Clinical Psychology Review: 10.1016/j.cpr.2016.09.006

Treating child and adolescent anxiety effectively: Overview of systematic
reviews
Kathryn Bennett, Katharina Manassis, Stephanie Duda, Alexa Bagnell,

Gail A. Bernstein, E. Jane Garland, Lynn D. Miller, Amanda Newton, Lehana
Thabane, Pamela Wilansky
PII: S0272-7358(16)30017-4
DOI: doi: 10.1016/j.cpr.2016.09.006
Reference: CPR 1545
To appear in: Clinical Psychology Review
Received date: 27 January 2016

Revised date: 30 August 2016
Accepted date: 18 September 2016
Please cite this article as: Bennett, K., Manassis, K., Duda, S., Bagnell, A., Bernstein,
G.A., Garland, E.J., Miller, L.D., Newton, A., Thabane, L. & Wilansky, P., Treating child
and adolescent anxiety effectively: Overview of systematic reviews, Clinical Psychology
Review (2016), doi: 10.1016/j.cpr.2016.09.006
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Running Head: TREATING CHILD AND ADOLESCENT ANXIETY 1
Treating Child and Adolescent Anxiety Effectively: Overview of Systematic Reviews
Kathryn Bennett a,*, Katharina Manassis b, Stephanie Duda a, Alexa Bagnell c, Gail A. Bernstein d,
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E. Jane Garland e, Lynn D. Miller f, Amanda Newton g, Lehana Thabane a, Pamela Wilansky b
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Author Note
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a
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton,
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Ontario, Canada; b Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; c
Department of Psychiatry, Dalhousie University and IWK Health Centre, Halifax, Nova Scotia,
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Canada; d Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, United
States of America; e Department of Psychiatry, University of British Columbia and BC

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Children’s Hospital, Vancouver, British Columbia, Canada; f Department of Educational and

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Counselling Psychology and Special Education, University of British Columbia, Vancouver,
British Columbia, Canada; g Department of Pediatrics, University of Alberta, Edmonton, Alberta,

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Canada
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This research was supported by a grant from the Canadian Institutes of Health Research (KA1-
119793).
*Address correspondence to: Kathryn Bennett, Department of Clinical Epidemiology and
Biostatistics, McMaster University, 1280 Main Street West., HSC 3V43D, Hamilton, Ontario,
L8S 4K1, Canada; kbennett@mcmaster.ca; 1-905-525-9140.

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TREATING CHILD AND ADOLESCENT ANXIETY 2
Abstract
We conducted an overview of systematic reviews about child and adolescent anxiety treatment
options (psychosocial; medication; combination; web/computer-based treatment) to support
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evidence informed decision-making. Three questions were addressed: (i) Is the treatment more
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effective than passive controls? (ii) Is there evidence that the treatment is superior to or non-
inferior to (i.e., as good as) active controls? (iii) What is the quality of evidence for the
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treatment? Pre-specified inclusion criteria identified high quality systematic reviews (2000-2015)
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reporting treatment effects on anxiety diagnosis and symptom severity. Evidence quality (EQ)
was rated using Oxford evidence levels [EQ1 (highest); EQ5 (lowest)]. Twenty-two of 39
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eligible reviews were high quality (AMSTAR score ≥3/5). CBT (individual or group, with or
without parents) was more effective than passive controls (EQ1). CBT effects compared to active
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controls were mixed (EQ1). SSRI/SNRI were more effective than placebo (EQ1) but
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comparative effectiveness remains uncertain. EQ for combination therapy could not be
determined. RCTs of web/computer-based interventions showed mixed results (EQ1).

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CBM/ABM was not more efficacious than active controls (EQ1). No other interventions could
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be rated. High quality RCTs support treatment with CBT and medication. Findings for
combination and web/computer-based treatment are encouraging but further RCTs are required.
Head-to-head comparisons of active treatment options are needed.
Keywords: Anxiety, Child, Adolescent, Clinical Decision Making, Therapeutics, Review

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Introduction
Anxiety disorders are the most common child and adolescent psychiatric conditions.
Worldwide it is estimated that 6.5% of 6 to 18 year olds suffer from at least one of the 11 anxiety
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sub-types [i.e., generalized anxiety disorder, panic disorder, agoraphobia, separation anxiety
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disorder, social anxiety disorder (social phobia), specific phobia, selective mutism,
substance/medication-induced anxiety disorder, anxiety disorder due to another medical
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condition, other specified anxiety disorder, and unspecified anxiety disorder] (Polanczyk, Salum,
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Sugaya, Caye, & Rohde, 2015). Anxiety disorders are characterized by excessive, persistent fear
or worry that inhibits functioning (American Psychiatric Association, 2013; Connolly, Bernstein,
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& the Work Group on Quality Issues, 2007). Somatic complaints such as stomachache may also
be reported (American Psychiatric Association, 2013; Connolly, Bernstein, & the Work Group
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on Quality Issues, 2007). Impairments associated with anxiety can be profound, pervading
activities of daily living and disrupting school performance and relationships with peers and
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family members (Connolly, Bernstein, & the Work Group on Quality Issues, 2007). In childhood,
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comorbidity between anxiety and other disorders may occur, for example attention deficit
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hyperactivity disorder, oppositional defiant disorder, and obsessive-compulsive disorder
(Kendall et al., 2010). Moreover, lifetime co-morbidity between anxiety and other disorders
(primarily depression) is substantial (Bittner et al., 2004; Bittner et al., 2007; Kessler et al., 1996;
Lewinsohn, Zinbarg, Seeley, Lewinsohn, & Sack, 1997; Regier et al., 1990). Anxiety disorders
during adolescence confer a strong risk for an anxiety or depressive disorder in adulthood
(Kessler et al., 1994; Kim-Cohen et al., 2003; Pine, Cohen, Gurley, Brook, & Ma, 1998).
Psychosocial interventions and medication (alone and in combination) (Ipser, Stein,
Hawkridge, & Hoppe, 2009; James, James, Cowdrey, Soler, & Choke, 2015; Walkup et al.,
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2008) and web/computer-based treatment (Reyes-Portillo et al., 2014) have been shown in
randomized controlled trials (RCTs) to reduce the prevalence and burden of suffering associated
with child and adolescent anxiety disorders. However, widely acknowledged barriers limit access
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to and use of this knowledge by practitioners and policymakers. These barriers centre on the
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large volume and variable quality of relevant primary studies, systematic reviews and meta-
analyses available in numerous peer-reviewed journals and research repositories (Grimshaw,
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Eccles, Lavis, Hill, & Squires, 2012; Hoagwood, Burns, Kiser, Ringeisen, & Schoenwald, 2001;
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Novins, Green, Legha, & Aarons, 2013). Practitioners and policymakers simply may not have
the time, or the skills, to search for and identify high-quality studies and reviews to guide their
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work. As a result, what is known about effective and ineffective treatment options may not be
considered when decisions are made about clinical care and health services.
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Overviews of systematic reviews (OSR) address these information needs and barriers to
research use (Becker & Oxman, 2008; Cooper & Koenka, 2012). Their purpose is twofold. First,
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they can facilitate rapid access to high quality, up-to-date, consolidated research evidence about
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the effectiveness of therapeutic intervention options for a specific health problem and thereby
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facilitate evidence informed decision-making by practitioners and health service decision-makers.
By focusing on findings reported in high quality systematic reviews and meta-analyses of all
available and relevant primary studies (i.e., the body of evidence), OSRs avoid demonstrated
risks associated with relying on the findings of single primary studies. For example, although a
single primary study may report a clinically and statistically significant treatment effect,
subsequent primary studies may fail to replicate this finding, and/or report a reduced treatment
effect size (Ioannidis, 2005a; Ioannidis, 2005b). Second, OSRs provide methods that can
generate new knowledge and inform future research agendas. Accordingly, OSR findings can
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contribute to: i) narrowing the research to practice gap by informing health care provider
knowledge and intentions, influencing care process decisions, and improving child and
adolescent anxiety outcomes; and ii) identifying important knowledge gaps that need to be
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addressed in new research and questions where further research is unlikely to substantively
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change our knowledge base.
One OSR about child and adolescent anxiety treatment is currently available, but it was
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published in 2010 and is limited to 3 reviews published in the Cochrane Database of Systematic
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Reviews (Manassis, Russell, & Newton, 2010). The OSR reported below addresses the need for
a comprehensive up-to-date synthesis that consolidates what we know and don’t know about
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effective anxiety treatment drawing on both Cochrane as well as non-Cochrane systematic
reviews and meta-analyses published in the peer-reviewed literature. Three questions about
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anxiety treatment options [psychosocial intervention, medication, combined treatment (i.e.,
psychosocial intervention combined with medication), and web-based treatment] selected to

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inform decisions that practitioners and policymakers routinely face are addressed: (i) Does the
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treatment reduce the presence of an anxiety diagnosis or symptom severity compared to passive
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controls at (a) post-treatment and (b) follow-up? (ii) Is there evidence that the treatment is
superior to or non-inferior to (i.e., as good as) active controls at (a) post-treatment and (b)
follow-up? and (iii) What is the quality of evidence for the treatment?
Methods
This OSR adheres to Cochrane Collaboration methods and PRISMA (Preferred Reporting
Items for Systematic Reviews and Meta-Analyses) reporting standards (Higgins & Green, 2011;
Moher, Liberati, Tetzlaff, Altman, & The PRISMA Group, 2009). Since reporting standards
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specific to OSRs are not currently available we followed guidance provided by (Hartling,
Chisholm, Thomson, & Dryden, 2012). The protocol is available from the authors upon request.
Literature Search
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A research librarian (MR) searched the following databases from January 2000 to
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September 2015 to identify systematic reviews and meta-analyses of treatment interventions for
anxiety in children and adolescents: MEDLINE (including HealthSTAR), PsycINFO (including
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Dissertation Abstracts International), EMBASE, CINAHL, the Cochrane Database of Systematic
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Reviews (CDSR), Social Science Abstracts, and Applied Social Sciences Index and Abstracts
(ASSIA). The search strategy was developed for MEDLINE and adapted for the other databases
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as required. The MEDLINE-OVID search strategy is shown in Appendix A, available online.
Similar strategies were used for other databases and are available from the first author.
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Review Inclusion/Exclusion Criteria
Reviews meeting the following criteria were eligible: i) any review that labeled itself a
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systematic review or meta-analysis, or any review that reported minimum methodologic features
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of a systematic review – namely a description of a non-selective literature search strategy and

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explicit primary study inclusion/exclusion criteria; ii) published in English in the peer-reviewed
literature or CDSR since the year 2000; iii) reviewed the effectiveness of at least one DSM-5
anxiety diagnosis treatment (American Psychiatric Association, 2013); iv) population aged 18
years or younger (inclusion of participants > 18 years of age was permitted as long as findings
for youth ≤ 18 years of age could be extracted); v) included RCTs or controlled clinical trials
(CCT; inclusion of other study designs was permitted as long as findings from RCTs and CCTs
could be extracted); and vi) outcomes reported included anxiety diagnosis or anxiety symptom
scores. Reviews focused solely on obsessive-compulsive disorder (OCD) or post-traumatic stress

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disorder (PTSD) were excluded as these disorders require distinct therapeutic approaches and are
no longer classified as anxiety disorders in DSM-5 (American Psychiatric Association, 2013).
Finally, some reviews reported on more than one type of treatment comparison, for example,
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CBT versus waitlist and CBT versus attention controls. When this was the case, we required that
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the review include at least 2 RCTs or CCTs for a given comparison for us to include the results
in our synthesis.
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Screening, Quality Assessment and Data Extraction
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First, reviewers participated in training sessions. Two reviewers received a detailed
introduction to the study protocol and then independently screened a sub-sample of retrieved
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records (n = 25) to pilot test screening forms. Disagreements were resolved through discussion
with the principal investigator. In addition, inter rater reliability was measured using the kappa
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statistic (Higgins & Deeks, 2011; Orwin, 1994). When kappa was less than excellent (i.e., <
0.75) screening forms were revised for clarity and re-piloted until excellent agreement was
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achieved (Higgins & Deeks, 2011; Orwin, 1994). Similar processes were used for training
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reviewers in the use of the quality assessment and data extraction forms.
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Following training, two reviewers completed screening, quality assessment and data
extraction independently. Disagreements were resolved through consultation with the principal
investigator (KB). Eligible reviews were quality assessed using AMSTAR, a measurement tool
used to assess the methodological quality of systematic reviews (Shea et al., 2007). Quality
scores were based on five AMSTAR items that align with the Cochrane risk of bias criteria
(Higgins, Altman, Sterne, Cochrane Statistical Methods Group, & Cochrane Bias Methods
Group, 2011): i) a priori design provided; ii) comprehensive literature search; iii) included and
excluded studies provided; iv) characteristics of included studies provided; and v) appropriate
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use of scientific quality in formulating conclusions. The five items were selected based on the
judgment of the author team. Reviews that achieved ≥ 3/5 of these AMSTAR items were eligible
for inclusion in our OSR. This method was designed to exclude reviews that did not meet
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minimal criteria related to avoiding risk of bias. Data from eligible reviews was extracted using a
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standardized form.
Treatment Categories
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Treatments reported in eligible reviews were classified as: i) psychosocial treatment; ii)
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medication; iii) combined psychosocial and medication; iv) web/computer-based treatment; and
v) other. Categories i through iii were restricted to treatments provided through face-to-face
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interaction with a clinician service provider with no web-based component. In Category iv, the
main treatment delivery modality was web/computer-based with little or no face-to-face

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interaction with a clinician. Category v allowed the identification of additional strategies that
emerged during the review process.

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Control Groups
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Passive controls were defined as waitlist controls or no intervention. Active controls

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included placebo controls, attention controls, treatment as usual (TAU) or other active treatments.
Outcomes
Evidence of anxiety treatment effectiveness was sought at post-treatment and follow-up
for: i) anxiety disorder remission; or ii) anxiety symptom reduction.
Summary Statistics
Effect sizes are reported as odds ratios (OR) or relative risk/risk ratio (RR) for categorical
outcomes. Standardized mean differences (SMD) and 95% confidence intervals (CI) derived
using Cohen’s d or Hedges’ g are provided for continuous outcomes (Norman & Streiner, 2008).
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Pooled effect size estimates are reported whenever available (i.e., systematic reviews with a
meta-analysis). Study level effect sizes are reported when no pooled data are available, or to
supplement available pooled data.
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Evidence Quality Rating
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Oxford levels of evidence were used to evaluate evidence quality (EQ) for specific
interventions as follows: Level 1 – systematic review of RCTs; Level 2 – RCT or observational
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study with large effect size; Level 3 – non-randomized CCT; Level 4 – Case-series, case-control
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studies, or historically controlled studies; and Level 5 – Mechanism-based reasoning (Oxford
Centre for Evidence Based Medicine Levels of Evidence Working Group, 2011).
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Results
Search and Screening

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Nine hundred sixty two unduplicated records were identified by our search and screened
for eligibility as shown in Figure 1. Following quality assessment using AMSTAR, 22/39
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(56.4%) eligible reviews were deemed high quality and included for full review. Reviews not
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meeting quality criteria (n = 17) are listed in Appendix B, available online. Appendix C
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(available online) shows complete AMSTAR ratings for all 11 items for all 39 reviews.
Eligible Review Characteristics
Table 1 displays the characteristics of the 22 eligible reviews grouped by treatment type.
Thirteen reviews reported the effects of psychosocial interventions. Eleven of the 13 reviews
employed meta-analytic methods and provide pooled estimates of treatment effect size. Study
level data are reported for the two systematic reviews that did not contain pooled estimates. Four
reviews synthesized medication studies. All four contained meta-analyses, but one review
included adults in the pooled effect size reported. Therefore, we extracted study level data
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relevant to children and adolescents from this review. No review synthesized two or more studies
on combination treatment (i.e., psychosocial treatment with medication). Five reviews reported
on web/computer-based treatment. Two of the five contained meta-analyses, but one of these
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meta-analyses included primary studies that did not meet our eligibility criteria (see Table 1 for
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reasons). Therefore, for this review we report study level data from included studies that met our
inclusion criteria. Study level data are also reported from the three systematic reviews that did
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not contain pooled effect sizes.
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Ten of 22 eligible reviews report on anxiety diagnosis remission. Among these 10, only 4
reviews specified the type of diagnostic remission reported. Specifically, primary anxiety
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disorder remission was reported in three reviews and any anxiety disorder remission was
reported in one review. Eighteen of 22 reviews report on anxiety symptom reduction. Amongst
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these 18, only 1 review specified the sub-type of anxiety disorder symptoms reported, namely,
social anxiety disorder. Finally, the eligible treatment comparisons within each included review
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as well as the instances where data was not extracted from a given review because it failed to
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meet our OSR eligibility criteria are noted (specific reasons provided in Table 1).
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Psychosocial Interventions
Thirteen reviews reported on the effectiveness of psychosocial interventions. We report
the effects of cognitive behavioral therapy (CBT) compared to passive and active controls first,
followed by what is known about the effects of other types of psychosocial interventions.
Cognitive behavioral therapy (CBT).
Question 1a: Is the treatment effective compared to passive controls at post-treatment?
Six reviews (Cartwright-Hatton, Roberts, Chitsabesan, Fothergill, & Harrington, 2004; Chu &
Harrison, 2007; Ewing, Monsen, Thompson, Cartwright-Hatton, & Field, 2015; James et al.,
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2015; Reynolds, Wilson, Austin, & Hooper, 2012; Silverman, Pina, & Viswesvaran, 2008)
provided pooled data on the effect of CBT compared to waitlist controls and all reported that
CBT was clinically and statistically significantly better than waitlist controls at post-treatment
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(Table 2). Specifically, three of six reviews reported on anxiety diagnosis remission and found
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the odds of remission were 3.27-7.85 times higher amongst those receiving CBT compared to
passive controls (Cartwright-Hatton et al., 2004; Ewing et al., 2015; James et al., 2015). One of
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the three reviews specified that diagnostic remission pertained to any anxiety disorder (James et
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al., 2015); two did not specify (Cartwright-Hatton et al., 2004; Ewing et al., 2015). Four of six
reviews reported on anxiety symptom outcomes with three reviews reporting a statistically
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significant reduction [based on child/adolescent report in two reviews (James et al., 2015;
Reynolds et al., 2012); informant not specified in one review (Chu & Harrison, 2007)]. However,
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a fourth review reported a statistically significant reduction in anxiety symptoms based on
child/adolescent reports (k=37), but no statistically significant difference based on parent report
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(k=4) (Silverman et al., 2008). This difference may be explained by inadequate statistical power.
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Two reviews (James et al., 2015; Silverman et al., 2008) investigated the effect of CBT
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format (i.e., individual or group; child focused or family/parental CBT) compared to waitlist
controls based on pooled analyses. One review addressed diagnostic remission and reported each
CBT format led to statistically significant anxiety remission compared to waitlist controls (James
et al., 2015). Both reviews reported on anxiety symptom reduction and concluded that all formats
were statistically significantly superior to waitlist controls for anxiety symptom reduction at
post-treatment (James et al., 2015; Silverman et al., 2008).
Question 1b: Is the treatment effective compared to passive controls at follow-up? One
review addressed this question using pooled data and reported no statistically significant
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difference between CBT and waitlist controls at follow-up for anxiety diagnosis remission (k=3
RCTs) or symptom reduction (k=4 RCTs) (James et al., 2015). Duration of follow-up varied
from 6 to 24 months in the 3 trials that reported length of follow-up (James et al., 2015). Table
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D.1 in Appendix D (available online) presents available follow-up outcome data.
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Question 2a: Is there evidence that the treatment is superior to or non-inferior to (i.e.,
as good as) active controls at post-treatment?
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CBT versus non-CBT active controls (i.e., attention controls, placebo or informal
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psychosocial treatments that do not include CBT elements). Three reviews (Chu & Harrison,
2007; James et al., 2015; Reynolds et al., 2012) addressed this question using pooled data (see
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Table 3). James et al (2015) reported based on 9 unique RCTs that CBT did not differ from
active controls with respect to remission of anxiety diagnosis (k=6 RCTs), or reduced symptom
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severity (k=8 RCTs) at post-treatment. In contrast, Chu and Harrison (2007) and Reynolds et al
(2012) reported that CBT reduced anxiety symptoms at post-treatment compared to active
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controls. However, four of the five RCTs included in the Chu and Harrison review (2007) were
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not included in the James et al (2015) review. Three did not meet James’ inclusion criteria; the
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fourth study is not mentioned by James. Reynolds et al (2012) based their findings on 14 RCTs
of CBT, but the specific studies included in their analysis are not reported. It is possible
Reynolds et al included PTSD and OCD treatment studies, and this may explain the discordant
findings regarding anxiety symptom reduction at post-treatment.
CBT versus TAU. One review reported on this comparison. James et al (2015) pooled
RCT data comparing CBT and TAU and found no statistically significant difference in
diagnostic remission (k=2 RCTs) or symptom reduction (k=3 RCTs) at post-treatment (Table 3).
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Individual versus group CBT. No reviews provided pooled or study level data from
RCTs/CCTs that conducted direct comparisons of these two treatment formats.
Child-focused CBT versus CBT with family/parent involvement. One review provided
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pooled post-treatment data on this comparison (Table 3). Thulin, Svirsky, Serlachius, Andersson
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and Ost (2014) reported no statistically significant difference in anxiety diagnosis remission
(k=14 RCTs) or symptom reduction (k=16 RCTs) based on pooled data comparing CBT with
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family/parent involvement and child-focused CBT.
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CBT versus medication. One review reported on this comparison. Segool and Carlson
(2008) compared the pooled effects of CBT treatments to the pooled effects of selective
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serotonin reuptake inhibitors (SSRIs) and concluded SSRIs were more effective than CBT in
reducing social anxiety symptoms. However, because their results were based on between study
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comparisons of effect size, not direct comparisons of CBT and medication conducted within the
same study, confirmation based on within study comparisons obtained in RCTs comparing
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groups of youth who received either SSRI or CBT is required. No review synthesized studies of
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this type, since only one RCT is currently available which enables a comparison of groups of
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youth who received CBT alone or medication alone (Walkup et al., 2008).
Question 2b: Is there evidence that the treatment is superior to or non-inferior to (i.e.,
as good as) active controls at follow-up?
CBT versus non-CBT active controls (i.e., attention controls, placebo or informal
psychosocial treatments that do not include CBT elements). One review examined this question.
James et al (2015) provided pooled data on the effect of CBT compared to non-CBT active
controls at follow-up (see Table D.2 in Appendix D, available online). CBT was observed to out-
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perform active controls with respect to diagnostic remission (k=2 RCTs) but not symptomatic
reduction (k=4 RCTs) (James et al., 2015).
CBT versus TAU. No review addressed the effects of CBT compared to TAU at follow-
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up.
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Child-focused CBT versus CBT with family/parent involvement. One review, Thulin et al
(2014), provided pooled data comparing CBT with family/parent involvement to child-focused
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CBT at follow-up and reported no statistically significant difference for anxiety diagnosis
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remission or symptom reduction (see Table D.2 in Appendix D, available online).
CBT versus medication. No review addressed the effects of CBT versus medication at
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follow-up.
Other psychosocial interventions.

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No review addressed the effects of a specific non-CBT psychosocial intervention for anxiety
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compared to passive controls at post-treatment.

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Question 1b: Is the treatment effective compared to passive controls at follow-up? No

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review addressed the effects of a specific non-CBT psychosocial intervention for anxiety
compared to passive controls at follow-up.
as good as) active controls at post-treatment? Two reviews provided pooled data on cognitive
bias modification (CBM) and attention bias modification (ABM), both conceptually similar non-
CBT psychosocial interventions, in comparison with active controls at post-treatment.
Specifically, a meta-analysis of 15 RCTs of CBM/ABM conducted by Cristea, Mogoase, David
and Cuijpers (2015) revealed a small, statistically non-significant reduction in anxiety outcomes
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(SMD = -0.17, 95% CI = -0.36 to 0.01). Similarly, Pennant et al (2015) pooled 2 RCTs of ABM
and reported no statistically significant difference in anxiety symptoms compared to active
controls (SMD = -0.19, 95% CI = -0.69 to 0.32). Using study level data, Lowther and Newman
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(2014) reported reductions in anxiety symptoms in 5 out of 6 studies of ABM compared to ABM
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controls, but p-values and CIs were not reported.
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as good as)active controls at follow-up? No review examined the effects of a non-CBT
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psychosocial intervention compared to active controls at follow-up.
Other eligible reviews of psychosocial interventions not discussed above. Erford,

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Kress, Giguere, Cieri and Erford (2015) pooled studies of different types of counseling and
psychotherapy interventions [e.g., CBT, behavioral treatment, social effectiveness training (SET),
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skills for social and academic success (SSAS), eye movement desensitization and reprocessing
(EMDR), psychodynamic therapy, parenting interventions, bibliotherapy, emotive imagery,

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school-based interventions, etc.] compared to three different types of controls – waitlist, placebo
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and TAU – at both post-treatment and follow-up. These authors concluded that counseling and
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psychotherapy interventions considered as one group produce a statistically significant reduction
in anxiety symptoms at post-treatment when compared with each of three control group types
(i.e., waitlist controls, placebo and TAU). Statistically significant symptom reductions were also
found at follow-up for comparisons against waitlist and placebo, but not TAU. Unfortunately,
because different intervention types were included in each pooled analysis it is not possible to
draw conclusions about the effects of specific types of interventions. Data for Erford et al (2015)
are reported in Table D.3 in Appendix D (available online).

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Finally, Davis, Mansur de Souza, Rigatti and Heldt (2014) conducted a systematic review
of RCTs of CBT that included a follow-up period of 12 months or greater. Although the review
concluded that CBT benefits were maintained at follow-up, 5/10 eligible studies did not meet our
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eligibility criteria (see Table 1 for reasons).
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Medication
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This question is not applicable to reviews of medication trials.
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Question 1b: Is the treatment effective compared to passive controls at follow-up? This
question is not applicable to reviews of medication trials.

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as good as) active controls at post-treatment?

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Medication versus placebo. Three reviews (Ipser et al., 2009; Strawn, Welge, Wehry,
Keeshin, & Rynn, 2015; Uthman & Abdulmalik, 2010) provided pooled data on the effect of
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medication compared to placebo. Strawn et al (2015) pooled 9 placebo controlled RCTs of

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SSRIs [fluoxetine (k=2), fluvoxamine (k=1), paroxetine (k=1), sertraline (k=2)] and selective
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norepinephrine reuptake inhibitors (SNRI) [venlafaxine (k=2), duloxetine (k=1)] and found a
statistically significant reduction in anxiety symptoms at post-treatment favoring SSRIs/SNRIs
(SMD = 0.62, 95% CI = 0.34 to 0.89, p<0.05). Ipser et al (2009) pooled 9 placebo controlled
RCTs and concluded that SSRIs [fluoxetine (k=3), fluvoxamine (k=1), paroxetine (k=1),
sertraline (k=2)] and SNRIs [venlafaxine (k=2)] were about twice as effective as placebo in
improving ratings on the Clinical Global Impressions Improvement Scale (CGI-I; RR = 2.01,
95% CI = 1.59 to 2.55, p<0.05). Statistically significant symptom scale score reductions were
also found (SMD = -0.82, 95% CI = -1.30 to -0.33, p< 0.05) based on 4 RCTs [fluoxetine (k=1),
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fluvoxamine (k=1), and sertraline (k=2)] that compared SSRI versus placebo (Ipser et al., 2009).
Uthman and Abdulmalik (2010) (Table 4) concluded that SSRI/SNRI are superior to placebo
based on five separate pooled analyses of RCTs of the following drugs [SSRIs: fluoxetine (k=6),
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fluvoxamine (k=2), paroxetine (k=2), sertraline (k=4); SNRI: venlafaxine (k=2)]. Study level
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data provided by Hidalgo, Tupler and Davidson (2007) on anxiety symptom reduction amongst
children and adolescents treated with SSRIs for generalized anxiety disorder were concordant
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(statistically significant effect in favor of SSRIs based on two RCTs [sertraline, k=1 and
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fluvoxamine, k=1]).
Comparisons of alternate medications. Uthman and Abdulmalik (2010) conducted pair-

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wise comparisons between each of five medications (fluoxetine, fluvoxamine, paroxetine,
sertraline, and venlafaxine) using network meta-analysis. This method, which uses direct and
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indirect evidence from available trials, synthesizes evidence from networks of RCTs in order to
“permit inferences into the comparative effectiveness of interventions that may or may not have
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been evaluated directly against each other” (Mills, Thorlund, & Ioannidis, 2013). Table 5 shows
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RR and critical intervals [interpreted as a 95% probability that the parameter takes a value in this
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range (Statisticat, Year Not Reported; Uthman & Abdulmalik, 2010)] for all possible
comparisons. Venlafaxine was found to be less efficacious than fluvoxamine and paroxetine
(Uthman & Abdulmalik, 2010).
as good as) active controls at follow-up? Follow-up data were not available in eligible reviews.
Combined Therapies
No review included two or more studies of combination therapy.
Web/computer-based Treatment
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One review provided pooled data on the effects of web/computer-based CBT interventions
compared to passive controls at post-treatment. Specifically, Ebert et al (2015) reported a
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statistically significant reduction in anxiety symptoms at post treatment (SMD = 0.68, 95% CI =
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0.45 to 0.92, p<0.05) based on 7 RCTs (BRAVE ONLINE, k=2; Camp Cope-A-Lot, k=1; Cool
Teens, k=1; program unspecified, k=3). However, 3 of the 7 trials are not relevant to our
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research question (one trial focused on participants with OCD, one trial included participants up
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to age 21, and one trial used a placebo control).
Four reviews provided study-level data on the BRAVE ONLINE program (Calear &
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Christensen, 2010; Reyes-Portillo et al., 2014; Richardson, Stallard, & Velleman, 2010; Ye et al.,
2014). Three of them reported effects on anxiety remission diagnosis (Reyes-Portillo et al., 2014;
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Richardson et al., 2010; Ye et al., 2014). Specifically, Reyes-Portillo et al (2014) reported that
two trials comparing BRAVE (Clinic), BRAVE (Internet) and waitlist control found statistically
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significant anxiety diagnosis remission in each of the BRAVE conditions compared to waitlist
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while one trial found no significant difference in anxiety diagnosis remission between BRAVE
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(Internet) and waitlist control. The other two reviews also reported mixed results for anxiety
diagnosis remission. Three of the four reviews reported BRAVE ONLINE effects on anxiety
symptoms. All three reported a statistically significant reduction in anxiety symptoms (Calear &
Christensen, 2010; Richardson et al., 2010; Ye et al., 2014).
Question 1b: Is the treatment effective compared to passive controls at follow-up? No
review provided follow-up data based on two or more studies of web/computer-based
interventions compared to passive controls.

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as good as) active controls at post-treatment? No review provided pooled data to answer this
question. Study level data from Reyes-Portillo et al (2014) revealed two trials compared BRAVE
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(Clinic) and BRAVE (Internet) and reported no statistically significant differences between
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conditions at post-treatment.
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as good as) active controls at follow-up? Reyes-Portillo et al (2014) reported no significant
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difference between BRAVE (Clinic) and BRAVE (Internet) at 6 month or 12 month follow-up
based on two trials.

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What is the Evidence Quality?
Evidence summaries and Oxford EQ levels for specific interventions are as follows: (i)
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CBT regardless of format (individual or group, with or without parents) was significantly more
effective than passive controls (EQ1); (ii) findings for CBT compared to active controls were
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mixed at post-treatment and follow-up (EQ1); (iii) CBM/ABM is not more effective than active
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controls (EQ 1); (iv) SSRI/SNRI are statistically significantly more effective than placebo (EQ1)
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but comparative effectiveness is uncertain; (v) EQ for combination therapy could not be
determined; and (vi) RCTs of web/computer-based interventions showed mixed results (EQ1).
No other interventions could be rated.
Discussion
Main Findings
Treatment of child and adolescent anxiety with either CBT or SSRI/SNRI is supported by
high quality research (EQ1). Relevant reviews were concordant that CBT, regardless of format
(e.g., individual or group CBT, with or without parent involvement), is superior to waitlist
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controls at post-treatment and follow-up. However, regarding CBT compared to active controls,
relevant high quality reviews revealed that few RCTs are currently available, their results at post-
treatment and follow-up are mixed, and further RCTs are needed to draw conclusions about
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whether CBT is superior, equivalent or inferior to other active controls. Only one review
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addressed whether CBT with parent/family involvement was superior to child only CBT and
reported no difference in anxiety diagnosis remission or anxiety symptom reduction.
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Similarly, reviews of medication treatment effects were concordant. Compared to placebo,
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pooled analyses of RCTs showed that four SSRIs (i.e., fluoxetine, fluvoxamine, paroxetine,
sertraline) and one SNRI (i.e., venlafaxine) are associated with benefit on the CGI-I. However,
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RCTs of between-drug comparisons have not been conducted and are needed. Comparative
effectiveness findings based on a network meta-analysis are available, but questions concerning
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validity and the interpretation of network meta-analysis findings require further investigation
(Mills et al., 2013; Puhan et al., 2014).

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Findings from the sole RCT of combination therapy, the Child/Adolescent Anxiety
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Multimodal Study (CAMS) (Walkup et al., 2008) show that combination therapy (CBT plus
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sertraline) is superior to CBT alone, sertraline alone and placebo at post-treatment. Uncontrolled
follow-up data showed that most CAMS-treated youth experienced sustained treatment benefit at
24 and 36 weeks although the magnitude of effect of combination therapy and monotherapy may
converge over time (Piacentini et al., 2014). Taken together, results for combination therapy are
encouraging, but replication is needed including RCTs conducted in youth representing other
ethnicities and socio-economic backgrounds, as well as youth who are older than age 12.
CBT has been evaluated more often than any other treatment for child and adolescent
anxiety. Only two reviews reported on the effectiveness of any other specific psychosocial
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intervention, namely CBM/ABM. Reviews were concordant that this approach does not result in
statistically significant reductions in anxiety symptoms compared to active controls. Whether
CBM/ABM may augment the benefits of other treatments is currently being investigated (for
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example, Riemann, Kuckertz, Rozenman, Weersing, & Amir, 2013).
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Findings for combination and web/computer-based treatment are encouraging but call for
further research . Relevant reviews were concordant that the small number of variable quality
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RCTs comparing web/computer-based strategies to passive and active controls provide mixed
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results that can inform further studies of promising and newly emerging approaches.
Practitioners and policymakers who face barriers related to the time and special skills
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required to find and use research evidence can use the evidence assembled in this OSR to guide
decisions about individual patients, and the provision of effective services within health systems.
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Researchers can use this OSR to identify critical knowledge gaps and areas where further
research is unlikely to substantively change our knowledge base. For example, our findings
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reveal the need for: head-to-head comparisons; trials that assist with decisions regarding whether
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and how specific treatments should be integrated into treatment pathways; controlled long-term
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follow-up studies; identification of treatment outcome moderators; and studies to elucidate
causal mechanisms associated with specific psychotherapies.
Rigor of Systematic Reviews/Meta-analyses
We found significant gaps in the methodologic quality of currently available systematic
reviews and meta-analyses relevant to anxiety treatment effects in children and adolescents.
Forty-four percent of eligible reviews (17/39) were excluded because they did not meet
minimum risk of bias quality criteria assessed using AMSTAR. Excluded reviews failed to: i)
provide an ‘a priori’ design (3/17 excluded reviews); ii) perform a comprehensive literature
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search (15/17 excluded reviews); iii) document which studies were included and excluded (17/17
excluded reviews); iv) report the characteristics of included studies (8/17 excluded reviews); and
v) consider the quality of included studies when formulating review conclusions (16/17 excluded
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reviews). Failure to perform a comprehensive literature search may result in the omission of
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relevant, high quality primary studies. Lack of information about included and excluded studies
leaves open to question whether effect size estimates may be biased due to the inappropriate
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inclusion or exclusion of specific primary studies. Similarly, failure to report the methodologic
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quality of included primary studies precludes judgments regarding whether effect size estimates
may be biased. Authors of systematic reviews and meta-analyses also need to ensure their
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methods specify anxiety treatment outcomes in terms of remission of the primary anxiety
disorder, any anxiety disorder or specific sub-types (for example) so that review findings can be
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interpreted appropriately.
Increased adherence to international methodologic standards is needed to improve the

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quality of systematic reviews/meta-analyses relevant to the treatment of child and adolescent

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anxiety. The weaknesses we identified can be easily remedied in future reviews, increasing the
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level of certainty that can be attached to review conclusions and reducing the harm and waste
that may be caused if practitioners and policymakers make decisions based on flawed reviews.
For example, collaboration between groups working on the same synthesis questions can
facilitate achievement of labor intensive quality criteria resulting in fewer, yet higher quality
systematic reviews and meta-analyses.
Strengths and Limitations
The strengths of this OSR centre on the use of Cochrane Collaboration methods to search,
identify, assemble and critically appraise eligible systematic reviews and meta-analyses. For
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example, we posed explicit review questions that followed a PICOT (population, intervention,
comparison, outcome, time) (Guyatt, Meade, Richardson, & Jaeschke, 2008) format specifying
the population (adolescents ≤ 18 years of age with DSM-5 anxiety diagnosis), interventions
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(psychosocial, medication, combination, web/computer-based), comparisons (passive or active
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controls), outcomes (anxiety diagnosis remission; anxiety symptom reduction) and timing (post-
treatment and follow-up). We evaluated the quality of the reviews using AMSTAR, a reliable
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and valid quality assessment tool. We excluded reviews that did not achieve ≥3/5 on 5 AMSTAR
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items that align with Cochrane risk of bias criteria. The goal was to ensure that all included
reviews met minimum standards regarding minimizing the potential for risk of bias in the
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findings reported. Our methods called for: i) reviewer training; ii) duplicate screening, quality
assessment, and data extraction; and iii) consensus resolution of inter-rater differences to
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minimize the likelihood of error or misinterpretation of the content of eligible reviews. Quality
of evidence ratings are provided using widely recognized Oxford levels of evidence to
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communicate the strength of evidence supporting each OSR finding. Finally, our methods enable
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the identification of discordant reviews; one instance occurred and methodologic reasons for the
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difference are provided.
Potential limitations of this OSR are as follows. First, our review revealed that only 5/22
of the included high quality reviews specified whether the anxiety outcomes reported pertained
to the primary anxiety disorder, any anxiety disorder or a specific type of anxiety disorder. Thus,
the specificity of our findings with respect to anxiety outcomes is limited by what is available in
the included reviews. A second potential limitation concerns the paucity of data available on the
sustainability of CBT treatment effects. We report review findings at post treatment and follow-
up, but the inclusion of controlled follow-up data in primary studies is limited. However, as
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noted above, uncontrolled follow-up data collected from CAMS participants at 24 and 36 months
is encouraging as is uncontrolled follow-up data from two older trials of CBT (Benjamin,
Harrison, Settipani, Brodman, & Kendall, 2013; Piacentini et al., 2014). A third possible
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limitation concerns the currency of the included reviews, and the possibility that primary studies
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have been missed that could change our conclusions (Cooper & Koenka, 2012; Moher et al.,
2008; Pieper, Buechter, Jerinic, & Eikermann, 2012; Shojania et al., 2007; Smith, Devane,
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Begley, & Clarke, 2011; Thomson et al., 2013). At present, there is no consensus on whether or
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not OSR should include a synthesis of primary studies published after the included reviews.
Pieper et al (2012) note that only 5% of the 126 overviews included in their systematic review of
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overview quality included a search for primary studies and state that little empirical evidence is
available to guide decisions about when and how to update reviews. Our search strategy included
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any review published up to September 2015. We did not search for primary studies published
after the time period covered by included reviews. However, given the currency of the included
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reviews it seems unlikely that we have missed new primary studies that would change our
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overall conclusions in any substantive way. Fourth, there is overlap between eligible reviews in
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the primary studies included. However, because the goal of this OSR is to synthesize eligible
reviews with respect to concordant and discordant conclusions and possible explanations, and
not to pool data to estimate treatment effect size, double counting of primary studies due to
overlap between individual reviews is not a source of bias in our findings or conclusions. Fifth,
because consensus on the best method to deal with poor quality reviews in OSRs has not yet
been determined, the selection of AMSTAR items used to identify high quality reviews eligible
for inclusion in this OSR was based on the judgment of our author team. Empirical evidence
examining the potential for risk of bias associated with including or excluding poor quality
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reviews is needed to evaluate the extent which our approach introduced limitations into our
findings and conclusions. Finally, practitioners and policymakers need to note that most primary
studies included in the eligible reviews were conducted under ideal conditions and therefore
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constitute evaluations of treatment efficacy, rather than effectiveness.
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Conclusion
Much is known about interventions to treat child and adolescent anxiety. This OSR consolidates
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that knowledge in order to facilitate evidence-informed decision-making by clinicians, policy-
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makers, youth and their families. At the same time, important knowledge gaps are evident.
Increased attention to these gaps by researchers is needed to advance knowledge and further
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strengthen the foundations of clinical practice and mental health services for youth affected by
anxiety disorders.
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Acknowledgements: Maureen Rice, MA, MLIS, McMaster University, Hamilton, Ontario
designed and performed the literature search.

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Psychology, 37, 105-130. MA

Smith, V., Devane, D., Begley, C., & Clarke, M. (2011). Methodology in conducting a systematic
ED
review of systematic reviews of healthcare interventions. BMC Medical Research Methodology,
11(1), 15.
PT
Statisticat, L. (Year Not Reported). Probability intervals vs. confidence intervals. Retrieved from
CE
http://www.bayesian-inference.com/credible.
AC
Strawn, J. R., Welge, J. A., Wehry, A. M., Keeshin, B., & Rynn, M. A. (2015). Efficacy and tolerability
of antidepressants in pediatric anxiety disorders: A systematic review and meta-analysis.
Depression and Anxiety, 32, 149-157.
Thomson, D., Foisy, M., Oleszcuk, M., Wingert, A., Chisholm, A., & Hartling, L. (2013). Overview of
reviews in child health: Evidence synthesis and the knowledge base for a specific population.
Evidence-Based Child Health: A Cochrane Review Journal, 8, 3-10.

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Thulin, U., Svirsky, L., Serlachius, E., Andersson, G., & Ost, L. (2014). The effect of parent
involvement in the treatment of anxiety disorders in children: A meta-analysis. Cognitive Behaviour
Therapy, 43(3), 185-200.
P T
Uthman, O. A., & Abdulmalik, J. (2010). Comparative efficacy and acceptability of
RI
pharmacotherapeutic agents for anxiety disorders in children and adolescents: a mixed treatment
SC
comparison meta-analysis. Current Medical Research and Opinion, 26(1), 53-59.
NU
Walkup, J. T., Albano, A. M., Piacentini, J., Birmaher, B., Compton, S. N., Sherrill, J. T., . . . Kendall,
P. C. (2008). Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety. New

MA
England Journal of Medicine, 359(26), 2753-2766.
ED
Ye, X., Bapuji, S. B., Winters, S. E., Struthers, A., Raynard, M., Metge, C., . . . Sutherland, K. (2014).
Effectiveness of internet-based intervention for children, youth and young adults with anxiety
PT
and/or depression: A systematic review and meta-analysis. BMC Health Services Research, 14, 313.
CE
AC
ACCEPTED MANUSCRIPT
Figure 1: PRISMA Flow Diagram

Identification
P T
1347 records identified through database 4 additional records identified
searching through other sources
RI
SC
962 records after duplicates removed
Screening
NU
730 records excluded
962 records screened + 24 full-text articles not
found
MA
Eligibility
208 full-text articles assessed 169 full-text articles excluded; reasons:

for eligibility  Not a systematic review or meta-
ED
analysis (n=82)
 Not English (n=4)
 Not published in peer reviewed
39 Eligible Reviews literature (n=2)
PT
 Did not review the

efficacy/effectiveness of
Included
interventions designed to treat

CE
22/39 Reviews anxiety disorders (n=48)

(AMSTAR RoB Score ≥ 3)  Did not include extractable data re:
youth ≤ 18 years of age (n=10)
 Did not include RCTs or CCTs as
AC
primary studies (n=6)

 Outcomes did not include anxiety
diagnosis or symptoms (n=3)
 Review includes < 2 RCTs or
CCTs on a specific anxiety
treatment in youth ≤ 18 years of
age (n=9)
 Out of Date Review (n=2)
 Analytic Errors (n=2)
 Comparison (Control) Groups Not
Reported (n=1)
ACCEPTED MANUSCRIPT
Table 1: Review Characteristics and Data Eligible for Inclusion in OSR

Review Review Data
Characteristi Review Data Eligible for OSR Not Eligible for
cs OSR
Anxiet
Anxiety
y
T
Outcomes
Primary Studies with Eligible, Extractable Data #, (%)

Outco
Specified
P
mes
RI
Total Included Primary Studies, #
Specific Anxiety Disorder Sub-Type

SC
Study Level Effect Size
Last Year Searched
Age Range (years)

Pooled Effect Size
AMSTAR Score
Primary Anxiety Disorder

Any Anxiety Disorder
Review
Symptom Reduction
Diagnosis Remission
Eligible Primary Studies
NU
MA
Not Specified
Comparisons, # Excluded with
Studies Reason, #
MA
ED
PT
Psychosocial Interventions
15/  CBM/ABM  8/23
(Criste
20 2 23 vs. Control, k 9.4- (  Studies without
a et al., 5   
CE
14 3 (65 =15 18.3* S anxiety

2015)
.2) ) outcomes, k=8
 Counseling/psy 23/80
chotherapy vs.  Uncontrolled
AC
Waitlist, k = pretest-posttest
39 studies, k=23
57/ 
(Erford  Counseling/psy
3. 20 8 80 6.3- (
et al.,   chotherapy vs. 
5 13 0 (71 15.8* S
2015) Placebo, k =
.3) )
12
 Counseling/psy
chotherapy vs.
TAU, k = 7
20/  CBT vs. no  0/20
(Ewing
20 2 20 treatment/waitl (
et al., 5   4-18 
12 0 (10 ist, k = 20 D
2015)
0) )
Anxiety 0/41
Diagnosis
41/ Remission @  
(James
20 4 41 Post: ( (
et al., 5   4-18  
12 1 (10  CBT vs. D S
2015)
0) Waitlist, k = ) )
26
 ICBT vs.
ACCEPTED MANUSCRIPT
Review Review Data

cs OSR
Anxiet
Anxiety
y
Outcomes

Outco
Specified
mes
P T
RI
Last Year Searched
Age Range (years)

Pooled Effect Size
AMSTAR Score

SC
Review
Symptom Reduction
Diagnosis Remission
MA
Not Specified
Studies Reason, #
NU
MA
ED
Waitlist, k =
7
 GCBT vs.
PT
Waitlist, k =
13
 Family/Paren
CE
tal CBT vs.

Waitlist, k =
12
 CBT vs.
AC
Active
Controls, k =
6
 CBT vs.
TAU, k = 2
Anxiety
Diagnosis
Remission @
Follow-up:
 CBT vs.
Waitlist, k =
3
 CBT vs.
Active
Controls, k =
2
Anxiety Symptom
Reduction @
Post:
 CBT vs.
Waitlist, k =
ACCEPTED MANUSCRIPT
Review Review Data

cs OSR
Anxiet
Anxiety
y
Outcomes

Outco
Specified
mes
P T
RI
Last Year Searched
Age Range (years)

Pooled Effect Size
AMSTAR Score

SC
Review
Symptom Reduction
Diagnosis Remission
MA
Not Specified
Studies Reason, #
NU
MA
ED
30
 ICBT vs.
PT
Waitlist, k =
8
 GCBT vs.
Waitlist, k =
CE
15
 Family/Paren
tal CBT vs.
AC
Waitlist, k =
13
 CBT vs.
Active
Controls, k =
8
 CBT vs.
TAU, k = 3
Anxiety Symptom
Reduction @
Follow-up:
 CBT vs.
Waitlist, k =
4
 CBT vs.
Active
Controls, k =
4
(Penna 2/2  ABM vs.  25/27
nt et 20 2 7 Active 9.6- (  Depression,
5   
al., 13 7 (7. Control, k = 10.1* S k=4
2015) 4) )
ACCEPTED MANUSCRIPT
Review Review Data

cs OSR
Anxiet
Anxiety
y
Outcomes

Outco
Specified
mes
P T
RI
Last Year Searched
Age Range (years)

Pooled Effect Size
AMSTAR Score

SC
Review
Symptom Reduction
Diagnosis Remission
MA
Not Specified
Studies Reason, #
NU
MA
ED
2  Participants >
18 years of age,
PT
k=8
 General
Population/Pre
vention, k=2
CE
 OCD, k=1
 PTSD, k=1
 Transdiagnostic
AC
, k=1
 Outcomes Not
Extractable,
k=2
 Comparisons
with < 2
Studies, k=6
o Computeri
zed
exposure
vs. in-vivo
exposure
vs. EMDR,
k =1
o ABM &
CBM vs.
Group
CBT vs.
No
treatment,
k =1
o CBM for
ACCEPTED MANUSCRIPT
Review Review Data

cs OSR
Anxiet
Anxiety
y
Outcomes

Outco
Specified
mes
P T
RI
Last Year Searched
Age Range (years)

Pooled Effect Size
AMSTAR Score

SC
Review
Symptom Reduction
Diagnosis Remission
MA
Not Specified
Studies Reason, #
NU
MA
ED
spider
phobia vs.
PT
Neutral
Training,
k=1
o CBM for
CE
anxiety
disorders
vs. Neutral
AC
Training,
k=1
o Internet/Co
mputer-
based CBT
(Camp
Cope-A-
Lot) vs.
Active
Controls, k
=1
o Internet/Co
mputer-
based CBT
(Cool
Teens) vs.
Waitlist
Controls, k
=1
(Davis 5/1  GCBT vs.  5/10
3. 20 1  
et al., 0  GCBT + 8-26‼ (  OCD, k=1
5 12 0
2014) (50 Parents, k = 5 S  Comparisons
ACCEPTED MANUSCRIPT
Review Review Data

cs OSR
Anxiet
Anxiety
y
Outcomes

Outco
Specified
mes
P T
RI
Last Year Searched
Age Range (years)

Pooled Effect Size
AMSTAR Score

SC
Review
Symptom Reduction
Diagnosis Remission
MA
Not Specified
Studies Reason, #
NU
MA
ED
) ) with < 2 Studies,

( k=4
PT
D o GCBT vs.
) Individual
Self-Control
vs. Individual
CE
Contingency
Management,
k =1
o GCBT vs.
AC
GCBT +
Parents vs.
Waitlist
Controls, k
=1
o GCBT, k=1
o Psychoeducat
ion vs.
GCBT +
Parents, k =1
 ABM vs. 4/10
(Lowth
6/1 ABM   Non-randomized,
er &
20 1 0 controls (2- 9.6- ( uncontrolled
Newma 5  
14 0 (60 arm, 3-arm & 15.6* S studies, k=4
n,
.0) 4-arm )
2014)
comparisons)
Symptom 0/16
16/  
(Thulin Reduction:
20 1 16   ( (
et al., 5    Child CBT 5-18
13 6 (10 D S
2014) vs. CBT +
0) ) )
Family or
ACCEPTED MANUSCRIPT
Review Review Data

cs OSR
Anxiet
Anxiety
y
Outcomes

Outco
Specified
mes
P T
RI
Last Year Searched
Age Range (years)

Pooled Effect Size
AMSTAR Score

SC
Review
Symptom Reduction
Diagnosis Remission
MA
Not Specified
Studies Reason, #
NU
MA
ED
Parent, k =
16 @ Post-
PT
Treatment; k
= 15 @
Follow-up
Diagnosis
CE
Remission:
 Child CBT
vs. CBT +
AC
Family or
Parent, k =
14 @ Post-
Treatment; k
= 13 @
Follow-up
 CBT vs. 7/55
Passive  Not CBT, k=7
(Reyno 48/ Control, k = 
lds et 20 5 55 34 (
4   2-19 
al., 10 5 (87  CBT vs. S
2012) .3) Active )
Control, k
=14
 CBT vs. N/A
(Segool 14/ 
SSRI
& 20 1 14 (
4   (Indirect 5-19 
Carlson 06 4 (10 S
Comparison),
, 2008) 0) )
k = 14
(Silver Pooled Anxiety  NR₰
N 3 NR
man et 3   Symptom NR  (  Non-CBT data,
R 2 
al., Reduction (Youth D
ACCEPTED MANUSCRIPT
Review Review Data

cs OSR
Anxiet
Anxiety
y
Outcomes

Outco
Specified
mes
P T
RI
Last Year Searched
Age Range (years)

Pooled Effect Size
AMSTAR Score

SC
Review
Symptom Reduction
Diagnosis Remission
MA
Not Specified
Studies Reason, #
NU
MA
ED
2008) Report): ) k = NR₰

 CBT vs. (
PT
Waitlist, k S
=37 )
 ICBT vs.
Waitlist, k =
CE
16
 GCBT vs.
Waitlist, k =
AC
9
 ICBT +
Parents vs.
Waitlist, k =
4
 GCBT +
Parents vs.
Waitlist, k =
6
Pooled Anxiety
Symptom
Reduction (Parent
Report):
 CBT vs.
Waitlist, k
=4
 CBT vs. 14/28
(Chu & 14/ 
Waitlist, k =  Depression,
Harriso 20 2 28 (
3   9 5-17  k=14
n, 06 8 (50 S
 CBT vs. )
2007) .0)
Active
ACCEPTED MANUSCRIPT
Review Review Data

cs OSR
Anxiet
Anxiety
y
Outcomes

Outco
Specified
mes
P T
RI
Last Year Searched
Age Range (years)

Pooled Effect Size
AMSTAR Score

SC
Review
Symptom Reduction
Diagnosis Remission
MA
Not Specified
Studies Reason, #
NU
MA
ED
Control, k =
5
PT
(Cartwr  CBT vs. 0/10

10/ 
ight- Waitlist, k =
4. 20 1 10 (
Hatton   10 6-16 
5 03 0 (10 D
et al.,
CE
0) )
2004)
Medication
(Straw 9/9  SSRI/SNRI  0/9
AC
20 vs. Placebo, k (
n et al., 4  9 (10  5-17 
14 =9 S
2015) 0)
)
 Fluoxetine 0/16
vs. Placebo, k
=6
 Sertraline vs.
Placebo, k =
4
(Uthma  Fluvoxamine
16/ 
n& vs. Placebo, k
20 1 16 8.5- (
Abdul 3   =2 
09 6 (10 13.6* D
malik,  Paroxetine )
0)
2010) vs. Placebo, k
=2
 Venlafaxine
vs. Placebo, k
=2
 Pairwise
Comparisons
(Ipser 5  20 2 9/2  Treatment 8.5-    13/22
ACCEPTED MANUSCRIPT
Review Review Data

cs OSR
Anxiet
Anxiety
y
Outcomes

Outco
Specified
mes
P T
RI
Last Year Searched
Age Range (years)

Pooled Effect Size
AMSTAR Score

SC
Review
Symptom Reduction
Diagnosis Remission
MA
Not Specified
Studies Reason, #
NU
MA
ED
et al., 08 2 2 Response: 13.6* (  OCD, k =11

2009) (40  SSRI/SNRI D  Anxious + non-
PT
.9) vs. Placebo, k ) anxious

=9 ( sample, k= 1
Symptom S  Comparisons
Reduction: ) with < 2
CE
 SSRI vs. Studies, k=1

Placebo, k=4 o Benzodiaz
epine vs.
AC
Placebo, k
=1
2/2  CBT vs.  19/21
(Hidalg
20 2 1 SSRI, k =2 (  Adults, k =19
o et al., 3   NR 
03 1 (9. S
2007)
5) )
Web/Computer-based
 Web/Comput 6/13
7/1 
(Ebert er-based  Depression,
4. 20 1 3 (
et al.,   CBT vs. 6-18  k=4
5 13 3 (53 S
2015) Control, k =7
)  Transdiagnostic
.8)
, k=2
 Clinic 22/25
BRAVE vs.  Depression,
Internet k=10
(Reyes- 3/2 
BRAVE, k  Participants >
Portillo 4. 20 2 5 (
 =2 7-18  18 years of age,
et al., 5 13 5 (12 D
 BRAVE k=5
2014) .0) )
Online vs.  No target
Waitlist, k diagnosis, k=5
=3  Secondary data
ACCEPTED MANUSCRIPT
Review Review Data

cs OSR
Anxiet
Anxiety
y
Outcomes

Outco
Specified
mes
P T
RI
Last Year Searched
Age Range (years)

Pooled Effect Size
AMSTAR Score

SC
Review
Symptom Reduction
Diagnosis Remission
MA
Not Specified
Studies Reason, #
NU
MA
ED
analysis, k=1
 Comparisons
PT
with < 2
Studies, k=1
o CBM vs.
GCBT vs.
CE
No
Treatment
Control, k
AC
=1
 BRAVE 5/7
Online vs.  OCD, k=1
Waitlist, k =  Depression,
2 k=1
 Participants >
 18 years of age,
( k=1
(Ye et 2/7 D  Emotional/men
20  
al., 5  7 (28  NR ) tal health
12
2014) .6) ( issues, k=1
S  Comparisons
) with < 2
Studies, k=1
o Internet
CBT vs.
Waitlist,k=
1
(Calear 2/8  BRAVE  6/8
3. 20
& 8 (25  Online vs. 7-14  (  Depression or
5 09
Christe .0) Waitlist, k = S Anxiety
ACCEPTED MANUSCRIPT
Review Review Data

cs OSR
Anxiet
Anxiety
y
Outcomes

Outco
Specified
mes
P T
RI
Last Year Searched
Age Range (years)

Pooled Effect Size
AMSTAR Score

SC
Review
Symptom Reduction
Diagnosis Remission
MA
Not Specified
Studies Reason, #
NU
MA
ED
nsen, 2 ) Prevention, k
2010) =6
PT
8/10  BRAVE
(Richar 2/1  
 Depression, k Online vs.
dson et 20 1 0 ( (
4  7-14   =6 Waitlist, k =
al., 08 0 (20 D S
 Case Series, 2
CE
2010) .0) ) )
k=2
Abbreviations: ABM = Attention Bias Modification; CBM = Cognitive Bias Modification; CBT = Cognitive Behavioral
Therapy; D = Diagnosis Remission; EMDR = Eye Movement Desensitization and Reprocessing; GCBT = Group CBT; ICBT
AC
= Individual CBT; MA = Meta-analysis; NR = Not Reported; OCD = Obsessive Compulsive Disorder; PTSD = Post
Traumatic Stress Disorder; S = Symptom Reduction; SNRI = Selective Norepinephrine Reuptake Inhibitor; SSRI = Selective
Serotonin Reuptake Inhibitor; TAU = Treatment as Usual
Notes: * = average age range; ‼ = age at follow-up (1 to 13 years post-intervention);  = one study provided both placebo
and waitlist comparisons;  = Eligible primary studies are those contained in the meta-analyses of CBT vs. Waitlist,
however the number of studies included in the meta-analyses are not reported (review only reports the number of independent
samples included in each meta-analysis);  = k is the number of independent samples that contributed to an effect size (rather
than the number of primary studies); ₰ = non-eligible primary studies are those not included in the meta-analyses of CBT vs.
Waitlist, however the number of studies excluded from the meta-analyses are not reported;  = 2 studies are counted in both
comparisons because they include both active and passive controls.
ACCEPTED MANUSCRIPT
Table 2: CBT vs. Waitlist Control at Post-treatment

Diagnosis Remission Symptom Reduction
Intervention Review I C p< SMD p<
k OR 95% CI k 95% CI
(%) (%) 0.05 § 0.05
T
a,b b
(James et al., 2015) 26 58.9 16.0 7.85 5.31 to 11.60  30 -0.98 -1.21 to -0.74 
P
(Reynolds et al., 2012) NR NR NR NR NR NR 34 -0.77c -1.00 to -0.55 
(Cartwright-Hatton et al., 2004) 10 56.5 34.8 3.27a 1.92 to 5.55  NR NR NR NR
RI
CBT
(Ewing et al., 2015) 20 NR NR 3.65a 2.95 to 4.52  NR NR NR NR
(all formats)
(Chu & Harrison, 2007) NR NR NR NR NR NR 9 -0.74 NR 
SC
37† -0.44*† -0.83 to -0.04 † †
(Silverman et al., 2008) NR NR NR NR NR NR
4‡ -0.91*‡ -1.99 to 0.16 ‡ X‡
a,d
 -0.59d 
NU
(James et al., 2015) 7 NR NR 7.92 3.37 to 18.63 8 -0.84 to -0.34
Individual CBT
(Silverman et al., 2008) NR NR NR NR NR NR 16 -0.46* -0.90 to -0.03 
(James et al., 2015) 13 NR NR 7.86a,d 3.83 to 16.12  15 -1.20d -1.64 to -0.75 
Group CBT
MA
Family/ Parental CBT (James et al., 2015) 12 NR NR 8.65a,e 5.01 to 14.92  13 -1.00e -1.39 to -0.61 
Individual CBT with
Parents
ED
Group CBT with
Parents
Abbreviations: C= Control; CBT = Cognitive Behavioral Therapy; CI = Confidence Interval; I = Intervention; k = number of primary studies; NR = Not Reported; OR =
Odds Ratio; SMD = Standardized Mean Difference
PT
Notes:  = Yes; X = No; § = SMD reported as Hedges’ g unless otherwise noted; * = Cohen’s d;  = Negative SMD (magnitude of difference in decrease in anxiety
CE
symptoms for intervention relative to waitlist control); † = Anxiety symptoms reported by child/adolescent; ‡ = Anxiety symptoms reported by parent; a = OR favors CBT
(likelihood of recovery from anxiety disorder increased compared to waitlist); b = analysis includes 4 studies on autism spectrum disorder with anxiety; c = analysis
includes studies on OCD, PTSD, autism spectrum disorder with anxiety, and school refusal; d = analysis includes 1 study on autism spectrum disorder with anxiety; e =
AC
analysis includes 2 studies on autism spectrum disorder with anxiety.

ACCEPTED MANUSCRIPT
Table 3: CBT vs. Active Control at Post-treatment

Diagnosis Remission Symptom Reduction
Comparison Review SMD
k OR 95% CI p <0.05 k 95% CI p <0.05
§
T
a b
(James et al., 2015) 6 1.51 0.77 to 2.96 X 8 -0.50 -1.09 to 0.09 X
CBT (all formats) vs.
P
(Chu & Harrison, 2007) NR NR NR NR 5 -0.37 NR 
Non-CBT Active Controls
(Reynolds et al., 2012) NR NR NR NR 14 -0.39 -0.64 to -0.15 
RI
CBT vs. TAU (James et al., 2015) 2 0.53c 0.23 to 1.25 X 3 -0.19b -0.79 to 0.40 X
Parent/Family CBT vs.
SC
(Thulin et al., 2014) 14 1.06d NR X 16 -0.10e -0.23 to 0.04 X
Child CBT
Abbreviations: CBT = Cognitive Behavioral Therapy; CI = Confidence Interval; k = number of primary studies; NR = Not Reported; OR = Odds Ratio; SMD =
NU
Standardized Mean Difference; TAU = Treatment as Usual
Notes:  = Yes; X = No; § = SMD reported as Hedges’ g unless otherwise noted;  = Negative SMD [magnitude of difference in decrease in anxiety symptoms for
intervention A relative to intervention B (i.e., A vs. B format as reported in comparison column)]; a = OR favors CBT (likelihood of recovery from anxiety disorder
MA
increased compared to active treatment); b = analysis includes 1 study on autism spectrum disorder with anxiety; c = OR favors TAU (likelihood of recovery from anxiety
disorder decreased for CBT compared to TAU); d = OR does not favor either treatment condition (no difference in likelihood of recovery for parent/family CBT
compared to child CBT); e = analysis includes 2 studies on PTSD and 1 study on OCD.
ED
PT
CE
AC
ACCEPTED MANUSCRIPT
Table 4: Medication vs. Placebo at Post-treatment

Diagnosis Remission
Comparison Review
k RR* 95% CI
T
SSRI vs. Placebo
P
Fluoxetine vs. Placebo (Uthman & Abdulmalik, 2010) 6 3.35†a 2.11 to 5.07
RI
Fluvoxamine vs. Placebo (Uthman & Abdulmalik, 2010) 2 3.61†b 2.25 to 5.47
Paroxetine vs. Placebo (Uthman & Abdulmalik, 2010) 2 3.23†b 2.40 to 4.26
SC
Sertraline vs. Placebo (Uthman & Abdulmalik, 2010) 4 2.79†c 1.95 to 3.88
SNRI vs. Placebo
Venlafaxine vs. Placebo (Uthman & Abdulmalik, 2010) 2 2.06† 1.54 to 2.69
NU
Abbreviations: CI = Critical Interval; k = number of primary studies; RR = Relative Risk; SNRI = Selective Norepinephrine Reuptake Inhibitor; SSRI = Selective
Serotonin Reuptake Inhibitor
Notes: * = Treatment response on Clinical Global Impressions – Improvement Scale (CGI-I); † = RR favors SSRI/SNRI (risk of anxiety improvement is greater for the
MA
medication group compared to placebo); a = analysis includes 3 studies on OCD; b = analysis includes 1 study on OCD; c = analysis includes 2 studies on OCD.
ED
PT
CE
AC
ACCEPTED MANUSCRIPT
Table 5: Alternate Medication Comparisons at Post-treatment

Diagnosis Remission
Comparison Review
k RR*,† 95% CI
SSRI vs. SSRI
Fluvoxamine vs. Fluoxetine ‡ (Uthman & Abdulmalik, 2010) NA 1.12 0.61 to 1.83
Paroxetine vs. Fluoxetine ‡
T
(Uthman & Abdulmalik, 2010) NA 1.01 0.61 to 1.54
Sertraline vs. Fluoxetine ‡ (Uthman & Abdulmalik, 2010) NA 0.87 0.51 to 1.38
P
Paroxetine vs. Fluvoxamine ‡ (Uthman & Abdulmalik, 2010) NA 0.94 0.56 to 1.49
Sertraline vs. Fluvoxamine ‡ (Uthman & Abdulmalik, 2010) NA 0.81 0.47 to 1.31
RI
Sertraline vs. Paroxetine ‡ (Uthman & Abdulmalik, 2010) NA 0.88 0.57 to 1.30
SSRI vs. SNRI
SC
Venlafaxine vs. Fluoxetine ‡ (Uthman & Abdulmalik, 2010) NA 0.64 0.38 to 1.01
Venlafaxine vs. Fluvoxamine ‡ (Uthman & Abdulmalik, 2010) NA 0.60 0.35 to 0.95
vs. Venlafaxine vs. Paroxetine ‡ (Uthman & Abdulmalik, 2010) NA 0.65 0.44 to 0.93
Venlafaxine vs. Sertraline ‡ (Uthman & Abdulmalik, 2010) NA 0.76 0.49 to 1.13
NU
Abbreviations: CI = Critical Interval; k = number of primary studies; NA = Not Applicable; RR = Relative Risk; SNRI =
Selective Norepinephrine Reuptake Inhibitor; SSRI = Selective Serotonin Reuptake Inhibitor
Notes: * = Treatment response on Clinical Global Impressions – Improvement Scale (CGI-I); ‡ = Indirect Comparison; † =
All pairwise comparisons presented in Table 5 include studies on OCD.
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Highlights
 Overviews of systematic reviews facilitate evidence-informed decisions about anxiety treatment
options for children and youth
 High quality RCTs support treatment with CBT and medication
 Findings for combination and web/computer-based treatment are encouraging but further RCTs are
T
needed

P
Head-to-head comparisons in RCTs of active treatment options are needed
 Many relevant systematic reviews have avoidable methodologic weaknesses
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Clinical Psychology Review: 10.1016/j.cpr.2016.09.006

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 

Kathryn Bennett, Katharina Manassis, Stephanie Duda, Alexa Bagnell,

To appear in: Clinical Psychology Review

Received date: 27 January 2016

Treating Child and Adolescent Anxiety Effectively: Overview of Systematic Reviews

States of America; e Department of Psychiatry, University of British Columbia and BC

Children’s Hospital, Vancouver, British Columbia, Canada; f Department of Educational and

Counselling Psychology and Special Education, University of British Columbia, Vancouver,

British Columbia, Canada; g Department of Pediatrics, University of Alberta, Edmonton, Alberta,

*Address correspondence to: Kathryn Bennett, Department of Clinical Epidemiology and

L8S 4K1, Canada; kbennett@mcmaster.ca; 1-905-525-9140.

options (psychosocial; medication; combination; web/computer-based treatment) to support

comparative effectiveness remains uncertain. EQ for combination therapy could not be

determined. RCTs of web/computer-based interventions showed mixed results (EQ1).

Head-to-head comparisons of active treatment options are needed.

Keywords: Anxiety, Child, Adolescent, Clinical Decision Making, Therapeutics, Review

substance/medication-induced anxiety disorder, anxiety disorder due to another medical

hyperactivity disorder, oppositional defiant disorder, and obsessive-compulsive disorder

Psychosocial interventions and medication (alone and in combination) (Ipser, Stein,

analyses available in numerous peer-reviewed journals and research repositories (Grimshaw,

facilitate evidence informed decision-making by practitioners and health service decision-makers.

anxiety treatment options [psychosocial intervention, medication, combined treatment (i.e.,

psychosocial intervention combined with medication), and web-based treatment] selected to

anxiety in children and adolescents: MEDLINE (including HealthSTAR), PsycINFO (including

Review Inclusion/Exclusion Criteria

of a systematic review – namely a description of a non-selective literature search strategy and

scores. Reviews focused solely on obsessive-compulsive disorder (OCD) or post-traumatic stress

no longer classified as anxiety disorders in DSM-5 (American Psychiatric Association, 2013).

main treatment delivery modality was web/computer-based with little or no face-to-face

emerged during the review process.

Passive controls were defined as waitlist controls or no intervention. Active controls

Evidence of anxiety treatment effectiveness was sought at post-treatment and follow-up

for: i) anxiety disorder remission; or ii) anxiety symptom reduction.

supplement available pooled data.

interventions as follows: Level 1 – systematic review of RCTs; Level 2 – RCT or observational

Search and Screening

Eligible Review Characteristics

Thirteen reviews reported on the effectiveness of psychosocial interventions. We report

Cognitive behavioral therapy (CBT).

Question 1a: Is the treatment effective compared to passive controls at post-treatment?

a fourth review reported a statistically significant reduction in anxiety symptoms based on

post-treatment (James et al., 2015; Silverman et al., 2008).

as good as) active controls at post-treatment?

findings regarding anxiety symptom reduction at post-treatment.

RCTs/CCTs that conducted direct comparisons of these two treatment formats.

as good as) active controls at follow-up?

reduction (k=4 RCTs) (James et al., 2015).

Other psychosocial interventions.

Question 1a: Is the treatment effective compared to passive controls at post-treatment?

compared to passive controls at post-treatment.

Question 1b: Is the treatment effective compared to passive controls at follow-up? No

compared to passive controls at follow-up.

CBT psychosocial interventions, in comparison with active controls at post-treatment.

Specifically, a meta-analysis of 15 RCTs of CBM/ABM conducted by Cristea, Mogoase, David

and reported no statistically significant difference in anxiety symptoms compared to active

Other eligible reviews of psychosocial interventions not discussed above. Erford,

(EMDR), psychodynamic therapy, parenting interventions, bibliotherapy, emotive imagery,

psychotherapy interventions considered as one group produce a statistically significant reduction

are reported in Table D.3 in Appendix D (available online).

Question 1a: Is the treatment effective compared to passive controls at post-treatment?

question is not applicable to reviews of medication trials.

as good as) active controls at post-treatment?

medication compared to placebo. Strawn et al (2015) pooled 9 placebo controlled RCTs of