Psychiatric Annals

CME Article 

Pediatric Depression: The Latest in Diagnosis and Treatment

Salma Malik, MD, MS, DFAACAP, FAPA; Muhammad Waqar Azeem, MD, DFAACAP, DFAPA

Abstract

Depressive disorders in children and adolescents constitute a significant burden on social and public health. The impairment can affect several domains of functioning including family, school, and social. Depression is also a significant risk factor in suicide and other psychiatric disorders. The prevalence of major depressive disorder is estimated to be 2% in children and 4% to 8% in adolescents. The rates are much higher in subsyndromal depression, which also affects the functioning of youth. Most youth do recover; however, recurrence is common, with 40% to 70% of youth experiencing relapse within 3 to 5 years. Biopsychosocial assessment of depression requires gathering information from multiple informants and synthesizing the information to diagnose depression. Treatment of pediatric depression consists of social, psychological, and pharmacological interventions. [Psychiatr Ann. 2017;47(10):502–506.]

Abstract

Depressive disorders in children and adolescents constitute a significant burden on social and public health. The impairment can affect several domains of functioning including family, school, and social. Depression is also a significant risk factor in suicide and other psychiatric disorders. The prevalence of major depressive disorder is estimated to be 2% in children and 4% to 8% in adolescents. The rates are much higher in subsyndromal depression, which also affects the functioning of youth. Most youth do recover; however, recurrence is common, with 40% to 70% of youth experiencing relapse within 3 to 5 years. Biopsychosocial assessment of depression requires gathering information from multiple informants and synthesizing the information to diagnose depression. Treatment of pediatric depression consists of social, psychological, and pharmacological interventions. [Psychiatr Ann. 2017;47(10):502–506.]

Depression in youth is a serious public health issue with substantial morbidity and mortality. Depression is a familial, recurrent illness that also effects psychosocial, family, and academic outcomes. Pediatric depression can continue into adulthood; therefore, early diagnosis and intervention is critical.1

Epidemiology

The prevalence of major depressive disorder (MDD) is estimated to be approximately 2% in children and 4% to 8% in adolescents.2 There is a male-to-female ratio of 1:1 during childhood and 1:2 during adolescence.2 It is also important to know that 5% to 10% of the youth with MDD will present with subsyndromal symptoms; they have psychosocial impairment that affects their functioning. They can also develop MDD and are at an increased risk for suicide.3

Clinical Presentation

The clinical presentation of depression is similar to adults but there are some differences that should be considered that are due to the child's physical, emotional, cognitive, social, and developmental stages. For example, children may have mood lability, irritability, low frustration tolerance, temper tantrums, somatic complaints, and/or social withdrawal instead of overt verbalizing of depression.2,3

Diagnostic Criteria

The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)4 contains several new depressive disorders including disruptive mood dysregulation disorder (DMDD) and premenstrual dysphoric syndrome. DMDD was added to address concerns about the overdiagnosis of bipolar disorder for children who exhibit persistent irritability with frequent episodes of extreme behavioral dyscontrol. Another change in DSM-5 is conceptualization of chronic depression; dysthymia is now under the persistent depressive disorder category.

A diagnosis of MDD requires, according to the DSM-5 criteria, five or more of the following symptoms in Criterion A to be present during the same 2-week period and represent a change from previous functioning: (1) depressed mood nearly every day; (2) markedly diminished interest or pleasure in all or most activities; (3) significant weight loss when not dieting or weight gain; (4) insomnia or hypersomnia nearly every day; (5) psychomotor agitation or retardation nearly every day; (6) fatigue or loss of energy nearly every day; (7) feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day; (8) diminished ability to think or concentrate (or indecisiveness) nearly every day; (9) recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.4

Clinical Course and Risk Factors

An MDD episode usually lasts for approximately 7 to 8 months, but subsyndromal symptoms continue for a longer period. Some of the variables identified with longer time to recovery include early age of onset, greater severity, suicidality, double depression, comorbid anxiety disorder, disruptive behavior disorders, and adverse family environments. Predictors of increased risk of recurrence include greater severity, psychotic symptoms, suicidality, past history of recurrent MDD, subthreshold symptoms after recovery, recent stressful life events, adverse family environments, and family history of MDD.5

Modifiable risk factors include frequency and quantity of alcohol use, Cannabis use, other illicit drugs, poly drug use, tobacco use, dieting, negative coping strategies, disruption in normal sleep, and increase in weight.6 These factors have sound evidence. Similarly protective factors with sound evidence include healthy diet, positive coping strategies, and an adequate amount of sleep.6 There are other protective factors that have emerging evidence: physical activity, relationships with positive peers, self-disclosure to parents (which may indicate a supportive relationship).6

Etiology

There is modest heritability of MDD, but environment plays a significant role especially during childhood and adolescence.7 Adoption and twin studies indicate that MDD is a familial disorder. The single, most predictive factor associated with the risk of developing MDD is high family loading for this disorder.8

Numerous factors have been associated with the onset and duration of a depressive episode such as age, gender, socioeconomic status, preexisting diagnosis, subsyndromal symptoms, temperament, and negative cognitive style. Familial factors such as parental psychopathology, early onset mood disorders, and high familial loading play a significant role. Stressors such as losses, abuse, neglect, ongoing conflicts as well as psychosocial stressors such as poor support, negative peer relationships, bullying, stressful life events, and maladaptive parenting can also be contributory. Other factors such as psychiatric comorbidity, medical illness and biological and sociocultural factors can be related to depressive symptomology.9–11

Comorbidity

Many children and adolescents with MDD will also meet criteria for other psychiatric disorders. A meta-analysis study by Angold et al.12 showed that children and adolescents with depression were 8.2 times more likely to meet the criteria for anxiety disorders, 6.6 times more likely to meet criteria for conduct disorder, and 5.5 times more likely to meet the criteria of attention-deficit/hyperactivity disorder. There is also increased comorbidity with oppositional defiant disorder, substance abuse, eating, and developmental disorders.12

Assessment

Separate clinical interviews, using open-ended questions, with the young person and their parent(s) are required. Careful medical and psychiatric review of symptoms is needed to screen and diagnose comorbid medical and psychiatric disorders. Assessment of social factors such as school functioning, family and peer relationships, and stressors as well as risk factors and safety are all important (Table 1).

Assessment of Depressive Disorders

Table 1:

Assessment of Depressive Disorders

Self-reporting depression rating scales can be used to assess symptoms: Beck Depression Inventory, Mood and Feeling Questionnaire, and Patient Health Questionnaire. The scales can also be clinician administered: Children Depression Rating Scale Revised and Clinical Global Impression Improvement Scale.13

Differential Diagnosis

Several psychiatric and medical disorders can co-occur with depressive symptoms or can mimic depression. These should be carefully assessed in the evaluation of children and adolescents (Table 2).

Differential Diagnosis of Depressive Disorders

Table 2:

Differential Diagnosis of Depressive Disorders

Treatment

The treatment of depression is divided into three phases: acute, continuation, and maintenance. The main goal of the acute phase is to get response and eventually full symptomatic remission. Response is defined as at least 50% reduction of symptoms for 2 weeks; remission is having no or few symptoms of depression for at least 2 weeks and up to 2 months, whereas recovery is the absence of significant symptoms for more than 2 months14–16(Table 3).

Treatment for Depressive Disorders

Table 3:

Treatment for Depressive Disorders

Phases

After the acute phase treatment, the continuation treatment is required to consolidate the response and avoid relapse and then maintenance treatment is recommended to avoid recurrences. Each phase of the treatment includes important elements of psychoeducation, supportive management, family and school involvement with consideration for therapy as well as medications as indicated.17

Acute treatments of MDD that have shown superiority over placebo include monotherapies such as selective serotonin reuptake inhibitors (SSRIs), cognitive-behavioral therapy (CBT), and interpersonal therapy (IPT). Combination treatment of medication and CBT has demonstrated superiority over monotherapy in some but not all clinical trials.17

Psychosocial

CBT and IPT have evidence supported by clinical trials. Other types of therapies are used in clinical practice with some evidence. These include supportive therapy, psychodynamic therapy and family therapy. A meta-analysis study by Weisz et al.18 showed that the overall effects of psychotherapy in acute treatment of depressed youth are modest.

CBT is effective for treatment of children and adolescents with depression as shown by another meta-analysis study by Compton et al.19 CBT is effective even if there are comorbidities, suicidal ideation, and hopelessness. However, it doesn't perform as well when there is history of sexual abuse and when one of the parents is depressed.20

IPT is another form of psychotherapy that has been proven to be effective for depressive symptoms. IPT uses discussing and teaching interpersonal problem-solving, and helping the adolescent improve communication.21

Psychopharmacological

Fluoxetine and escitalopram are the only antidepressants approved by the US Food and Drug Administration (FDA) for the treatment of adolescent depression. Other SSRIs, such as sertraline and citalopram, are prescribed based on factors such as comorbid conditions (anxiety, obsessive-compulsive disorder), side-effect profile, and family history of response.

The Treatment of Adolescent Depression Study (TADS) was a landmark National Institute of Mental Health-funded study that randomized 439 depressed adolescents to 4 arms: CBT alone, fluoxetine alone, CBT with fluoxetine and pill placebo.22 Results showed that CBT did not perform better in acute treatment than placebo and less well than the medication-only arm. At 12 weeks, the response rates were 71% for combination of CBT and fluoxetine, 61% for fluoxetine, 43% for CBT, and 35% for placebo.22 However, in the open follow-up, all the different treatment options caught up. At 36 weeks, the estimated remission rates were 60% for combination treatment, 55% for fluoxetine, and 64% for CBT.23

Overall the rate of response for children and adolescents who have participated in antidepressant randomized controlled trials (RCTs) is 61% for antidepressants and 50% for placebo yielding a number needed to treat (NNT) of 10. Fluoxetine has a NNT of 5, which could be due to better-designed studies and longer half-life with minimal effect even if there is occasional nonadherence. Pediatric RCTs are hampered by a high rate of placebo response.24

Special Considerations

Black-Box Warning

In 2004, the FDA issued a black-box warning regarding antidepressants indicating that they were associated with an increased risk of suicidal thinking, feeling, and behavior in young people.25 The warning came after the FDA had conducted a series of meta-analyses of 372 randomized clinical trials of antidepressants involving nearly 100,000 participants, which showed that the rate of suicidal thinking or suicidal behavior was approximately 4% among patients assigned to receive an antidepressant, as compared with approximately 2% among those assigned to receive placebo, although none of the suicide attempts documented were fatal.25

Given the concerns, the FDA has recommended a monitoring system for patients who are started on antidepressants.25 It is suggested to monitor for response, emergence of suicidality, and worsening depression. Suggested frequency of the visits are weekly for the first 4 weeks, then biweekly for 4 weeks, then monthly, and finally determined by individual needs. According to the Practice Parameters from the American Academy of Child & Adolescent Psychiatry, the recommendation is that the suggested frequency and the nature of monitoring should be individualized.26

Treatment-Resistant Depression

There was a landmark study for adolescents who had resistant depression called the Treatment of Resistant Depression in Adolescents Study (TORDIA).27,28 In this study, adolescents who had failed an adequate trial of one SSRI were randomly assigned to switch to another SSRI or venlafaxine, another SSRI and CBT, or venlafaxine and CBT. In this study,27 fluoxetine and citalopram performed similarly with a response rate of approximately 55% and better than paroxetine (response rate of approximately 38%), but the difference was not statistically significant. There was no difference in the response rate between the two medication switch strategies. The TORDIA study also found that switching medications and adding CBT was superior to a medication switch alone (55% for combination and 41% for medication alone). The remission rate was 61% by week 72, independent of the initial treatment in TORDIA.28

Conclusion

Given the effect of depression during the critical developmental period for children and adolescents, which can manifest in physical, social, cognitive, emotional, educational, relational, and vocational development, it is imperative to focus on preventive strategies and efforts as well as early diagnosis and interventions incorporating biopsychosocial treatment planning.

Combination treatment, which include therapy and medication, can be more effective. It's important to consider family, school, social, and vocational aspects when planning treatment interventions. Even with the available treatments, the remission rates for moderate to severe depression are low. This means we must do better with the available treatments. The TORDIA study showed that in adolescents who were depressed for 2 years and had a failed SSRI trial, just switching medication resulted in additional 50% response, with even higher rates of response if CBT was added.

References

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Assessment of Depressive Disorders

Comprehensive psychiatric evaluation from multiple informants with cultural sensitivity

Developmental history

Trauma history

Family history

Current depressive symptoms

Functioning (social, academic)

Medical history

Stressors (past and ongoing)

Psychiatric history

Safety assessment including inquiry about access to guns

Treatment history

Family functioning assessment

Individual assessment

Strengths and weaknesses

Review of other psychiatric symptoms

Mental status examination

Risk assessment (suicidality and homicidality)

Substance abuse

Trauma and other stressors

Physical screening and laboratory tests

Physical examination

Consider laboratory tests such as thyroid profile, complete blood count, and other laboratory assessments

Standardized assessments

Child Depression Rating Scale

Columbia Suicidal Severity Rating Scale

Other psychological testing as indicated

Differential Diagnosis of Depressive Disorders

Psychiatric disorders

Anxiety disorders

Conduct disorder

Attention-deficit/hyperactivity disorder

Oppositional defiant disorder

Substance use disorders

Eating disorders

Depressive disorder due to another medical condition

Manic episodes with irritable mood or mixed episode

Substance/medication-induced depressive disorders

Adjustment disorder with depressed mood

Persistent depressive disorder

Premenstrual dysphoric disorder (dysthymia)

Other specified depressive disorder

Unspecified depressive disorder

Medical disorders

Thyroid abnormalities

Anemia

Poor nutrition

Sleep disorders

Tumors

Other endocrine disorders

Treatment for Depressive Disorders

Psychoeducation

Supportive psychotherapeutic management

Family involvement

School involvement

Psychotherapies

Supportive psychotherapy

Cognitive-behavioral therapy

Interpersonal psychotherapy

Family therapy

Pharmacotherapy

Treatment of comorbid conditions

Adequate monitoring and follow-up

Authors

Salma Malik, MD, MS, DFAACAP, FAPA, is the Senior Attending Physician and Training Director, Department of Psychiatry, Sidra Medical and Research Center. Muhammad Waqar Azeem, MD, DFAACAP, DFAPA, is the Chair, Department of Psychiatry, Sidra Medical and Research Center; and a Professor of Psychiatry, Weill Cornell Medicine, Cornell University.

Address correspondence to Salma Malik, MD, MS, DFAACAP, FAPA, Sidra Medical and Research Center, Department of Psychiatry, P. O. Box 26999, Doha, Qatar; email: smalik@sidra.org.

Disclosure: Salma Malik discloses research support from Forest Pharmaceuticals and Pzifer for clinical trials. The remaining author has no relevant financial relationships to disclose.

10.3928/00485713-20170911-01

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