Evidence Summary

Anxiety 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; Sara M. 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. 2022;328(14):1445-1455. doi:10.1001/jama.2022.16303).

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Importance: Anxiety in children and adolescents is associated with impaired functioning, educational underachievement, and future mental health conditions.

Objective: To review the evidence on screening for anxiety in children and adolescents to inform the US Preventive Services Task Force.

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; diagnostic test accuracy studies; RCTs of cognitive behavioral therapy (CBT) or US Food and Drug Administration–approved 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, all-cause mortality, functioning, suicide-related symptoms or events, adverse events.

Results: Thirty-nine studies (N = 6065) were included. No study reported on the direct benefits or harms of screening on health outcomes. Ten studies (n = 3260) reported the sensitivity of screening instruments, ranging from 0.34 to 1.00, with specificity ranging from 0.47 to 0.99. Twenty-nine RCTs (n = 2805) reported on treatment: 22 on CBT, 6 on pharmacotherapy, and 1 on CBT, sertraline, and CBT plus sertraline. CBT was associated with gains on several pooled measures of symptom improvement (magnitude of change varied by outcome measure), response (pooled relative risk [RR], 1.89 [95% CI, 1.17 to 3.05]; n = 606; 6 studies), remission (RR, 2.68 [95% CI, 1.48 to 4.88]; n = 321; 4 studies), and loss of diagnosis (RR range, 3.02-3.09) when compared with usual care or wait-list controls. The evidence on functioning for CBT was mixed. Pharmacotherapy, when compared with placebo, was associated with gains on 2 pooled measures of symptom improvement—mean difference (Pediatric Anxiety Rating Scale mean difference, −4.0 [95% CI, −5.5 to −2.5]; n = 726; 5 studies; and Clinical Global Impression–Severity scale mean difference, −0.84 [95% CI, −1.13 to −0.55]; n = 550; 4 studies) and response (RR, 2.11 [95% CI, 1.58 to 2.98]; n = 370; 5 studies)—but was mixed on measures of functioning. Eleven RCTs (n = 1293) reported harms of anxiety treatments. Suicide-related harms were rare, and the differences were not statistically significantly different.

Conclusions and Relevance: Indirect evidence suggested that some screening instruments were reasonably accurate. CBT and pharmacotherapy were associated with benefits; no statistically significant association with harms was reported.

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Anxiety is a common condition in children and adolescents. The 2020 National Survey of Children’s Health estimated that 7.8% of children aged 3 to 17 years had a current anxiety disorder; 0.7% had severe anxiety.1 Longitudinal studies of anxiety disorders suggest that early anxiety may lead to an increased risk for secondary depression.2-4 In addition, childhood anxiety often interferes with social, emotional, and academic development5,6 that can result in substance abuse, dependence, or both; suicide; educational underachievement; and functional impairment.7,8 The rationale for routine screening is to identify undiagnosed youth who may benefit from effective treatment for anxiety disorders. This systematic review evaluated the evidence on screening for anxiety in children and adolescents to inform a new recommendation by the US Preventive Services Task Force (USPSTF).

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Scope of Review

The analytic framework and key questions that guided the review are shown in Figure 1. Detailed methods, evidence tables, and contextual information are available in the full evidence report.10

Data Sources and Searches

PubMed, the Cochrane Library, PsycINFO, CINAHL, and ClinicalTrials.gov were searched for English-language articles (eMethods in the JAMA Supplement). Searches for treatment of anxiety were limited to articles published from January 1, 2017, to July 19, 2021, because evidence from prior to 2017 was identified from an existing comprehensive Agency for Healthcare Research and Quality (AHRQ) review.11 Reference lists of pertinent articles and studies suggested by reviewers were also evaluated. 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.

Study Selection

Two investigators independently reviewed titles, abstracts, and full-text articles using prespecified inclusion criteria for each key question (eMethods in the JAMA Supplement); disagreements were resolved by discussion or by a third reviewer. English-language studies that included children and adolescents 18 years or younger, were of fair or good methodological quality, and were conducted in countries categorized as very highly developed by the 2018 United Nations Human Development Index were eligible.12 For screening, studies that included unselected participants without known anxiety were eligible. For treatment, selection was restricted to studies of participants diagnosed with at least 1 anxiety disorder (ie, generalized anxiety disorder, social anxiety disorder, panic disorder, agoraphobia, separation anxiety disorder, and selective mutism). For studies of nonpharmacological interventions, inclusion was restricted to cognitive behavioral therapy (CBT), the most common therapy.

Eligible pharmacotherapy interventions included agents approved by the US Food and Drug Administration 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 anxiety symptoms measured by validated instruments, clinical response, or remission; all-cause mortality; quality of life measured using validated scales or instruments; and functioning measured by validated scales, missed days of school, or sleep-related outcomes. Eligible harms of treatment included treatment avoidance, deterioration in patient-clinician relationship, labeling or stigma, unnecessary treatment, serious adverse effects, withdrawal 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 included studies from a prior AHRQ evidence review on anxiety treatment in youth11 were spot checked and carried forward. All other studies were rated dually and independently using predefined criteria established by the USPSTF (eMethods in the JAMA Supplement) and others.11,13-16 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 6 in the JAMA 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) software 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.9,19 Two senior reviewers independently developed initial strength of evidence assessments; disagreements were resolved through discussion or input of a third senior reviewer.

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Thirty-nine studies (N = 6065) in 50 publications were eligible (Figure 2), including 10 studies reporting on screening test accuracy21-30 and 29 randomized clinical trials (RCTs) reporting on treatment interventions.31-70 The results in this publication focus on pooled analyses when available. Additional results are available in the full report.10 A list of full-text articles that were screened but excluded is provided in the JAMA Supplement (List of Excluded Studies).

Benefits of Screening

Key Question 1. Do anxiety screening programs in primary care or comparable settings result in improved health outcomes in children and adolescents?

No trial directly assessed the benefits of screening children or adolescents for anxiety in the primary care setting.

Accuracy of Screening Instruments

Key Question 2. Do instruments to screen for anxiety accurately identify children and adolescents with anxiety in primary care or comparable settings?

Ten fair-quality studies assessed the accuracy of 12 different screening instruments for detecting anxiety21-30 (n = 3260) (eTables 7 and 8 in the JAMA Supplement). Some studies assessed multiple instruments, some instruments were examined in multiple studies, and some studies examined instrument versions for children, adolescents, or both or included parents, youth, or both as respondents. Five studies21,23,28-30 examined instrument accuracy for detection of social anxiety disorder, 3 studies24-26 for generalized anxiety disorder, 2 studies24,27 for panic disorder, 1 study25 for separation anxiety disorder, and 1 study for global anxiety not specific to any given disorder.22

The prevalence of anxiety disorders in included studies, based on diagnostic clinical interviews, ranged from 2.5% to 24%. Table 1 provides the sensitivity and specificity by screening instrument (additional detail is provided in eTable 9 in the JAMA Supplement). Across all instruments and respondents, sensitivity ranged from 0.34 to 1.00 and specificity ranged from 0.47 to 0.99.

Findings Within Age Groups

Seven studies of adolescents (mean age, 14.8 years) reported on 8 instruments,21,23,24,27,28,30 and 4 studies on school-aged children and adolescents aged 7 to 17 years (mean age, 11.0 years) reported on 7 instruments.21,22,71,72 No study included children younger than 7 years.

Only 1 study21 reported results for adolescents and children separately for the same instruments; these results did not suggest consistent differences in sensitivity and specificity by age of the youth, and variations in instruments and thresholds may explain differences in results. Across instruments and conditions reported in other included studies, differences in reported accuracy between studies on adolescents alone vs studies including both adolescents and children did not suggest age-related patterns (eTable 9 in the JAMA Supplement).

Harms of Screening

Key Question 3. What are the harms associated with screening for anxiety in primary care or comparable settings in children and adolescents?

No trial directly assessed the harms of screening children or adolescents for anxiety in the primary care setting.

Benefits of Treatment

Key Question 4. Does treatment (cognitive behavioral therapy or pharmacotherapy) of anxiety result in improved health outcomes in children and adolescents?

Benefits of treatment for anxiety are summarized in Table 2.

Twenty-nine RCTs (described in 40 articles) of good or fair quality were eligible (n = 2805).31-70 All studies are new to this report because this topic has not been addressed previously by the USPSTF. Detailed study, population, and intervention characteristics and results are reported in eTable 10 in the JAMA Supplement; detailed outcomes are reported in eTables 11 through 19 in the JAMA Supplement; and results from meta-analyses are provided in eFigures 1 through 17 in the JAMA Supplement. Sixteen studies enrolled children with any type of anxiety disorder.31,43,45,46,52,54-59,62,64,66-68 The most common primary diagnoses in these studies were social anxiety disorder and generalized anxiety disorder. Of the studies requiring specific anxiety disorders for trial eligibility, 5 required generalized anxiety disorder,41,53,63,65,70 4 required social anxiety disorder,42,47,60,69 2 required selective mutism,44,61 and 2 required either generalized anxiety disorder, social anxiety disorder, or separation anxiety disorder.32-40,48-51 Nine studies set a threshold for severity.41,48-50,57,58,60,62,63,65 Nine of 29 studies had a majority of male participants.48-52,55-58,63,64

The mean age of enrolled populations ranged from 4.1 to 17.4 years. Three studies focused on early childhood (ages 3-7 years57,66,68), 11 focused on school-aged children (6-14 years44,47,52,55,56,58,60,64,65,67,69), 11 spanned childhood and adolescence,31-41,45,46,48-51,53,59,61-63 and 4 focused solely on adolescence.42,43,54,70 Results below are summarized overall and then by age group when available.

Twenty-two RCTs evaluated CBT,31,42-47,52-60,64-67 6 evaluated pharmacotherapy,41,48-51,61-63,70 and 1 evaluated CBT, sertraline, and CBT plus sertraline separately.32-40 The results below focus on CBT and pharmacotherapy; detailed results for combination therapy are available in the full report.10

Reported outcomes included (1) anxiety symptoms, (2) clinical response or remission, and (3) functioning. CBT was associated with clinically important and statistically significant benefits on several pooled estimates of effect for end-of-treatment measures of anxiety symptoms (Table 2). These measures included the clinician severity rating on the Anxiety Disorders Interview Schedule (mean difference, −2.01 [95% CI, −2.74 to −1.29]; n = 579; 11 RCTs31,43-45,53,54,57,59,65,68,73), the child-rated Spence Children’s Anxiety Scale (SCAS) (mean difference, −7.81 [95% CI, −10.99 to −4.63]; n = 668; 9 RCTs31,43,45,52,54-56,59,65), the parent-rated SCAS (mean difference, −6.06 [95% CI, −9.58 to −2.56]; n = 652; 9 RCTs31,43,45,52,54-56,59,65), and the Revised Children’s Manifest Anxiety Scale (mean difference, −3.08 [95% CI, −5.91 to −0.24]; n = 241; 3 RCTs56,64,67). For pharmacotherapy, pooled estimates of effect suggested clinically important and statistically significant improvements for symptom improvement (Pediatric Anxiety Rating Scale mean difference, −4.0 [95% CI, −5.5 to −2.5]; n = 726; 5 RCTs;32-41,48-51,62,70 Clinical Global Impression–Severity scale mean difference, −0.84 [95% CI, −1.13 to−0.55]; n = 550; 4 RCTs32-41,63,70) (Table 2).

CBT was also associated with a favorable clinical response (pooled relative risk [RR], 1.89 [95% CI, 1.17 to 3.05]; n = 606; 6 RCTs32,44,46,54,57,66), increased remission (pooled RR, 2.68 [95% CI, 1.48 to 4.88]; n = 321; 4 RCTs31,43,56,59), loss of any anxiety diagnosis (pooled RR, 3.09 [95% CI, 1.98 to 4.80]; n = 1414; 15 RCTs31,43,45,46,52-54,58,59,64-68), and loss of the primary anxiety diagnosis (pooled RR, 3.02 [95% CI, 1.84 to 4.95]; n = 1079; 13 RCTs31,43-46,52-54,58-60,65,68,73). Pharmacotherapy was also associated with a favorable clinical response (pooled RR, 2.11 [95% CI, 1.58 to 2.98]; n = 370; 5 RCTs32-40,61-63,70), but results from 3 studies were inconsistent for remission.32-41,63 Regarding functioning, both CBT and pharmacotherapy were associated with statistically significant improvement on the Children’s Global Assessment Scale (mean difference for CBT, 7.54 [95% CI, 2.84 to 12.23]; n = 811; 8 RCTs;32-40,44,46,53,54,58,65,68 mean difference for pharmacotherapy, 5.14 [95% CI, 3.21 to 7.08]; n = 551; 3 RCTs32-41,62), whereas the evidence on other measures was not statistically significant.

Findings Within Age Groups

Three studies enrolled children aged 3 to 7 years57,66,68 and 4 studies enrolled only adolescents aged 13 to 20 years.42,43,54,70 The remaining studies focused on school-aged children aged 5 to 14 years (12 studies44,45,47,55,56,58,60,64,65,67,69) or children and adolescents aged 7 to 18 years (10 studies31,32,41,46,48,53,59,61-63).

No significant difference in results was observed between age groups enrolled. For younger children, all 3 studies focused on CBT and reported consistent statistically significant benefits for anxiety symptoms in 257,68 of 357,66,68 studies. Two studies reported on response, and both reported statistically significant differences favoring CBT.57,66 One study reported on remission57 and 1 reported on functioning,68 and both suggested statistically significant differences favoring CBT. One66 of 266,68 studies reported statistically significant differences favoring CBT for loss of diagnosis.

For studies enrolling only adolescents, 3 studies42,43,54 reported on CBT and 1 reported on escitalopram.70 Two42,43 of the 3 CBT studies42,43,54 reported consistent statistically significant improvement in anxiety symptoms, response, and remission; 1 reported no statistically significant differences.54 Only 1 CBT study reported on loss of diagnosis and found no statistically significant differences.54 Two studies reported on functioning, and neither consistently found statistically significant differences across a range of outcome measures.43,54 The escitalopram study reported improvement in symptoms and response.70

Harms of Treatment

Key Question 5. What are the harms of treatment (cognitive behavioral therapy or pharmacotherapy) in children and adolescents who are treated for anxiety?

Eleven good- or fair-quality studies (described in 22 articles) that addressed benefits also addressed harms (n = 1293). In the JAMA Supplement, key characteristics of included studies for harms are provided in eTable 20, detailed outcomes are provided in eTables 21 and 22, and results from meta-analyses are provided in eFigures 18 and 19. Outcomes reported include (1) suicide-related harms, (2) withdrawal due to adverse events, (3) and serious adverse events. Regarding suicide-related harms, 2 CBT studies reported on suicidal ideation, attempts, or self-harm behavior.32-40,54 One study of 60 participants54 reported that 2 participants in the wait-list control group only withdrew from the study because of risk of suicide by 17 weeks. A second child-focused study comparing CBT with placebo reported on self-harm behavior without suicidal attempt (1/139 [0.7%] vs 0/76 [0%]), suicidal ideation (5/139 [3.6%] vs 1/76 [1.3%]), and suicidal attempts (no event in either group) by 12 weeks.32-40 Three pharmacotherapy studies reported on suicide-related harms at the end of treatment at 8 to 12 weeks (duloxetine,41 escitalopram,70 and sertraline32-40). No study reported on suicide deaths, 2 studies reported on suicide attempts (1/26 events for escitalopram vs 0/25 events for placebo;70 no event occurred for sertraline or placebo in 1 study32-40), 3 studies reported on suicidal ideation or worsening of suicidality (1/135 for duloxetine vs 0/137 for placebo;41 6/26 for escitalopram vs 2/25 for placebo;70 0/133 for sertraline vs 1/76 for placebo32-40), and 2 studies reported on self-injurious behavior (2/26 for escitalopram vs 1/25 for placebo;]]70]] 1/133 for sertraline vs 0/76 for placebo32-40). Suicide-related harms were rare, and the differences between treatment and placebo groups were not statistically significantly different.

Regarding withdrawal due to adverse events, the pooled RR for CBT trials was 0.39 (95% CI, 0.08 to 1.87; n = 372; 4 studies32-40,43,53,54). The pooled RR across all pharmacotherapy trials was 1.72 (95% CI, 0.57 to 5.18; n = 734; 5 RCTs32-41,48-51,62,70).

For both CBT and pharmacotherapy, serious adverse events were rare and the differences between treatment and placebo groups were not statistically significantly different.

Findings Within Age Groups

No study reported on harms in young children. Results for studies of adolescents were consistent with results for the overall body of evidence: outcomes were rare and differences between treatment and comparison groups were not statistically significant.

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This systematic review evaluated screening for anxiety in children and adolescents. Table 3 summarizes the evidence, including strength-of-evidence ratings. No study 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. Two of the most widely used screeners (ie, Screen for Anxiety Related Emotional Disorders and the Social Phobia Inventory) were reasonably accurate, leading to low-to-moderate strength of evidence.

Consistent, precise, statistically significant differences for most anxiety outcomes for CBT and pharmacotherapy led to strength-of-evidence ratings of moderate for benefit for nearly all outcomes. Treatment studies covered a wide range of ages, from preschool through adolescence, although 4 studies focused exclusively on adolescents (13-20 years42,43,54,70). Studies focusing on younger children aged 3 to 7 years57,66,68 were consistent with the overall findings in demonstrating benefits for symptoms and clinical response.

Few CBT trials reported on harm outcomes leading to a strength-of-evidence rating of insufficient. The evidence suggests that suicide-related harms, serious adverse events, and withdrawal due to adverse events are rare in pharmacotherapy studies but more frequent in the treatment group; thus, strength of evidence for pharmacotherapy was rated as low for harms.

Few studies reported analyses for populations of interest. Studies reporting on analyses of anxiety symptoms consistently reported no differences in effect of treatment by age, but there is insufficient evidence available on effect of treatment on anxiety symptoms by race or ethnicity.

Limitations

This review has several limitations. First, no available study compared screening with no screening. Second, only limited evidence was available on long-term outcomes and on test accuracy and treatment in children. Third, the review was limited to CBT and drugs approved for pediatric use by the US Food and Drug Administration.

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Indirect evidence suggested that some screening instruments were reasonably accurate for detecting anxiety. CBT and pharmacotherapy were associated with benefits; no statistically significant association with harms was reported.

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Source: This article was first published online in the Journal of the American Medical Association on October 11, 2022 (JAMA. 2022;328(14):1445-1455. doi:10.1001/jama.2022.16303).

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, and Contract 75Q80120D00007, Task Order 05, 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, or 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; and 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, Sarah Barringer, Michelle Bogus, Teyonna Downing, 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 1 federal partner reviewer (Erin Abramsohn, DrPH, Centers for Disease Control and Prevention). Comments from reviewers were presented to the USPSTF during its deliberation of the evidence and were considered by the authors in preparing the final evidence review.

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41. Strawn JR, Prakash A, Zhang Q, et al. A randomized, placebo-controlled study of duloxetine for the treatment of children and adolescents with generalized anxiety disorder. J Am Acad Child Adolesc Psychiatry. 2015;54(4):283-293. doi:10.1016/j.jaac.2015.01.008
42. Salzer S, Stefini A, Kronmüller KT, et al. Cognitive-behavioral and psychodynamic therapy in adolescents with social anxiety disorder: a multicenter randomized controlled trial. Psychother Psychosom. 2018;87(4):223-233. doi:10.1159/000488990
43. Stjerneklar S, Hougaard E, McLellan LF, Thastum M. A randomized controlled trial examining the efficacy of an internet-based cognitive behavioral therapy program for adolescents with anxiety disorders. PLoS One. 2019;14(9):e0222485. doi:10.1371/journal.pone.0222485
44. Cornacchio D, Furr JM, Sanchez AL, et al. Intensive group behavioral treatment (IGBT) for children with selective mutism: a preliminary randomized clinical trial. J Consult Clin Psychol. 2019;87(8):720-733. doi:10.1037/ccp0000422
45. Cobham VE, Filus A, Sanders MR. Working with parents to treat anxiety-disordered children: a proof of concept RCT evaluating Fear-less Triple P. Behav Res Ther. 2017;95:128-138. doi:10.1016/j.brat.2017.06.004
46. Ginsburg GS, Pella JE, Pikulski PJ, Tein JY, Drake KL. School-Based Treatment for Anxiety Research Study (STARS): a randomized controlled effectiveness trial. J Abnorm Child Psychol. 2020;48(3):407-417. doi:10.1007/s10802-019-00596-5
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48. Pine DS, Walkup JT, Labellarte MJ, et al; Research Units on Pediatric Psychopharmacology Anxiety Study Group. Fluvoxamine for the treatment of anxiety disorders in children and adolescents. N Engl J Med. 2001;344(17):1279-1285. doi:10.1056/NEJM200104263441703
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This figure is an analytic framework depicting the key questions within the context of the populations, interventions, comparisons, outcomes, time frames, and settings (PICOTS) relative to the effectiveness and harms of screening and treatment for anxiety in children and adolescents. The figure illustrates screening of adolescents and children in populations representative of primary care, followed by possible harms of screening; diagnosis of anxiety disorder; possible harms of treatment; and health outcomes.

Evidence reviews for the US Preventive Services Task Force (USPSTF) use an analytic framework to visually display the key questions that the review will address 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.9

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This figure documents the results of the literature searchers. It is a preferred reporting of systematic review and meta-analysis (PRISMA) tree that summarizes the search and selection of articles: There were 37,706 new references identified through database searching. The titles and abstracts of the new references were screened for potential inclusion. Of these, 37,157 were excluded and 549 were deemed appropriate for full-text review to determine eligibility. There were also 212 additional records from the previous reviews assessed at full-text and 37 records from other sources, including handsearch, assessed at full-text, for a total of 798 full-text articles assessed for eligibility. After full-text review, 718 were excluded: 15 for non-English language, 171 for wrong population, 102 for wrong intervention, 115 for wrong comparator, 35 for wrong setting, 17 for wrong country, 59 for wrong study design, 18  for wrong publication type, 78 for wrong outcome, 10 for duplicate, 16 for relevant protocol or ongoing study, 26 for companion publication of included study, 5 for superseded by paper publication, and 51 for poor quality. There were 80 studies reported in 106 publications that were included. No studies were included for key question 1. Seventeen studies were included for key question 2. Two studies were included for key question 3. 60 studies were included for key question 4. 20 studies were included for key question 5.

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 depression or suicide risk. 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. KQ indicates key question.
a Combined searches were conducted on anxiety, depression, and suicide risk. Results for depression and suicide risk are presented in a separate publication.20
b Study may address more than 1 KQ.

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Condition Screening Age range, y No. of studies Sensitivity Specificity
Generalized anxiety disorder PHQ-A 13–18 124 0.50 0.98
SCARED-GAD subscale 7-14 125 0.64 0.63
PI-ED-anxiety subscale 8-17 126 0.88 0.85
Panic disorder ANSQ (various thresholds) 12-18 127 1.00 0.47-0.65
PHQ-A 13–18 124 0.42 0.99
Separation anxiety disorder SCARED-SAD subscale 7-14 125 0.88 0.73
Social anxiety disorder SCARED-social phobia scale
(various thresholds)
8-16 121 0.78-0.83 0.69-0.81
SAS (various thresholds) 8-18 221,23 0.75-0.93 0.74-0.80
SAS-A 12-18 123 0.93 0.79
SPAI-Brief 12-18 123 0.86 0.88
SPIN/Mini-SPIN (various thresholds) 12-17 328-30 0.80-0.86 0.77-0.85
SWQ (various thresholds) 13-17 121 0.67-0.83 0.84-0.94
Any anxiety disorder SCARED 7-18 224,25 0.50-0.88 0.56-0.98

Abbreviations: ANSQ, Autonomic Nervous System Questionnaire; PHQ-A, Patient Health Questionnaire for Adolescents; PI-ED, Paediatric Index of Emotional Distress; SAS, Social Anxiety Scale; SAS-A, Social Anxiety Scale for Adolescents; SCARED, Screen for Child Anxiety Related Disorders; SCARED-GAD, Screen for Child Anxiety Related Disorders–Generalized Anxiety Disorder; SCARED-SAD, Screen for Child Anxiety Related Disorders–Separation Anxiety Disorder; SPAI, Social Phobia and Anxiety Inventory; SPIN, Social Phobia Inventory; SWQ, Social Worries Questionnaire.

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Intervention (mode of delivery for psychotherapy interventions) Time of outcome measurement (from baseline) 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 effect size
(95% CI); I2
Change in symptoms
CBT
   Individual-, group/child-, parent-, or child + parent-focused (in-person, email, telephone, or internet) 4-17 wk Primary diagnosis of ADIS-CSR or all diagnoses 0-8 Score of 4 (moderate degree of impairment) or greater indicates a clinical diagnosis 1.9-4.2 3.6-6.2 1131,43-45,53,54,57,59,65,68,73 (579) Mean difference, −2.01 (−2.74 to −1.29)
I2 = 83%
6-17 wk SCAS-C 0-114 Cutoffs vary by age and sex, from 33 to 50 (higher scores represent worse outcomes) 21.6-34.9 29.4-42.1 931,43,45,52,54-56,59,65 (668) Mean difference, −7.81 (−10.99 to −4.63)
I2 2
6-17 wk SCAS-P 0-114 Cutoffs vary by age and sex, from 33 to 50 (higher scores represent worse outcomes) 18.8-33.1 24.2-41.3 931,43,45,52,54-56,59,65 (652) Mean difference, −6.06 (−9.58 to −2.56)
I2 58%
   Individual/child-focused or parent-led (in-person) 5-12 wk CGI-S 1-7 Score of 2: borderline ill; 3, mildly ill; 4, moderate illness 2.0-4.0 3.3-4.2 332-40,46,57 (453) Mean difference, −0.60 (−1.14 to −0.06)
I275%
   Individual-, group/child-, or child + parent-focused (in-person) 12 wk MASC 0-117 Cutoff scores may not be possible to establish 40.9-48.8 42.9-54.7 332-40,58,60,73 (435) Mean difference, −4.66 (−9.66 to 0.34)
I66%
   Individual-, group/child-, or child + parent-focused (in-person, email, telephone, or internet) 10-12 wk RCMAS 0-28 Score ≥19 indicates clinically significant levels of anxiety 6.6-10.9 9.8-15.7 356,64,67 (241) Mean difference, −3.08 (−5.91 to −0.24)
I271%
Pharmacotherapy
   Fluoxetine, fluvoxamine, duloxetine, escitalopram, or sertraline 8-12 wk PARS 0-25 Score >11.5 discriminates youth without anxiety disorders from those with anxiety disorders 8.1-9.8 9.3-15.9 532-41,48-51,62,70 (726) Mean difference, −4.0 (−5.5 to −2.5)
I2 = 81%
   Duloxetine, escitalopram, or sertraline 8-12 wk CGI-S 1-7 Score of 2: borderline ill; 3, mildly ill; 4, moderate illness 2.4-3.0 3.1-3.9 432-41,63,70 (550) Mean difference, −0.84 (−1.13 to −0.55)
I2 = 75%
Clinical response, remission, and loss of diagnosis
CBT
   Individual-, group/child-, parent-, or child + parent-focused (in-person) 4 wk to 6 mo Proportion with a clinical response (CGI score of 1 or 2) 0%-100% CGI-I scores of 1 and 2 indicate moderate marked improvement, proportion threshold unclear 40%-83% 0%-37% 632,44,46,57,66 (606) RR, 1.89 (1.17 to 3.05)
I264%
   Individual-, group/child-, parent-, or child + parent-focused (in-person, email, telephone, or internet) 8-16 wk Remission from anxiety symptoms on SCAS-C 0%-100% Unclear; “clinically significant change” 43%-62% 6%-38% 431,43,56,59 (321) RR, 2.68 (1.48 to 4.88)
I48%
8-16 wk Loss of all anxiety diagnoses 0%-100% No diagnosis following a structured clinical interview 15%-80% 0%-35% 1531,43,45,46,52-54,58,59,64-68 (1414) RR, 3.09 (1.98 to 4.80)
I2 = 65%
6 wk to 12 mo Loss of primary anxiety diagnosis 0%-100% No diagnosis following a structured clinical interview 7%-80% 0%-43% 1331,43-46,52-54,58-60,65,68,73 (1079) RR, 3.02 (1.84 to 4.95)
I2 75%
Pharmacotherapy
   Escitalopram, fluoxetine, or sertraline 8-12 wk Proportion with a clinical response (CGI score of 1 or 2) 0%-100% for proportion CGI-I scores of 1 and 2 indicate moderate marked improvement, proportion threshold unclear 50%-91% 9%-44% 532-40,61-63,70 (370) RR, 2.11 (1.58 to 2.98)
I18%
Functional status
CBT
   Individual-, group/child-, parent-, or child + parent-focused (in-person, telephone, internet, or combination) 8-12 wk CAIS 0-81 Score <7: no anxiety diagnosis 6.4-21.8 15.2-19.6 333,52,54 (403) Mean difference, −2.23 (−5.88 to 1.43)
I38%
4-12 wk CGAS 1-100 Score >70: no clinically significant functional impairment

Score <41: major impairment to functioning in several areas

53.6-82.1 52.5-61.9 832-40,44,46,53,54,58,65,68 (811) Mean difference, 7.54 (2.84 to 12.23)
I90%
Pharmacotherapy
   Duloxetine, fluoxetine, or sertraline 10-12 wk CGAS 1-100 Score >70: no clinically significant functional impairment

Score <41: major impairment to functioning in several areas

62.1-68.5 59.3-64.6 332-41,62 (551) Mean difference, 5.14 (3.21 to 7.08)
I0%

Abbreviations: ADIS-CSR, Anxiety Disorders Interview Schedule–Clinician Severity Rating; CAIS, Children’s Anxiety Impact Scale; CBT, cognitive behavioral therapy; CGAS, Children’s Global Assessment Scale; CGI, Clinical Global Impression scale; CGI-I, Clinical Global Impression–Improvement; CGI-S, Clinical Global Impression–Severity; MASC, Multidimensional Anxiety Scale for Children; PARS, Pediatric Anxiety Rating Scale; RCMAS, Revised Children’s Manifest Anxiety Scale; RR, relative risk; SCAS, Spence Children’s Anxiety Scale; SCAS-C, Spence Children’s Anxiety Scale–Child-rated; SCAS-P, Spence Children’s Anxiety Scale–Parent-rated.

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No. of studies, study designs No. of participants Summary of findings Consistency, precision Limitations Strength of evidence Applicability
KQ1: Benefits of screening
None   NA NA NA Insufficient NA
KQ2: Accuracy of screening instruments
10 Studies21-30 3260 Varies by screener, threshold, and condition

Sensitivity range, 0.34-1.00

Specificity range, 0.47-0.99

Consistency unknown for individual screeners; imprecise No replication of results for specific thresholds and screeners; unclear whether thresholds were established a priori or whether index and reference standard results were blinded Low to moderate (varies by instrument) Participants were primarily adolescents, but school-aged children were included in 4 studies

Applicable to both primary care and school-based settings

A variety of different screeners were used, of which only 2 (SCARED and SPIN) are used widely in practice for detecting anxiety

KQ3: Harms of screening
None   NA NA NA Insufficient NA
KQ4: Benefits of treatment
29 RCTs (22 on CBT; 6 on pharmacotherapy; 1 on CBT, sertraline, and combination)31-70 2805 CBT: Statistically significant differences favoring CBT on several pooled measures of symptom improvement

Statistically significant improvement on CGAS but not on CAIS

Pharmacotherapy: Statistically significant differences favoring pharmacotherapy on pooled measures of symptom improvement and response

Statistically significant differences favoring pharmacotherapy on pooled CGAS but not on other measures of functioning

Mostly consistent; mostly precise Potential for bias from attrition

Additionally, CBT studies cannot mask treatments, leading to the potential for bias in outcomereporting

Moderate for anxiety symptoms, response, remission, and loss of diagnosis; low for functioning 15 CBT studies targeted any anxiety disorders; only 1 pharmacotherapy study targeted any anxiety disorders

Studies addressed youth aged 3 to 20 y, but 11 were conducted exclusively in adolescents

Psychotherapy studies were limited to CBT; pharmacotherapy studies were limited to drugs with FDA approval for pediatric use

KQ5: Harms of treatment
11 RCTs (4 on CBT; 6 on pharmacotherapy; 1 on CBT, sertraline, and combination)32-43,48-51,53,54,61-63,70 1293 Psychotherapy: Inconsistent results on suicide-related events; harms were events and were not statistically significant

Pharmacotherapy: More suicide-related events and withdrawals due to adverse events in the pharmacotherapy group, but harms were rare and not statistically significant

Consistent to mostly consistent; imprecise CBT interventions cannot mask treatment, leading to the potential for bias in outcome reporting Psychotherapy: insufficient evidence

Pharmacotherapy: low for harms

Two of 4 CBT studies included any anxiety disorders; 1 of 7 pharmacotherapy studies included any anxiety disorders

Studies addressed children aged 5 to 20 y, but 4 were conducted exclusively in adolescents

Psychotherapy studies were limited to CBT; pharmacotherapy studies were limited to drugs with FDA approval for pediatric use

Abbreviations: CAIS, Children’s Anxiety Impact Scale; CBT, cognitive behavioral therapy; CGAS, Children’s Global Assessment Scale; FDA, US Food and Drug Administration; KQ, key question; NA, not applicable; RCT, randomized clinical trial; SCARED, Screen for Anxiety Related Emotional Disorders; SPIN, Social Phobia Inventory.

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