Final Evidence Summary
Depression and Suicide Risk in Children and Adolescents: Screening
October 11, 2022
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.
By Meera Viswanathan, PhD; Ina F. Wallace, PhD; Jennifer Cook Middleton, PhD; SaraM. Kennedy, MPH; Joni McKeeman, PhD; Kesha Hudson, PhD; Caroline Rains, MPH; Emily B. Vander Schaaf, MD, MPH; Leila Kahwati, MD, MPH
The information in this article is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This article is intended as a reference and not as a substitute for clinical judgment.
This article may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
This article was published online in JAMA on October 11, 2022 (JAMA. doi:10.1001/jama.2022.16310).
Importance: Depression, suicidal ideation, and self-harm behaviors in youth are associated with functional impairment and suicide.
Objective: To review the evidence on screening for depression or suicide risk in children and adolescents to inform the US Preventive Services Task Force (USPSTF).
Data Sources: PubMed, Cochrane Library, PsycINFO, CINAHL, and trial registries through July 19, 2021; references, experts, and surveillance through June 1, 2022.
Study Selection: English-language, randomized clinical trials (RCTs) of screening for depression or suicide risk; diagnostic test accuracy studies; RCTs of psychotherapy and first-line pharmacotherapy; RCTs, observational studies, and systematic reviews reporting harms.
Data Extraction and Synthesis: Two reviewers assessed titles/abstracts, full-text articles, and study quality and extracted data; when at least 3 similar studies were available, meta-analyses were conducted.
Main Outcomes and Measures: Test accuracy, symptoms, response, remission, loss of diagnosis, mortality, functioning, suicide-related events, and adverse events.
Results: Twenty-one studies (N = 5433) were included for depression and 19 studies (N = 6290) for suicide risk. For depression, no studies reported on the direct effects of screening on health outcomes, and 7 studies (n = 3281) reported sensitivity of screening instruments ranging from 0.59 to 0.94 and specificity from 0.38 to 0.96. Depression treatment with psychotherapy was associated with improved symptoms (Beck Depression Inventory pooled standardized mean difference, −0.58 [95% CI, −0.83 to −0.34]; n = 471; 4 studies; and Hamilton Depression Scale pooled mean difference, −2.25 [95% CI, −4.09 to −0.41]; n = 262; 3 studies) clinical response (3 studies with statistically significant results using varying thresholds), and loss of diagnosis (relative risk, 1.73 [95% CI, 1.00 to 3.00; n = 395; 4 studies). Pharmacotherapy was associated with improvement on symptoms (Children’s Depression Rating Scale–Revised mean difference, −3.76 [95% CI, −5.95 to −1.57; n = 793; 3 studies), remission (relative risk, 1.20 [95% CI, 1.00 to 1.45]; n = 793; 3 studies) and functioning (Children’s Global Assessment Scale pooled mean difference, 2.60 (95% CI, 0.78 to 4.42; n = 793; 3 studies). Other outcomes were not statistically significantly different. Differences in suicide-related outcomes and adverse events for pharmacotherapy when compared with placebo were not statistically significant. For suicide risk, no studies reported on the direct benefits of screening on health outcomes, and 2 RCTs (n = 2675) reported no harms of screening. One study (n = 581) reported on sensitivity of screening, ranging from 0.87 to 0.91; specificity was 0.60. Sixteen RCTs (n = 3034) reported on suicide risk interventions. Interventions were associated with lower scores for the Beck Hopelessness Scale (pooled mean difference, −2.35 [95% CI, −4.06 to −0.65]; n = 644; 4 RCTs). Findings for other suicide-related outcomes were mixed or not statistically significantly different.
Conclusions and Relevance: Indirect evidence suggested that some screening instruments were reasonably accurate for detecting depression. Psychotherapy and pharmacotherapy were associated with some benefits and no statistically significant harms for depression, but the evidence was limited for suicide risk screening instruments and interventions.
Depression and suicidal behaviors have long-term effects involving functional impairment, increased risk for substance abuse, and premature mortality.1-4 Routine screening may result in early identification and treatment. In 2016, the US Preventive Services Task Force (USPSTF) issued a recommendation for screening for major depressive disorder (MDD) in adolescents aged 12 to 18 years (B recommendation).5 The USPSTF also concluded that the current evidence was insufficient to assess the balance of benefits and harms of screening in younger children. In 2014, the USPSTF concluded there was insufficient evidence to assess the balance of benefits and harms of screening for suicide risk in adolescents, adults, and older adults in primary care (I statement).6 This review updated the evidence on screening for depression and suicide risk for children and adolescents to inform updated recommendations by the USPSTF.
Scope of the Review
Data Sources and Searches
PubMed, Cochrane Library, PsycINFO, CINAHL, and ClinicalTrials.gov were searched for English-language articles (eMethods in the Supplement). Depression searches were limited to articles published from January 1, 2015, through July 19, 2021; suicide risk searches were limited to articles published between June 1, 2012, and July 19, 2021. Evidence prior to these dates was identified from existing reviews.9,10 Reference lists of pertinent articles and studies suggested by reviewers were also reviewed. Article alerts and targeted searches of journals to identify major studies published in the interim that may affect the conclusions or understanding of the evidence and the related USPSTF recommendation were used as part of ongoing surveillance. The last surveillance was conducted on June 1, 2022.
Two investigators independently reviewed titles, abstracts, and full-text articles using prespecified criteria for each KQ (eMethods in the Supplement); disagreements were resolved by discussion or by a third reviewer. English-language studies of persons 18 years or younger, on average, that met all study selection criteria, were fair or good methodological quality, and were conducted in countries categorized as very highly developed by the 2018 United Nations Human Development Index11 were eligible. Studies included in the prior reviews for the USPSTF were reassessed against the study selection criteria. For screening, studies that included unselected participants without known risk of depression or increased risk of suicide were eligible. For depression, treatment studies that included at least half of participants with MDD were eligible. For suicide risk, treatment studies were restricted to participants with increased suicide risk. Eligible interventions included psychotherapy or first-line pharmacotherapy approved for pediatric use (eg, clonidine, duloxetine, fluoxetine, escitalopram, sertraline, fluvoxamine). Interventions were required to be relevant to or referable from primary care. Eligible outcomes for benefits of screening and treatment included depression symptoms as measured through validated instruments, clinical response, or remission; suicide deaths, suicide attempts, and deliberate self-harm or suicidal ideation; all-cause mortality; quality of life measured using validated instruments; and functioning (validated scales, days of missed school, sleep-related outcomes). Eligible harms of treatment included treatment avoidance, deterioration in patient-clinician relationship, labeling or stigma, unnecessary treatment, serious adverse effects, withdrawals due to adverse effects, and suicidality.
Data Extraction and Quality Assessment
For each included study, 1 reviewer abstracted relevant study characteristics and outcomes into a structured form. A second reviewer checked all data for completeness and accuracy. Methodological quality ratings for studies included from a prior Agency for Healthcare Research and Quality (AHRQ) evidence review on depression treatment in youth12 were spot-checked and carried forward. All other studies were assessed dually and independently using predefined criteria established by the USPSTF (eMethods in the Supplement) and others.13-16
Disagreements in study quality ratings were resolved through discussion or by a third senior reviewer. Detailed study quality assessments are provided in eTables 1 through 7 in the Supplement.
Data Synthesis and Analysis
Data were synthesized in tabular and narrative forms. When at least 3 similar studies were available, a quantitative synthesis was performed using random-effects models with the inverse-variance weighted method of DerSimonian and Laird in Comprehensive Meta-Analysis version 3.3 to generate pooled estimates of effect.17 The I2 statistic was calculated to assess statistical heterogeneity in effects.18 Significance testing was based on the exclusion of the null value by the 95% CI around the pooled estimate; all testing was 2-sided.
The strength of evidence was assessed as high, moderate, low, or insufficient using methods developed for the USPSTF and the AHRQ Evidence-based Practice Center program.7,19 Two senior reviewers independently developed initial strength-of-evidence assessments; disagreements were resolved through discussion or input of a third senior reviewer.
Forty studies in 54 publications (N = 11,220 from screening accuracy studies and randomized clinical trials [RCTs]) were eligible (Figure 2). For depression, 7 screening test accuracy studies21-27 and 13 treatment RCTs28-47 (N = 5433) were identified in addition to 1 meta-analysis.48 Two studies of screening accuracy,22,25 7 treatment trials,28,32,33,35,37,38,40,42,47 and the meta-analysis48 are new to this update. For suicide risk, 1 screening test accuracy study, 492 studies of screening harms,50,51 and 16 treatment RCTs were identified (N = 6290).52-74 Nine trials are new to this update.52-55,58,60,64-72 The results in this publication focus on pooled analyses when available. Additional results are available in the full report.8 A list of full-text articles that were screened but excluded is provided in the Supplement (List of Excluded Studies).
Benefits of Screening
Key Question 1. Do depression or suicide risk screening programs in primary care or comparable settings result in improved health outcomes in children and adolescents?
No trials directly assessing the benefits of screening children or adolescents in the primary care setting for MDD or suicide risk compared with no screening were found.
Accuracy of Screening Instruments
Key Question 2. Do instruments to screen for depression or suicide risk accurately identify children and adolescents with depression or increased risk of suicide in primary care or comparable settings?
Seven fair-quality studies of diagnostic test accuracy (n = 3316) were included;21-27 2 were new to this update.22,25 Authors assessed 7 different screening instruments (eTables 8 and 9 in the Supplement describe index tests and reference standards, respectively). Some authors assessed more than 1 instrument or more than 1 threshold for a positive screen result for the same instrument, and few studies prespecified thresholds for a positive screen result. All but 1 study25 were restricted to adolescents.
The prevalence of MDD based on reference standard diagnostic clinical interviews ranged from 3% to 9% across studies enrolling persons recruited from school or community-based settings21,23,26,27 and was 11% in all 3 of the studies enrolling persons from nonpsychiatric clinical settings.22,24,25 Table 1 provides a summary of sensitivity and specificity (additional detail is provided in eTable 10 in the Supplement). Excluding 2 outliers,26 the sensitivity across these instruments for identifying MDD ranged from 0.73 to 0.94, and the specificity ranged from 0.38 to 0.97.
One fair-quality study (n = 580) conducted in the US that recruited potential high school dropouts aged 14 to 20 years evaluated the 20-item Suicide Risk Screen (SRS).49 The prevalence of increased suicide risk ranged from 19% to 22%, depending on the reference standard used. The sensitivity and specificity of the SRS compared with one reference standard were 0.91 and 0.60, respectively, and were 0.87 and 0.60 against another reference standard.49
Harms of Screening
Key Question 3. What are the harms associated with screening for depression or suicide risk in primary care or comparable settings in children and adolescents?
No trials directly assessing the harms of screening children or adolescents in the primary care setting for MDD compared with no screening were found.
Benefits of Treatment
Key Question 4. Does treatment (psychotherapy, pharmacotherapy, or collaborative care) of depression or suicide risk result in improved health outcomes in children and adolescents? Benefits of treatment for depression and increased suicide risk are summarized in Table 2.
Thirteen fair-quality RCTs (20 publications) were identified (n = 2152).28-47 Seven RCTs28,32,33,35,37,38,40,42,47 were new in this update. Key characteristics of included depression studies are provided in eTable 11 in the Supplement, detailed outcomes are provided in eTables 12 through 27 in the Supplement, and results from meta-analyses are provided in eFigures 1 through 8 in the Supplement.
Eleven RCTs enrolled youth meeting Diagnostic and Statistical Manual (DSM) criteria for MDD.28,29,31,33-40 Two RCTs enrolled a sample in which more than 50% of participants met DSM criteria for MDD but also admitted youth with MDD, dysthymia, or depressive disorder not otherwise specified.30,32 Mean ages ranged from 5 to 17.5 years.33,38,42 One RCT focused on early childhood (3-6 years),33,42 2 focused on school-aged children and adolescents (ages ranged from 7-14 years and 6-17 years),32,39 and 10 focused on adolescents (ages ranged from 12-17 years and 15-19 years).28-31,34-38,40 Two had majority male participants.32,33,42
Two pharmacotherapy trials compared escitalopram with placebo.31,39 One 3-group trial compared fluoxetine, cognitive behavioral therapy (CBT), and placebo.34 One trial compared collaborative care with enhanced usual care.36 Six studies focused on CBT,28-30,32,37,38 and 3 focused on counseling other than CBT.33,35,40 Comparisons included treatment as usual, wait-list, placebo, attention control, and supportive contact. The results reported here focus on psychotherapy and pharmacotherapy trials; detailed results for collaborative care and combination therapy are available in the full report.8
Outcomes reported included (1) depression symptoms; (2) response, remission, or loss of diagnosis; and (3) quality of life and functioning. Regarding depression symptoms, pooled estimates suggested improved symptoms associated with psychotherapy (Beck Depression Inventory [BDI] pooled standardized mean difference, −0.58 [95% CI, −0.83 to −0.34]; n = 471; 4 RCTs30,35,37,38 and Hamilton Depression Scale pooled mean difference, −2.25 [95% CI, −4.09 to −0.41]; n = 262; 3 RCTs29,30,35) or pharmacotherapy (Children’s Depression Rating Scale– Revised mean difference, −3.76 [95% CI, −5.95 to −1.57]; n = 793; 3 RCTs31,34,39) in some but not all measures of symptom severity. Regarding clinical response, 3 studies reported responses on the BDI and BDI-II (BDI version 2) scale35,37,38 favoring pharmacotherapy but results could not be pooled because of the various thresholds used. Results favored pharmacotherapy for remission (relative risk [RR], 1.20 [95% CI, 1.00 to 1.45]; n = 793; 3 RCTs31,34,39,45) and psychotherapy for loss of diagnosis (RR, 1.73 [95% CI, 1.00 to 3.00]; n = 395; 4 RCTs30,34,37,38), but CIs included the null. Studies reported improved functioning, measured by the Children’s Global Assessment Scale for pharmacotherapy (mean difference, 2.60 [95% CI, 0.78 to 4.42]; n = 793; 3 RCTs31,34,39) but not for psychotherapy (mean difference, 1.52 [95% CI, −1.54 to 4.58]; n = 601; 4 RCTs).28,29,34,35
Two psychotherapy studies focused on or included children; 1 reported improvements in symptoms, loss of diagnosis, and functioning,33 and a second reported no differences for symptoms or remission.32 One pharmacotherapy study that included children reported no differences in symptoms, response, or functioning.39
Sixteen RCTs of good or fair quality (described in 23 articles) were identified.52-74 Nine were new to this update (n = 3034).52-55,58,60,64-72 Key characteristics of included studies are described in eTable 28 in the Supplement, detailed outcomes included in pooled results are provided in eTables 29 and 30 in the Supplement, and results from meta-analyses are provided in eFigures 9 through 15 in the Supplement.
Fourteen studies enrolled adolescents based on elevated suicide risk,52-55,57-72,74 and 2 studies admitted adolescents with suicide risk and self-reported depressive symptoms (BDI >1973 or BDI >2056). Mean ages ranged from 14 to 18 years. All included studies focused on adolescents52-74 and included a majority of female participants.
All included studies examined psychotherapy, counseling, support, or a combination with variable intensity and duration. Fifteen studies compared these interventions with treatment as usual,52-59,61-74 which often included active psychosocial treatment, and 1 study compared the intervention with attention control.60 Duration of treatment ranged between 1 single session to weekly sessions over 12 months. No evidence was captured that examined pharmacotherapies.
Outcomes reported included (1) suicide deaths, (2) suicide attempts and deliberate self-harm or suicidal ideation, (3) all-cause mortality, and (4) functioning. Three studies reported no deaths or no statistically significant differences in suicide deaths at the end of treatment (19 weeks to 12 months).57,62,65-68 Pooled results for suicide attempt, deliberate self-harm, or suicidal ideation generally indicated no statistically significant differences for self-harm events (RR of self-harm events, 0.88 [95% CI, 0.63 to 1.24]; n = 1040; 5 RCTs;53-55,57,59,72,74 mean difference in self-harm events,−0.76 [95% CI, −2.15 to 0.63]; n = 972; 3 RCTs53-55,65-68,74) or suicide-related hospitalization or emergency use (RR, 1.00 [95% CI, 0.67 to 1.50]; n = 978; 3 RCTs53-55,65-70). The exception was measures of suicidal ideation: studies reported benefits associated with the intervention on the Beck Hopelessness Scale (mean difference, −2.35 [95% CI, −4.06 to −0.65]; n = 644; 4 RCTs62,64-68,73). Pooled results for the Suicidal Ideation Questionnaire (SIQ) and SIQ-Junior scales also favored the intervention group but were not statistically significantly different (standardized mean difference,−0.18 [95% CI, −0.36 to 0.01]; n = 1111; 7 RCTs56,57,59,62,64-68,74). Regarding all-cause mortality, a long-term follow-up of a study on a youth-nominated support team approach,62 11 to 14 years after psychiatric hospitalization for suicide risk (baseline for the study), found a higher number of deaths in the National Death Index in the treatment-as-usual group when compared with the active treatment group (13/225 vs 2/223; hazard ratio,6.62 [95% CI, 1.49 to 29.35]).63 The same study did not demonstrate an effect on the primary outcome of suicidal ideation; as a result, findings by chance or through other mechanisms of action (such as improved problem solving) cannot be ruled out. The studies reported no statistically significant differences in functioning on the Health of the Nation Outcome Scales for Children and Adolescents (mean difference, −0.40 [95% CI, −2.55 to 1.78]; n = 509; 4 RCTs57,59,71,74) or the Children’s Global Assessment Scale (mean difference, 1.30 [95% CI, −2.52 to 5.12]; n = 195; 3 RCTs59,66,70).
Harms of Treatment
Key Question 5. What are the harms of treatment (psychotherapy, pharmacotherapy, or collaborative care) in children and adolescents who are treated for depression or suicide risk?
Seven studies (described in 12 articles) were included (n = 1408 from primary studies).28,31,34,36,39-41,43-46,48 All 7 studies are also included in the discussion of benefits except for 1 meta-analysis, which was new to this update.48 Key characteristics of included depression studies are provided in eTable 31 in the Supplement, and detailed outcomes are provided in eTables 32 through 40 in the Supplement. Studies reported on suicide-related events (suicide deaths, attempts, deliberate self-harm, or suicidal ideation) and other adverse events. Regarding psychotherapy, the Treatment of Adolescents With Depression (TADS) trial with 2 active interventions (CBT and fluoxetine) reported varying results in the placebo group in different publications; as a result, the relative risk of suicide-related outcomes could not be calculated with certainty. A second trial reported 5 of 106 (4.7%) suicide-related events for CBT plus treatment as usual vs 2 of 106 (1.9%) for treatment as usual alone;28 differences were not statistically significant. For pharmacotherapy, inconsistent reporting across different publications on harms from the TADS trial led to uncertainty regarding the relative risk of suicide-related outcomes with fluoxetine vs placebo. Other evidence for escitalopram studies indicated rates of suicide-related outcomes that are not statistically significantly different compared with placebo (1/129 [0.8%] vs 2/132 [1.5%];39 6/57 [3.8%] vs 6/155 [3.9%]31). The meta-analysis also reported similar rates for escitalopram vs placebo (15/290 [5%] vs 15/294 [5%]; 2 studies) and fluoxetine vs placebo (51/521 [10%] vs 44/514 [9%]; 7 studies).48 No statistically significant differences were reported for other harms for psychotherapy (deteriorated on the Quick Inventory of Depressive Symptomatology for Adolescents: 1 vs 340; harm-related adverse events: 5/111 participants [4.5%] vs 6/112 participants [5.4%]; OR, 0.80 [95% CI, 0.25 to 2.81]34). For pharmacotherapy, 2 escitalopram trials reported no statistically significant differences for withdrawals (4/155 [2.6%] vs 1/157 [0.6%];31 2/131 [1.5%] vs 2/133 [1.5%]39) or serious adverse events (4/155 [2.6%] vs 2/157 [1.3%];31 2/131 [1.5%] vs 3/133 [2.3%]39). The TADS trial reported a higher but not statistically significant difference in adverse events for fluoxetine compared with placebo (13/109 participants [11.9%] vs 6/112 [5.4%]; OR, 2.4 [95% CI, 0.87 to 6.54]).34
Two studies53-55,58 reported on adverse events (n = 885). One study53-55 reported on adverse events, serious adverse events, and other harms during the 12- to 18-month follow-up period. Similar numbers of adverse events, including attendance at minor injury units, walk-in centers, and accident and emergency centers and rereferral to mental health services, occurred in the family therapy group (54%) and treatment-as-usual group (52%). Serious adverse events, defined as hospital attendance, also occurred at similar rates across the intervention (38%) and control (34%) groups. Two participants assigned to the family therapy group died between 3 and 4 years after randomization. Neither death was related to self-harm. One additional study58 reported 5 adverse events among 4 participants, but the occurrences were not considered trial-related and were not reported by group.
This systematic review evaluated screening for depression and suicide risk in children and adolescents. Table 3 summarizes the evidence, including strength-of-evidence ratings. No studies reported on the direct benefits or harms of screening. The discussion below focuses on the indirect evidence from studies describing test accuracy, benefits of treatment, and harms of treatment.
The standard of evidence for test accuracy was rated as low to moderate for sensitivity and moderate for specificity.
The depression module (Patient Health Questionnaire 9 [PHQ-9]) of the full PHQ is the instrument highlighted for use in screening for depression by the American Academy of Pediatrics.76 One study of the accuracy of the full PHQ modified for adolescents was included, but no studies evaluating the PHQ-9 were identified. Based on the accuracy characteristics for the 1 included study of the Patient Health Questionnaire—Adolescents (PHQ-A),24 per 1000 screening tests conducted, 58 false-positives and 8 false-negatives would be generated at the low end of MDD prevalence (3%) observed in this updated review, and 53 false-positives and 30 false-negatives would be generated at the high end of prevalence (11%). Positive screening results would require additional diagnostic evaluation to determine true-positives from false-positives, but it is likely that some youth screening positive but not meeting diagnostic criteria for MDD may have persistent depressive disorder (formerly known as dysthymia) or other behavioral health conditions with symptoms similar to depression. The consequences of a false-negative would largely depend on the severity of the missed diagnosis; the likelihood of missing a severely depressed youth is small because most screen-detected depression is likely to be mild to moderate. However, even mildly to moderately depressed youth may have suicidal ideation, and the consequences of missing such symptoms could be serious.
The updated evidence on psychotherapy suggested some benefits for symptom improvement and clinical response, but the results were not consistent across all measures for other outcomes. The evidence for pharmacotherapy suggested benefit for symptom improvement, but the results were not consistent across all measures for other outcomes. Thus, the strength of evidence for psychotherapy and pharmacotherapy was rated as low for benefit. The evidence on harms was very limited; no statistically significant differences were observed. One multigroup trial (TADS) with inconsistent reporting on suicide-related events across its various publications contributed to the evidence on psychotherapy, pharmacotherapy, and their combination. These discrepancies increased the uncertainty regarding harms of treatment and have led to a call for independent reanalysis of the TADS results.77,78 The US Food and Drug Administration (FDA) noted a higher frequency of suicide-related events in boxed warnings for antidepressants.79 The underlying FDA review for this warning relied on drug trials in populations ineligible for this review.80
Only 1 eligible study assessed the accuracy of screening for suicide risk in adolescents evaluated against a clinical diagnostic interview reference standard; the instrument used was the SRS, a 20-item instrument embedded in a longer questionnaire, and the study population was recruited from youth identified as potential high school dropouts.49 The strength of evidence for screening was rated as insufficient because of inconsistencies in estimates based on the reference standard used, imprecision, and study limitations. Given that many depression screening instruments include an assessment of suicidal ideation, it is unclear whether a separate, stand-alone instrument to screen for increased suicide risk has value for universal screening in primary care practice. The Ask Suicide Screening Questions (ASQ) is a brief 4-item instrument that was initially developed for youth 8 years or older in emergency department settings but has since been evaluated in other medical settings, including outpatient specialty and primary care.81,82 The Joint Commission recommends suicide risk screening for all medical patients in all medical settings, including outpatient practices.83 The National Institute for Mental Health developed an ASQ toolkit to support implementation of suicide risk screening in medical settings, including for youth in primary care.84 One study evaluating the ASQ in outpatient settings, including primary care, was identified, but it was excluded because its accuracy was compared against another suicide risk screening instrument and not against a diagnostic clinical interview by a qualified professional.82
The updated evidence base suggests improvements in suicidal ideation resulting from psychotherapy interventions, but this finding was statistically significant for only 1 measure. The evidence suggested no statistically significant differences on all other measures. All trials included treatment-as-usual comparators, which for ethical reasons must be active comparators, such as standard psychotherapy, individual counseling, family sessions, medication assessment and review, medication, and other care coordination activities. Comparable intensity of therapy in study groups, coupled with low-event rates for some outcomes (such as suicide deaths, hospitalizations, and suicide attempts), is likely to make differences between study groups difficult to detect. The evidence was rated as low for benefit on suicidal ideation; insufficient for evaluating outcomes such as suicide attempts, hospitalizations, and deaths; and low for no harm.
This study has several limitations. First, no studies were available that compared screening with no screening. Second, only limited evidence was available on long-term outcomes, test accuracy, and suicide risk and depression treatment in children. Third, treatment-as-usual comparators for suicide risk interventions included active treatments, which may have led to lack of statistically significant differences between study groups. Fourth, the review was limited to first-line drugs approved for pediatric use by the FDA.
Indirect evidence suggested that some screening instruments were reasonably accurate for detecting depression. Psychotherapy and pharmacotherapy were associated with some benefits and no statistically significant harms for depression, but the evidence was limited for suicide risk screening instruments and interventions.
Source: This article was first published online in the Journal of the American Medical Association on October 11, 2022 (JAMA. doi:10.1001/jama.2022.16310).
Conflict of Interest Disclosures: Dr Vander Schaaf reported that she is a Fellow of the American Academy of Pediatrics and member of American Academy of Pediatrics CATCH Committee. No other disclosures were reported.
Funding/Support: This study was funded under contract HHSA-290-2015-00011-I, Task Order 15, from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services (HHS), under a contract to support the US Preventive Services Task Force (USPSTF
Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions for this review. AHRQ had no role in study selection, quality assessment, or synthesis. AHRQ staff provided project oversight, reviewed the report to ensure that the analysis met methodological standards, and distributed the draft for peer review. Otherwise, AHRQ had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript findings. The opinions expressed in this document are those of the authors and do not represent the official position of AHRQ or HHS.
Additional Contributions: We acknowledge the following individuals for their contributions to this project: AHRQ staff Iris Mabry-Hernandez, MD, MPH, and Tracy Wolf, MD, MPH; current and former members of the USPSTF who contributed to topic deliberations; RTI International–University of North Carolina Evidence-based Practice Center staff Christiane Voisin, MSLS, Candi Wines, MPH, Nila A. Sathe, MA, MLIS, Carol Woodell, BSPH, Sharon Barrell, MA, Staci Rachman, BA, Michelle Bogus, Sarah Barringer, and Loraine Monroe. USPSTF members, peer reviewers, and federal partner reviewers did not receive financial compensation for their contributions.
Additional Information: A draft version of the full evidence report underwent external peer review from 4 content experts (Gregory Simon, MD, MPH, University of Washington; Joan Asarnow, PhD, University of California, Los Angeles; Natalie Cort, PhD, William James College; and Raquel Halfond, PhD, American Psychological Association) and a federal partner reviewer (Erin Abramsohn, DrPH, MPH, Centers for Disease Control and Prevention). Comments from reviewers were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review.
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Evidence reviews for the US Preventive Services Task Force (USPSTF) use an analytic framework to visually display the key questions that the review addressed to allow the USPSTF to evaluate the effectiveness and safety of a preventive service. The questions are depicted by linkages that relate interventions and outcomes. Refer to the USPSTF Procedure Manual for interpretation of the analytic framework.7 KQ indicates key question.
Reasons for exclusion: Population: Study was not conducted in an included population. Comparator: Study did not use an included comparator. Intervention: Study did not use an included intervention. Outcomes: Study did not report relevant outcomes. Design: Study did not use an included design. Other target condition: Study reported on anxiety. Quality: Study was poor quality. Setting: Study was not conducted in settings representative of primary care. Publication type: Publication was a commentary. Country: Study was not conducted in a country relevant to US practice. Protocol or ongoing study: Study was a protocol or ongoing study and did not report eligible outcomes. Language: Study was not in English. Duplicate: Study was a duplicate of other studies in the review. Superseded by publication: Study findings were wholly superseded by another publication.
a Combined searches were conducted on anxiety, depression, and suicide risk. Results for anxiety are presented in a separate publication.20
b Study may address more than 1 key question (KQ).
|Condition||Screening||Age range||No. of studies||Sensitivity||Specificity|
|Major depressive disorder||Beck Depression Inventory (threshold = 11)||15-18.5||221,27||0.84-0.90||0.81-0.86|
|Center for Epidemiologic Studies Depression Scale (various thresholds)||7-14||226||0.18a-0.85||0.38-0.83|
|Clinical Interview Schedule–Revised||8-17||126||0.18a||0.97b|
|Hopkins Symptom Checklist||12-18||122||0.85||0.78|
|Patient Health Questionnaire–Adolescents||13–18||124||0.73||0.94|
|Paediatric Index of Emotional Distress–Depression subscale||8-17||125||0.94||0.81|
|World Health Organization 5-Item Well-being Index||7-14||122||0.88||0.80|
|Suicide risk||Suicide Risk Screen||7-18||149||0.87-0.91c||0.60|
a Across the 2 studies, 5 thresholds were evaluated. The sensitivity for most ranged between 0.59 and 0.85 except for the thresholds of 20 or greater and 22 or greater among boys, which were 0.19 and 0.18, respectively.
b These estimates were from an analysis weighted for selection into the second phase of the study; calculated sensitivity without weighting was 0.74 and specificity was 0.78.
c This instrument was evaluated against 2 different reference standards.
|Intervention||Time of outcome measurement||Outcome measure, range, threshold||Outcome range||Outcome threshold indicating clinically meaningful effect||Treatment range at follow-up||Comparator range at follow-up||No. of studies
(No. of participants)
|Pooled resultsa (95% CI); I2|
|Depression—change in symptoms|
|Internet-based individual CBT group; in-person CBT with and without parents; interpersonal psychotherapyb||4-17 wk||BDI or BDI-II||BDI: 0-3935
Score <10: minimal depression
Score 10-18: mild to moderate depression
Score 19-29: moderate to severe depression
Score ≥30: severe depression21,27
|430,35,37,38||Standardized mean difference, −0.58 (−0.83 to −0.34)
I2 = 0%
|Individual in-person youth CBT; group in-person CBT with and without parents; interpersonal psychotherapyb||8-52 wk from baseline||HAM-D||Unclear (2 studies used a 14-item version of HAM-D)||Unclear||4.9-8.7||6.5-12.8||329,30,35 (262)||Mean difference, −2.25 (−4.09 to −0.41)
I2 = 0%
|Individual in-person CBT; family CBT||12-52 wk from baseline||CDRS-R||17-113||Score ≥40 indicates depression
Score ≤28 indicates remission (minimal or no symptoms)
|30.0-42.1||28.2-41.8||328,32,34 (471)||Mean difference, 0.77 (−0.97 to 2.48)
I2 = 0%
|Escitalopram; fluoxetine||8-12 wk from baseline||CDRS-R||17-113||Score ≥40 indicates depression
Score ≤28 indicates remission (minimal or no symptoms)
|36.4-41.8||331,34,39 (793)||Mean difference, −3.76 (−5.95 to −1.57)
I2 = 49%
|Depression—remission and loss of diagnosis|
|CBT||8-12 wk from baseline||Loss of diagnosis measured by clinical interviews||0%-100%
|NA||56%-71%||16%-60%||430,34,37,38 (395)||RR, 1.73 (1.00 to 3.00)
I2 = 81%
|Escitalopram; fluoxetine||8-12 wk from baseline||Remission from depression symptoms (CDRS-R ≤28)||0%-100%
|CDRS-R ≤28 indicates moderate marked improvement, proportion threshold unclear||23%-46%||17%-38%||331,34,39,45 (793)||RR, 1.20 (1.00 to 1.45)
I2 = 0%
|Depression—change in functioning|
|Individual in-person CBT; interpersonal psychotherapy||12-52 wk from baseline||CGAS||1-100||Score >70: no clinically significant functional impairment
Score <41: major impairment to functioning in several areas
|60.0-72.3||59.3-74.1||428,29,34,35 (601)||Mean difference, 1.52 (−1.54 to 4.58)
I2 = 66%
|Escitalopram; fluoxetine||8-12 wk from baseline||CGAS||1-100||Score >70: no clinically significant functional impairment
Score <41: major impairment to functioning in several areas
|62.1-68.5||59.3-64.6||331,34,39 (793)||Mean difference, 2.60 (0.78 to 4.42)
I2 = 0%
|Suicide risk—suicide-related outcomes|
|Group psychotherapy; family therapy; mentalization-based treatment; developmental group therapy||6-18 mo||Proportion with self-harm events||0-100||NA||0.55%-88%||1.1%-83%||553-55,57,59,72,74 (1040)||RR, 0.88 (0.63 to 1.24)
|Family therapy; DBT; developmental group therapy||19 wk to 18 mo||Mean No. of self-harm events||NA||NA||0.6-9.0||1.2-22.50||353-55,65-68,74 (972)||Mean difference, −0.76 (−2.15 to 0.63)
I2 = 68%
|Youth-nominated support team; motivational interviewing; DBT; IPT-A-IN||2 mo to 19 wk||Suicidal ideation: BHS||0-20||Score >9 indicative of suicide intentions||5.66-7.74||7.80-12.42||462,64-68,73 (644)||Mean difference, −2.35 (−4.06 to −0.65)
|Attachment-based family therapy; group psychotherapy; group therapy; youth-nominated support team; motivational interviewing; DBT; developmental group therapy||2 mo to 71 wk||SIQ or SIQ-JR||SIQ: 0-180
|SIQ score >41 indicative of suicidal ideation
SIQ-JR score >31 indicative of suicidal ideation
|756,57,59,62,64-68,74 (1111)||SMD, −0.18 (−0.36 to 0.01)
I2 = 45%
|Family therapy; DBT; therapeutic assessment||18 mo to 2 y||Proportion with suicide-related hospitalization or emergency department use||NA||NA||1%-88%||1%-94%||353-55,65-70 (978)||RR, 1.00 (0.67 to 1.50)
I2 = 21%
|Attachment-based therapy and internet CBT||8-24 wk||Clinical response: SIQ-JR or perceived burdensomeness||SIQ-JR: 0-90; Perceived burdensomeness: 6-42||Clinical response: SIQ-JR scores (defined as <13)
Perceived burdensomeness <14.61
Perceived burdensomeness: 10%
|256,60 (146)||Results from individual studies: OR for SIQ-JR clinical response, 6.30 (1.76-22.61)56
No significant differences at 24 wk for perceived burdensomeness (OR, 2.82 [0.80-9.91])60
|Suicide risk—change in functioning|
|Group psychotherapy; group therapy; developmental group therapy; psychoeducation for parents||8 wk to 7 mo||Functioning: Health of the Nation Outcome Scales for Children and Adolescents||0-52||Scores >13 indicate impairment of clinical significance||8.4-16.8||6.9-17.6||457,59,71,74 (509)||Mean difference, −0.40 (−2.55 to 1.78)
I2 = 56%
|Therapeutic assessment; individual and family DBT; group therapy||8-71 wk||Functioning: CGAS||1-100||Score >70: no clinically significant functional impairment
Score <41: major impairment to functioning in several areas
|58.5-65.7||60.1-64.22||3[[59,66,70 (195)||Mean difference, 1.30 (−2.52 to 5.12)
I2 = 30%
Abbreviations: BDI, Beck Depression Inventory; BDI-II, Beck Depression Inventory version 2; Beck Hopelessness Scale, CBT, cognitive behavioral therapy; CDRS-R, Children’s Depression Rating Scale–Revised; CGAS, Children’s Global Assessment Scale; DBT, dialectical behavior therapy; HAM-D, Hamilton Depression Rating Scale; IPT-A-IN, intensive interpersonal bxpsychotherapy for depressed adolescents with suicidal risk; NA, not applicable; OR, odds ratio; RR, relative risk; SIQ, Suicidal Ideation Questionnaire; SIQ-JR, Suicidal Ideation Questionnaire– Junior; SMD, standardized mean difference.
a Results from pooled analyses unless otherwise specified.
b The results across groups for the study were averaged (mean values calculated), with multiple treatment groups (group in-person CBT with or without parents30) compared with wait-list.
|No. of studies, study designs (No. of participants)||Summary of findings||Consistency and precision||Limitations||Strength of evidence||Applicability|
|KQ1: Benefits of screening|
|KQ2: Accuracy of screening|
|Depression: 7 studies (n = 3281)21-27||Varies by screener and threshold, excluding outliers
Sensitivity range, 0.59-0.94
Specificity range, 0.38-0.96
|Consistent when multiple studies are available; precise for specificity, precision varies for sensitivity||Unclear whether thresholds were established a priori or whether index and reference standard results were blinded; no replication of approaches for most screeners||Low to moderate for sensitivity (varies by instrument); moderate for specificity||Primarily adolescents, as only 1 study included children younger than 12 y; 7 different screeners evaluated but most not being used in practice|
|Suicide: 1 study (n = 581)||Sensitivity, 0.87 and 0.91 (varies by reference standard)
|Consistency unknown; imprecise||Unclear whether thresholds were established a priori or whether interviewers were blinded; single study||Insufficient||
Participants were potential high school dropouts; instrument was a 20-item screener embedded into a longer questionnaire, so unclear whether feasible in primary care
|KQ3: Harms of screening tests|
|Suicide: 2 RCTs50,51 (n = 2675)||No significant difference in suicidal ideation between students exposed to screening items and those not exposed (1 RCT)
No significant differences in measures of short-term distress/emotions for students exposed to suicide screening items compared with those not exposed (2 RCTs)
|Consistent; precise||Fair-quality trials with some attrition; only evaluated measures of immediate and short-term emotions (over 1-2 d)||Low for no short-term harms from screening for suicide risk; insufficient for screening for depression and anxiety||High school students; 1 study entirely comprised boys|
|KQ4: Benefits of treatment|
|Depression: 13 RCTs28-40,42 (2 on pharmacotherapy; 9 on psychotherapy; 1 on CBT, fluoxetine, and their combination; 1 on collaborative care) (n = 2152)||Psychotherapy:
Varied by measure, with some pooled estimates of effect favoring psychotherapy for symptoms, clinical response, and loss of diagnosis, but other outcome measures did not consistently demonstrate a statistically significant difference
Pooled differences favored pharmacotherapy but were not statistically significant for remission
Other outcome measures did not demonstrate a statistically significant difference
|Mostly consistent; mostly imprecise||Psychotherapy cannot mask treatment, leading to the potential for bias in outcome reporting||Psychotherapy: low for benefit for all outcomes other than remission
Pharmacotherapy: low for benefit for all outcomes other than response
Collaborative care: low for benefit for symptoms, response, and remission; insufficient for functioning
|Studies addressed youth aged 3 to 19 y, but 9 were conducted exclusively in adolescents
Pharmacotherapy studies were limited to first-line drugs with FDA approval for pediatric use
|Suicide: 16 RCTs52-62,64-74 (3034)||Statistically significant difference favoring interventions for suicidal ideation on the Beck Hopelessness Scale, nonstatistically differences favoring suicide risk interventions on the SIQ and SIQ-JR, mixed on other measures
No statistically significant differences on suicide deaths, hospitalization or emergency department visits, number of self-harm events, proportion with self-harm events, or functioning
All-cause mortality: statistically significant difference favoring interventions (hazard ratio for treatment as usual, 6.62 [95% CI, 1.49-29.35]; n = 448; 1 study)
|Consistent; imprecise||Interventions cannot mask treatment, leading to the potential for bias in outcome reporting; all comparison groups are treatment-as-usual comparisons, which in many cases were active treatments and could bias results toward null effects||Psychotherapy: Low for benefit for suicidal ideation and clinical response; insufficient for all other outcomes||Applicable to adolescents (predominantly females); no studies recruited children younger than 11 y; most recruited from mental health or specialist settings|
|KQ5: Harms of treatment|
|Depression: 6 RCTs28,31,34,36,39-41,43-46 (3 on pharmacotherapy; 2 on psychotherapy; 1 on CBT, fluoxetine, and their combination; 1 on collaborative care) (n = 1408 from trials) and 1 meta-analysis48||Psychotherapy: no statistically differences in negative effects in 2 trials; however, precise effects unclear because 1 trial had inconsistent reporting
Pharmacotherapy: nonsignificant but higher risk of suicide-related outcomes, withdrawal due to adverse events and serious adverse events, precise effects unclear owing to inconsistent study reporting
Collaborative care: inconsistent results for psychiatric hospitalizations and emergency department visits
|Consistent to inconsistent; imprecise||Psychotherapy trials cannot mask treatment, leading to the potential for bias in outcome reporting, inconsistent results across publications from 1 trial||Psychotherapy: insufficient
Pharmacotherapy: low for harms
Collaborative care: insufficient
|Studies addressed youth aged 6 to 18 y, but 5 were conducted exclusively in adolescents
Pharmacotherapy studies were limited to first-line drugs with FDA approval for pediatric use
|Suicide: 2 RCTs53,58 (885)||No statistically significant differences on adverse events (such as minor injury, walk-in, accident and emergency centers, re-referral to mental health service, and hospital attendance)||Consistent; imprecise||Interventions cannot mask treatment, leading to the potential for bias in outcome reporting; all comparison groups are treatment-as-usual comparisons, which in many cases were active treatments and could lead to bias toward null effects||Insufficient||Applicable to adolescents, primarily females, recruited from mental health or specialist settings|
Abbreviations: CBT, cognitive behavioral therapy; FDA, US Food and Drug Administration; KQ, key question; NA, not applicable; PHQ-A, Patient Health Questionnaire-Adolescents; RCT, randomized clinical trial; SIQ, Suicidal Ideation Questionnaire; SIQ-JR, Suicidal Ideation Questionnaire–Junior.