Burden of Disease

Although it is normal for children and adolescents to experience occasional feelings of sadness and other symptoms of depression, those with MDD have 1 or more major depressive episodes that last at least 2 weeks and cause significant functional impairment across social, occupational, or educational domains. In some children and adolescents with MDD, these symptoms may present as periods of disruptive mood and irritability rather than as a sad mood and may last for weeks, months, or even years. Major depressive disorder is associated with significant morbidity and mortality. Morbidity in children and adolescents may be demonstrated through decreased school performance, poor social functioning, early pregnancy, increased physical illness, and substance abuse. Depressed adolescents have more psychiatric and medical hospitalizations than those who are not depressed. Children with depressive disorders have increased health care costs (including general medical and mental health care) compared with those without mental health diagnoses or those with other mental health diagnoses (except conduct disorder). Major depressive disorder also increases the risk for suicide. Ten percent of children aged 5 to 12.9 years and 19% of adolescents aged 13 to 17.9 years with MDD attempt suicide.2

The mean age of onset of MDD in childhood and adolescence is about 14 to 15 years, and onset is earlier in girls than boys. In 2 nationally representative U.S. surveys, about 8% of adolescents reported having MDD in the past year. Little is known about the prevalence of the disorder in children. The 2005 National Health and Nutrition Examination Survey found that among children and adolescents aged 8 to 15 years, 2% of males and 4% of females reported having MDD in the past year. However, the prevalence of depression in primary care settings is often higher in studies with community samples of children and adolescents. Only 36% to 44% of children and adolescents with depression receive treatment, suggesting that the majority of depressed youth are undiagnosed and untreated.3

Scope of Review

The USPSTF commissioned a systematic evidence review to update its 2009 recommendation on screening for child and adolescent MDD among primary care populations.3, 4 To focus on the population most likely to benefit from screening and intervention, the scope of the review was narrowed to focus on screening for and treatment of MDD. In addition, studies of paroxetine were excluded because of the 2003 FDA recommendation that it not be used to treat MDD in children and adolescents because of reports of possible suicidal ideation and suicide attempts in children and adolescents receiving paroxetine for depression. As a result, many studies included in the 2009 review were not included in the updated review. The USPSTF examined the evidence on the benefits and harms of screening; the accuracy of primary care–feasible screening tests; and the benefits and harms of treatment with psychotherapy, medications, and collaborative care models in patients aged 7 to 18 years. Treatment studies were limited to those that were implemented in or received referrals from primary care settings to ensure that the patient population was similar to those who would be identified through screening.

Accuracy of Screening Tests

The USPSTF found 5 good- or fair-quality studies of the accuracy of MDD screening instruments in children and adolescents. One study recruited adolescents from a primary care setting and compared the PHQ-A with a full diagnostic interview by a mental health professional. Four studies recruited adolescents from school settings and compared the screening test with a diagnostic interview or a different screening test. One study evaluated the BDI, 1 evaluated the Center for Epidemiologic Studies Depression Scale (CES-D), 1 evaluated the BDI and the CES-D, and 1 evaluated the Clinical Interview Schedule–Revised. No studies included children younger than 11 years.

The PHQ-A study had the highest positive predictive value. The authors did not report a diagnostic cutoff score but reported sensitivity of 73% and specificity of 94% for a positive test result.5 Results were not stratified by age, sex, or ethnicity. The 2 BDI studies reported sensitivity ranging from 84% to 90% and specificity ranging from 81% to 86% when a cutoff score of 11 was applied.6, 7 One study7 reported a higher area under the curve for males than for females, but neither of the BDI studies reported results by age or ethnicity.

The CES-D studies used different diagnostic cutoff scores.7, 8 One study enrolled a slightly younger population than the other (age range of 11 to 15 years vs. average age >16 years). Sensitivity ranged from 18% to 84% and specificity ranged from 38% to 83%, depending on the cutoff score used. Results by sex were inconsistent, and neither study stratified results by age or ethnicity. One study evaluated the Clinical Interview Schedule–Revised.9 The mean age was 15.7 years, and sensitivity and specificity were 18% and 97%, respectively. The study did not report other outcomes or stratify results by age, race, or ethnicity.

Effectiveness of Treatment

The USPSTF found 8 fair- or good-quality RCTs that reported health outcomes in children or adolescents with screen-detected MDD who were treated with SSRIs (4 RCTs), psychotherapy (2 RCTs), SSRIs combined with psychotherapy (1 RCT), or collaborative care (1 RCT). Most trials were restricted to adolescents aged 12 to 14 years or older; only 2 of the SSRI trials included children aged 7 or 8 years. Outcomes included treatment response, which was defined differently across studies; symptom severity; and global functioning. Depression outcomes were reported after 8 to 12 weeks of SSRI treatment or psychotherapy, whereas the collaborative care study reported outcomes at 52 weeks.

SSRIs

One good-quality study (n = 221) compared fluoxetine with placebo in adolescents aged 12 to 17 years.10-12 Two fair-quality studies (n = 268 and 316) compared escitalopram with placebo in children and adolescents13 and adolescents only.14 One fair-quality study (n = 178) compared citalopram with placebo in children and adolescents.15 The absolute difference in response favored SSRIs in all 4 studies (range, 2.4% to 25%) and was significant in 2 of the 4 trials. When other outcomes, such as symptom severity or global functioning, were reported, they also favored the SSRI group. One trial examined the efficacy of escitalopram by age group (children vs. adolescents) and found that it was superior to placebo in improving depression symptoms, depression symptom severity, and global functioning in adolescents but not children.13 No trials examined efficacy across sex or race/ethnicity subgroups.

Psychotherapy

Two studies evaluated the benefits of cognitive behavioral therapy (CBT) compared with placebo (waitlist control or clinical monitoring) in adolescents with MDD and reported nonsignificant improvements in response (43.2% vs. 34.8%) and recovery (odds ratio [OR], 2.15 [95% CI, 0.87 to 5.33]).10, 11, 16 Results for remission (16% vs. 17%) did not differ significantly between groups.

SSRIs Combined With Psychotherapy

One CBT study also compared CBT plus fluoxetine with placebo.10 The CBT plus fluoxetine group showed a 71% response rate versus a 35% response rate in the placebo group, which received a placebo drug and weekly clinical monitoring (P = 0.001).

Collaborative Care

One recent RCT (n = 101) evaluated a 12-month collaborative care intervention in adolescents aged 13 to 17 years who screened positive for depression (60% with MDD) in 9 primary care clinics within 1 health system.17 The intervention was based on the IMPACT (Improving Mood–Promoting Access to Collaborative Treatment) model and was adapted for adolescents. Patients randomly assigned to the collaborative care group had an initial in-person session that included their parents, choice of treatment type, and regular follow-up with depression care managers (28% received psychotherapy alone, 4% received pharmacotherapy alone, and 54% received both). Patients randomly assigned to the usual care control group received screening results and could access mental health services through the usual health care system. Compared with the control group, patients in the collaborative care group had greater reductions in depressive symptoms at 6 and 12 months (8.5- and 9.4-point reductions on the Children’s Depression Rating Scale–Revised, respectively; P < 0.0001 for interaction), better response rates (≥50% score reduction from baseline) at 12 months (OR, 3.3 [CI, 1.4 to 8.2]) and 6 months (not significant), and higher likelihood of remission at 6 months (OR, 5.2 [CI, 1.6 to 17.3]) and 12 months (OR, 3.9 [CI, 1.5 to 10.6]).

Potential Harms of Screening and Treatment

The USPSTF found no direct evidence on the harms of screening for MDD in adolescents or children.

SSRIs

Five SSRI trials reported on harms and found no significant differences between intervention groups, although none of these studies were powered to detect these differences. Four trials (2 for escitalopram, 1 for citalopram, and 1 for fluoxetine) reported on suicidality (this included worsening suicidal ideation or a suicide attempt; no completed suicides were reported). No studies found significant differences but, again, none were sufficiently powered for this outcome. No studies examined subgroup differences in harms. The USPSTF found no evidence on the long-term (>12 weeks) effects of SSRIs.

Psychotherapy

One CBT trial reported on harms and found no apparent differences in harms-related, suicide-related, or psychiatric adverse events between the CBT and placebo groups.10

SSRIs Combined With Psychotherapy

The same trial also reported on the harms of CBT plus fluoxetine versus placebo and found no apparent differences.10

Collaborative Care

The single trial of collaborative care found no differences in the number of psychiatric hospitalizations between the intervention and control groups (6% vs. 4%). More patients in the control group had an emergency department visit with a primary psychiatric diagnosis (10% vs. 2%). However, this study was not powered to detect differences.17

Estimate of Magnitude of Net Benefit

The USPSTF found adequate evidence that screening tests can accurately identify MDD in adolescents. It also found adequate evidence that treatment of adolescents with screen-detected MDD is associated with beneficial reductions in symptoms. Although the data are limited, the USPSTF concludes that the evidence on the frequency of medication-related adverse events in adolescents is adequate to estimate that the magnitude of harms of pharmacotherapy is small if patients are closely monitored. The USPSTF concludes that the evidence on the harms of psychotherapy and collaborative care in adolescents is adequate to estimate that the magnitude of harms is small to none. Therefore, the USPSTF concludes with moderate certainty that screening for MDD in adolescents aged 12 to 18 years is associated with moderate net benefit.

The USPSTF found inadequate evidence that screening tests can accurately identify MDD in children and inadequate evidence on the effectiveness of treatment for children with screen-detected MDD. As a result, the USPSTF concludes that the evidence is insufficient to make a recommendation on screening for MDD in children aged 7 to 11 years.

Response to Public Comment

A draft version of this recommendation statement was posted for public comment on the USPSTF Web site from 8 September to 5 October 2015. Many comments focused on the phrase “adequate systems.” Some commenters requested a more detailed definition of what constitutes an adequate system for screening, others recommended removing the conditional term “when,” and others recommended that the requirement for adequate systems be stronger. To clarify the recommendation, the USPSTF separated it into 2 statements: one to support screening, and a second to explain how screening should be implemented. The USPSTF also revised the section on implementation to clarify that a range of staff types, organizational arrangements, and settings can support the goals of depression screening.