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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
- Mann JJ, Emslie G, Beardslee W, et al. Preliminary report of the task force on SSRIs and suicidal behavior is youth. Am Coll Neuropshopharmacol. 2004; https://www.acnp.org/asset.axd?id=aad01592-01b2-4672-ad28-119537460ffa. Accessed September 20, 2017.
- Birmaher B, Ryan ND, Williamson DE, et al. Childhood and adolescent depression: a review of the past ten years. Part I. J Am Acad Child Adolesc Psychiatry. 1996;35:1427–1439. doi:. doi:10.1097/00004583-199611000-00011 [CrossRef]
- Fergusson DM, Horwood LJ, Ridder EM, Beautrais AL, Subthreshold depression in adolescence and mental health outcomes in adulthood. Arch Gen Psychiatry. 2005;62:66–72. doi:. doi:10.1001/archpsyc.62.1.66 [CrossRef]
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.
- Birmaher B, Arbelaez C, Brent D. Course and outcome of child and adolescent major depressive disorder. Child Adolesc Clin N Am. 2002;11:619–637. doi:10.1016/S1056-4993(02)00011-1 [CrossRef]
- Cairns KE, Yap MB, Pilkington PD, Jorm AF. Risk and protective factors for depression that adolescents can modify: a systematic review and meta-analysis of longitudinal studies. 2014;169:61–75. doi:10.1016/j.jad.2014.08.006 [CrossRef].
- Bergen SE, Gardner CO, Kendler KS. Age related changes in the heritability of behavioral phenotypes over adolescence and young adulthood: a meta-analysis. Twin Res Hum Genet. 2007;10:423–433. doi:. doi:10.1375/twin.10.3.423 [CrossRef]
- Nomura Y, Wickramaratne PJ, Warner V, Mufson L, Weissman MM. Family discord, parental depression, and psychopathology in offspring: ten-year follow-up. J Am Acad Child Adolesc Psychiatry. 2002;41:402–409. doi:. doi:10.1097/00004583-200204000-00012 [CrossRef]
- Kovacs M, Akiskal S, Gatsonis C, Parronte PL. Childhood-onset dysthymic disorder. Arch Gen Psychiatry. 1994;51:365–374. doi:10.1001/archpsyc.1994.03950050025003 [CrossRef]
- Kaufman J, Martin A, King RA, Charney D. Are child, adolescent and adult onset depression one and the same disorder?Biol Psychiatry. 2001;49:980–1001. doi:10.1016/S0006-3223(01)01127-1 [CrossRef]
- Capsi A, Sugden K, Moffitt T, et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003;301:386–389. doi:. doi:10.1126/science.1083968 [CrossRef]
- Angold A, Costello EJ, Erkanali A. Comorbidity. J Child Psychol Psychiatry. 1999;40:57–87. doi:10.1111/1469-7610.00424 [CrossRef]
- Choe C, Emslie G, Mayes T. Depression. Child Adolesc Psychiatric Clin N Am. 2012;21:807–829. doi:. doi:10.1016/j.chc.2012.07.002 [CrossRef]
- Birmaher B, Brent DA, Kolko D, et al. Clinical outcome after short term psychotherapy for adolescents with major depressive disorder. Arch Gen Psychiatry. 2000;57:29–36. doi:10.1001/archpsyc.57.1.29 [CrossRef]
- Emslie GJ, Rush AJ, Weinberg WA, Kowach RA, Carmody T, Mayes FL. Fluoxetine in child and adolescent depression: acute and maintenance treatment. Depress Anxiety. 1998;7:32–39. doi:10.1002/(SICI)1520-6394(1998)7:1<32::AID-DA4>3.0.CO;2-7 [CrossRef]
- Frank E, Prien RF, Jarrett RB, et al. Conceptualization and rationale for consensus definitions of terms in major depressive disorder: remission, recovery, relapse, and recurrence.Arch Gen Psychiatry. 1991;48:851–855. doi:10.1001/archpsyc.1991.01810330075011 [CrossRef]
- Birmaher B, Brent D, AACAP Work Group on Quality Issues et al. Practice parameter for the assessment and treatment of children and adolescents with depressive disorders. J Am Acad Child Adolesc Psychiatry. 2007;46:1503–1526. doi:. doi:10.1097/chi.0b013e318145ae1c [CrossRef]
- Weisz JR, McCarty CA, Valeri SM. Effects of psychotherapy for depression in children and adolescents: a meta-analysis. Psychol Bull. 2006;132:132–149. doi:. doi:10.1037/0033-2909.132.1.132 [CrossRef]
- Compton SN, March JS, Brent D, Albano AM 5th, Weersing R, Curry J. Cognitive behavioral psychotherapy for anxiety and depressive disorders in children and adolescents: an evidence based medicine review. J Am Acad Child Adolesc Psychiatry. 2004;43:930–959. doi:10.1097/01.chi.0000127589.57468.bf [CrossRef]
- Brent DA, Kolko D, Birmaher B, et al. Predictors of treatment efficacy in a clinical trial of three psychosocial treatments for adolescent depression. J Am Acad Child Adolesc Psychiatry.1998;37:906–914. doi:. doi:10.1097/00004583-199809000-00010 [CrossRef]
- Maalouf FT, Brent DA. Child and adolescent depression intervention overview: what works, for whom and how well?Child Adolesc Psychiatric Clin N Am. 2012;21:299–312. doi: . doi:10.1016/j.chc.2012.01.001 [CrossRef]
- March J, Silva S, Petrycki S, et al. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression. Treatment for Adolescents with Depression Study (TADS) randomized controlled trial. JAMA. 2004;292:807–820. doi:. doi:10.1001/jama.292.7.807 [CrossRef]
- Kennard B, Silva S, Vitello B, et al. Remission and residual symptoms after short-term treatment in the Treatment of Adolescents with Depression Study (TADS). J Am Acad Child Adolesc Psychiatry. 2006;45:1404–1411. doi:. doi:10.1097/01.chi.0000242228.75516.21 [CrossRef]
- Bridge JA, Lyengar S, Salary CB, et al. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA. 2007;297:1683–1696. doi:. doi:10.1001/jama.297.15.1683 [CrossRef]
- Turnipseed B, Magid M. Antidepressants and suicide risk: considerations in treating patients with major depression. Hosp Physician. 2008; http://www.turner-white.com/memberfile.php?PubCode=hp_may08_suicide.pdf. Accessed September 20, 2017.
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- Vitello B, Emslie G, Clarke G, et al. Long-term outcome of adolescent depression initially resistant to selective serotonin reuptake inhibitor treatment: a follow-up study of the TORDIA sample. J Clin Psychiatry. 2010;72:388–396. doi:. doi:10.4088/JCP.09m05885blu [CrossRef]
Assessment of Depressive Disorders
Comprehensive psychiatric evaluation from multiple informants with cultural sensitivity
Current depressive symptoms
Functioning (social, academic)
Stressors (past and ongoing)
Safety assessment including inquiry about access to guns
Family functioning assessment
Strengths and weaknesses
Review of other psychiatric symptoms
Mental status examination
Risk assessment (suicidality and homicidality)
Trauma and other stressors
Physical screening and laboratory tests
Consider laboratory tests such as thyroid profile, complete blood count, and other laboratory assessments
Child Depression Rating Scale
Columbia Suicidal Severity Rating Scale
Other psychological testing as indicated
Differential Diagnosis of Depressive Disorders
Oppositional defiant disorder
Substance use 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
Other endocrine disorders
Treatment for Depressive Disorders
Supportive psychotherapeutic management
Treatment of comorbid conditions
Adequate monitoring and follow-up