Chapter 39. Bipolar Disorder

DSM-IV-TR Criteria for a Manic Episode

1. A distinct period of abnormally and persistently elevated, expansive, or irritable mood for at least 1 week (or any duration if hospitalization is necessary).

2. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:

   1. inflated self-esteem or grandiosity

   2. decreased need for sleep (e.g., feels rested after only 3 hours of sleep)

   3. more talkative than usual or pressure to keep talking

   4. flight of ideas or subjective experience that thoughts are racing

   5. distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)

   6. increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation

   7. excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)

3. The symptoms do not meet criteria for a Mixed Episode.

(Reprinted, with permission, from the Diagnostic and Statistical Manual of Mental Disorders. 4th edn. Text Revision. Washington, DC: American Psychiatric Association, 2000.)

DSM-IV-TR Criteria for a Hypomanic Episode

1. A distinct period of persistently elevated, expansive, or irritable mood, lasting throughout at least 4 days, that is clearly different from the usual nondepressed mood.

2. Same as B criterion for Manic Episode.

3. The episode is associated with an unequivocal change in functioning that is uncharacteristic of the person when not symptomatic.

4. The disturbance in mood and the change in functioning are observable by others.

5. The episode is not severe enough to cause marked impairment in social or occupational functioning, or to necessitate hospitalization, and there are no psychotic features.

6. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).

(Reprinted, with permission, from the Diagnostic and Statistical Manual of Mental Disorders. 4th edn. Text Revision. Washington, DC: American Psychiatric Association, 2000.)

DSM-IV-TR Criteria for a Mixed Episode

1. The criteria are met both for a Manic Episode and for a Major Depressive Episode (except for duration) nearly every day during at least a 1-week period.

2. The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.

3. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).

(Reprinted, with permission, from the Diagnostic and Statistical Manual of Mental Disorders. 4th edn. Text Revision. Washington, DC: American Psychiatric Association, 2000.)

DSM-IV-TR Criteria for Bipolar I Disorder, Most Recent Episode Manic

1. Currently (or most recently) in a Manic Episode.

2. There has previously been at least one Major Depressive Episode, Manic Episode, or Mixed Episode.

3. The mood episodes in Criteria A and B are not better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified.

(Reprinted, with permission, from the Diagnostic and Statistical Manual of Mental Disorders. 4th edn. Text Revision. Washington, DC: American Psychiatric Association, 2000.)

DSM-IV-TR Criteria for Bipolar II Disorder

1. Presence (or history) of one or more Major Depressive Episodes.

2. Presence (or history) of at least one Hypomanic Episode.

3. There has never been a Manic Episode or a Mixed Episode.

4. The mood symptoms in Criteria A and B are not better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified.

5. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

(Reprinted, with permission, from the Diagnostic and Statistical Manual of Mental Disorders. 4th edn. Text Revision. Washington, DC: American Psychiatric Association, 2000.)

Epidemiology

Given the controversy in characterizing pediatric bipolar disorder (BP), there is no data on the prevalence of prepubertal BP. One published study by Lewinsohn shows a lifetime BP prevalence of approximately 1% in youths 14–18 years old (predominantly BP type II and cyclothymia). An additional 5.7% youths have subsyndromal BP symptoms. Retrospective reports of adults with BP show that 60% report the onset of BP before 20 years of age and 10–20% report BP onset before 10 years of age. BP affects both sexes equally.

Etiology

Contributors to the etiology and course of BP are hypothesized to include genetics, neurobiology, and family environment. Biological etiologies are suggested by correlations between genetics and neuroimaging findings and BP. A family environment including stress and abuse is associated with earlier age of onset and more difficult course.

Genetics

BP is highly familial as evidenced by the increase of BP spectrum disorders in high-risk studies with offspring of BP parents. Adoption, twin, and family studies point to a familial, and most likely a genetic, etiology.

Signs & Symptoms

Although the presentation of BP in mid to late adolescence is considered similar to adult BP, the presentation of pediatric BP is debated. Many children have less than the 4–7-days duration specified in the DSM-IV-TR criteria for hypomania or mania, respectively. Pediatric BP is characterized by a predominance of mixed episodes and/or rapid cycling, irritability, chronicity with long episodes, and a high rate of comorbid attention-deficit hyperactivity disorder (ADHD) and anxiety disorder. The National Institute of Mental Health Research Roundtable on pubertal BP (2001) categorized pediatric bipolar phenotypes as “narrow” (DSM-IV-TR definitions of mania and hypomania) and “broad” (including the common clinical presentation of severe irritability, mood lability, temper outbursts, depression, anxiety, hyperactivity, poor concentration, and impulsivity). The diagnosis of BP should consider the developmental context in deciding what constitutes psychopathology. For example, increased self-esteem and goal-directed activity may be consistent with normal child development. Psychosis, most commonly auditory hallucinations, has been reported in 16–60% of youth with BP. The prevalence of psychosis is lower in adolescent mania than adult mania.

In summary, it is difficult to diagnose pediatric BP because of the variability in the clinical presentation, high comorbidity, and symptom overlap with other psychiatric disorders, the role of development in symptom expression, the difficulty experienced by children in reporting their symptoms, and social context in which the BP is developing (e.g., family conflicts). However, evidence is emerging that pediatric BP is a spectrum disorder (from BP Not Otherwise Specified [NOS] through BP-I) with a consistent course and outcome.

Psychological Testing

Although psychological testing is not involved in the diagnosis of BP, BP often is associated with cognitive deficits in children and adolescents. A study by Dickstein and Leibenluft using the computerized Cambridge Neuropsychological Test Automated Battery (CANTAB) reported difficulties in attentional set shifting and visuospatial memory in pediatric BP. A study by McClure and Leibenluft comparing children with BP to children with anxiety disorders and healthy controls showed that children with BP misinterpreted sad, happy, and fearful child faces as angry as compared with anxious and healthy groups. Interestingly, children with BP did not misinterpret adult faces.

Laboratory Findings

No specific laboratory findings are diagnostic of BP in children and adolescents.

Neuroimaging

Although much new research exists on neuroimaging, most of the studies are preliminary. Structural magnetic resonance imaging (MRI) studies suggest that white matter hyperintensitites in both cortical and subcortical brain regions and smaller amygdalar size are correlated with pediatric BP. In addition, smaller parietal and temporal lobe cortical gray matter, bilateral and left sided reductions in amygdala size, and bilateral decrease in hippocampal volume have been noted in pediatric BP. Studies have also indicated reduced gray matter volume in the dorsolateral prefrontal cortex (DLPFC). Bilateral larger basal ganglia, particularly an increase in putamen size, was identified in adolescent BP. Functional MRI studies show increased left thalamus and putamen activation and both cortical and subcortical dysfunction.

Preliminary proton magnetic resonance spectroscopy studies have suggested that substances which are markers for neuronal integrity such as N-acetyl-aspartate, choline, myoinositol, and creatine/phosphocreatine are affected in the fronto-striatal region, cingulate cortex, DLPFC, and other areas of the brain. These results are preliminary because they include small sample size and subjects in various phases of illness (e.g., depressed, hypomanic, euthymic). In addition, many subjects had comorbid disorders and were taking medication, which may have confounded the findings.

Course of Illness

Retrospective studies and naturalistic longitudinal studies of children and adolescents with BP report that 40–100% will recover, within 8 consecutive weeks, without meeting criteria for mania, hypomania, depression, or a mixed affective state, 1–2 years later. Of patients who recover, 60–70% show recurrence of symptoms within 10–12 months with hospitalization, psychosis, suicide attempts and completion, and poor psychosocial functioning.

As there is controversy over the presentation of pediatric BP, it is useful to study the course of the full spectrum of BP phenotypes. A recent study lead authored by Birmaher (2006) followed BP spectrum disorders (BP-I, BP-II, and BP-NOS). BP-NOS is defined as (1) elated mood plus two DSM-IV-TR BP symptoms or irritability plus three DSM-IV-TR BP symptoms; (2) at least 4 hours of symptoms in a 24 hour period; and (3) of 4 days lifetime total of symptoms. This study found that, compared with BP-I adults, BP-I youths spend significantly more time symptomatic with more mixed/cycling episodes, mood symptom changes, and polarity switches. A significant 25% of BP-NOS subjects converted to BP-I or BP-II. Furthermore, 70% of subjects with BP recovered from the index episode whereas 50% had at least one syndromal recurrence, most commonly a depressive episode. During follow-up, for 60% of the time, subjects had syndromal or subsyndromal symptoms with many changes in symptoms and shifts of polarity. Three percent of the subjects experienced psychosis. Twenty percent of BP-II subjects coverted to BP-I. Early onset, BP-NOS, long duration of mood symptoms, low-socioeconomic status, and psychosis were associated with poorer outcomes and rapid mood changes.

At this time, although suggested by familial transmission, it is not clear that pediatric BP is continuous with adult BP. In a community-based, adolescent longitudinal study, 5.7% of patients with abnormal mood, defined as persistently elevated, expansive, and irritable mood, did not go on to meet full DSM-IV-TR criteria of BP by the early twenties. In a retrospective interview of a large sample of individuals with adult BP, approximately 30% reported the onset of symptomatology before 13 years of age and approximately 40% during 13–18 years of age.

Earlier onset BP symptoms are associated with greater rates of anxiety and substance-abuse disorders, more recurrence, more rapid mood changes, shorter periods of euthymia, a higher incidence of suicide attempts, violence, and a history of abuse.

Depressed children and adolescents are at increased risk (10–20%) of developing BP, particularly if they present with psychotic symptoms, develop hypomania in response to pharmacological treatment of depression, and have a strong family loading for BP.

BP shares symptoms with several other psychiatric diagnoses, which may lead to a challenging differential diagnosis. A diagnosis of BP should only be made definitively after following a patient longitudinally. ADHD is commonly associated with symptoms commonly seen in BP including irritability, talkative/pressured speech, hyperactivity, pursuit of high risk yet pleasurable activities, and distractibility. BP can be differentiated from ADHD because of grandiosity, elated mood, accelerated ideas, and hypersexuality. Thought disorder and mood-incongruent delusions and hallucinations, which are symptoms of BP, may be mistaken as schizophrenia. Irritability, mood dysregulation, and disinhibition that might be confused with symptoms of mania may be symptoms of a pervasive developmental disorder. Evaluation should exclude child abuse, non-mood-related emotional and behavioral disturbances, developmental delays, delirium, tumors, infections, and seizure disorders. Substance use should be considered, especially the use of steroids, amphetamines, and cocaine.

Most children and adolescents presenting with BP also present with other psychiatric disorders. Some of the disorders cited as comorbid with BP include ADHD, oppositional defiant disorder, conduct disorder, anxiety disorder, substance-use disorder, and pervasive developmental disorder. The risk of panic disorder may be elevated in pediatric BP. It is worth-noting that comorbidity varies with age: Pediatric BP is commonly associated with ADHD, whereas adolescent-onset BP has a greater risk of substance abuse.

Psychopharmacologic Interventions

There are no controlled studies in children and adolescents of the treatment of BP-II. For acute phase medication treatment for BP-I, manic or mixed episode without psychosis, monotherapy with traditional mood stabilizers (lithium, divalproex, and carbamazepine), and atypical antipsychotics (olanzapine, quetiapine, and risperidone) is first-line treatment. The American Academy of Child and Adolescent Psychiatry (AACAP) practice parameters recommend lithium or divalproex as the first medication choice for nonpsychotic mania. Recent studies have suggested that atypical antipsychotic medication, such as olanzapine or quetiapine, are equally effective as traditional mood stabilizers and appear to yield a quicker response.

For children demonstrate only moderate to minimal improvement with monotherapy, an augmenting agent is recommended: Either another mood stabilizer or an atypical antipsychotic. The combination of two traditional mood stabilizers such as lithium and divalproex, or a traditional mood stabilizer and an atypical antipsychotic appears to be superior to mood stabilizer monotherapy for the acute treatment of manic or mixed episodes. For children having no response to initial monotherapy, or for children having intolerable side effects, monotherapy with another agent is recommended.

For children with BP-I, manic, or mixed episode without psychosis, a mood stabilizer combined with an atypical antipsychotic is recommended as the first choice, although atypical antipsychotic monotherapy may be considered as an alternative.

Children with BP experience long bouts of syndromal or subsyndromal depressive symptoms. There have been no randomized controlled treatment trials and few open-label studies of children with acute bipolar depression. In adults, monotherapy with lithium, divalproex, atypical antipsychotics, or lamotrigine and the combination of traditional mood stabilizers and atypical antipsychotics with serotonin reuptake inhibitors or bupropion is effective in the treatment of bipolar depression. Recognizing that most children and adolescents with BP have comorbid psychiatric disorders, such as ADHD, treatment should also be directed to the comorbid disorders.

Maintenance treatment consists of the same medications recommended for acute phase treatment. Medication tapering or discontinuation should be considered if the patient has been in remission for at least 12–24 consecutive months with close monitoring for symptom recurrence.

Psychotherapeutic Interventions

Child and family focused cognitive–behavioral therapy is effective in 8–18-year olds with BP. This therapy integrates reward-based CBT with interpersonal psychotherapy, which has a focus on empathetic validation. Psychoeducation and skills building, based in part on family systems and cognitive–behavioral intervention, has been shown to be effective in BP treatment. Psychoeducation consists of teaching parents and teachers about the symptoms, course, and treatment of BP. Skills-building focuses on communication and problem solving on symptom management, emotion regulation, and impulse control. Family-focused therapy (FFT) addresses the concerns of adolescents with BP and builds resources to manage stress and lower expressed emotion within the family.

Other Interventions

Case series exist on the effectiveness of electroconvulsive therapy in the treatment of acute mania and bipolar depression in adolescents. Omega-3 fatty acids (OFA) have been used in adults as well as children with BP. The U.S. Food and Drug Administration has approved the use of 3 g/day of OFA in adults. Approval for children and adolescents has not been granted.

One of the concerns about pharmacologic treatment is a lack of long-term safety data available for many of the medications used for BP. Mood stabilizers and atypical antipsychotic medications are associated with weight gain and its metabolic problems (diabetes mellitus, hyperlipidemia, and elevation of liver function tests). Atypical antipsychotic medications have side effects including neuroleptic malignant syndrome, movement disorder, prolactin elevation (especially with risperidone), and cardiac conduction problems (especially with ziprasidone). Working memory deficit and cognitive dulling have been reported with mood stabilizers and atypical antipsychotics. Polycystic ovarian syndrome has been linked to the long-term use of divalproex in women. Divalproex carries a “black–box” warning about rare, but potentially life-threatening, pancreatitis. Lithium is associated with hypothyroidism, weight gain, and changes in renal function.

Selective serotonin reuptake inhibitors and other antidepressants can trigger mania, hypomania, mixed episodes, or rapid cycling, particularly when used without concomitant mood stabilizer medication. Depressed children under the age of 14 years are vulnerable. Attention should be paid for increase in agitation, suicidality, and the serotonin syndrome (see Chapter 40).

BP is often a chronic and disabling illness. Early childhood BP has a lower rate of recovery, with a longer duration of mixed and rapid cycling episodes, more symptoms, and more frequent polarity changes than BP of later in life. Compared with adults, adolescents with BP often have a prolonged early course and are less responsive to treatment. Youth with BP show high-lifetime rates of psychosis, which is associated with poor prognosis. Adolescents with BP are at increased risk for suicide relative to children with other psychiatric disorders. Comorbid substance abuse further increases the suicide risk. Nevertheless, open treatment studies and small randomized trials of both pharmacological and psychosocial intervention suggest reason for cautious optimism.