Pediatric Bipolar Affective Disorder

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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. Polygenic investigations indicate that this disorder is phenotypically separate (with or without psychosis) from schizoaffective disorders and schizophrenia. [1]

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) does not distinguish adult-onset from childhood- or adolescent-onset symptoms of bipolar disorder. The diagnostic criteria for bipolar disorder are the same regardless of the patient’s age at the onset of symptoms. [2]

DSM-5 uses universal symptoms to define the diagnostic criteria for mood episodes, including major depressive and manic episodes. At least 1 true manic episode, with or without psychotic features, is the necessary and sufficient criterion for type I bipolar disorder (BPI). A depressive episode is insufficient for this diagnosis, even in the presence of a strong family history of bipolar disorder. Type II bipolar disorder (BPII) is diagnosed on the basis of at least 1 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. Outcome studies show that compared with unipolar depression, bipolar disorder causes more work disability and overall poorer outcome 15 years after an index hospitalized manic episode even when mania is in remission for at least 1 year. [3] Randomized controlled trials of combination mood stabilizer treatment (more than one mood stabilizer such as atypicals + lithium + valproate) suggest this may improve outcome by increasing the time to relapse for any mood episode compared with monotherapy as maintenance therapy for Bipolar I. [4]

Early identification of medication nonresponders would be extremely helpful in the treatment of bipolar disorder. Genome-wide association studies (GWASs) potentially can help to identify whether lithium is likely to be effective or if other medication such as atypical antipsychotic medication or antiepileptic medication will be more likely effective in bipolar disorder to stabilize mood. A GWAS study in China differentiated patients with a good response and those with a poor response to lithium with a sensitivity of 93% and showed the strongest association with a response to lithium when the exons, exon-intron boundaries, and part of the promoter of the gene encoding glutamate decarboxylase-like protein 1 (GADL1) was sequenced for association with a single-nucleotide polymorphism (SNP) of two SNPs in high-linkage disequilibrium, rs17026688 and rs17026651, that are located in the introns of GADL1. [5]

Go to Bipolar Affective Disorder for complete information on this topic.

Hallmark symptoms of mania include an abnormal, often expansive, and elevated mood lasting for at least 1 week. They 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. Associated delusions frequently center on an expansive sense of self that goes well beyond narcissism (eg, believing oneself to have special 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, bipolar disorder may be a more severe form with increased risk of suicide attempts and 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. [6]

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.

DSM-5 criteria for a manic episode are as follows.

First, 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).

Second, 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 talkativeness than usual, often characterized by pressured speech with a sense of a need to keep talking

Flight of ideas or a subjective feeling that thoughts are racing


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)

Third, the symptoms do not meet the criteria for a mixed episode.

Fourth, 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.

Fifth, the symptoms are not due to the direct physiologic effects of a substance or a general medical condition.

Hypomania is somewhat similar to true mania but is less severe and less debilitating. As such, it 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 and are often more difficult to recognize and diagnose in children than in adults. Some of the difficulty arises in recognizing atypical symptoms, including irritability, tantrums, physical aggression, and other behavioral problems (eg, expressions of mood disruptions) and may include difficulty in differentiating bipolar mania from hyperactivity as found in ADHD or irritability as found in DMDD. Parental history of ADHD increases the risk of DMDD by 4 times that in control populations, however, risk of DMDD is 20 times higher in families where there are offspring with DMDD. [7]

Comorbid diagnosis of autism spectrum disorder (ASD), especially with ADHD symptoms, are predictive of a more challenging clinical course that may require multiple different medications for remission. [8]

The strongest predictors of bipolar prodrome appear to be baseline anxiety/depression with proximal affective lability and full or subsyndromal manic symptoms, increasing the risk of bipolar prodrome from 2% (baseline risk due to family history) to 49%. [9]

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 (eg, expressions of mood disruptions). Perhaps this difficulty is best demonstrated in symptom recognition as there has been recent controversy over potential overdiagnosis of bipolar disorder in youths due to recent US National trends of an increase as much as 40-fold of bipolar diagnosis in youth in outpatient settings and up to a 4-fold increase in inpatient psychiatric hospitalization of youth with bipolar disorder. [6]

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 DSM-5 criteria at least 1 discrete episode of mania or hypomania is necessary to diagnose BPI or BPII. Childhood-onset bipolar disorder frequently has an insidious onset with affective storms often associated with the presentation of mental illness.

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 meet specific criteria for BPI or BPII. However, in the DSM-5, children with chronically irritable mood states and aggression can be diagnosed with disruptive mood dysregulation disorder instead of bipolar NOS, which is hoped to decrease the numbers of children and adolescents diagnosed with bipolar disorder who do not actually have that disorder.

Bipolar disorder and other mood disorders are increasingly understood in the context of neurochemical imbalances in the brain that may interact with underlying anatomical changes in the brain that adversely impact neural functional connectivity. 

Smaller subfield hippocampal volumes may reflect underlying pathophysiology of bipolar disorder and impact long term functioning. [10]

Alterations in functional connectivity of areas of the brain involved in executive functioning, decision making – so-called default and salience networks – are other areas being studied. The clinical implications of impaired default mode and salience network functioning in bipolar disorder may be helpful in both diagnosis and treatment of mania especially in the presence of co-morbid ADHD as well as possible markers of the disorder. [11]

Exciting research areas also include the identification of youth at higher risk of bipolar disorder.

In Australia, it appeared that the use of ultra–high-risk criteria for bipolar disorder, also called bipolar at-risk (BAR), may provide the possibility of identification of persons prior to the onset of mania/hypomania. [12]

Objective testing, including the use of brain scanning techniques and magnetoencephalography (MEG), can be used to look at preattentive auditory dysfunction as a potential trait marker of severe bipolar disorder symptoms. Preattentive auditory dysfunction was reflected by the presence of reduced pitch-MMNm responses. [13]

Mood lability may be a result or the cause of brain changes seen on neuroimaging, such as reduction in grey matter volume and decreased amygdala and prefrontal functional connectivity. [14]

This may help to understand the underlying mechanism of why some youths experience chronic irritability and thus anticipate or trigger, by their behaviors, negative social interactions with others (eg, rejection) by misinterpreting the emotional valence of others and, specifically, facial emotional expression.

A relatively small (N=82) functional MRI study (subjects average age, 13-14 years) analyzed whether differences in brain function could be detected when comparing youths with different diagnoses to one another. The study used a cognitive task involving response reversal to see if cognitive flexibility differed as reflected in differences in brain activation of areas reflective of differences in neural network activation, such as a lack of appropriate activation in areas such as the (right) inferior frontal gyrus and caudate between healthy youths, youths with bipolar disorder, youths with severe mood dysregulation (youths who did not meet criteria for bipolar disorder but had significant chronic irritability), and youths who had attention-deficit/hyperactivity disorder (ADHD) and either severe mood dysregulation or bipolar disorder.

Although the study attempted to correct for the presence of opposition defiant disorder (ODD) and ADHD, it did include youths treated with medication and the types of medication were not separated out as the data appeared to be pooled, so the results may not be completely generalizable. It is possible that medication influenced emotion processing; however, the study did seem to show that cognitive inflexibility can, to some extent, be objectively measured using functional MRI techniques looking at connectivity of neural networks. [15]

Although the circuits of the brain that modulate mood, cognition, and behavior are not yet fully defined, the database of neuroimaging studies, especially resting state connectivity 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 are ongoing. [16]

A study found that the Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P), the first specific interview for emerging BP symptoms, in 205 youth aged 12-23 years and/or their caregivers showed good internal consistency for the BPSS-P mania (Cronbach’s α = 0.87), depression (Cronbach’s α = 0.89), and general symptom indices (Cronbach’s α = 0.74) and high inter-rater reliability for the BPSS-P total score (intraclass correlation [ICC] = 0.939) and BPSS-P mania (ICC = 0.934), depression (ICC = 0.985), and general (ICC = 0.981) indices. The BPSS-P total score discriminated BPI/BPII/cyclothymia from depression spectrum patients, and the BPSS-Mania Index differentiated all three bipolar spectrum groups from depression spectrum patients. [17]

An association of neurotransmitters acts upon various brain regions and circuits to modify and regulate brain activity. Central nervous system (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

Gamma-aminobutyric acid (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.

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, [16] decreased protein kinase in platelets, [19] and dopamine D4 receptor genotype and abnormalities of the dopamine transporter gene SLC6A3. [20]

Pharmacotherapy for the regulation of bipolar mood swings is thought to be based on the use of medications that facilitate the regulation of neurotransmitters as well as receptor sensitivity and perhaps other neurochemical modulators to restore normal mood and cognition. Meditation and deep relaxation, including regular exercise, may also indirectly modulate receptor sensitivity and resting state connectivity as well as neurotransmitter levels impacting endogenous opioid and nicotinic receptor function.

Although relatively small (N=28; after dropouts, n=21), one study attempted to explain why mood stabilizers such as divalproex and atypical antipsychotics such as risperidone are helpful in bipolar mania in youth. Compared with healthy controls, youth with mania had a reduction in Young Mania Rating Scale (YMRS) score with increased brain activity in the ventrolateral prefrontal cortex also the left inferior frontal gyrus. This speaks to the effect of medication in possibly decreasing impulsive risk taking behaviors in those with bipolar disorder. A replication study will be helpful to confirm these results. [21]

Genetic and familial factors play an important role 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 symptoms, such as aggression, mood shifts, or attention difficulties, are at a greater genetic risk (family loading) for BPI than adolescents with more adult-related psychotic symptoms, such as grandiosity.

Youths with early-onset bipolar disorder tend to have a poorer or less effective response to usual medications such as lithium (administered as eskalith), valproic acid, or atypical antipsychotic medications and an associated increased risk of alcohol-related disorders in the family members of the probands even though lithium appears to be more chemoprotective of suicide than other agents used. [22]

There appears to be increased psychopathology in children who have at least one biologic parent with BPI or BPII; high-risk offspring (defined by having 1 parent with confirmed bipolar disorder) had an increased lifetime risk of a broad spectrum of disorders, including bipolar disorder (hazard ratio [HR] = 20.89; P = .04), major depressive disorder (HR = 17.16; P = .004), anxiety (HR = 2.20; P = .03), sleep (HR = 28.21; P = .02), and substance use disorders (HR = 2.60; P = .05) compared with controls. Offspring from lithium-nonresponsive parents specifically developed psychotic disorders. Childhood anxiety disorder predicted an increased risk of major mood disorder, and evidence supported a progressive transition through clinical stages, from nonspecific psychopathology to depressive, and thenmanic or psychotic episodes.

There is increased psychopathology in children who have at least one biologic parent with BPI or BPII. 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 1 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%. [23] Children with bipolar disorder show a higher incidence of psychotic features than older adolescents or adults. [24, 25, 26]

Faraone et al further delineated the differences among children with mania, adolescents with childhood-onset mania, and adolescents with adolescence-onset mania. [27] 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 2 groups with mania. [27] ADHD was more common in children and adolescents with childhood-onset mania than in patients with adolescent-onset mania, and in some youth ADHD symptoms may be a marker for juvenile-onset mania.

Data from this and other studies [28] 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, 29]

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. [30, 23, 31]

Preschool children with early behavioral disinhibition [32] 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. [33, 34] Emotion processing seems to be impaired in individuals with bipolar disorder because of a lack of flexibility in thought processing. [35, 34, 16]

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. [36] These delays occur in language, social, and motor development approximately 10-18 years before affective symptoms appear. [37]

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. [38]

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. [29, 39, 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. [38]

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.

Future research directions include the impact of the microbiome and intestinal microbiota in causing depression and irritability, which has so far only been proven in animal models. If the intestinal microbiota of humans is determined to play a causal role, then dietary interventions and testing of the microbiome might help with both diagnosis and treatment of bipolar disorder. [40]

Rates of early-onset bipolar disorder in youth range between 1 and 1.8% according to one meta-analysis. The overall prevalence of BPI in adolescents is approximately 1%, whereas the prevalence in children is 0.2–0.4%. Bipolar disorder has roughly equal prevalence across different cultures. [7, 9]

Most patients with bipolar disorder present in early adulthood (age 20–30 years). The second most common age group at presentation is 15–19 years.

In contrast to the 1921 report stating that 38% of patients had an onset when younger than 20 years, more recent estimates are that 20–30% of adults with BPI 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 year).

Pediatric and adolescent bipolar disorder does not appear to have a sexual predilection, although more males with the disorder than females are referred for treatment. [41, 42]

Go to Bipolar Affective Disorder for complete information on this topic.

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.

All persons with bipolar disorder have an increased risk of suicide. 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.

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.

Other sources of morbidity and mortality are associated with poor judgment exercised by individuals with acute mania or psychosis. For example, serious cardiovascular complications (eg, 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.

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.

A 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 nurture strong relationships.

A 2017 article in the Journal of Clinical Psychology ephasizes the role of family-focused therapy to reduce the risk of suicide for bipolar youth by decreasing the negative effects of perceived criticism; often, suicide attempts are preceeded by negative parental interactions that youths perceive to be rejcting and criticizing. [43]

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 section provides a user-friendly fact and information sheet to families about bipolar disorder and its treatment in the pediatric population.

The Balanced Mind Parent Network (formerly known as 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.

Other sources of information include Web sites such as the American Psychological Association, National Alliance on Mental Illness, and Depression and Bipolar Support Alliance.

For patient education resources, see the Depression Center, as well as Depression and Bipolar Disorder.

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Conduct Disorder

Euphoric in mania

Dyphoric in mixed or depressed state


Common Adverse Effects

Pediatric Doses

Special Concerns

Lithium carbonate (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; up-titrate 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

Approved for patients 12 y and older

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; up-titrate on twice- or thrice-daily schedule

Elevated liver enzymes or liver disease, drug-drug interactions, bone marrow suppression

Approved for patients 12 y and older

Aripiprazole (Abilify, Abilify Discmelt)

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

Approved for patients 12 y and older

Carbamazepine (Equetro)

Suppressed WBCs, dizziness, drowsiness, rashes, liver toxicity (rare)

10-20 mg/kg/d; dose must be adjusted by monitoring serum blood levels; up-titrate on twice-daily schedule

Drug-drug interactions, bone marrow suppression

Asenapine (Saphris)

Somnolence, oral paraesthesia

2.5 mg SL q12h initially; may increase to 5 mg SL q12hr after 3 days and to 10 mg SL q12hr after 3 additional days

Pediatric patients are more sensitive to dystonia with initial dosing when recommended escalation schedule not followed

Approved for patients 10 y and older

Risperidone (Risperdal, Risperdal Consta, Risperdal M-Tab)

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

Approved for patients 10 y and older

Quetiapine (Seroquel, Seroquel XR)

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 or hyperglycemia

Approved for patients 10 y and older

Olanzapine (Zyprexa, Zyprexa Zydis, Zyprexa Relprevv)

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

Clonazepam (Klonopin)

Sedation, abnormal coordination, ataxia

0.01-0.04 mg/kg/d PO at bedtime or divided bid

Caution with renal/hepatic impairment and asthma

Fluoxetine (Prozac)

Headache, nausea, insomnia, anorexia, anxiety, asthenia, diarrhea, somnolence

10 mg PO qd; may consider increasing to 20 mg/d after 1 wk

Long half-life; potential to exacerbate manic symptoms when not coadministered with an antimanic or mood-stabilizing agent

Ziprasidone (Geodon)

Akathisia, nausea

Off-label: 20 mg PO at bedtime; can increase to 40 mg (not to exceed 60 mg), usually in 2 divided doses for children

Risk of sudden cardiac death due to torsades des pointes due to prolonged QT prolongation, which makes this medication undesirable for individuals with a family history of cardiac sudden death related to cardiac conduction abnormalities

WBC—white blood cell.

Bettina E Bernstein, DO Distinguished Fellow, American Academy of Child and Adolescent Psychiatry; Distinguished Fellow, American Psychiatric Association; Clinical Assistant Professor of Neurosciences and Psychiatry, Philadelphia College of Osteopathic Medicine; Clinical Affiliate Medical Staff, Department of Child and Adolescent Psychiatry, Children’s Hospital of Philadelphia; Consultant to theVillage, Private Practice; Consultant PMHCC/CBH at Family Court, Philadelphia

Bettina E Bernstein, DO is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, American Psychiatric Association

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Caroly Pataki, MD Health Sciences Clinical Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, David Geffen 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, Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Pediatric Bipolar Affective Disorder

Research & References of Pediatric Bipolar Affective Disorder|A&C Accounting And Tax Services