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Draft Recommendation Statement

Depression in Children and Adolescents: Screening

September 07, 2015

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

Importance

Depression is a leading cause of disability in the United States. Children and adolescents with MDD typically have functional impairments in their performance at school or work, as well as in their interactions with their families and peers. Depression can also negatively affect the developmental trajectories of affected youth. MDD in children and adolescents is strongly associated with recurrent depression in adulthood; other mental disorders; and increased risk for suicidal ideation, suicide attempts, and suicide completion.

In nationally representative U.S. surveys, about 8% of adolescents reported having major depression in the past year. Little is known about the prevalence of MDD in children. Among children and adolescents ages 8 to 15 years, 2% of males and 4% of females reported having MDD in the past year.

Detection

The USPSTF found adequate evidence that screening instruments for depression can accurately identify MDD in adolescents ages 12 to 18 years in primary care settings. The USPSTF found no studies of screening instruments for depression in children age 11 years and younger in primary care (or comparable) settings, and concluded that the evidence is inadequate.

Benefits of Early Detection and Intervention/Treatment

The USPSTF found no studies that directly evaluated whether screening for MDD in adolescents in primary care (or comparable) settings leads to improved health and other outcomes. However, the USPSTF found adequate evidence that treatment of MDD detected through screening in adolescents is associated with moderate benefit (e.g., improved depression severity, depression symptoms, and/or global functioning scores).

The USPSTF found no studies that directly evaluated whether screening for MDD in children age 11 years and younger in primary care (or comparable) settings leads to improved health and other outcomes, and found inadequate evidence on the benefits of treatment in children detected through screening.

Harms of Early Detection and Intervention/Treatment

The USPSTF found no direct evidence on the harms of screening for MDD in adolescents. Medications for the treatment of depression, such as selective serotonin reuptake inhibitors (SSRIs), have known harms. However, the magnitude of harms of pharmacotherapy is small if patients are closely monitored, as recommended by the U.S. Food and Drug Administration (FDA). The USPSTF found adequate evidence on the harms of psychotherapy and psychosocial support in adolescents and estimates that the magnitude of these harms is small to none.

The USPSTF found inadequate evidence on the harms of screening for or treatment of MDD in children age 11 years and younger.

USPSTF Assessment

The USPSTF concludes with moderate certainty that screening for MDD in adolescents ages 12 to 18 years has a moderate net benefit.

The USPSTF concludes that the evidence on screening for MDD in children age 11 years and younger is insufficient. Evidence is lacking, and the balance of benefits and harms cannot be determined.

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Patient Population Under Consideration

This recommendation applies to children and adolescents age 18 years and younger who do not have a diagnosis of MDD. This recommendation focuses on screening for MDD and does not address screening for other depressive disorders, such as minor depression or dysthymia.

Assessment of Risk

The USPSTF recommends screening for MDD in all adolescents, but notes that several risk factors might help identify patients who are at higher risk for MDD. The causes of MDD are not fully known and likely involve a combination of genetic, biologic, and environmental factors. Risk factors for MDD in children and adolescents include female sex, older age, family (especially maternal) history of depression, prior episode of depression, other mental health/behavioral problems, chronic medical illness, overweight and obesity, and, in some studies, Hispanic race/ethnicity. Other psychosocial risk factors for MDD include childhood abuse or neglect, exposure to traumatic events (including natural disasters), loss of a loved one or romantic relationship, family conflict, uncertainty about sexual orientation, low socioeconomic status, and poor academic performance.

Screening Tests

Numerous instruments have been developed for use in primary care and have been used in adolescents. Two of the most often studied instruments are the Patient Health Questionnaire for Adolescents (PHQ-A) and the primary care version of the Beck Depression Inventory (BDI). Data on the accuracy of MDD screening instruments in younger children are limited.

Screening Intervals

The USPSTF found no evidence on appropriate or recommended screening intervals, and the optimum screening interval is unknown. Repeat screening may be most productive in adolescents with MDD risk factors. Opportunistic screening may be appropriate for adolescents, who may have infrequent health care visits.

Treatment or Interventions

Treatment options for MDD in children and adolescents include pharmacotherapy, psychotherapy, collaborative care, psychosocial support interventions, and complementary and alternative medicine approaches. Fluoxetine is approved by the FDA to treat MDD in children age 8 years and older, and escitalopram is approved to treat MDD in adolescents ages 12 to 17 years. The FDA has issued a black box warning for antidepressants, recommending that patients of all ages who start antidepressant therapy be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior.1 Collaborative care is a multicomponent, health care system–level intervention that uses case managers to link primary care providers, patients, and mental health specialists.

Suggestions for Practice Regarding the I Statement

In deciding whether to screen for MDD in children age 11 years and younger, primary care providers may want to consider the following issues.

Potential Preventable Burden

Little is known about the prevalence of MDD in children age 11 years and younger. The mean age of onset of MDD is about 14 to 15 years. Early onset is associated with worse outcomes. The average duration of a depression episode in childhood varies widely, from 2 to 17 months.

Potential Harms

The USPSTF found inadequate evidence on the harms of screening for MDD in children. The USPSTF concluded that MDD screening itself is unlikely to be associated with significant harms, aside from opportunity costs, labeling and potential stigma associated with a positive screening result, and referral for further evaluation and treatment.

Based on a previous review, the USPSTF concluded that the use of SSRIs in children is associated with harms, specifically risk for suicidality. Evidence on the harms of psychotherapy and the combination of psychotherapy and SSRIs in children is limited. Newer studies do not provide much additional evidence on treatment harms in children and adolescents, but do not suggest more risks. Only four studies examined the harms of treatment with SSRIs in children and adolescents. These studies found no increased risk for suicidality associated with antidepressant use. However, risk for rare events could not be precisely determined because the studies had limited statistical power. No trials of psychotherapy or combined interventions in children examined harms.

Current Practice

The USPSTF found no evidence on the current frequency of or methods used in primary care for screening for MDD in children.

Additional Approaches to Prevention

The Community Preventive Services Task Force recommends collaborative care for the management of depressive disorders, based on strong evidence of effectiveness in improving depression symptoms, adherence and response to treatment, and remission and recovery from depression. For this and other related recommendations from the Community Preventive Services Task Force, go to www.thecommunityguide.org/mentalhealth/index.html.

Useful Resources

In a separate recommendation statement, the USPSTF concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening for suicide risk in primary care settings, including among adolescents (I statement). Other USPSTF recommendations on mental health topics pertaining to children and adolescents, including illicit drug and alcohol use, can be found on the USPSTF Web site (www.uspreventiveservicestaskforce.org).

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Implementation

Many different screening tools are available to identify depression in children and adolescents, and some have been used in primary care. The number of items, administrative time to complete screening, and appropriate ages for screening vary. Screening positive on an initial screening test does not necessarily indicate the need for treatment. Screening is usually done in two phases: the initial screening is followed by a second phase in which skilled clinicians take into account contextual factors surrounding the patient’s current situation, either through additional probing or a formal diagnostic interview. In instances where treatment is recommended, treatment can be initiated either by the screening provider or through referral to another set of treatment providers. Screening negative on a screening test, however, does not always preclude referral when clinical judgment or parental concerns suggest otherwise.

Research Needs and Gaps

The systematic evidence review identified several critical research gaps, including the need for studies of screening for and treatment of MDD in children younger than age 11 years. Large, good-quality randomized, controlled trials (RCTs) are also needed to better understand the overarching effects of screening for MDD on intermediate and long-term health outcomes. It would be helpful to quantify the proportion of screen-detected individuals who are treated or referred, as well as their willingness and ability to obtain assessment and treatment.

The systematic review had eligibility requirements that excluded studies with subjects who had comorbid disorders. Children and adolescents with MDD more often have comorbid conditions than children and adolescents without MDD, particularly in primary care settings. This underscores the importance of additional research in child and adolescent populations that are similar to populations found in primary care settings to study the effects of comorbid conditions on screening accuracy, type of MDD treatment selected, and benefits and harms.

For treatment of MDD, research needs include well-designed studies of psychotherapy and combined treatments, as well as studies of the benefits and harms of other treatments (e.g., nonSSRI medications and complementary/alternative modalities). For rare events, meta-analyses are needed that include only children and adolescents with MDD and focus on current FDA-approved medications. Studies with long-term followup are also needed.

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Burden of Disease

Although it is normal for children and adolescents to experience occasional feelings of sadness and other symptoms of depression, children and adolescents with MDD experience one or more major depressive episodes, lasting at least 2 weeks, that 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. MDD 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 adolescents who are not depressed. Children with depressive disorders have increased health care costs (including general medical care and mental health care) compared with children without mental health diagnoses or children with other mental health diagnoses (except conduct disorder). MDD also increases the risk for suicide. Ten percent of children ages 5 to 12.9 years and 19% of adolescents ages 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 two nationally representative U.S. surveys, about 8% of adolescents reported having MDD in the past year. Little is known about the prevalence of MDD in children. The 2005 National Health and Nutrition Examination Survey found that among children and adolescents ages 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 objective of the review was to update the 2009 USPSTF recommendation on screening for child and adolescent MDD among primary care populations. In order 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 paroxetine not be used to treat MDD in children and adolescents because of reports of possible suicidal ideation and suicide attempts in children and adolescents taking paroxetine for depression. As a result, a number of studies included in the 2009 review were not included in the current 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 ages 7 to 18 years. Treatment studies were limited to those that were implemented in primary care settings or received referrals from primary care settings to ensure that the population was similar to those who would be identified through screening.

Accuracy of Screening Tests

The USPSTF found five 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 different depression screening test. One study evaluated the BDI, one study evaluated the Center for Epidemiologic Studies Depression Scale (CES-D), one study evaluated the BDI and the CES-D, and one study evaluated the Clinical Interview Schedule–Revised. No studies included children younger than age 11 years.

The PHQ-A study had the highest positive predictive value. The authors did not report a diagnostic cutoff but reported sensitivity for a positive test of 73% and specificity of 94%.4 Results were not stratified by age, sex, or ethnicity. The two BDI studies reported sensitivity ranging from 84% to 90% and specificity ranging from 81% to 86% when a cutoff of 11 was applied.5, 6 One study6 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 cutoffs.6, 7 One study enrolled a slightly younger population than the other (range of 11 to 15 years vs. average age of >16 years). Sensitivity ranged from 18% to 84%  and specificity ranged from 38% to 83%, depending on the cutoff used. Results by sex were inconsistent, and neither study stratified results by age or ethnicity. One study evaluated the Clinical Interview Schedule–Revised.8 The mean age was 15.7 years and sensitivity and specificity was 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 eight fair- or good-quality RCTs that reported health outcomes in children or adolescents with MDD detected through screening who were treated with SSRIs (four RCTs), psychotherapy (two RCTs), SSRIs combined with psychotherapy (one RCT), or collaborative care (one RCT). The majority of trials were restricted to adolescents ages 12 to 14 years and older; only two of the SSRI trials included children ages 7 or 8 years. Trial 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, while the collaborative care study reported outcomes at 52 weeks.

SSRIs

One good-quality study (n=221) compared fluoxetine with placebo in adolescents ages 12 to 17 years.9-11 Two fair-quality studies (n=268 and 316) compared escitalopram with placebo in children and adolescents12 and adolescents only.13 One fair-quality study (n=178) compared citalopram with placebo in children and adolescents.14 The absolute difference in response favored SSRIs in all four studies, ranging from 2.4% to 25%, and was statistically significant in two of the four trials. When other outcomes, such as symptom severity or global functioning, were reported, they also favored the SSRI group. One trial examined efficacy of escitalopram by age group (children vs. adolescents) and found that escitalopram was superior to placebo in improving depression symptoms, depression symptom severity, and global functioning in adolescents but not children.12 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 nonstatistically significant improvements in response (43.2% vs. 34.8%) or recovery (odds ratio [OR], 2.15 [95% confidence interval (CI), 0.87 to 5.33).9, 10, 15 Results for remission (16% vs. 17%) were not statistically significantly different between CBT and placebo groups.

SSRIs Combined With Psychotherapy

One CBT study also included an arm that compared CBT plus fluoxetine with placebo.9 The CBT plus fluoxetine group showed a 71% response rate versus a 35% response 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 ages 13 to 17 years who screened positive for depression (60% with MDD) in nine primary care clinics within one health system.16 The intervention was based on the IMPACT (Improving Mood–Promoting Access to Collaborative Treatment) model and adapted for adolescents. Patients randomized to the collaborative care group had an initial in-person session that included their parents, choice of treatment type(s), and regular followup with depression care managers (28% received psychotherapy alone, 4% received pharmacotherapy alone, and 54% received both). Patients randomized 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 [95% CI, 1.4 to 8.2]) and 6 months (not statistically significant), and higher likelihood of remission at both 6 and 12 months (OR, 5.2 [95% CI, 1.6 to 17.3] and OR, 3.9 [95% CI, 1.5 to 10.6], respectively).

Potential Harms of Screening and/or 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 statistically significant differences between intervention groups, although none of these studies were powered to detect these differences. Four trials reported on suicidality (this included worsening suicidal ideation or a suicide attempt; no completed suicides were reported)—two for escitalopram, one for citalopram, and one for fluoxetine. No studies found statistically significant differences, although, 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 in the CBT versus placebo groups.9

SSRIs Combined With Psychotherapy

The same trial also reported on the harms of CBT plus fluoxetine versus placebo and found no apparent differences.9

Collaborative Care

The single trial of collaborative care found no differences in psychiatric hospitalizations between the intervention and control groups (6% vs. 4%). More patients in the control group experienced an emergency department visit with a primary psychiatric diagnosis than in the intervention group (10% vs. 2%). However, this study was not powered to detect differences.16

Estimate of Magnitude of Net Benefit

The USPSTF found adequate evidence that screening tests can accurately identify MDD in adolescents. The USPSTF also found adequate evidence that treatment of adolescents identified through screening is associated with beneficial reductions in MDD 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 ages 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 identified through screening. As a result, the USPSTF concludes that the evidence is insufficient to make a recommendation regarding screening for MDD in children ages 7 to 11 years.

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In 2009, the USPSTF recommended screening for MDD in adolescents (ages 12 to 18 years) when systems are in place to ensure accurate diagnosis, psychotherapy (CBT or interpersonal), and followup, and concluded that the evidence was insufficient to make a recommendation regarding children (ages 7 to 11 years). The current recommendation reaffirms these positions, but removes the mention of specific therapies in recognition of decreased concern over the harms of pharmacotherapy in adolescents when patients are adequately monitored.

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The American Academy of Pediatrics’ Bright Futures program recommends screening annually in child and adolescent patients for emotional and behavioral problems.17 Medicaid’s child health component, the Early and Periodic Screening, Diagnosis, and Treatment program, recommends screening to detect physical and mental conditions at periodic, age-appropriate intervals and if risk is identified, followup with diagnostic and treatment coverage.18 The American Academy of Family Physicians recommends screening for MDD in adolescents (ages 12 to 18 years) when systems are accessible to ensure accurate diagnosis, treatment (psychotherapy), and followup.19 The Canadian Task Force on Preventive Health Care states that there is insufficient evidence to recommend for or against screening for depression in children or adolescents in primary care settings.20

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1. U.S. Food and Drug Administration. Antidepressant Use in Children, Adolescents, and Adults: Revisions to Product Labeling. 2007. Accessed at http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM173233.pdf on August 21, 2015.
2. Kramer T, Iliffe S, Gledhill J, et al. Recognising and responding to adolescent depression in general practice: developing and implementing the Therapeutic Identification of Depression in Young People (TIDY) programme. Clin Child Psychol Psychiatry. 2012;17(4):482-94.
3. Forman-Hoffman V, McClure E, McKeeman J, et al. Screening for Major Depressive Disorder in Children and Adolescents: A Systematic Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 116. AHRQ Publication No. 13-05192-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2015.
4. Johnson JG, Harris ES, Spitzer RL, et al. The Patient Health Questionnaire for Adolescents: validation of an instrument for the assessment of mental disorders among adolescent primary care patients. J Adolesc Health. 2002;30(3):196-204.
5. Canals J, Blade J, Carbajo G, Domenech-Llaberia E. The Beck Depression Inventory: psychometric characteristics and usefulness in nonclinical adolescents. Eur J Psychol Asses. 2001;17(1):63-8.
6. Roberts RE, Lewinsohn PM, Seeley JR. Screening for adolescent depression: a comparison of depression scales. J Am Acad Child Adolesc Psychiatry. 1991;30(1):58-66.
7. Garrison CZ, Addy CL, Jackson KL, et al. The CES-D as a screen for depression and other psychiatric disorders in adolescents. J Am Acad Child Adolesc Psychiatry. 1991;30(4):636-41.
8. Patton GC, Coffey C, Posterino M, et al. A computerised screening instrument for adolescent depression: population-based validation and application to a two-phase case-control study. Soc Psychiatry Psychiatr Epidemiol. 1999;34(3):166-72.
9. 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(7):807-20.
10. Kennard B, Silva S, Vitiello 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(12):1404-11.
11. Vitiello B, Rohde P, Silva S, et al. Functioning and quality of life in the Treatment for Adolescents with Depression Study (TADS). J Am Acad Child Adolesc Psychiatry. 2006;45(12):1419-26.
12. Wagner KD, Robb AS, Findling RL, et al. A randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents. Am J Psychiatry. 2004;161(6):1079-83.
13. Emslie GJ, Ventura D, Korotzer A, et al. Escitalopram in the treatment of adolescent depression: a randomized placebo-controlled multisite trial. J Am Acad Child Adolesc Psychiatry. 2009;48(7):721-9.
14. Wagner KD, Jonas J, Findling RL, et al. A double-blind, randomized, placebo-controlled trial of escitalopram in the treatment of pediatric depression. J Am Acad Child Adolesc Psychiatry. 2006;45(3):280-8.
15. Clarke GN, Rohde P, Lewinsohn PM, et al. Cognitive-behavioral treatment of adolescent depression: efficacy of acute group treatment and booster sessions. J Am Acad Child Adolesc Psychiatry. 1999;38(3):272-9.
16. Richardson LP, Ludman E, McCauley E, et al. Collaborative care for adolescents with depression in primary care: a randomized clinical trial. JAMA. 2014;312(8):809-16.
17. Hagan JF, Shaw JS, Duncan PM, eds. Bright Futures Guidelines for Health Supervision of Infants, Children, and Adolescents. 3rd ed. Elk Grove Village, IL: American Academy of Pediatrics; 2008.
18. Health Resources and Services Administration, Maternal and Child Health. EPSDT Overview. 2015. Accessed at www.mchb.hrsa.gov/epsdt/overview.html on August 21, 2015.
19. American Academy of Family Physicians. Clinical Preventive Service Recommendations: Depression, Children and Adolescents. 2009. Accessed at http://www.aafp.org/patient-care/clinical-recommendations/all/depression.html on August 21, 2015.
20. MacMillan HL, Patterson CJ, Wathen CN. Screening for Depression in Primary Care: Updated Recommendations From the Canadian Task Force on Preventive Health Care. London, Ontario: Canadian Task Force on Preventive Health Care; 2004.

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