. Daily dosages
are usually divided in b.i.d. or t.i.d. schedules.
Upon initiation of therapy, transient side effects may include drowsiness, dizziness, nausea, and
mild ataxia (Viesselman et al., 1993). Leukopenia occurs in children but is generally not clinically
significant unless the total white blood count drops below 3,000/mm3. Carbamazapine has been
reported to cause agranulocytosis and aplastic anemia (PDR, 1994). The greatest risk for
agranulocytosis occurs within 3 months of initiating therapy, although it has been reported as late
as 5 years after starting treatment (PDR, 1994). Finally, there are also reports of hepatic toxicity.
In children with seizure disorders, reported cognitive and behavior effects include impaired
performance on learning and memory tasks, irritability, agitation, insomnia, and emotional lability
(Carpenter and Vining, 1993). However, Stores et al. (1992) found no significant cognitive or
behavior effects after 1 year of therapy with either Carbamazapine or valproate.
Prior to initiating therapy, baseline blood counts and liver functions should be obtained.
Carbamazapine blood levels are obtained frequently (once per week or more) at first to adjust the
dose. Once the dosage is stabilized, periodic monitoring of serum levels, blood counts, and liver
functions is needed (every 3 to 6 months) (Rosenberg et al., 1994). Since periodic monitoring
does not ensure detection of granulocytosis, the patient and family need to be advised of
presenting symptoms (e.g., fever, easy bruising). If significant bone marrow suppression occurs,
the Carbamazapine should be stopped and the blood counts closely monitored, with referral for
specialized pediatric care. Finally, Carbamazapine may have teratogenic effects (especially with
first trimester exposure) and has been associated with neural tube defects (Rosa, 1991).
Benzodiazepines may be useful for treating agitated manic states (APA, 1994a; Viesselman et
al., 1993). These agents, used in conjunction with antimanic agents (i.e., lithium or
anticonvulsants) and in place of neuroleptics, are helpful for psychomotor agitation, irritability, and
insomnia in acutely manic patients (APA, 1994a; Viesselman et al., 1993). In adults, clonazepam
and lorazepam have been most often studied, but no literature is available on their use in children
and adolescents with mania (Werry and Arnan, 1993). The evidence is mixed as to whether
benzodiazepines have any specific antimanic activity or whether their therapeutic effects are due
solely to sedation (APA, 1994a). The few studies to date have had small sample sizes, and some
were confounded by the coadministration of neuroleptics (APA, 1994a). No controlled studies
examine the use of benzodiazepines for maintenance therapy or bipolar depression. Although
alprazolam has been reported to be helpful for major depression, it also can induce mania (APA,
1994a). Thus, benzodiazepines can be useful adjuncts to antimanic agents for patients with acute
mania. However, their long term use in children and adolescents with bipolar disorder should be
discouraged, given the lack of supporting research and potential dependency problems.
No studies examine the efficacy of neuroleptics for early-onset bipolar disorder (although they are
commonly used in clinical practice). In the adult literature, neuroleptics have been shown to be
effective for the treatment of acute mania (Goodwin and Jamison, 1990). However, it is not clear
whether the effects of neuroleptics are actually antimanic or due to sedation (Goodwin and
Jamison, 1990). Since their effects occur more rapidly than mood stabilizers, they may be useful
during the initial phases when patients are highly agitated or psychotic (APA, 1994a). Little
evidence indicates that neuroleptics, by themselves, should be used for maintenance treatment of
bipolar disorder (APA, 1994a). Some patients whose symptoms do not respond adequately to
antimanic agents alone may benefit from a combination of a mood stabilizer with an antipsychotic
The side-effect spectrum of neuroleptics dictates close monitoring of their use and periodic
reassessment of their ongoing use over the course of therapy (Campbell et al., 1993). Patients
with mood disorders may be at greater risk to develop tardive yskinesia (APA, 1991). In addition,
the combination of lithium and neuroleptics has been associated with an increased risk of
extrapyramidal side effects and neurotoxicity (Alessi et al., 1994).
OTHER ANTIMANIC AGENTS
Clozapine and the other atypical antipsychotic agents (e.g., risperidone), may have mood
stabilizing effects in patients with bipolar disorder, including those with psychotic features, mixed
episodes, and/or rapid cycling (APA, 1994a). Clozapine was reported to be effective in an
adolescent with bipolar disorder (Fuchs, 1994). Other agents with reported efficacy in the adult
literature include calcium channel blockers and thyroid hormones (usually as an adjunct to other
antimanic agents) (APA, 1994a). However, these agents have not been studied for the treatment
of early-onset bipolar disorder, and their use in this population should only be considered after
more standard regimens have been tried.
No studies with youth and only a few studies in the adult literature examine the efficacy of tricyclic
antidepressants for the treatment of bipolar depression (Zornberg and Pope, 1993). They are
more effective than placebos, but their usefulness either compared or used in conjunction with
antimanic agents, such as lithium, has not been systematically studied (Zornberg and Pope,
1993). There are even fewer studies examining monoamine oxidase inhibitors and selective
serotonin uptake inhibitors (Zornberg and Pope, 1993). Some evidence indicates that the
antidepressant bupropion may be less likely than other antidepressants to induce mania in
patients with bipolar disorder, although further study is needed (APA, 1994a; Haykal and Akiskal,
1990; Sachs et al., 1994). One case has been reported of the use of light therapy as an adjunct to
antimanic agents for treating depressive symptoms in seven young adults, aged 16 to 22 years
(Papatheodorou and Kutcher, 1995).
A major risk of antidepressant use in bipolar patients is the induction of mania and/or rapid
cycling. This risk has been noted with all classes of antidepressant agents (APA, 1994a). Thus,
they are generally used only as adjuncts to antimanic therapy for persistent depressive
Psychostimulants may exacerbate or induce psychosis/mania (Waters and Mitch, 1993).
However, there are case reports of stimulants having antimanic effects (Max et al., 1995). There
are two reports of using lithium and methylphenidate together in treating preadolescent children
(eight patients, total) with a combination of mood and disruptive behavior problems (Carlson et
al., 1992; Licamele and Goldberg, 1989). Some improvements were noted, without significant
side effects. Although the patients in these reports had some manic symptoms, none met the
criteria for mania. Psychostimulants must be used with caution in patients with bipolar disorder
and are best avoided during acute manic phases.
In adults, electroconvulsive therapy (ECT) is as effective as lithium for the treatment of mania
(APA, 1994a; Welch, 1989). Furthermore, it is the most effective therapy available for depression,
particularly for patients with psychotic depression or for those nonresponsive or intolerant of
medication therapy (APA, 1994a; Welch, 1989). Many patients with bipolar disorder respond
quickly to ECT. It is extremely safe as long as modern methods are used (i.e., appropriate
anesthesia, alterations in the delivery of the electrical stimulus, the selected use of unilateral
treatment, and cardiopulmonary monitoring) (APA, 1994a). For a more thorough review of
standard guidelines for the proper use and techniques, please see the APA Task Force on ECT
report (APA, 1990).
ECT is generally considered the treatment of choice for bipolar disorder in the following clinical
situations: (1) pregnancy; (2) catatonia; (3) neuroleptic malignant syndrome; and (4) any other
medical condition where more standard medication regimens are contraindicated (APA, 1990).
Although the literature is sparse, case reports indicate that ECT is beneficial for children and
adolescents with bipolar disorder, including mania, rapid cycling, and depressed phases
(Bertagnoli and Borchardt, 1990). Potential side effects include short-term cognitive impairment,
anxiety reactions, disinhibition, and altered seizure threshold (Bertagnoli and Borchardt, 1990).
Despite its potential efficacy, many centers do not use ECT for patients with early-onset bipolar
disorder due to a lack of experience and concern about its associated social stigma. Since ECT
may be the most appropriate treatment for some patients, it should not be denied because of
TREATMENT OF MIXED EPISODES AND RAPID CYCLING
Based on the adult literature, the treatment of mixed episodes is basically the same as that for
mania, although lithium may be less often effective (APA, 1994a; Prien and Potter, 1990).
Antidepressants are best avoided. The anticonvulsants may be particularly effective for mixed
episodes, but further research is needed (APA, 1994a; Prien and Potter, 1990).
Similar to patients with mixed episodes, those with rapid cycling may be less responsive to lithium
(APA, 1994a; Prien and Potter, 1990). Clinical experience suggests that antidepressants be
avoided and that a combination of antimanic agents is often necessary to relieve symptoms
(APA, 1994a). It is also important that patients with rapid cycling mania undergo a thorough
medical evaluation to rule out potential medical conditions (e.g., thyroid disorder, substance
abuse) that may be exacerbating the affective instability (APA, 1994a).
A comprehensive multimodal treatment approach combining psychopharmacology with adjunctive
psychosocial therapies is almost always indicated for early-onset bipolar disorder. Medications
help with the core symptoms of the illness, but they do not necessarily address the associated
functional impairment. Preexisting behavioral disorders, substance abuse disorders, learning
problems, and confounding psychosocial issues may all require additional treatment once the
affective episode is stabilized. Furthermore, psychotherapeutic interventions are needed to
promote medication compliance and avoid relapse.
Despite these clinical needs, the available research examining psycho social interventions for
bipolar disorder is quite limited, and there is essentially no literature regarding children and
adolescents (Kafantaris, 1995). No psychotherapy specific for the treatment of mania has been
defined, although some pilot work is examining cognitive therapy interventions in adult patients
(Kahn, 1990; Prien and Potter, 1990). A large literature addresses the effectiveness of cognitive
behavioral and interpersonal psychotherapist for the treatment of depression in adults (APA,
1989). The use of these psychotherapies with children and adolescents will be reviewed in a
separate practice parameter.
Extrapolating from the adult literature and clinical experience with this population suggests
several areas where psychotherapeutic interventions should be directed:
Psychoeducational Therapy. Information should be provided to both the patients and their
families on the disorder's symptoms and course, treatment options, potential impact on
psychosocial and family functioning, and heritability (Goodwin and Jamison, 1990; Kahn, 1990;
Prien and Potter, 1990).
Relapse Prevention. Education should be provided to the patient and family on the impact of
noncompliance with medications, the recognition of emergent relapse symptoms, and other
factors that may promote relapse (e.g., sleep deprivation, substance abuse). Medication
noncompliance is a major contributor to relapse. Estimates of noncompliance in adults range from
25% to 50% (Prien and Potter, 1990). In a study of adolescents with bipolar disorder, 90% of
those who were noncompliant with lithium relapsed over an 18-month period (Scrober et al.,
1990). Thus, efforts must be made to educate both the patient and family of the importance of
ongoing treatment. Establishing a strong therapeutic relationship and providing regular follow-up
assessments are important in maintaining compliance (Kahn, 1990). Reports of supportive group
therapies indicate that they are helpful for adult patients, but this modality has not been
systematically studied (Prien and Potter, 1990).
Similar to schizophrenia, measures of family patterns of expressed emotion and interactional
style are predictive of relapse in bipolar patients (Miklowitz et al., 1988). Preliminary evidence in
studies of adults with bipolar disorder suggests that psychoeducational therapies with both the
patient and family can effectively decrease relapse rates and improve overall functioning when
used in conjunction with pharmacotherapy (APA, 1994a; Clarkin et al., 1990; Miklowitz and
Goldstein, 1990; Prien and Potter, 1990). In these models, psychotherapeutic interventions are
directed at stress reduction, problem-solving skills, and family functioning.
Miklowitz and Goldstein (1990) modified the Behavioral Family Management program, a home-
based intervention designed for patients with schizophrenia (Falloon et al., 1984), to use with
adult patients who have bipolar disorder. This program utilizes psychoeducation and training to
enhance problem-solving and communication skills. Although further study is needed, use of this
program, in conjunction with pharmacotherapy, does appear to decrease relapse rates (APA,
Reduction of Morbidity. Bipolar disorder significantly affects social, family, academic, and
developmental functioning. Therefore, in addition to efforts directed at reducing further episodes,
psychosocial interventions are needed to address the myriad of disruptions that emerge in the
wake of the disorder.
There is a dearth of systematic research regarding the efficacy of standard psychotherapeutic
interventions with this population. Therefore, the use of these interventions is based solely on
clinical consensus. Individual (usually supportive) and family psychotherapies may be indicated to
deal with the various interpersonal, intrapsychic, and social conflicts that arise during the course
of the disorder. Cultural issues must be taken into account when devising psychotherapeutic
strategies. The use of more intensive forms of psychotherapy may be contraindicated insome
patients with bipolar disorder because they cannot tolerate the affect generated (Bemporad,
The educational needs of youth with bipolar disorder must be adequately addressed to help
promote long-term academic growth, especially given the high rates of comorbid disruptive
behavior disorders. School consultation is often necessary to help develop an appropriate
educational environment. Consultation with the school system and personnel can also be helpful
to alert them to early warning signs of mania or depression. Some youth will need specialized
educational programs, including day treatment/partial hospitalization programs.
Consultation may be needed with other involved community, juvenile justice, and/or social welfare
programs. Some youth, either because of the severity of the symptoms or confounding
environmental stressors, will need referral for intensive community-based services to continue
living in heir homes. Alternatively, some patients will need either foster care and/or residential
services. Finally, patients and families often benefit from participation with community support
and advocacy programs.
Bipolar disorder may first present during childhood and adolescence; therefore, clinicians working
with youth should be familiar with its diagnosis and treatment. Although the same diagnostic
criteria are used as for adults, issues regarding the developmental presentation of symptoms and
the co-occurrence of other psychiatric disorders must be recognized.
Treatment involves the combination of pharmacotherapy and adjunctive psychosocial therapies.
As in adults, early onset bipolar disorder may represent a lifelong condition that requires
longitudinal assessment, medication monitoring, and ongoing psychosocial interventions.
Treatment varies according to the phase of the disorder, with an overall focus on (1) amelioration
of acute symptoms, (2) prevention of relapse, (3) reduction of long-term morbidity, and (4)
promotion of long-term growth and development.
I. Diagnostic assessment.
A. Premorbid history.
1. Cognitive, motor, sensory, social, or other developmental problems.
2. Premorbid personality characteristics; i.e., temperament, mood, anxiety,
and/or behavioral problems.
B. History of present illness.
1. Document DSM-IV (APA, 1994b) target symptoms (both manic and
depressive symptoms), as well as associated phenomena (e.g.,
psychotic symptoms, suicidality). The symptoms should represent a
significant change from baseline functioning, with associated changes in
the child's mental status. Rapidity of onset and any precipitating
stressors should be noted.
2. Examine the longitudinal course of illness. It is often helpful to create a
life chart to identify cyclical and/or seasonal patterns.
3. Assessment for associated or confounding symptoms, especially
substance abuse, organic factors, and/or behavioral disorders.
C. Family history.
1. Obtain a thorough family history of mood, anxiety and psychotic
disorders, suicidality, impulse control disorders, neurological and medical
conditions, and substance abuse.
2. Family emotional, communicative, interactional, and coping styles and
D. School information.
1. Obtain information about school functioning, both premorbid and
subsequent to the onset of symptoms, either directly or from written
reports from appropriate staff, such as the principal, school psychologist/
counselor, teacher, and/or nurse after release of information is granted.
E. Neuropsychological functioning.
1. Suspected disabilities in either intellectual functioning, communication
abilities, and/or motor skills should be evaluated to help with the
differential diagnosis and/or to identify comorbid problems. Assessments
to consider include psychological testing (IQ, neuropsychological testing,
adaptive functioning, and/or academic testing), speech and language
assessment, and/ or an occupational/physical therapy evaluation.
F. Consultation and collaboration with other mental health and/or social service
providers as necessary.
G. Physical evaluation of the child. A thorough evaluation is needed to rule out
1. A pediatric examination is needed, including a thorough neurological
evaluation, especially in the presence of either psychotic symptoms and/
or catatonia, with consideration of neurological consultation, EEG, and
computed tomographic and magnetic resonance imaging head scans.
This may be done in collaboration with the primary family physician or
other health care providers.
2. Medical conditions that mimic either mania or depression, such as
metabolic, endocrine, infectious disorders, or acute
intoxication/withdrawal, need to be evaluated as indicated. Routine
laboratory tests (i.e., blood counts, renal and liver functions, thyroid
functions, toxicology screen, pregnancy test, and urinalysis) are usually
indicated, both as part of the organic workup and also as baseline
assessments for medication therapy. If the risk factors are present,
testing for HIV should be done, with appropriate informed consent.
II. Diagnostic formulation.
A. A diagnosis of bipolar disorder is made when the required DSM-IV (APA, 1994b)
target symptoms for mania/mixed state are present, either currently or by history,
and other disorders, such as schizophrenia or organic affective disturbances,
have been adequately ruled out. Once the diagnosis has been established, it
should be reassessed longitudinally to ensure accuracy.
B. In the assessment of children and adolescents presenting with symptoms
suggestive of bipolar disorder, evaluation includes consideration of:
1. Recent onset of biopsychosocial stresses.
2. Educational and vocational potential, disabilities, and achievement.
3. Peer, sibling, family, and sociocultural problems and strengths.
4. Environmental factors, including disorganized home, presence of child
abuse/neglect, and/or mental illness in parents or guardians.
5. Developmental abnormalities (motor and language delays).
6. Child/adolescent interpersonal strengths, especially the ability to form
adult and peer relationships.
C. Differential diagnosis.
1. The following conditions may be misdiagnosed as bipolar disorder:
b. Schizoaffective disorder or other psychotic disorders (delusional
disorders, schizophreniform disorder, psychosis not otherwise
c. Organic affective disorders.
d. Childhood disruptive behavior disorders.
e. Borderline personality disorder (or other personality
disorders/traits that present with affective instability and erratic
f. Posttraumatic stress disorder.
2. The following conditions often occur comorbidly with bipolar disorder:
a. Substance abuse disorders.
b. Childhood disruptive behavioral disorders.
c. Anxiety disorders.
3. The following medical conditions may mimic bipolar disorder:
a. Organic mania:
i. Organic mania due to substance abuse or withdrawal
(amphetamines, cocaine, phencyclidine, inhalants,
ii. Organic mania due to prescribed medications, such as
antidepressant agents (induced mania),
sympathomimetics, bromocriptine, stimulants, and/or
b. Neurological disorders (e.g., brain tumors, posttrauma, CNS
infections, including HIV, multiple sclerosis, temporal lobe
seizures, Kleine-Levin syndrome).
c. Metabolic conditions (e.g., hyperthyroidism, urermia, Wilson's
disease, collagen vascular disorders, delirium).
A. Substantial scientific evidence suggests that the only specific treatment of bipolar
disorder is medication therapy using a mood stabilizer. However, medications
need to be used in conjunction with a multimodal treatment model that also
includes psychoeducational services, individual and family supportive and
psychotherapeutic interventions, educational programs, and community support
services. Psychotherapeutic interventions must be sensitive to cultural issues.
Most of the treatment recommendations are based on studies of adults.
However, the limited available research on early-onset bipolar disorder, plus
clinical consensus within the field, suggests that these findings can be applied to
youth as long as pertinent developmental factors are incorporated into the
The following elements are necessary to develop a multimodal treatment
1. Thorough diagnostic assessment. Acute mania or severe depression
(especially psychotic depression) may require hospitalization, depending
on the severity and potential danger of the symptomatology, as well as
the social supports of the family. Hospitalization may be necessary
because of the extensive array of psychiatric and neurological evaluation
resources required to complete the initial assessment, and the need for a
more structured, safe environment in which to evaluate the patient.
2. Assessment for suicide potential, since this population is at significant
risk for attempting/completing suicide.
3. Identification of other pertinent issues, i.e., family dysfunction, school
difficulties, and premorbid and/or comorbid disorders, requiring ongoing
4. Evaluation and initiation of medication therapy.
5. Education of the patient and family as to the nature of the illness,
potential prognostic issues, and treatment needs.
6. Development of a long-term treatment plan, including medication
management, appropriate psychotherapy and psychoeducational
services for the patient, supportive services for the family (advocacy
groups, support groups), appropriate educational and vocational
services, and residential services when indicated.
7. Designation of a case manager for chronically disabled individuals
because of the wide range of services needed.
8. Provisions for long-term periodic diagnostic reassessments to ensure
accuracy of diagnosis.
B. Psychopharmacology. The phase of the illness needs to be considered when
making decisions on medication therapy.
1. Acute mania/mixed mania.
a. Prior to initiating medications, a thorough psychiatric evaluation
is needed, including documentation of the symptoms targeted for
therapy. Informed consent is needed from the parents and
adolescent patients, and assent, when possible, should be
obtained from preadolescents.
b. In adults, lithium has been the most extensively researched
antimanic agent, and its efficacy has been documented. The
anticonvulsants valproate and carbamazepine are also used,
with greater evidence supporting the efficacy of valproate. During
the acute phase, it may be necessary to augment the antimanic
agent with either an antipsychotic agent or a benzodiazepine to
address the associated psychomotor agitation and/or psychotic
c. To determine whether or not an antimanic medication is
effective, it must be used for at least 4 to 6 weeks at adequate
dosages and blood levels. If no effects are seen at that point,
consideration should be given to either adding or changing to a
different antimanic medication.
d. As the acute manic symptoms stabilize, the patient may cycle
through a period of confusion and disorganization. These
symptoms may also progress into a depressive episode. It is
important to recognize these as phases of the disorder;
otherwise, the tendency may be to make significant changes in
the medication regimen that may, in fact, only prolong recovery.
The antimanic agent should be maintained through this phase,
with modifications in dosage or augmenting agents to further
ameliorate the presenting symptomatology.
2. Depressed phase.
a. Care must be taken in using antidepressant agents because they
may induce a manic episode. Patients with established bipolar
disorder should be maintained on an antimanic agent prior to
initiating antidepressant therapy.
b. As patients recover from mania, it is common for them to cycle
through a depressive phase. This phase often resolves with
continued antimanic treatment; therefore, the addition of an
antidepressant may not be necessary unless the depressed
phase persists or becomes severe.
a. Long-term maintenance therapy with an antimanic agent is
indicated to prevent relapse. Data are inadequate to specify how
long prophylactic treatment should be maintained. However, one
study of youth suggests at least 18 months of therapy is
necessary, and, undoubtedly, some patients will need lifelong
b. If multiple psychotropic agents were needed to treat the patient's
acute symptoms, attempts to taper adjunctive agents (e.g.,
antipsychotic agents, benzodiazepines) should be made once
remission has been achieved and the patient is clinically stable.
Patients with bipolar disorder may be at increased risk for tardive
dyskinesia with long-term neuroleptic use. Similarly, if more than
one antimanic agent has been used to control manic symptoms,
an assessment is needed to determine if remission can be
maintained with a single agent. Close monitoring for relapse is
necessary during these changes.
4. Relapse of symptoms.
a. When symptoms relapse, it should first be determined whether
or not the patient was compliant with prophylactic therapy. If nor,
resumption of the antimanic medication should occur. If the
patient was compliant and had been previously responding to the
agent (without significant side effects), an increase in the
medication dose may stabilize the symptoms (keeping in mind
the standard dosage ranges and blood levels).
b. If symptoms relapse and the patient is not adequately
responding to the current antimanic agent (at adequate
dosages), a trial of a different antimanic, either alone or in
addition, should then be undertaken. Adjunctive agents (e.g.,
antipsychotics, benzodiazepines, antidepressants) may also be
indicated, depending on the symptom presentation.
c. Patients who relapse may require acute hospitalization. This
decision should be based on the severity of affective and
psychotic symptoms, potential danger to self or others, degree of
impairment in the patient's ability to maintain basic self care, and
availability of supportive services in the community.
5. Patients who do not respond to standard therapy.
a. Before it is decided that the patient is a nonresponder, the
patient should receive at least two adequate trials of different
antimanic agents, one of which should be lithium. An adequate
trial is defined both by duration (4 to 6 weeks) and dosage (using
maximal levels if necessary and tolerated).
b. In adults, other agents with reported antimanic activity include
clozapine, benzodiazepines, calcium channel blockers, and
thyroid hormones. However, these have not been studied in
children and adolescents. If clozapine is to be used, close
monitoring for potential seizures, agranulocytosis (with periodic
blood cell counts), and weight gain is necessary.
1. The efficacy of ECT for bipolar disorder, both mania and depression, is
well established for adults. There is also some literature supporting its
use in youth with bipolar disorder. It is generally used only for
medication-resistant cases. However, it may be considered as an Initial
treatment for severe psychotic depression and/or catatonia.
D. Psychosocial therapy.
1. Psychoeducational therapy for the patient, including ongoing education
about the illness, medication effects, social skills training, problem-
solving skills strategies, and basic life skills training. Part of the focus
should be on relapse prevention, including compliance with medications.
2. Psychoeducational therapy for the family, focusing on increasing the
understanding of the illness, treatment options and prognosis, relapse
prevention, and effective coping and parenting intervention strategies.
3. Specialized education programs and/or vocational training programs.
4. Individual (usually supportive rather than insight-oriented), group, or
family psychotherapy to address associated psychosocial problems that
E. Treatment of associated disorders or symptoms, such as substance abuse
disorders, disruptive behavior disorders, and/or suicidality.
F. Partial hospitalization or day treatment programs.
1. Many patients will need the specialized educational and psychiatric
services available in either a partial hospitalization or day treatment
program to be maintained at home within their community.
G. Residential treatment.
1. In some cases, the severity of the individual's illness or lack of effective
response to treatment (often in conjunction with chaotic social situations)
may necessitate long-term hospitalization or residential treatment. This
option should only be considered after less restrictive alternatives have
been unsuccessful. Once in a long-term residential setting, the patient's
status needs to be reassessed at regular intervals, with the goal of
returning to a less restrictive setting when possible.
H. Flexible models of care.
1. Many youth with bipolar disorder will be chronically impaired, with
complicated clinical and social needs, and may need an integrated
continuum of services, including: case management, intensive
community and family support, in-home services, out-of-home care
(including respite and specialized foster care), and specialized
CONFLICT OF INTEREST
In keeping with the requirement that practice parameters be developed by experienced clinicians
and researchers, some of the contributors to these practice parameters are in active clinical
practice. Through theirpractices, it is likely that most of these child and adolescentpsychiatrists
have received income related to treatments discussed inthese parameters. Some contributors are
primarily involved in research or other academic endeavors; it is possible that through such
activities,many of them have also received income related to treatments discussed inthese
parameters. A number of mechanisms are in place to minimize thepotential for producing biased
recommendations due to conflicts ofinterest. First, the development process calls for extensive
review of thedocument before it is finalized. All members of the Academy have theopportunity to
comment on the parameters before they are approved. Comments have been solicited and
received from a broad group of reviewers in child and adolescent psychiatry. Second, the
contributors and reviewershave all been asked to base their recommendations on an
objectiveevaluation of the available evidence. Third, we ask that contributors orreviewers who
believe that they have conflicts of interest that may biasor appear to bias their work notify the
LITERATURE REVIEW PROCESS
A National Library of Medicine search was initially done in May 1994, covering the preceding 5-
year period. The following topics were reviewed: bipolar disorder and adolescents (39 articles),
bipolar disorder and children (105 articles), and bipolar disorder and early onset (21 articles). This
search was updated periodically (most recently in December 1995) to identify new articles.
Searches were also undertaken to review specific topics (e.g., the use of lithium, valproate, and
carbamazepine in children and adolescents). The abstracts generated by these MEDLINE
searches were reviewed to identify articles relevant to early-onset bipolar disorder. Pertinent
papers published before the 5-year search period were also reviewed, as were review articles
and texts addressing the larger adult literature. Finally, the authors also drew from their own
research in this area. Articles most often used are marked with an asterisk in the reference
This literature review was used to develop the initial draft of the manuscript. After review by the
Committee on Quality Issues, this draft was then distributed to a panel of experts for comment.
The panel of experts included Hagop S. Akiskal, M.D., William Arroyo, M.D., Joseph Biederman,
M.D., Kelly Botteron, M.D., Charles Bowden, M.D., Stacy Bower, R.N., Ian Canino, M.D., Magda
Campbell, M.D., Gabrielle Carlson, M.D., Debbie Carter, M.D., Mark DeAntonio, M.D., Mina
Dulcan, M.D., Norbert Enzer, M.D., Robert Freeman, R.N., Mary A. Fristad, Ph.D., Barbara
Geller, M.D., Peter S. Jensen, M.D., Vivian Kafantaris, M.D., P. Keck, M.D., Wun Jung Kim, M.D.,
Maria Kovacs, Ph.D., Carlyn Lampert, M.S.W., Benjamin C.P. Lee, M.D., S. McElroy, M.D.,
Editha D. Nottelmann, Ph.D., Kambiz Pahlavan, M.D., Myrna Pollack, M.S.W., Elva Poznanski,
M.D., Andres Pumariega, M.D., David Rue, M.D., Neal Ryan, M.D., Susan Schmidt-Lackner,
M.D., Jeanne Spurlock, M.D., Michael Strober, Ph.D., Richard D. Todd, M.D., Ph.D., Michael W.
Vannier, M.D., Elizabeth Weller, M.D., Ronald Weller, M.D., and Deborah Zarin, M.D. Their
comments were then incorporated into the manuscript, which was then reviewed by the Academy
members at large, with a public forum at the Annual Meeting in New Orleans, October 19, 1995.
After incorporating the membership's input, a final draft was reviewed and adopted by the
Academy's Council June 15, 1996.
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