eMedicine Specialties > Pediatrics: Developmental and Behavioral > Medical Topics

Bipolar Disorder

Updated: Oct 12, 2009

Introduction

Background

Bipolar disorder is a mood disorder in which feelings, thoughts, behaviors, and perceptions are altered in the context of episodes of mania and depression. Previously known as manic depression, bipolar disorder was once thought to occur rarely in youth. However, approximately 20% of adults with bipolar disorder had symptoms beginning in adolescence.

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV TR) does not distinguish adult-onset from childhood- or adolescent-onset symptoms of bipolar disorder. Indeed, the diagnostic criterion for bipolar disorder is the same regardless of the patient's age at the onset of symptoms. Despite clinically important differences in the way mood disorders, particularly behavioral differences, may manifest in a child or an adolescent, no diagnostic accommodation has been made based on age.

The DSM-IV TR uses universal symptoms to define the diagnostic criteria for mood episodes, including major depressive and manic episodes. One true manic episode, with or without psychotic features, is the necessary and sufficient criterion for type I bipolar disorder. A depressive episode is insufficient for this diagnosis, even in the presence of a strong family history of bipolar disorder. Type II bipolar disorder is diagnosed based on at least one hypomanic episode. Therefore, bipolar disorders are viewed as having a spectrum of symptoms that range from mild hypomania to the most extreme mania, which may include life-threatening behaviors, dysphoria, and psychotic features.

Hallmark symptoms of mania include an abnormal, often expansive, and elevated mood lasting for at least 1 week. Mania may also include a decreased need for sleep, racing thoughts or a sense that thoughts are out of control, rapid and often pressured speech, increased goal-directed activities or projects, hypersexuality, reckless behaviors and risk-taking, and delusions of grandeur. Delusions associated with mania frequently center around an expansive sense of self that goes well beyond narcissism, eg, believing oneself to have special (eg, supernatural) powers or to be the chosen leader of the world or universe.

For some, the elevated and elated mood may transform into a state of dysphoria during which agitated and irritable behaviors may develop. Cognitive impairment in mania may manifest as episodes of confusion with a flight of ideas and disorganization of thought. In addition, increased risk-taking may involve physical, emotional, or financial endangerment. Poor insight into one's disorder or behaviors and poor judgment accompany mania. Therefore, the person's financial accounts or important relationships may be in such disarray as to lead to adverse outcomes, including loss of important friends and family support or connections, serious financial setbacks, job losses, legal problems, and homelessness.

Especially in older children and adolescents, the adverse effects of the disorder can contribute to dysfunction in the school setting, potentially leading to expulsion or peer rejection. In addition, adverse health outcomes have recently been associated with psychotic states, including psychosis associated with mania. Such effects include poor eating habits and an increased likelihood of substance abuse, including nicotine dependence, which is known to be associated with serious health consequences, such as early death due to cardiovascular complications of arteriosclerosis, stroke, diabetic ketoacidosis, and cancer.

According to the DSM-IV TR, criteria for a manic episode are as follows:

The individual has a distinct period of abnormally and persistently elevated, expansive, or irritable mood lasting at least 1 week (or any duration if hospitalization is necessary).
During the period of mood disturbance, 3 or more of the following symptoms persisted (4 if the mood is only irritable) and have been present to a significant degree:
- Inflated self-esteem to levels of grandiosity
- Decreased need for sleep
- More talkative than usual, often with pressured speech with a sense of a need to keep talking
- Flight of ideas or subjective feeling that thoughts are racing
- Distractibility
- Increased goal-directed activity or psychomotor agitation
- Excessive involvement in pleasurable activity that has a high potential for painful consequences (eg, hypersexuality, excessive spending, impetuous traveling)
The symptoms do not meet the criteria for a mixed episode.
The mood disturbance is severe enough to cause marked social impairment in occupational functioning, social activities, or relationships with others. Hospitalization may be necessary to prevent harm to self or others or if psychotic features are present.
The symptoms are not due to the direct physiologic effects of a substance or a general medical condition.

Hypomania is somewhat similar to mania but is less severe and less debilitating than true mania. As such, hypomania is defined as an elevated mood during which (1) no hospitalization has ever been necessary, and (2) no state of delusional or other psychotic thinking ever coincided with the elevated mood. Hypomanic and manic states must impair normal functioning to be considered pathologic states.

An abnormal behavioral episode may be designated a bipolar disorder after the frequency and type of abnormal mood are considered. Therefore, an episode may be reported as a bipolar disorder with a single manic episode, with recurrent manic episodes, or by the mood state of the most recent episode (eg, depressed, mixed, hypomanic, manic). Descriptors such as “with psychosis” or “without psychosis” are used to further clarify and reflect the severity of the state of the disorder.

Mood disturbances in children and adolescents are often more difficult to recognize and diagnose than those in adults. Some of the difficulty arises in recognizing atypical symptoms, including irritability, tantrums, physical aggression, and other behavioral problems, such as expressions of mood disruptions. Perhaps this difficulty is best demonstrated in symptom recognition and proper, but controversial, diagnosis of bipolar disorder in youths. The classic symptoms of mania, including racing thoughts, pressured speech, hypersexuality, and grandiosity, more often match the presentation of bipolar disorder in late adolescence. In childhood- or prepubertal-onset bipolar disorder, such a classic cluster of symptoms is uncommon. Nonetheless, as early as 1921, Kraepelin reported that 38% of his 900 patients who had manic episodes had symptom onset when younger than 20 years, and 0.4% had onset of symptoms when younger than 10 years.

Despite Kraepelin's early observation and description of childhood-onset and adolescent-onset bipolar disorders, the controversy about diagnosing bipolar disorder in young persons persists. This is partially driven by the requirement of discrete episodes of disturbed mood to diagnose bipolar disorder. Unlike what is noted in adults, well-defined and discrete episodes of abnormal mood are often missing in children and adolescents with this disorder. In particular, according to the DSM-IV TR criteria, at least 1 discrete episode of mania or hypomania is necessary to diagnose bipolar disorder type I or II.

Clinicians often use the diagnosis of bipolar disorder not otherwise specified (NOS) in children and adolescents with a chronically mixed or vacillating mood state. Children with this diagnosis may have clinically significant impairment though they do not meeting specific criteria for bipolar disorder type I or II.

Until the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) revisions are approved in 2012, limited nosology will continue to hamper efforts to distinguish among symptoms of adult-, adolescent-, or childhood-onset bipolar disorder, abnormal mood symptoms in adolescents and children, and normal developmental variation in behaviors, oppositional or defiant behaviors, inattention or hyperactivity, and conduct problems. Childhood-onset bipolar disorder frequently has an insidious onset with affective storms often associated with the presentation of mental illness.

Pathophysiology

A genetic predisposition to bipolar disorder may play a role in certain at-risk individuals. Significant early family stressors (eg, early history of abuse and neglect) and early experiences of catastrophic losses (eg, death of or abandonment by primary caregivers) may also predispose children and adolescents to bipolar disorder.

Frequency

United States

The overall prevalence of bipolar I disorder in adolescents is approximately 1%, whereas the prevalence in children is 0.2%-0.4%.

International

Bipolar disorder has roughly equal prevalence across different cultures.

Mortality/Morbidity

Suicide and suicide attempts account for significant sources of morbidity and mortality in individuals with bipolar disorder.

Other sources of morbidity and mortality are associated with poor judgment exercised by individuals with acute mania or psychosis. For example, serious cardiovascular complications, such as stroke and myocardial infarction, and an increased risk for cancer and diabetes can result from poor dietary choices and higher rates of alcohol and nicotine use and abuse.

Studies in the United States have also shown that many persons with serious mental illness (estimates upward of 40%), especially psychosis, obtain substandard medical care owing to noncompliance with medical treatment or the lack of resources to obtain needed treatment.

Sex

Pediatric and adolescent bipolar disorder does not appear to have a sexual predilection, although more males with the disorder are referred for treatment than are females.^1,2

Age

Most patients with bipolar disorder present in early adulthood (age 20-30 y). The second most common age group at presentation is 15-19 years.
In contrast to Kraepelin's report that 38% of his patients had an onset when they were younger than 20 years, more recent estimates are that 20%-30% of adults with bipolar I disorder had symptom onset when younger than 20 years. In addition, approximately 20% of youths in whom a major depressive disorder was previously diagnosed develop symptoms consistent with a manic state at a later age. Therefore, an adolescent or child who initially presents with depression may have a hidden bipolar disorder that becomes obvious later in life.
Patients with a childhood onset of bipolar symptoms may have a course of illness that is more severe, chronic, and refractory than that of patients with a later onset of symptoms of bipolar disorder. In addition, an early onset of bipolar symptoms seems to be associated with increased risk of mixed mood states (combined symptoms of depression and mania simultaneously) and rapid cycling (>3 episodes of mania in 1 y).

Clinical

History

No laboratory study can be used to confirm the diagnosis of bipolar disorder. Therefore, gathering the history of present and past disturbances of mood, behavior, and thought is critical to properly diagnose a psychiatric condition such as bipolar disorder. Unlike other areas of medicine in which the clinician often relies on laboratory or imaging studies to identify or characterize a disorder, mental health professionals rely almost exclusively on descriptive symptom clusters to diagnose mental disorders. As a consequence, the history is an essential part of the patient examination.

The appropriate first step in evaluating a person for a psychiatric disorder is to ensure that no other medical condition is causing the mood or thought disturbance. Therefore, evaluation of the patient is best started by obtaining their oral history of current and past medical and behavioral symptoms and treatments. To further clarify the problem, gathering additional information from family and friends is always urged for a person experiencing an altered mood or behavioral state.
After interviewing the patient, perform a physical examination. Gather information from family, friends, and perhaps other physicians who know the patient. The problem might be classified as being primarily caused by a physical health problem or by a mental health problem.
- While obtaining the history, the physician must explore the possibilities that substance abuse or dependence, trauma to the brain in the present or past, and/or seizure disorders may be contributing to or causing the current symptoms of illness.
- CNS insults, such as encephalopathy or medication-induced mood changes (ie, steroid-induced mania), must also be considered. Delirium should be excluded first in persons presenting with altered mental states or acute disturbances of mood and conduct, especially when encephalopathy of an infectious, metabolic, or toxic origin is possible.
- It is critical to take a careful history of alcohol use/abuse, including substance-abuse patterns, as acute drug-intoxication states may mimic bipolar disorder. In communities of lower socioeconomic status, huffing and ingestion of toxic substances, such as methyl alcohol (wood alcohol, gasoline), glue, and sprays, is extremely common among adolescents and can result in very rapid deterioration in mental status. In addition, such activities may result in hypoxia, potentially leading to permanent brain damage. In this setting, appropriate screening tests of blood, urine, and arterial blood oxygen and organ system function may be life-saving.
If the physical examination does not reveal a medical condition contributing to the patient's mental state, a thorough mental health evaluation is appropriate. Through observation and interviewing, mental health professionals may learn of mood, behavioral, cognitive, or judgment and reasoning abnormalities.
The mental status examination (MSE) is the essential component of a mental health evaluation. This examination goes beyond the mini-mental status examination (eg, Folstein Mini-Mental State Examination to screen for dementia) often used in emergency departments. Rather, the MSE is used to assess the general appearance and demeanor, speech, movement, and interpersonal relatedness of the patient with the examiner and others.
- Mood and cognitive abilities (eg, orientation to circumstance; attentiveness; immediate-, short-, and long-term modes of memory) are assessed in the MSE. The assessment should be age-appropriate (eg, serial threes test in younger children).
- Some of the most important components of the MSE are those addressing issues of safety of individuals and members of a community. Therefore, suicidal and homicidal issues are explored.
- Likewise, screens for the more subtle forms of psychosis, such as paranoid or delusional states, in addition to screens for overt psychosis, such as observing the patient responding to unseen others or other non–reality-based internal stimuli, are explored.
- Finally, insight into the patient's mental and physical states, the current circumstances of medical or mental healthcare, and the patient's ability to show age-appropriate insight and judgment are assessed and integrated into the evaluation of the global mental state of the patient at that moment. As examples, a child might be evaluated on his or her ability to verbalize potential environmental dangers (eg, why not to accept candy from a stranger, why not to run into the street, to explain how not to pick a fight with an older peer, or to describe the qualities that determine true friendship).
Because bipolar disorder may cause a transient but marked impairment of judgment, insight, and recall, several sources of information are crucial to understand a particular patient. Therefore, family members, friends, teachers, caregivers, or other physicians or mental healthcare workers may be interviewed to clarify the full clinical picture.
Nonetheless, the patient's subjective experience is essential in the evaluation and treatment processes, and the establishment of a therapeutic alliance and trust early in the assessment is vital to obtaining an accurate and useful history from the patient.
Knowledge of the family's psychiatric history is another essential part of the patient's history because bipolar disorder has genetic transmission and familial patterns. A genogram may be developed to further describe a particular patient's risk bipolar disorder based on familial and genetic attributes in the family system.

Physical

The physical examination must include a general neurologic examination, including examination of the cranial nerves, muscular bulk, and tone and deep tendon reflexes.
Cardiovascular, pulmonary, and abdominal examinations are also essential, as abnormal pulmonary function or poor vascular perfusion of the brain may cause abnormal mood, behavior, or cognition.
Both physical and laboratory thyroid examination should be performed because of the potential mood alteration in hypothyroid and hyperthyroid states and because of the need for baseline studies to ensure safety before and during medication treatment.
If these examinations do not reveal a medical condition contributory to the current mental state, a mental health evaluation should be performed (see History).

Causes

Genetic and familial factors seem to be highly important in the development of bipolar disorder. Early age of onset of bipolar disorder predicts a higher rate of mood disorder among first-degree relatives. Adolescents who have onset of true mania with childhood-associated psychotic symptoms, such as aggression, mood shifts, or attention difficulties, are at a greater genetic risk (family loading) for bipolar I disorder than adolescents with more adult-related psychotic symptoms, such as grandiosity.
Youths with early-onset bipolar disorder include (1) poor or ineffective response to lithium therapy (administered as Eskalith) and (2) an associated increased risk of alcohol-related disorders in the family members of the probands.
There is increased psychopathology in children who have at least one biologic parent with bipolar I or bipolar II disorder. Specifically, 28% of the children examined had attention deficit/hyperactivity disorder (ADHD), far above the prevalence of 3%-5% in the general population of school-aged children. In addition, 15% of the children had a bipolar disorder or cyclothymia. Approximately 90% of children who have bipolar disorders had comorbid ADHD. Moreover, both bipolar disorder and ADHD were more likely to be diagnosed in boys than in girls. Studies of bipolar disorder in twins showed a 14% concordance rate in dizygotic twins and a 65% concordance rate (range, 33%-90%) in monozygotic twins. The risk for bipolar disorder in the offspring of a couple in which one parent has bipolar disorder was estimated to be 30%-35%. For an offspring of a couple in which both parents have bipolar disorder, the risk was approximately 70%-75%.³
Children with bipolar disorder show a higher incidence of psychotic features than older adolescents or adults.^4,5,6
Faraone et al further delineated the differences among children with mania, adolescents with childhood-onset mania, and adolescents with adolescence-onset mania.⁷
- Socioeconomic status was statistically lower in families of children with mania and adolescents with childhood-onset mania than in others.
- Increased energy was twice as common in childhood mania as in other forms, euphoria was most common in adolescents with childhood-onset mania, and irritability was least common in adolescents with adolescent-onset mania.
- On statistical analysis, adolescents with adolescent-onset mania abused psychoactive drugs and had more impaired parent-child relationships than individuals in the other two groups with mania.
- ADHD was more common in children and adolescents with childhood-onset mania than in patients with adolescent-onset mania. This finding led the authors to theorize that ADHD may be a marker for juvenile-onset mania.
Data from this and other studies⁸ suggest that a subtype of bipolar disorder may exist. This subtype may have a high familial transmission rate, and affected individuals present with childhood-onset of mania symptoms suggestive of ADHD.
There are concerns that early-onset mania may be misdiagnosed as ADHD or that more children have comorbid ADHD and bipolar disorder, with a higher rate of familial transmission. One controversy is whether youths who are later diagnosed with bipolar disorder may have a prodromal phase in early life that appears to be ADHD or another behavioral disturbance or whether many simply have bipolar disorder and comorbid ADHD.^9,10
Cognitive and neurodevelopmental factors also seem to be involved in the development of bipolar disorder, especially in preschool-aged children who later go on to develop bipolar disorder.^11,3,12
Preschool children with early behavioral disinhibition¹³ and decreased frustration tolerance may be at a greater risk for bipolar disorder in adolescence or adulthood, as this may reflect underlying early abnormalities of temperament that reflect increased risk for both bipolar disorder and ADHD.^14,15
Emotion processing seems to be impaired in individuals with bipolar disorder because of a lack of flexibility in though processing.^16,15,17
Neither the neural nor the genetic basis of bipolar disorder has been definitively elucidated; however, interest has been focused on potential abnormalities in the corpus callosum,¹⁸ amygdala,¹⁷ decreased protein kinase in platelets,¹⁹ and dopamine D4 receptor genotype and abnormalities of the dopamine transporter gene SLC6A3.²⁰
A case-cohort study of adolescents with affective disorders revealed that neurodevelopmental delays are overrepresented in early-onset bipolar disorders, as well as in their "unaffected" siblings.²¹ These delays occur in language, social, and motor development approximately 10-18 years before affective symptoms appear.²²
Adolescents who had early developmental antecedents were at a higher risk of developing psychotic symptoms. In addition, intelligence quotient (IQ) scores were significantly lower in patients with early-onset bipolar disorder (mean full-scale IQ, 88.8) than in patients with unipolar depression (mean full-scale IQ, 105.8).
Finally, a statistically significant difference in the mean verbal IQ and mean performance IQ was found only in patients with bipolar disorder. The reason for this discrepancy is unclear but should be the subject of further investigation.
Overall, patients with severe bipolar disorder had a mean IQ lower than that of patients with mild-to-moderate forms of the disorder.
Environmental factors also contribute to the development of bipolar disorder. These may be behavioral, educational, family-related, toxic, or substance abuse–induced. Wilens et al (2008) implicated smoking as a potential causal element in patients with bipolar disorder.²³
Diagnoses of mental health problems increase the risk of suicide in adolescents compared with their healthy peers.
Adolescent patients in whom bipolar disorder is diagnosed are at higher risk of suicide than adolescents with other behavioral illnesses. Family conflict and substance abuse exponentially increase this risk.^10,24,9
Another risk factor for suicide in youths is legal problems. One study showed that 24% of adolescents who attempted suicide had faced legal charges or consequences in the preceding 12 months.²³
Males with bipolar disorder are at higher risk of death from suicide than are females, who are more likely to attempt suicide numerous times unsuccessfully. This does not imply that suicide attempts in females should not be of concern; rather, suicide attempts in males occur less often, as they tend to be suicide completers. In females, the disorder is also associated with social rejection from female peers.
Incarcerated youths have an inordinately high prevalence of mental illnesses. Some are facing legal consequences as a direct result of behaviors that arise from uncontrolled or untreated mental disorders. The manic state of bipolar disorder can be particularly problematic for adolescents, as the disinhibited risk-taking behaviors driven by the disorder can easily lead to legal problems, such as public disorderly conduct, theft, drug seeking or use, and an agitated and irritable mood that results in verbal and physical altercations.

Biologic and biochemical factors

Sleep disturbances often aid in defining abnormal mood states of bipolar disorder in either the manic or depressed state. As such, it is helpful to determine the patient's baseline euphonic state sleep pattern (eg, does the patient often get up early or stay up late?).
- A profoundly decreased need for sleep in the absence of a sense of fatigue is a strong indicator of a manic state. A change in the patient’s usual sleep pattern (eg, from being a "night owl" to an "early riser") may predict a significant change in the patient’s mood state. Sleep studies of the CLOCK genetic areas have utilized functional magnetic resonance imaging (fMRI) to differentiate groups of children and adolescents with bipolar disorder.²⁵
- An uncomfortable reduction of sleep is a pattern of an atypical depression episode in which more sleep is wanted but cannot be achieved. Conversely, a typical depression episode may be indicated by hypersomnolence, an excessive and irresistible need for sleep.⁶
- The biology that drives these sleep anomalies in mood disturbances is not fully appreciated. Some suggest that neurochemical and neurobiologic shifts cause these episodic sleep disturbances in conjunction with other shifts that occur in the evolution of manic or depressed states.
Bipolar disorder and other mood disorders are increasingly understood in the context of neurochemical imbalances in the brain.
- Although the circuits of the brain that modulate mood, cognition, and behavior are not well defined, the database of neuroimaging studies that facilitate increased appreciation of possible modulating pathways (particularly in the amygdala) that connect several brain regions to work in unison to regulate thoughts, feelings, and behaviors is constantly growing.¹⁷
- An association of neurotransmitters acts upon various brain regions and circuits to modify and regulate brain activity. CNS neurotransmitters in brain circuits and their putative effects in activity modification include the following:
  - Serotonin - Mood (happy, sad, euthymic)
  - Dopamine - Pleasure (hedonia, anhedonia)
  - Norepinephrine - Alertness, energy level (lethargy, frenzy, vigilance)
  - Acetylcholine - Memory and cognition
  - GABA - Inhibition of CNS neurons
  - Glutamate - Excitation of CNS neurons
- One proposal suggests that several neurotransmitters acting in unison but with dynamic balance act as modulators of mood states. In particular, serotonin, dopamine, and norepinephrine appear to modify mood, cognition, and sense of pleasure or displeasure.
- Pharmacotherapy for the regulation of bipolar mood swings is thought to be based on the use of medications that facilitate the regulation of these and perhaps other neurochemicals to restore a normal mood and cognition.
- Meditation and deep relaxation, including regular exercise, may also indirectly modulate neurotransmitter levels, increasing endogenous opioid and nicotinic receptor function.

Differential Diagnoses

Anxiety Disorder: Generalized Anxiety	Posttraumatic Stress Disorder in Children
Anxiety Disorder: Social Phobia and Selective Mutism	Schizophrenia and Other Psychoses
Attention Deficit Hyperactivity Disorder	School refusal
Conduct Disorder	Thyrotoxicosis
Delinquency/truancy
Oppositional defiant disorder

Behavior	Bipolar Disorder	ADHD	Conduct Disorder
Self-esteem	Inflated	Inflated and/or deflated	Inflated and/or deflated
Pleasure	Euphoric in mania Dysphoric in mixed or depressed state	Often dysphoric or euthymic	Pleasure in violating societal norms, especially if not caught
Attention	Distractible	Distractible	Normal to vigilant
Hyperactivity	Goal directed	Unproductive	Goal directed
Sleep	Episodic disturbances such as decreased need in mania	Chronic poor sleep; often late bedtimes	Not known to be disrupted except with substance abuse
Speech	Pressured or rapid in mania; slow in depression	Often rapid; may be pressured	May be normal rate
Impulsivity	Externally driven; reactionary	Internally driven	May have predatory or reactionary acts
Social	Often good	Often poor	Often poor
Academic	Often good	Often poor	Often poor
Psychomotor activity	Agitated in mania or mixed states; retarded in depressed states	Chronically agitated	Easily agitated

Workup

Laboratory Studies

Initial tests for substance and alcohol abuse are usually necessary to exclude drugs and alcohol as causative agents for behavior.
No specific blood or other laboratory tests aid in diagnosing bipolar disorder.
- Of interest, serum cortisol levels may be elevated, but this is neither of diagnostic nor clinical value.
- Thyroid studies may help to rule out a thyroid disorder as a cause of an altered mood. T3 levels may be elevated in agitated patients who have normal thyroid function. Additional thyroid tests, such as thyroid-stimulating hormone (TSH) and T4 studies, can be helpful, as well as consultation with an endocrinologist.
- Serum blood chemistries, such as basic metabolic panels and liver function tests, may help assess renal and hepatic health before certain medications are started or continued to help regulate or ameliorate bipolar symptoms.
- Mania and depression may both involve states of malnutrition secondary to the psychiatrically diminished awareness of or ability to maintain one's health and well-being. Thus, a metabolic panel, in addition to thiamine, albumin, and prealbumin studies (in extreme cases), may help determine the extent of self-neglect and compromised nutritional state. Levels of vitamin D, folate, vitamin B-12, vitamin B-6, and total protein can also be abnormal and should be checked, especially in the presence of acute mania or hypomania.
- After pharmacotherapy is implemented, periodic laboratory tests may be required to monitor drug levels and to ensure that no adverse response to the medication is harming renal or hepatic function or bone marrow.
- In patients with known hypersexuality, a very careful sexual history should be taken. An HIV test should also be administered, as well as HIV prevention counseling.

Imaging Studies

Initial studies suggest that developmental changes with maturity in children and adolescents with bipolar disorder differ from those in healthy peers. However, neuroimaging modalities are not yet diagnostically helpful in diagnosing bipolar disorder in individuals, but studies are ongoing to determine if this modality would be helpful in diagnosis. The diagnosis of pediatric and adult bipolar disorder still continues to rely on the clinical presentation of symptom clusters, as defined in the DSM-IV-TR, in addition to family and genetic histories.
In some studies, neuroimaging (ie, fMRI) in child and adolescent patients with bipolar disorder has shown abnormal neural activation for faces with negative emotions along with face-processing deficits.³² Adolescent patients failed to show normal developmental maturity changes with respect to total hippocampal volume in comparison to healthy controls. Other studies have shown abnormal corpus callosum myelination and enlarged ventricles with an increased number of hyperintensities compared with healthy control subjects.¹⁴

Other Tests

Before a psychotropic medication is started, a baseline ECG and echocardiogram, with measures of cardiac contractility, should be performed, as many medications (lithium, so trazodone, ziprasidone, risperidone, quetiapine, verapamil) may alter QT intervals or other features of the cardiac rhythm, thereby affecting cardiac contractility and output. This is especially critical if the patient has a family history of a structural or electrical heart abnormality.

Treatment

Medical Care

The treatment and management of bipolar disorder are complicated. Hence, most children and adolescents with this diagnosis require referral to a psychiatrist specializing in their age group. In general, a team approach is used in the clinical setting because several factors need to be addressed, including medication, family issues, social and school functioning, and, when present, substance abuse. In general, the treatment of bipolar disorder may be thought of as a 4-phase process: (1) evaluation and diagnosis of presenting symptoms, (2) acute care and crisis stabilization for psychosis or suicidal or homicidal ideas or acts, (3) movement toward full recovery from a depressed or manic state, and (4) attainment and maintenance of euthymia.

The treatment of adolescent or juvenile patients with bipolar disorder is modeled after treatments provided to adults, as it appears that adult bipolar disorder is continuous with pediatric bipolar disorder.³³

Adolescents and children with bipolar disorders often present at times of family or youth despair or family crises surrounding their behaviors. In such critical times, inpatient care is often indicated to assess the patient, diagnose the condition, and ensure the safety of the patient or others. Hospitalization is necessary for most patients with psychotic features and in almost all patients who have suicidal or homicidal ideations or plans. Inpatient care should always be considered in young persons who have suicidal or homicidal ideation and have access to firearms in their homes or communities and in those who abuse substances, particularly alcohol.^34,10

Depressive episodes are frequently the first presentation of bipolar disorders in youths. In these situations, the clinician is wise to recall that approximately 20% of adolescents who have a diagnosis of depression later reveal manic symptoms; thus, antidepressant therapy in a depressed youth should be initiated with a warning to the patient and family of the possibility of later development of mania symptoms. If a history of a manic state is known or suggested in a patient who is currently depressed, a mood stabilizer should be started first. Once a therapeutic level and response to the mood stabilizer are attained, an antidepressant may be considered as additional treatment needed for the current state of depression, with close monitoring for antidepressant-induced mania.^35,36,34

Inpatient treatment usually requires locked-unit care to assist in safety regulation. Rarely are young persons physically restrained in hospitals, but seclusion rooms should remain available in the event of severely agitated states that may culminate in threats or overt expression of physical aggression to self or others.

Mood stabilizers, such as lithium carbonate, sodium divalproex, and carbamazepine, have traditionally been the mainstays of treatment of patients with bipolar disorder. However, atypical antipsychotics are increasingly used in bipolar disorder, with or without psychotic symptoms. This class of medications includes risperidone, quetiapine, olanzapine, aripiprazole, ziprasidone, and clozapine. In addition, benzodiazepines may be used to improve sleep and to modulate agitation during hospitalization. After symptoms of psychosis, suicidality, or homicidality are absent or sufficiently diminished to a safe and manageable level, the patient is discharged to outpatient care.

Therapeutic interventions that appear to be helpful in bipolar disorder include social rhythm therapy,²⁴ interpersonal therapy (IPT), dialectical behavior therapy (DBT), cognitive behavior therapy (CBT), family therapy, group therapy. Supportive psychotherapy or psychoanalysis should be reserved for individuals who are more likely to respond to those therapies.³¹

Although electroconvulsive therapy (ECT) is well documented as an effective and safe treatment option in patients with depressive or psychotic states, most clinicians do not consider this a first-line intervention in children or adolescents. ECT is often initially administered on an inpatient basis because it is most frequently used in severe or refractory cases, and these patients are likely to require hospitalization more often. Still, ECT may be started at any point in treatment because each ECT treatment can be performed in a day-treatment setting. Therapy requires at least a 4-hour visit for pre-ECT preparations, delivery of the ECT, and monitoring during recovery from both ECT and anesthesia. All ECT treatments require the presence of an anesthesiologist or anesthetist throughout the administration of therapy.

ECT has been demonstrated to be both safe and therapeutic in adolescents and children. One favorable aspect of ECT is its therapeutic response time, which is more rapid than that of medications (days rather than weeks). One drawback to ECT is the associated memory loss surrounding the time just before and after treatments. An ECT treatment episode may involve 3-8 or more sessions, usually at a rate of 1 session every other day or 3 sessions per week. Despite the rapid effect of ECT on mood and psychotic symptoms, medications are still required in the maintenance phase of treatment.

Surgical Care

Trials of deep brain stimulation for refractory depression are currently ongoing.

Consultations

Consultations with a neurologist, nephrologist, cardiologist, endocrinologist, and/or for psychological testing may be needed if the patient fails to respond to first-line treatment or develops complications or adverse reactions to medications.

Diet

Many individuals with bipolar disorder forget to eat or excessively consume a very unbalanced diet (eg, "empty" calories without adequate fiber or vitamins) during agitated manic states. This can lead to depletion of nutritional stores of iron, vitamin B-6, vitamin B-12, and folate and can increase the risk of diabetes or long-term complications of hyperglycemia or hypoglycemia.

Activity

Many persons with bipolar disorder exhibit excessive risk-taking behaviors, potentially predisposing them to injury or dehydration. In contrast, individuals who experience periods of depression may be at higher risk of developing deep venous thrombosis (DVT) and cardiovascular complications due to hypersomnia and excessive bedrest.

Medication

Although it is common for children and adolescents with bipolar disorder to be treated with medications, very few agents except for aripiprazole, valproate, and lithium (in patients as young as 12 y) have received approval from the US Food and Drug Administration (FDA) for this application. Despite the paucity of data, pediatric treatment guidelines have evolved based on empirically derived plans. The Child Psychiatric Workgroup on Bipolar Disorder established guidelines based on the most up-to-date evidence.³⁵ In general, these guidelines involve algorithm-based use of mood stabilizers and atypical antipsychotic agents alone or in various combinations.

The use of mood-stabilizing agents in children and adolescents has unique considerations. In general, adolescents and children have metabolism than adults because of the efficiency of their hepatic functions. In addition, adolescents and children have faster renal clearance rates than adults. For example, lithium carbonate has an elimination half-life of 30-36 hours in an elderly patient, 24 hours in an adult, 18 hours in an adolescent, and less than 18 hours in children. Steady states are also achieved earlier in children than in adolescents and earlier in adolescents than in adults. Therefore, plasma levels may be drawn and assessed earlier in children and adolescents than in adults.

Consequences of the efficient metabolizing and clearance systems of young individuals are as follows: (1) Anticipated peak plasma drug levels may be higher in young patients than in adults, and (2) anticipated plasma trough levels may be lower in young patients than in adults. Therefore, children may require increased dosages of medications (milligrams/kilogram/day) to attain a therapeutic response. Special precautions must be taken when one doses psychiatric medications to treat adolescents and children to achieve therapeutic effect while staying safely below toxic levels.

Although the mood stabilizers have not been established as primary treatment for bipolar disorders in adolescents or children in large-scale controlled studies, they are used clinically in this context. Mood stabilizers include lithium carbonate, valproic acid or sodium divalproex, and carbamazepine. These medications are still considered first-line agents in managing bipolar disorders in pediatric patients, as case reports and limited studies have suggested that they have sufficient efficacy and safety to provide symptom relief and control.

Lithium carbonate is effective in approximately 60%-70% of adolescents and children with bipolar disorder and remains the first-line therapy in many settings. Approximately 15% of children receiving lithium have enuresis, primarily nocturnal enuresis. In those whose condition does not respond to lithium, sodium divalproex is generally the next agent of choice. As in adults with bipolar disorder, carbamazepine is often considered a third choice, after sodium divalproex and lithium carbonate have been tried at optimal doses for a sufficient period. This medication is often tried after an acute or crisis state is stabilized and when adverse effects of sodium divalproex or lithium carbonate are intolerable.

Lamotrigine has been approved for bipolar maintenance therapy in adults, but initial data in pediatric patients suggests that it does not prevent mania. Other antiepileptic medications (eg, gabapentin, oxcarbazepine, topiramate) have had mixed results in adults with bipolar disorder in case reports and studies. However, studies are beginning to show the potential usefulness of these medications in pediatric patients with bipolar disorder.

Emerging evidence indicates that atypical antipsychotic agents may be used in pediatric patients with bipolar disorder who present with or without psychosis. Given the antimanic properties demonstrated in adult and limited adolescent studies, olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal) may be considered first-line alternatives to lithium, valproate, or carbamazepine.

Pediatric studies with ziprasidone (Geodon) and aripiprazole (Abilify) are limited at this point; this limitation indicates that these agents should be considered second-line alternatives if first-line mood stabilizers or atypical antipsychotic agents are ineffective or if they result in intolerable adverse effects. Clozapine (Clozaril) may be considered only in treatment-refractory cases, as it is believed to provide similar protection against suicidality as lithium; however, it should not be a first-line medication because of the significant risk for agranulocytosis and the resulting need for frequent hematologic monitoring.

An important consideration with atypical antipsychotics is the potential for weight gain and metabolic syndrome. The patient's weight should be measured, and a fasting lipid profile and serum glucose level should be taken before these agents are started. These values should be monitored periodically during treatment. Patients and families should be advised of the need to appropriately manage diet and exercise. Limited data indicate that ziprasidone and aripiprazole may have a low potential for these adverse effects and that they may be considered in patients at high risk because of a family or personal history of metabolic abnormalities. Atypical antipsychotics also pose a potential risk for extrapyramidal symptoms and tardive dyskinesia.

These medications should be used cautiously during pregnancy, especially because of the potential for birth defects and impact on blood sugar levels. Metformin and troglitazone (oral antiglycemic agents) may be helpful in treating the secondary hyperglycemia, and atorvastatin (Lipitor) may be helpful in treating or reversing the abnormalities of serum lipids (hypertriglyceridemia, hypercholesterolemia) caused by therapy with atypical medications.

Table 2. First-Line Medications for Pediatric Bipolar Disorder: Common Adverse Effects and Special Concerns

Medication	Common Adverse Effects	Doses	Special Concerns
Lithium carbonate (Eskalith CR, Lithobid)	GI distress, lethargy or sedation, tremor, enuresis, weight gain, alopecia, cognitive blunting	10-30 mg/kg/d; dose must be adjusted by monitoring serum level and patient response; uptitrate on twice-daily schedule	Hypothyroidism, diabetes insipidus, toxic in dehydration, polyuria, polydipsia, renal disease; drug-drug interactions and sodium intake may alter therapeutic serum levels
Sodium divalproex/valproic acid (Depakote, Depakene)	Sedation, platelet dysfunction, liver disease, alopecia, weight gain	15-30 mg/kg/d; dose must be adjusted by monitoring serum levels; uptitrate on twice- or thrice-daily schedule	Elevated liver enzymes or liver disease, drug-drug interactions, bone marrow suppression
Aripiprazole (Abilify)	Less likely to cause prolactinemia than risperidone; may cause Stevens-Johnson syndrome; as with other atypical antipsychotics, may cause tardive dyskinesia, dystonia, parkinsonism, hyperglycemia; use with caution in seizure disorders and cardiac disorders, including problems with cardiac contractility and electrical activity	2 mg once daily can be increased to 5 mg, 10 mg, 15 mg, to a maximum of 30 mg to start titrate upwards at weekly to bimonthly intervals	Levels may need to be adjusted in patients who are concurrently receiving lamotrigine, topiramate, Depakote, lithium, or other serotonin-norepinephrine reuptake, selective serotonin reuptake, or cytochrome P450 inhibitors Do not administer if there is an unstable seizure disorder
Carbamazepine (Tegretol)	Suppressed WBC, dizziness, drowsiness, rashes, liver toxicity (rare)	10-20 mg/kg/d; dose must be adjusted by monitoring serum blood levels; uptitrate on twice-daily schedule	Drug-drug interactions, bone marrow suppression
Risperidone (Risperdal)	Weight gain, sedation, orthostasis	0.25 mg bid or 0.5 mg at bedtime initially; titrate as tolerated to target dosage of 2-4 mg/d; not to exceed 6 mg/d	Galactorrhea, extrapyramidal symptoms
Quetiapine (Seroquel)	Sedation, orthostasis, weight gain	50 mg bid initially; titrate as tolerated to target dosage of 400-600 mg/d	Decrease dosage with hepatic impairment, may cause neuroleptic malignant syndrome (NMS) or hyperglycemia
Olanzapine (Zyprexa)	Weight gain, dyslipidemia, sedation, or orthostasis	2.5-5 mg at bedtime initially; titrate as tolerated to target dosage of 10-20 mg/d	Metabolic syndrome, extrapyramidal symptoms

Calcium channel blockers (Verapamil), angiotensin-converting enzyme (ACE) inhibitors, and phenytoin (Dilantin) may be helpful in some individuals but have not been proven effective and have not been tested in children or adolescents for use in bipolar disorder.

Benzodiazepines, such as clonazepam and lorazepam, are generally avoided in children because of the long-term risk of dependence, but they may be temporarily useful in restoring sleep or in modulating irritability or agitation not caused by psychosis. Because of the slow-on and slow-off action of clonazepam (Klonopin), the risk of abuse is lower with this drug than with fast-acting benzodiazepines such as lorazepam (Ativan) and alprazolam (Xanax). In the outpatient setting, clonazepam may be preferred because of the efficacy and the lowered risks of abuse by the patient or others. Clonazepam can be dosed in the range of 0.01-0.04 mg/kg/d and it is often administered once per day at bedtime or twice per day. Lorazepam is dosed to 0.04-0.09 mg/kg/d and administered 3 times per day because of its short half-life.

When a patient with bipolar disorder is having a depressive episode, the use of an antidepressant may be considered after a mood stabilizer or atypical antipsychotic agent has been started and after a therapeutic response or level is achieved. Caution must be exercised in starting an antidepressant in a person with bipolar disorder because it may precipitate mania. An antidepressant with a potentially lowered risk of inducing mania is bupropion (Wellbutrin).

Selective serotonin reuptake inhibitors (SSRIs) should be used cautiously owing to the risk of mania; doses should be low and titration slow. The only SSRI currently FDA approved for the management of unipolar depression in adolescents is fluoxetine (Prozac). However, this agent should be used carefully in patients with bipolar disorder because of its long half-life and because of its potential to exacerbate manic symptoms when not coadministered with an antimanic or mood-stabilizing agent.

All medications used in pediatric bipolar disorder pose a risk of adverse effects or interactions with other medications. These risks should be clearly discussed with patients and families and weighed against the potential benefits. Medication should be started only after informed consent is obtained.

Mood stabilizers

These drugs are indicated for control of manic episodes occurring in bipolar disorder. Mood stabilizers include lithium carbonate, valproic acid or sodium divalproex, and carbamazepine.

Lithium (Eskalith, Lithane, Lithobid)

Considered first-line agent for long-term prophylaxis in bipolar illness, especially classic bipolar disorder with euphoric mania. Also used to treat acute mania, though cannot be uptitrated to effective level as quickly as valproic acid. Evidence suggests that lithium, unlike any other mood stabilizer, may have specific antisuicide effect. Monitoring blood levels critical with this medication.

Dosing

Adult

Maintenance, preventive use: 400-1200 mg/d PO; maintain serum levels of 0.6-1 mmol/L
Acute manic episode: 600-2400 mg/d PO divided bid/tid; maintain serum levels of 0.8-1.2 mmol/L

Pediatric

10-30 mg/kg/d PO; must adjust dosage by monitoring serum levels and patient's response; uptitrate on bid schedule

Interactions

Increases toxicity of thiazide diuretics, haloperidol, phenothiazines, neuromuscular blockers, carbamazepine, fluoxetine, and ACE inhibitors

Contraindications

Documented hypersensitivity; severe cardiovascular disease

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Toxicity closely related to serum levels and can occur at therapeutic doses; serum determinations required to monitor therapy

Valproic acid (Depacon, Depakene, Depakote)

Proven effectiveness in treating and preventing mania. Classified as mood stabilizer and can be used alone or in combination with lithium. Useful in treating rapid-cycling bipolar disorders and has been used to treat aggressive or behavioral disorders. Combination of valproic acid and valproate has been effective in treating persons in manic phase, with a success rate of 49%.

Dosing

Adult

Initial: 250 mg PO tid in increments until a serum level of 350-700 mmol/L (50-100 mcg/mL) achieved
Maintenance: 750-3000 mg PO qd in divided doses

Manic episode: Loading dose of 20 mg/kg/d PO

Stat dose: 20 mg/kg PO, with next dose in 12 h; then 10 mg/kg bid
Maintenance: 500-3500 mg PO qd to achieve plasma level of 50-125 mcg/mL

Pediatric

15-30 mg/kg/d PO divided bid/tid; must adjust dosage must by monitoring serum levels; uptitrate on bid/tid schedule

Interactions

Coadministration with cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may significantly reduce valproate levels; in pediatric patients, protein binding and metabolism of valproate decrease with concomitant salicylates; coadministration with carbamazepine may result in variable changes of carbamazepine concentrations with possible loss of seizure control; valproate may increase diazepam and ethosuximide toxicity (monitor closely); valproate may increase phenobarbital and phenytoin levels, and either may decrease valproate levels; valproate may displace warfarin from protein-binding sites (monitor coagulation); may increase zidovudine levels in HIV-seropositive patients

Contraindications

Documented hypersensitivity; hepatic disease or dysfunction; hyperammonemic encephalopathy and urea cycle disorders

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Thrombocytopenia and abnormal coagulation parameters have occurred; risk of thrombocytopenia substantially increases at total trough valproate plasma concentrations >110 mcg/mL in female patients and >135 mcg/mL in male patients; determine platelet counts and bleeding time before therapy, periodically, and before surgery; reduce dose or discontinue if hemorrhage, bruising, or hemostasis or coagulation disorder occurs; hyperammonemia may occur, resulting in hepatotoxicity; closely monitor patients for malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause drowsiness

Carbamazepine (Tegretol)

Anticonvulsant action may involve depressing activity in nucleus ventralis anterior of thalamus, reducing polysynaptic responses and blocking posttetanic potentiation. Reduces sustained, high-frequency, repetitive neural firing. Potent enzyme inducer that can induce own metabolism. Because of potentially serious blood dyscrasias, weigh benefit and risk before therapy.
Therapeutic plasma levels 4-12 mcg/mL for analgesic and antiseizure response. Serum levels peak in 4-5 h. Serum half-life 12-17 h with repeated doses. Metabolized in liver to active metabolite (epoxide derivative) with half-life of 5-8 h. Metabolites excreted in feces and urine.
Effective in cases that do not respond to lithium therapy. Has been effective in treating rapid-cycling bipolar disorder.

Dosing

Adult

Initial: 200 mg PO bid in divided doses with 100-mg increments 2 times/wk; if adverse effects occur, decrease dose by 200 mg
Dose range: 300-1600 mg PO qd
Serum-level range: 17-50 mmol/L (4-12 mcg/mL)
Manic episode: 200-1800 mg PO qd

Pediatric

10-20 mg/kg/d PO divided bid/tid; must adjust dosage by monitoring serum blood levels; uptitrate on bid schedule

Interactions

Serum levels may substantially increase within 30 d of danazol coadministration (avoid whenever possible); do not administer concurrently with MAOIs; cimetidine may increase toxicity, especially if taken in first 4 wk of therapy; may decrease primidone and phenobarbital levels (coadministration may increase carbamazepine levels)

Contraindications

Documented hypersensitivity; history of bone marrow depression; administration of MAOIs in last 14 d

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Not for relief of minor aches and pains; caution with increased intraocular pressure; obtain CBCs and serum-iron baseline before treatment, during first 2 mo, and yearly or every other year thereafter; can cause drowsiness, dizziness, and blurred vision; caution while driving or performing other tasks requiring alertness

Risperidone (Risperdal)

Binds dopamine D2-receptor with 20 times lower affinity than for 5-HT2-receptor. Indicated for short-term (3-wk) treatment of acute mania associated with bipolar disorder. May use alone or combined with lithium or valproate.

Dosing

Adult

2-3 mg PO qd up to 3 wk; may increase by 1 mg/d at 24-h intervals, not to exceed 6 mg/d

Pediatric

Data limited; 0.25 mg PO bid or 0.5 mg qhs initially; titrate as tolerated to target dosage of 2-4 mg/d; not to exceed 6 mg/d

Interactions

Coadministration with carbamazepine may decrease effects; may inhibit effects of levodopa; clozapine may increase levels; PO solution not compatible with cola or tea

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause extrapyramidal reactions, hypotension, tachycardia, and arrhythmias; hyperglycemia (some cases extreme) may occur, resulting in ketoacidosis, hyperosmolar coma, or death; do not split or chew PO disintegrating tablets

Quetiapine (Seroquel)

May act by antagonizing dopamine and serotonin effects. Newer antipsychotic used for long-term management. Improvements over earlier antipsychotics include fewer anticholinergic effects and less dystonia, parkinsonism, and tardive dyskinesia.

Dosing

Adult

Initial: 25 mg PO bid/tid; increase by 25-50 mg bid/tid on day 2 or 3 to achieve range 300-400 mg divided bid/tid by day 4; adjust as needed at intervals of >2 d with adjustments of 25-50 mg bid
Maintenance: 150-750 mg/d PO; not to exceed 800 mg/d

Pediatric

Data limited; 50 mg PO bid initially; titrate as tolerated to target dosage of 400-600 mg/d

Interactions

May antagonize levodopa and dopamine agonists; phenytoin, thioridazine, and other liver enzyme inducers may reduce levels; cytochrome P450 (CYP) 3A inhibitors (eg, ketoconazole, fluconazole, erythromycin) increase serum concentration

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May induce orthostatic hypotension associated with dizziness, tachycardia, and syncope; has been associated with NMS and tardive dyskinesia; hyperglycemia (some cases extreme) may occur, resulting in ketoacidosis, hyperosmolar coma, or death; caution in hepatic impairment (decrease dose)

Olanzapine (Zyprexa)

Mechanism of action for acute manic episodes associated with bipolar I disorder unknown. Available as tab, PO disintegrating tab (Zyprexa, Zydis), and IM dosage forms.

Dosing

Adult

10-15 mg PO qd; adjust by 5 mg/d at intervals >24 h; not to exceed 20 mg/d
Agitation associated with bipolar mania: 10 mg IM once; may repeat after 2 h; not to exceed 30 mg/24 h
Geriatric or debilitated individuals: 2.5-5 mg IM/dose

Pediatric

Data limited; 2.5-5 mg PO qhs initially; titrate as tolerated to target dosage of 10-20 mg/d

Interactions

Fluvoxamine may increase effects; antihypertensives may increase risk of hypotension and orthostatic hypotension; levodopa, pergolide, bromocriptine, charcoal, carbamazepine, omeprazole, rifampin, and cigarette smoking may decrease effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in narrow-angle glaucoma, cardiovascular disease, cerebrovascular disease, prostatic hypertrophy, seizure disorders, hypovolemia, and dehydration; hyperglycemia (some cases extreme) may occur, resulting in ketoacidosis, hyperosmolar coma, or death; administration of >1 IM injection associated with substantial orthostatic hypotension (33%), maintain patient in recumbent position and monitor blood pressure before repeating IM doses

Follow-up

Further Inpatient Care

Psychometric instruments can be helpful in diagnosis of bipolar disorder, particularly if coexisting ADHD is possible and if other disorders (eg, schizophrenia, intellectual disability) need to be ruled out³⁷
The goals of inpatient or outpatient treatment are to control and minimize symptoms of bipolar disorder, to prolong normal mood states or euthymia, to minimize the number of needed hospitalizations, to eliminate or minimize medication adverse effects to a tolerable level, and to optimize the quality of life for the patient. Quality-of-life issues for a young person include meaningful relationships with family, peers, mentors, coaches, and teachers; optimal academic performance; and optimal occupational performance as it pertains to endeavors such as music, art, dance, athletics, or other personally rewarding areas from which the adolescent derives a sense of competency, mastery, and pleasure.
The goals of individual therapy and family therapy should be individualized. Nonetheless, common goal themes include reduction of family stress, improvement of family communications, and a discussion of unresolved feelings of fear, hurt, or loss caused by a loved family member having a mental disorder. Family-focused therapy with a cognitive behavioral component is encouraged, as having a child with bipolar disorder requires the parents, the identified child, and siblings to adjust to the impact on the family system, necessitating a focus on improved communication.^10,9,31
- In family and individual sessions, medication issues and compliance should also be addressed so that optimal care can be attained in the outpatient setting.
- The patient and family need psychoeducation about bipolar disorder and its management, including management of medication side effects and sleep hygiene. In mental healthcare centers and in private practices, most patients and their families receive care from many professionals.
- Psychiatrists, psychologists, behavioral and developmental pediatricians, social workers, and many other therapists are involved in treating the patient, monitoring the response to and tolerance of medications, and providing psychotherapy to the family and the patient.
- In the ideal situation, these professionals work together in a team approach so optimal care can be attained in the medical, educational, family, and social realms.

Further Outpatient Care

Randomized controlled trials have recommended individual cognitive behavior therapy in children and adolescents to focus on suicide prevention, as well as to monitor and manage medication if family conflict and negative expressed emotions are absent,
Parent-focused interpersonal therapy and guidance are important when one or both parents have significant mood and/or anxiety disorder.
If there is negative emotional expressivity in family interactions, family therapy should be added.³⁸

Inpatient & Outpatient Medications

Therapy with atypical antipsychotics may predispose to neuroleptic malignant syndrome (NMS) in children and adolescents, so patients should be closely observed for such effects.³⁹
Studies of complementary medications such as omega-2 fatty acids and herbal preparations to increase sleep are ongoing, but it is not yet known if these are safe and effective in children and adolescents. There are concerns over long-term exposure risks associated with these medications in this population.^40,41,42

Deterrence/Prevention

Avoidance of prescribing medications that can precipitate acute mania if a diagnosis of bipolar disorder is unclear
Avoidance of situations (including substance abuse) that precipitate or aggravate decreased sleep duration, such as work or social situations that encourage or cause sleep deprivation or significant alterations of sleep pattern
Prompt medical and psychiatric attention upon development of symptoms such as pressured speech, psychosis, or lack of need for sleep or food
Adjunctive techniques such as meditation or muscle relaxation or deep breathing to lower stress and anxiety levels^43,35,10,41

Complications

Caution should be used when anticonvulsants and atypical antipsychotics are administered together because of the increased risk of hematologic side effects. Administration of multiple classes of anticonvulsants together should also be avoided, when possible.^{40,42,44,45,46}

Prognosis

In general, the onset of bipolar disorder in childhood and adolescence has revealed a stronger family history for bipolar disorder than later onset; therefore, individuals are at increased genetic and familial risk from the beginning of life.
- An emerging body of evidence indicates that optimal treatment for the genetic or familial form of bipolar disorder may differ from other treatment modalities of other bipolar conditions.
- Adverse outcomes of an early onset of bipolar disorder are as follows: (1) The course is generally more severe than that of late-onset disorder, and (2) the course of illness is more refractory to treatment than when the onset starts in adulthood.
As with so many psychiatric and medical disorders in children and adolescents, increased stress in home, school, and social settings may precipitate or exaggerate early mood disturbances of bipolar disorder. As the patient ages, the tendency for stress to contribute to a mood episode declines, and mood disruptions may occur spontaneously, even with medication and treatment compliance. This trend seems to be found in adults and not in children or adolescents; it is thought to be the result of kindling.
In the general population, suicide remains one of the top 10 causes of death in adolescents and young adults. It is the fourth most common cause of death in persons aged 10-15 years and the third most common cause of death in persons aged 15-25 years.
- All persons with bipolar disorder have an increased risk of suicide.
- The exact increase of the risk in youths is unknown; however, in young adults with bipolar disorder, suicide has a higher incidence in males within the first few years of the diagnosis. Current suicide rates in patients with bipolar disorder are 10-15%.
- In adults, treatment with lithium reduces the suicide rate; similar studies in adolescents and children do not exist, but lithium has been demonstrated to reduce substance use in adolescents with bipolar disorder.
Episodic mood events should be anticipated throughout the life cycle after bipolar disorder is diagnosed. The frequency and severity of each episode are not readily predictable, but trends have emerged. In the presence of medication and treatment compliance, relapses may occur, and hospitalization may be required. In the absence of compliance, the course of the illness can be more severe than it would be otherwise.
One potentially reassuring aspect of bipolar disorder is that patients may potentially have a full and normal life during the periods between mood swings. Therefore, many persons with bipolar disorder may continue their college education and careers with success, and they may foster and nuture strong relationships.

Patient Education

Psychoeducation of parents and patients is an important aspect of treating an adolescent or child in whom bipolar disorder is diagnosed.
- The young person must be given the relevant facts in an age-appropriate and developmentally appropriate manner.
- The diagnosis, benefits of treatment, and detriment of treatment noncompliance should be made clear and understandable.
- Inpatient and outpatient psychiatrists, psychologists, social workers, and other therapists involved in the care of the youth and the family should be able to aid the patient and family in the understanding and management of bipolar disorder in a loved one.
Families and patients can learn about adolescent or childhood bipolar disorders at the American Academy of Child and Adolescent Psychiatry Web site in the section titled Resources for Families. This provides a user-friendly fact and information sheet to families about bipolar disorder and its treatment in the pediatric population.
The Child & Adolescent Bipolar Foundation (CABF) provides important information and resources for families and clinicians.
Another resource is the Depressive and Manic-Depressive Association, a support group for patients and families of patients who have bipolar disorder. This group is mostly for adults, and parents are far more likely than adolescents or children to benefit from this group.
For excellent patient education resources, visit eMedicine's Depression Center. Also, see eMedicine's patient education articles, Depression and Bipolar Disorder.

Miscellaneous

Medicolegal Pitfalls

Sexual and/or physical abuse is common with bipolar disorder, especially in very young children (<6 y) and particularly in individuals with comorbid PTSD, psychosis, or conduct disorder. Prompt identification and treatment is warranted.⁴⁷
In general, a protracted and severe course of illness is associated with an early age of onset of bipolar disorder.¹⁰
Family conflict may decrease response to medication treatment and so should be addressed in a timely fashion.^11,48
Positive family history of abuse may increase the risk for suicide.⁴⁹
Treatment with mood stabilizers is a vital part of maintaining optimal functioning in children and adolescents with bipolar disorder; however, side effects such as weight gain and acne are particularly problematic with agents such as lithium, olanzapine, and valproate.^36,13,50
Comorbid conditions should be assessed in a timely fashion. Autism spectrum disorder and pediatric anxiety disorder may present with mood disturbances.²⁷
Comorbid substance abuse, especially nicotine abuse, presents along with ADHD.²³

Special Concerns

Personal caregivers and health care providers should not have false expectations that current mood may predict the safety of the patient or others in the future.
Other sources of information include Web sites such as the American Psychological Association, National Alliance on Mental Illness, and Depression and Bipolar Support Alliance.

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Keywords

bipolar disorder, BPD, BPAD, manic depression, mania, depression, hypomania, bipolar I disorder, bipolar II disorder, type I bipolar disorder, type II bipolar disorder, manic episode, conduct disorder, CD, extrapyramidal symptoms, EPS, tardive dyskinesia, TD

Contributor Information and Disclosures

Author

Bettina E Bernstein, DO, Assistant Professor, Department of Psychiatry, Philadelphia College of Osteopathic Medicine; Private Practice at the Wynnewood House; Consultant, Child Guidance Resource Centers, Early Elementary Education Program, Clinical Affiliate, Department of Child and Adolescent Psychiatry, Children's Hospital of Philadelphia
Bettina E Bernstein, DO is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry and American Psychiatric Association
Disclosure: Nothing to disclose.

Medical Editor

Carol Diane Berkowitz, MD, Executive Vice Chair, Department of Pediatrics, Professor, Harbor-University of California at Los Angeles Medical Center
Carol Diane Berkowitz, MD is a member of the following medical societies: Alpha Omega Alpha, Ambulatory Pediatric Association, American Academy of Pediatrics, American College of Emergency Physicians, American Medical Association, American Pediatric Society, and North American Society for Pediatric and Adolescent Gynecology
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

CME Editor

Carrie Sylvester, MD, MPH, Director of Education in Child and Adolescent Psychiatry, Professor, Departments of Psychiatry and Pediatrics, Northwestern University Medical School
Carrie Sylvester, MD, MPH is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, American Academy of Pediatrics, American Medical Women's Association, American Psychiatric Association, and American Society for Adolescent Psychiatry
Disclosure: Nothing to disclose.

Chief Editor

Caroly Pataki, MD, Professor of Clinical Psychiatry and Behavioral Sciences, Department of Psychiatry, Division Chair, Child and Adolescent Psychiatry, Director of Training, Child and Adolescent Psychiatry Residency Program, University of Southern California Keck School of Medicine
Caroly Pataki, MD is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, New York Academy of Sciences, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

Further Reading

eMedicine Specialties > Pediatrics: Developmental and Behavioral > Medical Topics

Bipolar Disorder

Introduction

Background

Pathophysiology

Frequency

United States

International

Mortality/Morbidity

Sex

Age

Clinical

History

Physical

Causes

Differential Diagnoses

Other Problems to Be Considered

Workup

Laboratory Studies

Imaging Studies

Other Tests

Treatment

Medical Care

Surgical Care

Consultations

Diet

Activity

Medication

Mood stabilizers

Lithium (Eskalith, Lithane, Lithobid)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Valproic acid (Depacon, Depakene, Depakote)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Carbamazepine (Tegretol)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Risperidone (Risperdal)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Quetiapine (Seroquel)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Olanzapine (Zyprexa)

Dosing

Adult

Pediatric

Interactions

Contraindications