Description

In the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), major depressive disorder is characterized by a distinct period of at least 2 wk (an episode, Table 24-1) in which there is a depressed or irritable mood that is present for most of the day nearly every day, and/or loss of interest or pleasure in nearly all activities. There also are associated vegetative and cognitive symptoms, including disturbances in appetite, sleep, and energy; impaired concentration; and thoughts of worthlessness, guilt, and suicide. To meet the syndromal diagnosis, 5 or more symptoms (including depressed or irritable mood or loss of interest or pleasure) must be present and must represent a distinct change from previous functioning, cause clinically significant distress or impairment, not be better accounted for by bereavement or by other psychiatric disorders, and not be due to the direct physiologic effects of a substance or a general medical condition.

Major depressive disorder is categorized as mild if few symptoms in excess of those required to make the diagnosis are present and the symptoms result in only minor functional impairment, and it is categorized as severe if several symptoms in excess of those required are present and the symptoms markedly interfere with functioning. Severe major depression is subcategorized as occurring with or without psychotic features (hallucinations or delusions). Moderate major depression is intermediate between mild and severe.

Overall, the clinical presentation of major depressive disorder in children and adolescents is similar to that in adults. The prominence of the symptoms can change with age; somatic complaints, irritability, and social withdrawal may be more common in children (who are less able to verbalize their feeling states), and psychotic and melancholic symptoms or suicidal behavior may be more common in adolescents.

Epidemiology

The prevalence of major depressive disorder is estimated to be approximately 2% in children and 4-8% in adolescents, with a male-female ratio of 1 : 1 during childhood and 1 : 2 during adolescence. The risk of major depression increases by a factor of 2 to 4 after puberty, and the cumulative incidence by age 18 yr is approximately 20%.

Differential Diagnosis

A number of psychiatric disorders, general medical conditions, and medications can generate symptoms of depression and irritability and must be distinguished from the depressive disorders. The psychiatric disorders include anxiety (Chapter 23), attention-deficit/hyperactivity disorder (ADHD) (Chapter 30), disruptive behavior (Chapter 27), developmental disorders (Chapter 28), substance abuse (Chapter 108), and adjustment disorders. Medical conditions include neurologic disorders, endocrine disorders, infectious diseases, tumors, anemia, uremia, failure to thrive, chronic fatigue disorder, and pain disorder. Medications include narcotics, chemotherapy agents, cardiovascular medications, corticosteroids, and contraceptives. The diagnosis of a depressive disorder should be made after these other explanations for the observed symptoms have been ruled out.

Comorbidity

Major depressive and dysthymic disorders (Chapter 24.3) often co-occur with other psychiatric disorders, and both can occur concurrently (double depression). Depending on the setting and source of referral, 40-90% of youths with a depressive disorder have other psychiatric disorders, and up to 50% have 2 or more comorbid diagnoses. The most common comorbid diagnosis is an anxiety disorder, followed by disruptive behavior, ADHD, and substance use disorder.

Clinical Course

The median duration of a major depressive episode approximates 8 mo for clinically referred youths and 1 to 2 mo for community samples. Prepubertal depressive disorders can exhibit more heterotypic than homotypic continuity; thus, depressed children may be more likely to develop nondepressive psychiatric disorders in adulthood than depressive disorders. Adolescents might exhibit greater homotypic continuity, with the probability of recurrence of depression reaching 70% after 5 yr. Between 20% and 40% of these adolescents develop a bipolar disorder (Chapter 24.2), and the risk is higher among adolescents who have a high family loading for bipolar disorder, who have psychotic depression, or who have had pharmacologically induced mania.

Sequelae

Approximately 60% of youths with major depression report thinking about suicide, and 30% actually attempt suicide (Chapter 25). The risk of suicidal behavior increases if there is a history of suicide attempts, exposure to adverse psychosocial circumstances, a family history of suicidal behavior, or comorbid psychiatric disorders. Youths with depressive disorders are also at high risk of substance abuse, impaired academic performance, impaired family and peer relationships, and poor adjustment to life stressors, including physical illness.

Etiology and Risk Factors

Major depression is a highly familial disorder, with both genetic and environmental influences. Environmental influences include parental psychopathology, impaired parenting, dysfunctional families, parent figure changes, loss of a parent, physical and sexual abuse, neglect, social isolation, lack of social supports, exposure to domestic and community violence, and other correlates of disadvantaged socioeconomic status. Longitudinal studies have suggested the greater importance of environmental influences in children who become depressed compared to adults who become depressed.

Prevention

Several experimental trials have demonstrated the effectiveness of cognitive-behavioral strategies in preventing the escalation of sub-syndromal to syndromal depression. These strategies include identifying negative mood states, linking mood states to environmental or cognitive precipitants, avoiding situations that are typically stressful, correcting automatic negative attributions, scheduling pleasurable activities, developing competencies to enhance self-esteem, and developing learning skills to deal with adversity. Other strategies that can prove helpful include lifestyle modification (e.g., regular and adequate sleep, exercise, and relaxation) and involvement with supportive mentors and peers.

Early Identification

Clinicians should screen all children and adolescents for the key depressive symptoms of sad mood, irritability, and anhedonia (Table 24-2). A diagnosis of a depressive disorder should be considered if these symptoms are present most of the time, affect the child’s functioning, and are beyond what would be expected for the given circumstances. The use of standardized depression rating scales (Chapter 18) designed for self- or parent report can be helpful in the screening process. If the screening indicates clinically significant depressive symptoms, the clinician should refer to a specialist for a comprehensive diagnostic evaluation to determine the presence of depressive and other comorbid psychiatric and medical disorders. The evaluation must include assessment of the potential for harm to self or others.

Table 24-2 SCREENING AND TREATMENT FOR MAJOR DEPRESSIVE DISORDER IN YOUTHS

For a summary of the evidence systematically reviewed in making these recommendations, the full recommendation statement, and supporting documents, please go to www.AHRQ.gov/clinic/USPSTF/USPSCHDEPR.htm.

Treatment

Treatment of the depressive disorders should begin with psychoeducation, family involvement, and school involvement. Psychoeducation refers to education of the family members and patient about the causes, symptoms, course, and different treatments for depression and the risks associated with each treatment and with no treatment. Written materials and reliable websites about depression can be helpful to the parents and patient. Because of the importance of environmental factors in the etiology of childhood depression, family involvement should focus on ameliorating these factors by strengthening the relationship between the identified patient and parent(s), providing parenting guidance, reducing family dysfunction, eliminating identified sources of stress, enhancing social supports, and facilitating treatment referral for parents as indicated.

With the patient’s and parents’ consent, school personnel should be informed about the need for accommodations until recovery has been achieved. Students with a depressive disorder may be eligible for an Individualized Education Program specifying school-based services and accommodations under the emotional disturbance disability category of the Individuals with Disabilities Education Act.

Because of the high rates of response to placebo and brief therapy in pediatric depression, it is reasonable in a patient with sub-syndromal (i.e., depressive disorder, not otherwise specified) or mild syndromal (i.e., dysthymic disorder or major depressive disorder) depression (Chapter 24.3), mild functional impairment, and absence of suicidality or psychosis to supplement the above-described interventions with 4 to 6 wk of weekly supportive therapy, focusing on enhancement of the youth’s coping capabilities and amelioration of adverse environmental influences. In youths with moderate to severe syndromal depression, significant functional impairment, and suicidality or psychosis, specialized treatment with specific psychotherapies and/or with medication is indicated.

Moderate syndromal depression may respond to cognitive-behavioral or interpersonal therapy without medication. These types of therapy, typically administered in weekly doses over 8 to 12 wk, are more efficacious than supportive therapy alone when depression is more than mild. Severe syndromal depression requires treatment with antidepressants. In addition to level of severity, treatment decisions are influenced by treatment availability, comorbid disorders, and family preference.

Studies of the effectiveness of selective serotonin reuptake inhibitors (SSRIs) are mixed. Within the positive studies, approximately 50% of youths with depression respond to the medication, but only around 30% experience symptom remission. Studies of other classes of antidepressant medications have not demonstrated clear superiority over placebo.

The SSRIs and other antidepressants have been well tolerated by children and adolescents. The most common side effects include irritability, gastrointestinal symptoms, sleep disturbance, restlessness, diaphoresis, headaches, changes in appetite, and sexual dysfunction. Approximately 5% of youths, particularly children, develop increased impulsivity, agitation, and irritability (behavioral activation) on SSRIs, and the SSRI must be discontinued. More rarely, the use of antidepressants has been associated with serotonin syndrome, increased predisposition to bleeding, and increased suicidal thoughts. The excess risk for such thoughts appears to approximate 1.8 (relative risk) in youths with major depression.

Except for lower initial doses to avoid unwanted effects, the doses of antidepressants in youths are similar to those used for adult patients (Chapter 19 and Table 19-4). Some studies have reported that the half-lives of sertraline, citalopram, paroxetine, and bupropion SR are much shorter in children than in adults; therefore daily withdrawal side effects can be observed with these medications if they are administered once daily.

Patients should be treated with adequate and tolerable doses of medication for at least 4 wk. Clinical response, tolerability, and emergence of behavioral activation, mania, or suicidal thoughts should be assessed frequently (as often as weekly) for the first 4 wk. If the youth has safely tolerated the antidepressant, the dose may be increased at 4 wk if an adequate response (at least 50% reduction in symptom severity) has not been achieved. Patients can then be monitored slightly less frequently (as often as biweekly) until remission (no longer meets diagnostic criteria) has been achieved, and approximately monthly thereafter. Because of the high rate of relapse, successful treatment should continue for 6 to 12 mo. At the conclusion of treatment, all antidepressants (except fluoxetine) should be discontinued gradually to avoid withdrawal symptoms (tiredness, irritability, severe somatic symptoms).

Patients with recurrent (two or more), chronic, or severe major depression can require treatment beyond 12 mo. Patients who have shown minimal or no response to antidepressant medication at 8 wk, and patients who have not achieved remission by 12 wk, are likely to need referral for specialized treatment. Switching to another antidepressant combined with cognitive-behavioral therapy may be helpful in those who do not respond to the initial SSRI. Depressed patients with suicidality, psychosis, seasonal depression, or bipolar depression also should be referred for specialized treatment.

Level Of Care

Most children and adolescents with mild to moderate depressive disorders can be safely and effectively treated as outpatients, provided that a schedule of approximately weekly visits can be maintained through the acute phase of treatment. Youths who are suicidal, psychotic, or melancholic usually require inpatient care.

Description

In the DSM-IV-TR, bipolar I disorder is characterized by one or more episodes of mania, often alternating or concurrent with one or more episodes of major depression. Mania is characterized by a distinct period of at least 1 wk (an episode, Table 24-3) in which there is an unusually happy (elated), unusually enthusiastic (expansive), or unusually irritable mood. The mood represents a distinct change from previous functioning. There also are associated cognitive and behavioral symptoms, including unrealistically high self-esteem (grandiosity), needing little sleep (not being tired after sleeping very little), feeling the need to talk all the time, feeling that thoughts are racing, having difficulty concentrating, feeling agitated or engaging in a flurry of activity to accomplish tasks, and impulsively doing things that can be pleasurable but have the potential for harm in excess (e.g., shopping sprees, gambling). Psychotic symptoms can be an associated feature of the disorder.

To meet the syndromal diagnosis, 3 or more cognitive or behavioral symptoms in addition to elevated, expansive or irritable mood must be present, cause clinically significant impairment in multiple settings or require hospitalization to prevent harm to self or others, not be better accounted for by other psychiatric disorders, and not be due to the direct physiologic effects of a substance or a general medical condition.

Bipolar II disorder is characterized by 1 or more episodes of major depression alternating with 1 or more episodes of hypomania. Hypomania is similar to mania, but is briefer (at least 4 days) and less severe (causes less impairment in functioning, is not associated with psychosis, and would not require hospitalization). To meet the syndromal diagnosis, there must never have been a manic episode, and the symptoms must cause clinically significant distress or impairment and not be better accounted for by another psychiatric diagnosis.

Cyclothymic disorder is characterized by a period of at least 1 yr in which there are numerous episodes of hypomania and sub-syndromal depression. To meet the syndromal diagnosis, the symptoms must cause clinically significant distress or impairment, not be better accounted for by other psychiatric disorders, and not be due to the direct physiologic effects of a substance or a general medication condition.

Bipolar disorder, not otherwise specified (sub-syndromal bipolar disorder) is diagnosed when some symptoms of bipolar disorder are present but not enough to meet full diagnostic criteria for the bipolar or cyclothymic disorders. Although this diagnosis increasingly has been applied to children with severe and chronic mood and behavioral dysregulation who do not precisely fit other diagnostic categories, the empiric support for the validity of this practice is sparse.

In adolescents, the clinical manifestation of bipolar disorder is similar to that in adults. Psychosis (delusions, hallucinations) often is an associated symptom, and episodes often are mixed (concurrent mania and depression). There is controversy about the applicability of the bipolar diagnostic criteria to prepubertal children. It may be developmentally normal for children to be elated, expansive, or grandiose, reducing the specificity of these symptoms to psychiatric disorder. This makes the diagnosis of the bipolar disorders difficult in young children.

Epidemiology

The lifetime prevalence of each of the bipolar disorders and cyclothymic disorder is estimated to approximate 0.6%; the male-female ratio approximates 1. Offspring of parents with bipolar disorders are at high risk for early-onset bipolar disorders. Twin and adoption studies provide strong evidence of a genetic influence; first-degree relatives of patients with bipolar I have a 4- to 6-fold increased risk of bipolar and depressive disorders.

Differential Diagnosis

A number of psychiatric disorders, general medical conditions, and medications can generate symptoms of mania and must be distinguished from the bipolar disorders. The psychiatric disorders include ADHD, oppositional defiant, post-traumatic stress, substance abuse, pervasive developmental, communication, and borderline personality disorders. Medical conditions include neurologic disorders, endocrine disorders, infectious diseases, tumors, anemia, uremia, and vitamin deficiencies. Medications include androgens, bronchodilators, cardiovascular medications, corticosteroids, chemotherapy agents, thyroid preparations, and certain psychiatric medications (benzodiazepines, antidepressants, stimulants). The diagnosis of a bipolar disorder should be made after these other explanations for the observed symptoms have been ruled out. Some suggest that a diagnosis of bipolar disorder should not be given to youths in the absence of the cardinal symptoms of elation and grandiosity and an episodic course.

Comorbidity

The bipolar disorders can be comorbid with a number of other psychiatric disorders, including ADHD, anxiety, eating, and substance use disorders.

Clinical Course

Premorbid problems are common in bipolar disorder, especially difficulties with mood and behavioral regulation. Premorbid anxiety also is common. The bipolar disorders are highly recurrent, and more than 90% of bipolar I patients have additional episodes. Recurrent episodes can approximate 4 in 10 years, with the interepisode interval shortening as the patient ages. Although the majority of patients with bipolar I return to a fully functional level between episodes, approximately one third continue to be symptomatic and functionally impaired between episodes.

Sequelae

Completed suicide occurs in 10-15% of patients with bipolar I disorder. Youths with bipolar disorders are also at high risk for substance abuse, antisocial behavior, impaired academic performance, impaired family and peer relationships, and poor adjustment to life stressors. Cyclothymic disorder is thought to be a temperamental predisposition to bipolar disorder and as such may be an important target for treatment.

Prevention

Although empiric support is lacking, the course of cyclothymic disorder suggests that treatment with specific therapies that focus on regulation of mood and possibly the use of mood-stabilizing medication can prevent the evolution of cyclothymia into bipolar disorder.

Early Identification

Clinicians should screen all children and adolescents for the cardinal manic symptoms of elation and grandiosity. The diagnosis of bipolar disorder should be considered if the symptoms occur in the context of distinct episodes and do not represent developmentally normal emotional and behavioral expressions. If the screening indicates clinically significant bipolar symptoms, the clinician should refer to a specialist for a comprehensive diagnostic evaluation to determine the presence of bipolar and other comorbid psychiatric and medical disorders. The evaluation must include assessment of the potential for harm to self or others.

Treatment

Treatment of the bipolar disorders should begin with psychoeducation, family involvement, and school involvement. Family involvement should include the importance of treatment compliance and stable, positive family relationships with control of expressed emotion. Family-focused treatment is often beneficial. Students with a bipolar disorder may be eligible for an Individualized Educational Program specifying school-based services and accommodations under the emotional disturbance disability category of the Individuals with Disabilities Education Act (Chapter 15).

For mania in classically defined bipolar I disorder, medication is the primary treatment; medications used with adults may be less effective with youths (<50% response rate). Standard pharmacotherapy includes lithium, valproate, or atypical antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone) (Chapter 19 and Table 19-6). The choice of medication is based upon empiric support for safety and efficacy, medical considerations, adherence considerations, and a positive response of a family member.

Medication trials should be systematic, and the duration of trials should be sufficient (generally 6-8 wk) to determine the agent’s effectiveness. Care should be taken to avoid unnecessary polypharmacy, in part by discontinuing agents that have not demonstrated significant benefit. Because all of these medications are associated with significant side effects, careful monitoring of baseline and follow-up indices is imperative. Side effects of lithium include cardiac, renal, thyroid, and hematologic effects; toxicity; and teratogenicity. Side effects of valproate include hematologic, hepatic, and ovarian effects and teratogenicity. Atypical antipsychotics cause weight gain, metabolic aberrations (diabetes, hyperlipidemia), and cardiac effects. Withdrawal of medication has been associated with increased risk of relapse.

The regimen needed to stabilize acute mania should be maintained for 12 to 24 mo. Maintenance therapy is often needed for youths with classic bipolar I disorder, and some patients need lifelong medication. Any attempts to discontinue prophylactic medication should be done gradually, while closely monitoring the patient for relapse.

For depression in bipolar II disorder, antidepressant medication may be used once a mood-stabilizing medication has been initiated. Lamotrigine as adjunctive or monotherapy also may be helpful for adolescents with bipolar depression. Comorbid ADHD can be treated with stimulant medication once a mood-stabilizing medication has been initiated.

Psychotherapy is a key adjunctive treatment for the bipolar disorders. The components deemed to be important in therapy include identification and management of unpleasant feeling states, mastering interpersonal skills, developing decision-making and problem-solving skills, and inculcating healthy lifestyle habits: getting regular sleep and exercise, reducing stress, stabilizing social relationships, and avoiding drugs, alcohol, and nonprescribed medications. Many of these components are present in dialectical behavioral therapy, which has emerging empiric support for the treatment of these disorders.

Level of Care

Most youths with bipolar disorders can be safely and effectively treated as outpatients, provided that a schedule of frequent visits and laboratory tests can be maintained through the acute phase of treatment. Youths who are suicidal or psychotic usually require inpatient care.