Cognitive behavioural therapy for anxiety disorders in children and adolescents

Anthony C James; Tessa Reardon; Angela Soler; Georgina James; Cathy Creswell

doi:10.1002/14651858.CD013162.pub2

. 2020 Nov 16;2020(11):CD013162. doi: 10.1002/14651858.CD013162.pub2

Cognitive behavioural therapy for anxiety disorders in children and adolescents

Anthony C James ^1,², Tessa Reardon ^1,^4,^5,^✉, Angela Soler ², Georgina James ³, Cathy Creswell ^1,^4,⁵

Editor: Cochrane Common Mental Disorders Group

PMCID: PMC8092480 PMID: 33196111

Abstract

Background

Previous Cochrane Reviews have shown that cognitive behavioural therapy (CBT) is effective in treating childhood anxiety disorders. However, questions remain regarding the following: up‐to‐date evidence of the relative efficacy and acceptability of CBT compared to waiting lists/no treatment, treatment as usual, attention controls, and alternative treatments; benefits across a range of outcomes; longer‐term effects; outcomes for different delivery formats; and amongst children with autism spectrum disorders (ASD) and children with intellectual impairments.

Objectives

To examine the effect of CBT for childhood anxiety disorders, in comparison with waitlist/no treatment, treatment as usual (TAU), attention control, alternative treatment, and medication.

Search methods

We searched the Cochrane Common Mental Disorders Controlled Trials Register (all years to 2016), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO (each to October 2019), international trial registries, and conducted grey literature searches.

Selection criteria

We included randomised controlled trials of CBT that involved direct contact with the child, parent, or both, and included non‐CBT comparators (waitlist/no treatment, treatment as usual, attention control, alternative treatment, medication). Participants were younger than age 19, and met diagnostic criteria for an anxiety disorder diagnosis. Primary outcomes were remission of primary anxiety diagnosis post‐treatment, and acceptability (number of participants lost to post‐treatment assessment), and secondary outcomes included remission of all anxiety diagnoses, reduction in anxiety symptoms, reduction in depressive symptoms, improvement in global functioning, adverse effects, and longer‐term effects.

Data collection and analysis

We used standard methodological procedures as recommended by Cochrane. We used GRADE to assess the quality of the evidence.

Main results

We included 87 studies and 5964 participants in quantitative analyses.

Compared with waitlist/no treatment, CBT probably increases post‐treatment remission of primary anxiety diagnoses (CBT: 49.4%, waitlist/no treatment: 17.8%; OR 5.45, 95% confidence interval (CI) 3.90 to 7.60; n = 2697, 39 studies, moderate quality); NNTB 3 (95% CI 2.25 to 3.57) and all anxiety diagnoses (OR 4.43, 95% CI 2.89 to 6.78; n = 2075, 28 studies, moderate quality).

Low‐quality evidence did not show a difference between CBT and TAU in post‐treatment primary anxiety disorder remission (OR 3.19, 95% CI 0.90 to 11.29; n = 487, 8 studies), but did suggest CBT may increase remission from all anxiety disorders compared to TAU (OR 2.74, 95% CI 1.16 to 6.46; n = 203, 5 studies).

Compared with attention control, CBT may increase post‐treatment remission of primary anxiety disorders (OR 2.28, 95% CI 1.33 to 3.89; n = 822, 10 studies, low quality) and all anxiety disorders (OR 2.75, 95% CI 1.22 to 6.17; n = 378, 5 studies, low quality).

There was insufficient available data to compare CBT to alternative treatments on post‐treatment remission of primary anxiety disorders, and low‐quality evidence showed there may be little to no difference between these groups on post‐treatment remission of all anxiety disorders (OR 0.89, 95% CI 0.35 to 2.23; n = 401, 4 studies)

Low‐quality evidence did not show a difference for acceptability between CBT and waitlist/no treatment (OR 1.09, 95% CI 0.85 to 1.41; n=3158, 45 studies), treatment as usual (OR 1.37, 95% CI 0.73 to 2.56; n = 441, 8 studies), attention control (OR 1.00, 95% CI 0.68 to 1.49; n = 797, 12 studies) and alternative treatment (OR 1.58, 95% CI 0.61 to 4.13; n=515, 7 studies).

No adverse effects were reported across all studies; however, in the small number of studies where any reference was made to adverse effects, it was not clear that these were systematically monitored.

Results from the anxiety symptom outcomes, broader outcomes, longer‐term outcomes and subgroup analyses are provided in the text.

We did not find evidence of consistent differences in outcomes according to delivery formats (e.g. individual versus group; amount of therapist contact time) or amongst samples with and without ASD, and no studies included samples of children with intellectual impairments.

Authors' conclusions

CBT is probably more effective in the short‐term than waiting lists/no treatment, and may be more effective than attention control. We found little to no evidence across outcomes that CBT is superior to usual care or alternative treatments, but our confidence in these findings are limited due to concerns about the amount and quality of available evidence, and we still know little about how best to efficiently improve outcomes.

Plain language summary

Cognitive behavioural therapy for anxiety in children and young people

Why is this review important?

Many children and young people experience problems with anxiety. Children and young people with anxiety disorders are more likely than their peers to have difficulty with friendships, family life, and school, and to develop mental health problems later in life. Therapies such as cognitive behavioural therapy (CBT) can help children and young people to overcome difficulties with anxiety by using new ways of thinking and facing their fears.

Who will be interested in this review?

Parents, children, and young people; people working in education and mental health services for children and young people; and general practitioners.

What questions does this review aim to answer?

This review updates and replaces previous Cochrane Reviews from 2005 and 2015, which showed that CBT is an effective treatment for children and young people with anxiety disorders.

This review aimed to answer the following questions:

• Is CBT more effective than a waiting list or no treatment?

• Is CBT more effective than other treatments and medication?

• Does CBT help to reduce anxiety for children and young people in the longer term?

• Are some types of CBT more effective than others? (e.g. individual versus group therapy)

• Is CBT effective for specific groups? (e.g. children with autism)

Which studies were included in the review?

We searched the databases to find all studies of CBT for anxiety disorders in children and young people published up to October 2019. In order to be included in the review, studies had to be randomised controlled trials (a type of study in which participants are assigned to one of two or more treatment groups using a random method) and had to include young people under 19 years of age with an anxiety disorder diagnosis. We included 87 studies with a total of 5964 participants in the analysis.

What does the evidence from the review tell us?

We rated the overall quality of the evidence as 'moderate’ or 'low'. There is evidence that CBT is more effective than a waiting list or no treatment in reducing anxiety in children and young people, although the findings did vary across studies. There is no clear evidence that CBT is more effective than other treatments. A small number of studies looked at outcomes six months after CBT was given and showed that reductions in anxiety continued. We found no clear evidence that one way of providing CBT is more effective than another (e.g. in a group, longer treatments, with parents) or that CBT is more or less effective for any specific group of children (e.g. children with autism spectrum disorders).

What should happen next?

Future research should compare CBT to alternative treatments and medication; identify who does and does not benefit from CBT and what those who do not benefit need; establish how to make CBT more accessible; and give far more consideration to neglected populations, including children and young people from low‐ and middle‐income countries.

Summary of findings

Background

Description of the condition

Anxiety disorders are amongst the most common psychiatric disorders, occurring in 6.5% of all children and adolescents (Polanczyk 2015). One of the diagnostic challenges in children and adolescents involves distinguishing normal, developmentally appropriate worries, fears, and shyness from anxiety disorders. For example, primary school‐age children commonly have worries about injury and natural events, whereas older children and adolescents typically have worries and fears related to school performance, social competence, and health issues (Beesdo 2009). Distinguishing features of pathological anxiety include severity, persistence, and associated impairment.

The International Classification of Diseases (ICD), WHO 1992, and Diagnostic and Statistical Manual of Mental Disorders (DSM‐5), APA 2013, diagnostic systems distinguish various types of anxiety disorders, including generalised anxiety disorder, panic disorder, social anxiety disorder, separation anxiety disorder, agoraphobia, specific phobias, and selective mutism. These anxiety disorders are often associated with significant impairment in personal, social, and academic functioning (Pine 2009). Comorbidities are common, in particular with other anxiety disorders in children and adolescents (Leyfer 2013), and depression in adolescents (Essau 2003).

The presentation of anxiety disorders varies with age. Separation anxiety disorders are more common in younger children than in adolescents, and difficulties with social anxiety are typically associated with greater disturbance in adolescence (Waite 2014). Anxiety disorders with an onset in childhood often persist into adolescence and early adulthood (Copeland 2014), and are also associated with adverse academic, health, and social functioning in adulthood (Copeland 2014; Essau 2014). Yet these often remain untreated, with an average delay of 9 to 23 years before anxiety disorders are first treated (Wang 2005). It is clear that anxiety disorders in this age group present serious ongoing health issues, therefore effective and readily accessible treatments are needed.

Description of the intervention

Current treatments for anxiety disorders in this age group include behavioural therapy, cognitive behavioural therapy (CBT), or medication, or a combination of some or all these. National Institute for Health and Care Excellence (NICE) guidelines are available for the treatment of social anxiety disorder, which recommend CBT that is specifically focused on social anxiety (NICE 2013). Given the prevalence of these disorders, the age of onset, and public views on the acceptability of pharmacological treatments, psychological treatments are often preferred as first‐line therapy (Brown 2007; Young 2006). CBT is a collaborative psychological treatment that can be delivered in various formats, individually or in groups, and with varying levels of parent or family involvement.

One of the first manualised CBT programmes was Coping Cat (Kendall 1994), which consists of psycho‐education, modification of negative cognitions, exposure, social competence training, coping behaviour, and self‐reinforcement sessions. Others have followed, including the Cool Kids programme (Hudson 2009; Rapee 2006), the Coping Koala programme (Barrett 1996), Skills for Academic and Social Success (SASS) (Masia‐Warner 2005), ACTION (Waters 2009), Intervention With Adolescents With Social Phobia (IAFS) (Sanchez‐Garcia 2009), the TAPS (Warner 2011), and Building Confidence programme (Galla 2012). Alternative programmes involve providing direct support to parents alone, guiding them to implement CBT strategies with their child (Guided Parent‐Delivered CBT (GPD‐CBT) (Lyneham 2006; Thirlwall 2013; Waters 2009). CBT programmes have typically adopted a generic approach and target a range of anxiety disorders (e.g. Coping Cat), but some are disorder‐specific, targeting, for example, social anxiety disorder (e.g. SASS). CBT programmes have been modified in various ways to make them appropriate for children with autism spectrum disorders (ASD), such as by including social stories, social coaching, visual aids, and structured worksheets (Ung 2015). Such programmes include the Multimodal Anxiety and Social Skills Intervention (MASSI) programme (White 2013), TAFF (Schneider 2011), Behavioural Interventions for Anxiety in Children with Autism (BIACA) (Wood 2009), and Facing Your Fears (FYF) (Reaven 2012).

How the intervention might work

CBT for anxiety disorders in children and adolescents typically involves helping the child to recognise anxious feelings and bodily or somatic reactions to anxiety, identify thoughts or cognitions in anxiety‐provoking situations (e.g. unrealistic or negative attributions and expectations), and modifying these anxiety‐provoking cognitions (e.g. testing out predictions based on anxious thoughts, modifying anxious self‐talk into coping self‐talk). A key CBT procedure is exposure (Creswell 2020b), which typically involves testing out and ‘facing’ fears, often in a gradually increasing hierarchy. Behavioural training strategies such as modelling and role playing are often applied as opportunities for developing coping skills (e.g. problem‐solving skills, social skills, relaxation training).

CBT for anxiety disorders in children and adolescents has traditionally begun with six to nine face‐to‐face sessions of anxiety management strategies (emotion identification, relaxation training, cognitive strategies), followed by exposure work (Barrett 1996; Kendall 2006). In one meta‐analysis (Reynolds 2012), this traditional format of anxiety management sessions followed by exposure was observed in 93% of studies. However, Ale 2015 found that treatment outcomes in CBT treatment trials for child and adolescent anxiety disorders were not related to the use of relaxation strategies or the timing of exposure work, and therefore suggested that relaxation training may not be an essential ingredient of CBT, and that it may not be necessary to delay exposure until after anxiety management sessions. Moreover, there is also some preliminary evidence that introducing exposure early in treatment, without any prior anxiety management sessions, could improve outcomes whilst requiring fewer appointments (Whiteside 2015).

Indeed, questions remain about the mechanism of change within CBT. Cognitive restructuring and exposure tasks have each been found to make substantial contributions to improvement in child and adolescent anxiety in line with CBT theory (Peris 2015). More time devoted to exposure has been linked to better outcomes, and greater time spent on more difficult exposure tasks has been shown to predict better outcomes (Peris 2017). Change in coping efficacy, but not anxious self‐talk, has been found to mediate change in anxiety symptoms associated with CBT, medication (sertraline), and their combination, compared to placebo control (Kendall 2016). Furthermore, therapists’ ratings of child compliance and mastery also predict better outcomes (Peris 2017). Cognitive development also plays an important role, and whilst targeting behavioural avoidance appears to be crucial for both children and adolescents, treatment that directly addresses interpretation biases may be particularly beneficial for adolescents, but less so for younger children (Waite 2015).

CBT has been adapted to include family and parents in treatment sessions; however, parents/family members have been included in a wide variety of ways, including, for example, providing education and information on the child‐focused CBT, and/or modifying parents’ beliefs and behaviours, and/or addressing parental anxiety. These different approaches are based on different conceptualisations of the mechanisms of change in child anxiety through parental involvement. It is important to note, however, that changes in parent and child responses are likely to be bidirectional. For example, one study found that child‐focused anxiety treatments resulted in improvements in non‐targeted parent symptoms and family functioning, particularly when children responded successfully to treatment (Keeton 2013).

It is generally assumed that CBT can be applied only after the child has reached a certain level of cognitive development. Kendall 1993 argued that the ability to measure a thought or belief against the notion of a rational standard and the ability to understand that a thought or belief can cause a person to behave and feel in a certain way were central to its proper use. The question arises: at what age does a child have the cognitive capacities to undertake these cognitive operations? One study reported positive effects of CBT in children younger than six years of age (Hirshfeld‐Becker 2010); however, it is not clear whether children this age are able to use the cognitive strategies that are included in traditional CBT protocols. In line with this, research suggests that young children may be more responsive to the behavioural than the cognitive elements of this approach (Essau 2004). With younger children, parental involvement appears particularly important. Indeed, the treatment of anxiety disorders in young children can be effective by applying CBT principles through working directly with parents alone (Cartwright‐Hatton 2011), although there are inconsistent findings in relation to whether child‐parent delivery format is superior to parent‐only or not (Monga 2015; Waters 2009).

Why it is important to do this review

Anxiety disorders in children and adolescents represent a considerable source of morbidity and are associated with later adult psychopathology and greater cost than any other mental health disorder (Fineberg 2013). However, despite high prevalence and substantial morbidity, anxiety disorders in childhood and adolescence can be difficult to diagnose, and may be under‐recognised (NICE 2013), and therefore undertreated (Pine 2009). It is widely reported that only a minority of children and adolescents with mental health problems receive treatment (Green 2004; Merikangas 2011); a recent UK survey reported that fewer than 40% of children with anxiety disorders receive any professional support, and less than 3% receive CBT (Reardon 2020). Limited service provision represents a key barrier to treatment access (Reardon 2017), highlighting the importance of maximising the efficiency of treatment delivery to help ensure that effective treatment is more readily available to children and young people when they need it.

The evidence base for the treatment of anxiety disorders in children and adolescents is growing. Initial trials of CBT were positive (Barrett 1996; Kendall 1994; Kendall 1997), and further randomised controlled trials and reviews followed. Several reviews suggest that CBT for anxiety disorders in this age group is effective (Ale 2015; Crowe 2017; James 2015; Reynolds 2012; Silverman 2008), including an overview of systematic reviews and a network meta‐analysis (Bennett 2016; Zhou 2019). Overall there was a moderate response rate (e.g. 59%; James 2015), and a recent review indicated that benefits extend to broader outcomes, including depressive symptoms and general functioning (Kreuze 2018). However, CBT has not been shown to be superior to active controls or treatment as usual (James 2015; Southam‐Gerow 2010). In some previous studies, the effect sizes associated with CBT for childhood anxiety disorders did not differentiate it from attention placebo, although CBT has been found to be more effective than waiting list control (Ale 2015). It remains unclear whether CBT is superior to alternative treatment approaches.

This review updates and replaces previous Cochrane Reviews of CBT for anxiety disorders in children and adolescents (James 2005; James 2015). The current review aims to provide comprehensive and up‐to‐date evidence on the efficacy and acceptability of CBT in the treatment of anxiety disorders in children and adolescents, with varying amounts of therapist contact time and differing delivery formats, including individual, group, with/without family/parent involvement, and parent‐led. Furthermore, we planned to examine the efficacy of CBT relative to treatment as usual, attention control, and alternative treatments. The question of the comparative efficacy of medication versus CBT and the combination of CBT and medication was also to be addressed.

A recent development is the issue of the reporting of remission of all anxiety diagnoses, as well as the primary anxiety diagnosis (Warwick 2016). Given the high level of comorbid anxiety disorders, this is an important issue, but surprisingly has been previously overlooked. Indeed, focusing solely on recovery from the primary anxiety diagnosis means that children with comorbid anxiety disorders that are present following treatment are often still classed as ‘recovered’. As such, this review distinguishes between and examines outcomes based on both the absence of the ‘primary anxiety disorder’ and the absence of all anxiety disorders. As well as providing evidence on anxiety outcomes (diagnoses and symptoms), we also planned to examine benefits in relation to broader outcomes, including depressive symptoms and global functioning.

We also aimed to assess whether treatment effects of CBT are maintained beyond post‐treatment and at longer‐term follow‐up. Whilst it would not be possible to determine the youngest age at which a child can benefit from CBT without individual patient data, we would identify the age of the youngest participants in trials of CBT for child and adolescent anxiety disorders. It is recognised that children and adolescents with ASDs have high rates of anxiety disorders (van Steensel 2013); however, studies of CBT for anxiety disorders in ASD have had mixed outcomes (Murphy 2017; Ung 2015). Furthermore, it is unclear how anxiety disorders are recognised or, indeed, treated in those with intellectual impairments, indicating a pressing need for work in this area. We planned to examine the efficacy of CBT in children and adolescents with ASD and those with intellectual impairments.

Previous Cochrane Reviews used a cutoff of nine sessions of CBT, based on the practice and thinking at the time (James 2005; James 2015). However, since the last Cochrane Review (James 2015), there have been several developments in the delivery of CBT for anxiety disorders. These include briefer or shorter interventions, in terms of not only the number of sessions, but also the total duration of treatment. As such, we would not set a threshold for the minimum number of sessions, and would explore how treatment effects differ with treatment duration. It is important to note that one potentially efficient means to deliver CBT is online or via digital devices (e.g. computerised CBT). But as online and digital CBT interventions for child anxiety disorders have been reviewed elsewhere (e.g. Pennant 2015), this review focused on face‐to‐face delivery models that include direct contact with either the child or parent alone, or the child and parent together.

Objectives

To carry out a meta‐analysis of identified studies to determine whether CBT leads to remission of 1) the primary child/adolescent anxiety disorder and 2) all anxiety diagnoses, and/or 3) a clinically significant reduction in anxiety symptoms in comparison with waiting list/no treatment, treatment as usual, attention control, alternative treatment, or medication.
To determine the comparative efficacy of CBT alone, and the combination of CBT and medication, versus drug placebo.
To determine if CBT is an acceptable treatment, relative to waiting list/no treatment, treatment as usual, attention control, alternative treatment, and medication.
To determine whether CBT for anxiety leads to a clinically significant reduction in depressive symptoms and/or improvements in global functioning.
To identify any adverse effects associated with CBT, relative to waiting list/no treatment, treatment as usual, attention control, alternative treatment, and medication.
To determine whether post‐treatment gains of CBT are maintained at longer‐term follow‐up.
To describe the age range of participants included in CBT trials in order to determine the age of the youngest participants.
To carry out subgroup analyses of different types of CBT according to 1) amount of therapist contact time; and 2) delivery format (individual and group; child‐focused, child and parent/family, and parent‐only).
To carry out a subgroup analysis of CBT for children and adolescents with ASD and for children and adolescents with intellectual impairments.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs), cross‐over trials, and cluster‐randomised trials.

Types of participants

Participant characteristics

Children and adolescents younger than 19 years.

Diagnosis

We included participants meeting diagnostic criteria of the DSM (DSM III, III‐R, IV, IV‐TR, 5), APA 1980; APA 1987; APA 1994; APA 2000; APA 2013, or the ICD‐9 and ICD‐10, WHO 1978; WHO 1992, for an anxiety disorder.

Diagnoses had to be made by reliable and valid structured interviews for DSM or ICD child and adolescent anxiety disorders. Disorders classified as anxiety disorders vary across different versions of the DSM, and we included participants meeting diagnostic criteria for one or more of the following disorders: generalised anxiety disorder or overanxious disorder, separation anxiety disorder, social phobia or social anxiety disorder, panic disorder, agoraphobia, simple or specific phobias, or selective mutism.

Comorbidity

We included all comorbidities allowable for anxiety disorders under the rules of DSM or ICD, such as ASD, intellectual impairment, depressive disorders, and physical disorders.

Settings

We included all settings, such as research settings (i.e. university outpatient clinics, inpatient services, community clinics, and schools).

Exclusion criteria

We excluded studies that only included participants with post‐traumatic stress disorder or obsessive compulsive disorder, or both, as they are covered by separate Cochrane Reviews (Gillies 2016; O'Kearney 2006), and are no longer classified as ‘anxiety disorders’ in the DSM‐5 (APA 2013).

Types of interventions

Experimental intervention

The intervention had to be manualised CBT, or modular CBT, alone or in combination with medication, following a documented, written protocol and provided by trained therapists. Since the last review (James 2015), where the number of sessions was arbitrarily fixed at nine, there are now several studies indicating that shorter treatment, in terms of number of sessions or duration of sessions, or both, may be effective. We therefore did not include a minimum number of sessions or duration of sessions as a requirement.

CBT had to be administered according to standard principles as a psychological model of treatment involving helping the child to recognise anxious feelings and somatic reactions to anxiety; identify cognitions in anxiety‐provoking situations; modify these anxiety‐provoking cognitions; and respond to behavioural training strategies with exposure in vivo or by imagination.

CBT could be delivered to children (child‐focused), to children and parents/family members (child and parent), or to parents alone (parent‐only). In child‐focused CBT, the child had direct face‐to‐face contact with a therapist, and the intervention was delivered to children only, with minimal or no parental involvement. CBT with direct parent/family involvement (child and parent) included face‐to‐face child sessions and conjoint or separate sessions with parents/family that included providing psycho‐education for parents or teaching parents to be co‐therapists. Parent‐delivered CBT (parent‐only) only involved direct face‐to‐face contact with parents, and provided support for parents to help them to implement CBT strategies in their child’s day‐to‐day life. Child‐focused, child and parent, and parent‐only CBT could be delivered individually or in a group format. We did not include CBT interventions delivered online or via digital devices (e.g. computerised CBT).

Where studies included medication for the treatment of anxiety (in combination with CBT or alone), no concurrent medication for the treatment of anxiety was to be administered naturalistically. Where studies did not include medication for the treatment of anxiety, any medications administered naturalistically needed to be stable before and during the study.

Comparator interventions

Where CBT was delivered alone

Waitlist and no treatment for anxiety during that period
Treatment as usual (usual treatment or care; where usual care includes therapy, it does not include elements of CBT)
Attention control (attention only, e.g. support or education, but with no elements of CBT)
Alternative treatment (one specific non‐pharmacological intervention for the treatment of anxiety that followed a documented protocol and did not include CBT elements)
Medication for the treatment of anxiety
Drug placebo

Where CBT was delivered in combination with medication for the treatment of anxiety

Drug placebo

Types of outcome measures

We included studies that met the above inclusion criteria and reported or provided data on at least one of the following outcomes.

Primary outcomes

Remission: the absence of the primary diagnosis of an anxiety disorder post‐treatment, made by reliable and valid structured interviews for DSM or ICD child and adolescent anxiety disorders, such as:
- Anxiety Disorder Interview Schedule for Children – Child and Parent (ADIS‐C/P) (Silverman 1987);
- Anxiety Disorder Interview Schedule for Children – Child (ADIS‐C) (Silverman 1987);
- Anxiety Disorder Interview Schedule for Children – Parent (ADIS‐P) (Silverman 1987);
- Diagnostic Interview Schedule for Children, Adolescents and Parents (DISCAP) (Holland 1995).
Acceptability: loss of participants to post‐treatment assessment

Secondary outcomes

Remission: defined as the absence of all diagnoses of an anxiety disorder post‐treatment, made by reliable and valid structured interviews for DSM or ICD child and adolescent anxiety disorders.
Reduction in anxiety symptoms post‐treatment: measured using psychometrically robust measures of anxiety symptoms that yield symptom scores on continuous scales (Myers 2002), such as:
- Screen for Child Anxiety Related Emotional Disorders (SCARED) (Birmaher 1999);
- Spence Children’s Anxiety Scale (SCAS) (Spence 1997);
- Revised Children’s Anxiety and Depression Scale (RCADS) – Anxiety Scale (Chorpita 2000);
- Revised Children’s Manifest Anxiety Scale (RCMAS) (Reynolds 1985);
- Multidimensional Anxiety Scale for Children (MASC) (March 1997);
- State‐Trait Anxiety Inventory for Children (STAI‐C) (Spielberger 1973);
- Social Phobia and Anxiety Inventory for Children (SPAI‐C) (Beidel 1995);
- Social Anxiety Scale for Adolescents (SAS‐A) (La Greca 1998).

These scales could be self‐report or completed by a parent or an independent rater. Multiple reporters are often used, but the reliability of each reporter is likely to vary with the child’s age (Evans 2017). We therefore determined reduction in anxiety symptoms separately for 1) self‐reported and 2) parent‐reported or independent rater, or both. Multiple measures are also often reported, and we included the most validated, best recognised, or most frequently used measures in the analysis.

A crucial issue is how well these measures discriminate between clinical and non‐clinical levels of anxiety. We prioritised symptom measures that were closely aligned with diagnostic categories, with strong discriminant validity (e.g. RCADS, SCAS, SCARED). We also prioritised broad measures of anxiety symptoms (e.g. SCAS, SCARED, MASC), rather than disorder‐specific symptom measures (e.g. SPAI‐C, SAS‐A). (See Appendix 1)

Reduction in depressive symptoms post‐treatment: measured using psychometrically robust measures of depressive symptoms that yielded symptom scores on continuous scales, such as:
- Children’s Depression Inventory (Kovacs 1989);
- Beck Depression Inventory (Beck 1996);
- Revised Children’s Anxiety and Depression Scale (RCADS) – Depression Scale (Chorpita 2000);
- Mood and Feelings Questionnaire (Angold 1995).

If multiple depressive symptom measures/reporters were used, we included the most validated, best recognised, or most frequently used measures in the analysis.

Improvement in global functioning post‐treatment: measured using psychometrically robust measures of global functioning that yield symptom scores on continuous scales, such as:
- Children’s Global Assessment Scale (CGAS) (Shaffer 1983).

If multiple global functioning measures/reporters were used, we included the most validated, best recognised, or most frequently used measures in the analysis.

Adverse events: we determined adverse events outcomes by the number and type of reported adverse events during the trial from randomisation to post‐treatment assessment (e.g. deterioration in anxiety symptoms, deterioration in global functioning, rates of self‐harm, suicide attempts).
Remission defined by the absence of the primary anxiety disorder diagnosis at a series of follow‐up time points (≤ 6 months post‐treatment, > 6 months post‐treatment but ≤ 12 months post‐treatment, and > 12 months post‐treatment).
Remission defined as the absence of all diagnoses of an anxiety disorder at a series of follow‐up time points (≤ 6 months post‐treatment, > 6 months post‐treatment but ≤ 12 months post‐treatment, and >12 months post‐treatment).
Reduction in anxiety symptoms at a series of follow‐up time points (≤ 6 months post‐treatment, > 6 months post‐treatment but ≤ 12 months post‐treatment, and > 12 months post‐treatment).

Search methods for identification of studies

We identified eligible studies (RCTs) of CBT for anxiety disorders in children and adolescents from the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR; all years to 2016) (Appendix 2).

Electronic searches

We also ran searches on the following databases using relevant keywords, subject headings (controlled vocabularies), and search syntax, appropriate to each resource (Appendix 3). Searches were initially conducted on 21 November 2018 and updated 10 October 2019.

Cochrane Central Register of Controlled Trials (CENTRAL; Issue 10 of 12, 2019) in the Cochrane Library
Ovid MEDLINE (2016 to 10 October 2019)
Ovid Embase (2016 to 2019 Week 40)
Ovid PsycINFO (all years to October Week 40 2019)

We applied no restriction on language or publication status to the searches.

We also searched the international trial registries (10 October 2019) (including US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (clinicaltrials.gov) and the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/)) to identify additional ongoing and unpublished studies.

Searching other resources

Grey literature

We searched the grey literature for dissertations and theses (all years to 14 October 2019) (Appendix 4), as follows.

Electronic Theses Online Service (EThOS) ‐ British Library (ethos.bl.uk/Home.do)
DART ‐ Europe e‐theses Portal (www.dart-europe.eu/basic-search.php)
Networked Digital Library of Theses and Dissertations (NDLTD) (search.ndltd.org/)
PQDT Open ‐ open access dissertations and theses (pqdtopen.proquest.com/search.html)
Proquest Dissertations & Theses Global (search.proquest.com/pqdtglobal/dissertations/)

Reference lists

We checked the reference lists of all included studies and relevant systematic reviews to identify additional studies missed from the original electronic searches (e.g. unpublished or in‐press citations).

Correspondence

We contacted study authors and subject experts for information on unpublished or ongoing studies, or to request additional data. Where studies included some eligible participants (i.e. some participants were younger than 19 years, or some participants met the diagnostic criteria for an anxiety disorder), we contacted the authors to request data on eligible participants.

Data collection and analysis

Selection of studies

Two review authors (AJ, TR) independently screened the titles and abstracts of all studies identified as a result of the search, coding them as ‘retrieve' (eligible or potentially eligible/unclear) or ‘do not retrieve'. We retrieved the full‐text study reports/publications, and two review authors (AJ, TR) independently screened the full texts to identify studies for inclusion, and identified and recorded reasons for exclusion of the ineligible studies. Any disagreements were resolved through discussion or by consulting a third review author (GJ, AS, CC) if required. We identified and excluded duplicate records and collated multiple reports that related to the same study so that each study, rather than each report, was the unit of interest in the review. We recorded the selection process in sufficient detail to complete a PRISMA flow diagram and ‘Characteristics of excluded studies' table (Moher 2015). We used Covidence software for the screening process (Covidence).

Data extraction and management

We used a data collection form created in Covidence to extract study characteristics and outcome data that we had piloted on two studies in the review. Two review authors (AJ, TR) extracted study characteristics and outcome data from the included studies. We extracted the following study characteristics.

Methods: study design, total duration of study, details of any ‘run‐in' period, number of study centres and location, study setting, withdrawals, and date of study
Participants: number, mean age, age range, gender, severity of condition, diagnostic criteria, comorbid conditions, inclusion criteria, and exclusion criteria
Interventions: intervention, comparison, concomitant medications, excluded medications, delivery format, therapist contact time, who delivers intervention
Outcomes: primary and secondary outcomes specified and collected, and time points reported
Notes: funding for study, and notable conflicts of interest of study authors

We noted in the ‘Characteristics of included studies' table if outcome data were not reported in a useable way. Any disagreements were resolved by consensus or by involving a third review author (GJ, AS, CC). One review author (TR) transferred data into the Review Manager 5 file (Review Manager 2014). We double‐checked that data were entered correctly by comparing the data presented in the systematic review with the study reports. A second review author (AJ) spot‐checked study characteristics for accuracy against the study report.

Main comparisons

CBT compared with waiting list and no treatment controls
CBT compared with treatment as usual
CBT compared with attention control
CBT compared with alternative treatments
CBT compared with medication or drug placebo
CBT and medication combination compared with drug placebo

Assessment of risk of bias in included studies

Two review authors (AJ, TR) independently assessed risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2017). Any disagreements were resolved by discussion or by involving another review author (GJ, CC). We assessed risk of bias according to the following domains.

Random sequence generation
Allocation concealment
Blinding of participants and personnel
Blinding of outcome assessment
Incomplete outcome data
Selective outcome reporting
Other bias, including therapy integrity

We judged each potential source of bias as low, high, or unclear and provided a supporting quotation from the study report together with a justification for our judgement in the ‘Risk of bias' table. We summarised the 'Risk of bias' judgements across different studies for each of the domains listed.

Selection bias: we assessed the adequacy of the randomisation process in terms of the description of adequacy of sequence generation and the concealment of treatment group allocation.

Performance bias: given the nature of psychological interventions, blinding of either participants or personnel delivering the treatments could only be possible in studies involving CBT versus treatment as usual, attention control, or alternative treatment, therefore we were only able to assess attempts at blinding in those studies.

Detection bias: we evaluated whether study personnel carrying out outcome assessments were blinded to the treatment status of participants.

Attrition bias: we determined whether studies provided a description of withdrawals and dropouts.

Other bias: we also assessed therapy integrity, including therapist competence and adherence to treatment protocol, for all included studies.

We did not exclude studies from meta‐analysis on the basis of the ‘Risk of bias’ assessment. We conducted sensitivity analyses for the primary outcome, excluding trials with high or unclear risk of bias ratings for allocation concealment, and excluding trials with high or unclear risk of bias for blinding of outcome assessment if appropriate. We reported the remainder of the ‘Risk of bias' assessments for these trials, and included discussion of this assessment in the Results and Discussion sections.

Measures of treatment effect

In order to assess post‐treatment outcomes, we used dichotomous data on remission of primary anxiety diagnosis and all anxiety diagnoses, and continuous data on anxiety symptoms, depressive symptoms, and global functioning, with the use of standardised measures. We used data from the assessment administered immediately after treatment (or the assessment closest to the end of treatment) to assess post‐treatment outcomes. We also used these measures to evaluate the maintenance of treatment effects at a series of follow‐up time points (≤ 6 months post‐treatment, > 6 months post‐treatment but ≤ 12 months post‐treatment, and > 12 months post‐treatment). Where studies reported follow‐up data at multiple time points within one category (e.g. one‐month and three‐month follow‐up), we used data from the longer follow‐up period. To assess acceptability, we used frequency data on the numbers of participants who were lost to post‐treatment assessment. Adverse events were determined by the number and type of adverse events during the trial, from randomisation to the post‐treatment assessment.

Dichotomous data

We analysed dichotomous data as odds ratios (OR) and 95% confidence intervals (CI).

Continuous data

We analysed continuous data as mean difference (MD) or standardised mean difference (SMD). We entered data presented as a scale with a consistent direction of effect.

We narratively described skewed data reported as medians and interquartile ranges.

Unit of analysis issues

Cluster‐randomised trials

We included cluster‐randomised controlled trials based in schools. Cluster‐randomised trials can, in principle, be combined with individually randomised trials in the same meta‐analysis (Deeks 2017). We did not anticipate that there would be many cluster‐randomised trials, therefore we included identified cluster‐randomised trials in the meta‐analyses and sensitivity analyses that we planned to undertake to investigate the robustness of any conclusions drawn. To correct the influence of any cluster trials, we used an average intraclass correlation coefficient of 0.02 (Health Services Research Unit 2004).

The effective sample size of a single intervention group in a cluster‐randomised trial is its original sample size divided by the ‘design effect’. The design effect is 1 + (M − 1) ICC, where M is the average cluster size and ICC is the intracluster correlation coefficient (Rao 1992). For dichotomous data, we divided both the number of participants and the number experiencing the event by the same design effect. For continuous data, only the sample size was reduced; we did not alter means and standard deviations (SDs).

Cross‐over trials

We did not anticipate that there would be many cross‐over trials, and the data required to include a paired analysis in a meta‐analysis is often not reported (Higgins 2011). We therefore planned to include any identified cross‐over trials in the meta‐analysis, but only data from the first trial period (i.e. prior to the ‘cross‐over').

Studies with multiple treatment groups

Where multiple trial arms were reported in a single trial, we included only the relevant arms. Studies with more than two intervention arms can pose analytical problems in pair‐wise meta‐analysis. Where studies had two or more relevant active treatment arms to be compared against controls, we managed data as follows.

Continuous data

We divided the control group equally into two or more groups to compare the means and SDs of these groups against the means and SDs of the two treatment arms.

Dichotomous data

For trials with two or more active treatment arms and a control group, we split participants in the control arm group equally between the active treatment arms.

Dealing with missing data

We contacted investigators or study sponsors in order to verify key study characteristics and to obtain missing numerical outcome data where possible (e.g. when we identified a study as abstract only, when a study included a post‐treatment diagnostic assessment but did not report the required remission outcomes, or when a study did not report standard errors or SDs). We documented all correspondence with study authors and reported which study authors responded to our queries.

Missing statistics

In the first instance, we attempted to contact the original researchers for any missing data. If the study only reported standard errors, we calculated SDs.

Missing participants

We undertook intention‐to‐treat (ITT) analyses. When analysing dichotomous data, we assumed that all non‐completers in the CBT group were treatment failures, and non‐completers in the control group were treatment successes, thereby yielding the most conservative treatment estimate.

For dichotomous outcomes, we also undertook completer analysis, using only data from participants who completed post‐treatment assessments.

We did not use any statistical or other methods to impute missing data for continuous outcomes, as we did not have access to raw data.

Assessment of heterogeneity

We assessed clinical heterogeneity by comparing differences in the distribution of important participant factors between studies (e.g. age, gender, specific diagnosis, duration and severity of disorder, associated comorbidities). We assessed methodological heterogeneity by comparing trial factors (randomisation, concealment, blinding of outcome assessment, losses to follow‐up). We used the Chi² test, Deeks 2017, and the I² statistic, Higgins 2003, to assess heterogeneity. We set significance at P < 0.1. The Cochrane Handbook for Systematic Reviews of Interventions recommends using a range for the I² statistic and a guide to interpretation (Deeks 2017). If we found either moderate heterogeneity (I² in the range of 30% to 60%) or substantial heterogeneity (I² in the range of 60% to 90%), we performed subgroup and sensitivity analyses where possible.

Assessment of reporting biases

Where a minimum of 10 studies were included, we investigated publication bias using funnel plots, Sterne 2017, and subjected any asymmetry found to statistical investigation using Egger’s test (Stata 2012).

Data synthesis

We undertook meta‐analyses only where this was meaningful, that is if the treatments, participants, and the underlying clinical question were similar enough for pooling to make sense. We undertook ITT and completer analyses.

We planned to carry out separate analyses to identify whether CBT was more effective post‐treatment than waiting list/no treatment; treatment as usual, attention controls, alternative treatments, medication; and drug placebo; and also to identify whether CBT in combination with medication was more effective than drug placebo.

We used follow‐up data for each comparison to assess maintenance of treatment gains. If it was meaningful to do so, we pooled data separately for each follow‐up time point (≤ 6 months post‐treatment, > 6 months post‐treatment but ≤ 12 months post‐treatment, and > 12 months post‐treatment). Where studies reported follow‐up data at multiple time points within one category (e.g. 9‐month and 12‐month follow‐up), we included data from the longer follow‐up period.

Dichotomous data

We used ORs and 95% CIs based on the random‐effects model, with pooling of data via the inverse variance method of weighting. We set significance at P < 0.05. Where available, we used combined data from an interview with the child or adolescent and the parent; otherwise we used data from one interview (child/adolescent or parent interview). We calculated the number needed to treat for an additional beneficial outcome (NNTB) with 95% CIs (Stata 2012). We calculated a summary statistic of all those responding to treatment as a percentage of the total number of participants for each comparison.

Continuous data

We conducted analysis of continuous data based on the random‐effects model, with pooling of data via the inverse variance method of weighting. We used the SMD to pool continuous data measured in different ways across studies but conceptually the same (i.e. measuring anxiety or depressive symptoms or global functioning). For continuous data measuring anxiety symptoms, we pooled child/adolescent report and parental/clinician reports separately. Where both endpoint and change data were available for the same outcome, we presented the endpoint. We set significance at P < 0.05.

Tables and figures

We transferred data into Review Manager 5 (Review Manager 2014), and presented them graphically, so that the area to the left of the line of no effect (or right for remission outcomes) indicated a favourable outcome for CBT. We used tables to display characteristics of the included studies. We presented a brief list of excluded studies in a table with their reasons for exclusion. We summarised risk of bias in the included studies in a figure, and included a PRISMA flow chart (Moher 2015).

Subgroup analysis and investigation of heterogeneity

The critical need to improve access to treatment for child anxiety disorders means that it is particularly important to explore the efficacy of approaches that may help maximise treatment efficiency, including alternative delivery formats and briefer interventions that involve less therapist contact time than traditional approaches. As outlined above, there are also unanswered questions in relation to the benefits of CBT for children and adolescents with ASD and intellectual impairments. We therefore set out to explore the efficacy of different delivery formats and of briefer and shorter interventions, and to examine treatment effects amongst children and adolescents with ASD and those with intellectual impairment, using subgroup analyses. Specifically, where it was possible and meaningful to do so, we undertook subgroup analyses to examine differences between:

delivery formats (child‐focused, child and parent, and parent‐only; individual and group);
interventions with a varying amount of therapist contact time (< 10 hours, ≥ 10 hours and < 20 hours, ≥ 20 hours);
children and adolescents with and without ASDs;
children and adolescents with and without intellectual impairments.

To examine differences between age groups, we also undertook post hoc subgroup analyses evaluating the differences between studies where all participants were age 12 or younger (≤ 12 years); all participants were age 12 or older (≥ 12 years); and studies that included participants under and over age 12 (< 12 years and ≥ 12 years).

We undertook subgroup analyses for the primary outcome (remission of primary anxiety disorder) across comparisons. For the main comparison with the largest number of studies (CBT versus waitlist/no treatment), we also undertook subgroup analyses for the most frequently reported secondary outcomes (remission of all anxiety diagnoses post‐treatment and reduction in child‐ and parent‐reported anxiety symptoms post‐treatment). To ensure subgroup analyses were meaningful, we only undertook these analyses where there were data from at least three studies for each subgroup.

We assessed statistical heterogeneity for all analyses and between groups with the Chi² test and the I² statistic, and set significance at P < 0.1.

Sensitivity analysis

Sensitivity analysis is the study of how the uncertainty in the output of an analysis can be apportioned to different sources of uncertainty in its inputs. Sensitivity analyses can therefore be carried out to test the robustness of decisions made in the review process. We carried out sensitivity analyses where there was evidence of the following:

significant heterogeneity: we inspected forest plots and examined each study in turn to determine the source of any significant heterogeneity;
selection bias: we excluded those studies judged to be at high risk of selection bias from the main analysis;
allocation concealment: we excluded those studies judged to be at high risk of bias for allocation concealment from the main analysis.

Where appropriate, we undertook all of the above sensitivity analyses for the ITT and completer analyses.

Where meta‐analyses examining anxiety symptoms included broad measures of anxiety symptoms and disorder‐specific symptom measures, we also undertook sensitivity analyses excluding studies that only reported disorder‐specific symptom measures.

GRADE and ‘Summary of findings' table

We created a ‘Summary of findings' table including the following primary outcomes:

remission of primary anxiety diagnosis post‐treatment;
acceptability in terms of dropouts from randomisation to the post‐treatment assessment;

and the following secondary outcomes:

remission of all anxiety diagnoses post‐treatment;
reduction in anxiety symptoms (self‐reported and parent‐reported) post‐treatment;
reduction in depressive symptoms post‐treatment;
improvement in global functioning post‐treatment;
adverse events from randomisation to the post‐treatment assessment.

We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of a body of evidence as it relates to the studies that contribute data to the meta‐analyses for the prespecified primary and secondary outcomes. Two review authors (AJ, TR) independently assessed risk of bias, and in case of disagreement sought consensus between four review authors (AJ, TR, GJ, CC). We used the methods and recommendations described in Section 8.5, Higgins 2017, and Chapter 12, Schünemann 2017, of the Cochrane Handbook for Systematic Reviews of Interventions, employing GRADEpro GDT software (GRADEpro GDT). We justified all decisions to downgrade or upgrade the quality of studies using footnotes, and made comments to aid the reader's understanding of the review where necessary. We considered whether there was any additional outcome information that could not be incorporated into the meta‐analyses, noting this in the comments and stating if it supported or contradicted the information from the meta‐analyses.

Results

Description of studies

See Characteristics of included studies and Table 5.

1. Summary of characteristics of included studies.

Study

Comparison 1

Comparison 2

Comparison 3

Broad vs specific anxiety measure

Delivery mode

ASD vs not ASD

Therapist contact time (hours)

Age

Setting

Disorder‐specific

Other comorbid conditions (required)

Afshari 2014

CBT vs Wait list / no treatment

Broad

Child focused

Group

Not ASD

10 to 20

mix

clinic

Arendt 2016

CBT vs Wait list / no treatment

Broad

Child+parent

Group

Not ASD

20+

mix

clinic (university)

Barrett 1996

CBT vs Wait list / no treatment

Broad

Child focused and child+parent

Individual

Not ASD

10 to 20

mix

clinic (university)

Barrett 1998

CBT vs Wait list / no treatment

Child focused and child+parent

Group

Not ASD

20+

mix

clinic (university)

Barrington 2005

CBT vs TAU

Broad

Child+parent

Individual

Not ASD

10 to 20

mix

clinic (CAMHS)

Berge 2017

CBT vs Wait list / no treatment

Specific

Child focused

Individual

Not ASD

less than 10

mix

clinic ‐dental

Specific Phobia

Cartwright Hatton 2011

CBT vs Wait list / no treatment

Parent only

Group

Not ASD

20+

≤ 12

clinic‐university hospital

Chalfant 2007

CBT vs Wait list / no treatment

Broad

Child+parent

Group

ASD

20+

mix

clinic

Cheung 2016

CBT vs Wait list / no treatment

CBT vs Alternative treatment

Broad

Child focused

Individual

Not ASD

10 to 20

≤ 12

clinic‐CAMHS

Chiu 2013

CBT vs Wait list / no treatment

Broad

Child focused

Individual

Not ASD

10 to 20

≤ 12

school

Cobham 2017

CBT vs Wait list / no treatment

Broad

Parent only

Group

Not ASD

less than 10

mix

clinic (university)

Cornacchio 2019

CBT vs Wait list / no treatment

Child+parent

Group

Not ASD

20+

≤ 12

clinic

Selective mutism

Creswell 2017

CBT vs Alertnative treatment

Broad

Parent only

Individual

Not ASD

less than 10

≤ 12

clinic (CAMHS)

Dadds 1997

CBT vs Wait list / no treatment

Broad

Child focused

Group

Not ASD

10 to 20

mix

school

Flannery Schroeder 2000

CBT vs Wait list / no treatment

Broad

Child focused

Individual and group

Not ASD

10 to 20 and 20+

mix

clinic (university)

Fujii 2013

CBT vs TAU

Child+ parent

Individual

ASD

20+

≤ 12

clinic

Gallagher 2004

CBT vs Wait list / no treatment

Broad

Child focused

Group

Not ASD

less than 10

≤ 12

clinic

Social anxiety disorder

Ginsburg 2002

CBT vs Attention control

Broad

Child focused

Group

Not ASD

less than 10

≥ 12

school

Ginsburg 2012

CBT vs TAU

Broad

Child focused

Individual

Not ASD

less than 10

mix

school

Ginsburg 2019

CBT vs TAU

Child focused

Individual

Not ASD

less than 10

mix

school

Hancock 2018

CBT vs Wait list / no treatment

Broad

Child +parent

Group

Not ASD

10 to 20

mix

clinic (university)

Herbert 2009

CBT vs Attention control

Specific

Child focused

Group and Individual

Not ASD

20+ and 10 to 20

≥ 12

clinic (university)

Social anxiety disorder

Hirshfeld Becker 2010

CBT vs Wait list / no treatment

Child + parent

Individual

Not ASD

20+

≤ 12

clinic (university)

Holmes 2014

CBT vs Wait list / no treatment

Broad

Child + parent

Group

Not ASD

10 to 20

≤ 12

clinic (university)

GAD

Hudson 2009

CBT vs Attention control

Broad

Child +parent

Group

Not ASD

20+

mix

clinic (university)

Ingul 2003

CBT vs Attention control

Broad

Child focused

Individual and Group

Not ASD

10 to 20

≥ 12

schools

Social anxiety disorder

Ishikawa 2019

CBT vs Wait list / no treatment

Broad

Child +parent

Individual

Not ASD

less than 10

mix

clinic

Kendall 1994

CBT vs Wait list / no treatment

Broad

Child focused

Individual

Not ASD

10 to 20

mix

clinic (university)

Kendall 1997

CBT vs Wait list / no treatment

Broad

Child focused

Individual

Not ASD

10 to 20

mix

clinic (university)

Kendall 2008

CBT vs Attention control

Broad

Child focused and child+parent

Individual

Not ASD

10 to 20

mix

clinic (university)

Kennedy 2009

CBT vs Wait list / no treatment

Broad

Parent only

Group

Not ASD

10 to 20

≤ 12

clinic (university)

Khanna 2010

CBT vs Attention control

Broad

Child focused

Individual

Not ASD

10 to 20

mix

clinic (university)

Kidd 2018

CBT vs Wait list / no treatment

Broad

Child + parent

Group

ASD

20+

≥ 12

clinic (university)

Last 1998

CBT vs Attention control

Broad

Child and parent

Individual

Not ASD

10 to 20

mix

clinic (university)

School refusal

Lau 2010

CBT vs Wait list / no treatment

Broad

Child focused

Group

Not ASD

10 to 20

≤ 12

clinic

Lau 2017

CBT vs Wait list / no treatment

Broad

Child +parent

Group

Not ASD

10 to 20

≤ 12

child centres and preschools

Lebowitz 2019

CBT vs Alternative treatment

Broad

Child focused

Individual

Not ASD

10 to 20

≤ 12

clinic

Leutgeb 2012

CBT vs Wait list / no treatment

Broad

Child focused

Individual

Not ASD

less than 10

mix

university

Specific Phobia

Masia Warner 2005

CBT vs Wait list / no treatment

Specific

Child focused

Group focused

Not ASD

10 to 20

≥ 12

School

Social anxiety disorder

Masia Warner 2007

CBT vs Attention control

Specific

Child focused

Group focused

Not ASD

10 to 20

≥ 12

School

Social anxiety disorder

Masia Warner 2011

CBT vs Wait list / no treatment

Child focused

Individual

Not ASD

10 to 20

mix

primary care/special clinic

functional physical complaints

Masia Warner 2016

CBT vs Attention control

Specific

Child focused

Group focused

Not ASD

10 to 20

≥ 12

School

Social anxiety disorder

McConachie 2014

CBT vs Wait list / no treatment

Broad

Child + parent

Group

ASD

20+

mix

clinic (university)

McNally Keehn 2013

CBT vs Wait list / no treatment

Broad

Child focused

Individual

ASD

20+

mix

clinic (university)

Melfsen 2011

CBT vs Wait list / no treatment

Specific

Child and parent

Individual

Not ASD

20+

mix

clinic

Social anxiety disorder

Muris 2002

CBT vs Attention control

Broad

Child focused

Group

Not ASD

less than 10

≤ 12

school

Murphy 2017

CBT vs Alternative treatment

Broad

Child focused

Individual focused

ASD

10 to 20

≥ 12

CAMHS

O'Brien 2007

CBT vs TAU

Child and parent

Group

Not ASD

10 to 20

mix

clinic

Olivares 2005

CBT vs Wait list / no treatment

Specific

Child focused

Group

Not ASD

10 to 20

≥ 12

school

Social anxiety disorder

Olivares 2014

CBT vs Wait list / no treatment

Specific

Child focused

Group

Not ASD

10 to 20

≥ 12

school

Social anxiety disorder

Olivares 2019

CBT vs Wait list / no treatment

Child focused

Group

Not ASD

10 to 20

≥ 12

school

Social anxiety disorder

Ollendick 2009

CBT vs Wait list / no treatment

CBT vs Attention control

Broad

Child focused

Individual

Not ASD

less than 10

mix

clinic

Specific Phobia

Ost 2001

CBT vs Wait list / no treatment

Broad

Child focused and child+parent

Individual

Not ASD

less than 10

mix

referrals from clinic and schools

Specific Phobia

Perrin 2019

CBT vs Wait list / no treatment

Broad

Child focused

Individual

Not ASD

10 to 20

mix

CAMHS

GAD

Pincus 2010

CBT vs Attention control

Broad

Child focused

Individual

Not ASD

less than 10

≥ 12

clinic (university)

Panic Disorder

Rapee 2005

CBt vs Wait list / no treatment

Broad

Parent only

Group

Not ASD

less than 10

≤ 12

preschools

Rapee 2006

CBT vs Wait list / no treatment

Broad

Child+parent

Group

Not ASD

10 to 20

≤ 12

clinic (university)

Reaven 2012

CBT vs TAU

Child+parent

Group

ASD

10 to 20

mix

clinic (university)

Reigada 2015

CBT vs Alternative treatment

Specific

Child focused

Individual

Not ASD

10 to 20

mix

clinic (university)

IBD

Rosa‐Alcazar 2009

Cbt vs Attention control

CBT vs Attention control

CBT vs Wait list / no treatment

Specific

Child focused

Group

Not ASD

10 to 20

≥ 12

School

Social anxiety disorder

Salari 2018

CBT vs Wait list / no treatment

Broad

Parent only

Group

Not ASD

10 to 20

≤ 12

clinic (university)

Salum 2018

CBT vs Attention control

CBT vs Alternative treatment

Broad

Child+parent

Group

Not ASD

10 to 20

≤ 12

clinic

Sanchez Garcia 2009

CBT vs Wait list / no treatment

Specific

Child focused

Group

Not ASD

10 to 20

mix

School

Social anxiety disorder

Santucci 2013

CBT vs Wait list / no treatment

Broad

Child +parent

Group

Not ASD

20+

≤ 12

clinic (university)

Separation anxiety disorder

Schneider 2011

CBT vs Wait list / no treatment

Broad

Child +parent

Individual

Not ASD

10 to 20

≤ 12

clinic (university)

Separation anxiety disorder

Sciberras 2018

CBT vs TAU

Broad

Child+parent

Individual

Not ASD

10 to 20

≤ 12

clinic ADHD

ADHD

Shahnavaz 2016

CBT vs TAU

Specific

Child+parent

Individual

Not ASD

10 to 20

mix

dental clinics

Specific Phobia

Sharma 2017

CBT vs TAU

Broad

Child focused

Group

Not ASD

20+

mix

clinic (university)

Headaches

Shortt 2001

CBT vs Wait list / no treatment

Broad

Child+parent

Group

Not ASD

10 to 20

≤ 12

clinic (university)

Silk 2018

CBT vs Alternative treatment

Broad

Child focused

Individual

Not ASD

10 to 20

mix

Silverman 1999a

CBT vs Attention control

Broad

Child+parent

Individual

Not ASD

10 to 20

mix

clinic (university)

Silverman 1999b

CBT vs Wait list / no treatment

Broad

Child + parent

Group

Not ASD

10 to 20

mix

clinic (university)

Simon 2011

CBt vsWait list / no treatment

CBT vs Wait list / no treatment

Broad

Child focused and parent only

Group

Not ASD

less than 10 and 10 to 20

mix

School

Smith 2014

CBT vs Wait list / no treatment

Broad

Parent only

Individual

Not ASD

10 to 20

mix

clinic (university)

Southam Gerow 2010

CBT vs TAU

Broad

Child focused

Individual

Not ASD

10 to 20

mix

clinics

Spence 2000

CBT vs Wait list / no treatment

Broad

Child focused and child+parent

Group

Not ASD

20+ and 10 to 20

mix

clinic (university)

Social anxiety disorder

Spence 2006

CBT vs Wait list / no treatment

Broad

Child+parent

Group

Not ASD

10 to 20

mix

clinic (university)

Spence 2011

CBT vs Wait list / no treatment

Broad

Child+parent

Individual

Not ASD

10 to 20

≥ 12

clinic (university)

Storch 2013

CBT vs TAU

Broad

Child+parent

Individual

ASD

20+

≤ 12

clinic (university)

Storch 2015

CBT vs TAU

Broad

Child+parent

Individual

ASD

20+

≥ 12

clinic (university)

Thirlwall 2013

CBT vs Wait list / no treatment

Broad

Parent only

Individual

Not ASD

less than 10

≤ 12

clinic

Villabo 2018

CBT vs Wait list / no treatment

Broad

Child focused

Individual and Group

Not ASD

10 to 20

mix

clinic

Waters 2009

CBT vs Wait list / no treatment

Child+Parent and parent only

Group

Not ASD

10 to 20 and 20 +

≤ 12

clinic (university)

Wergelenad 2014

CBT vs Wait list / no treatment

Broad

Child+parent

Individual and group

Not ASD

10 to 20

mix

clinics‐CAMHS

White 2013

CBT vs Wait list / no treatment

Broad

Child+parent

Individual

ASD

20+

≥ 12

clinic (university)

Wood 2009

CBT vs Wait list / no treatment

Broad

Child+parent

Individual

ASD

20+

mix

clinic (university)

Wood 2015

CBT vs Wait list / no treatment

Broad

Child+parent

Individual

ASD

20+

mix

clinic (university)

CBT compared with waitlist for children and adolescents with anxiety disorders
Patient or population: children and adolescents with anxiety disorders Settings: outpatient clinics/schools Intervention: CBT Comparison: waitlist/no treatment
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Waitlist¹	CBT
Remission of primary anxiety diagnosis post‐treatment (ITT)	178 per 1000	541 per 1000 (458 to 622)	OR 5.45 (3.90 to 7.60)	2697 (39 studies)	⊕⊕⊕⊝ moderate²	Subgroup analyses: Difference in outcomes for different delivery formats (child‐focused, child and parent, parent only) (Chi² = 8.57, df = 2, P = 0.01, I² = 76.7%) No difference in outcomes for individual versus group formats (Chi² = 0.90, df = 1, P = 0.34; I² = 0%) No difference in outcomes for interventions with different amounts of therapist contact (Chi² = 0.52, df = 2, P = 0.77; I² = 0%) No difference in outcomes for participants with and without ASD (Chi² = 2.25, df = 1, P = 0.13; I² = 55.5%)
Acceptability (number of participants lost to post‐treatment assessment)	104 per 1000	112 per 1000 (90 to 141)	OR 1.09 (0.85 to 1.41)	3158 (45 studies)	⊕⊕⊝⊝ low³
Remission of all anxiety diagnoses post‐treatment (ITT)	191 per 1000	512 per 1000 (406 to 616)	OR 4.43 (2.89 to 6.78)	2075 (28 studies)	⊕⊕⊕⊝ moderate²	Subgroup analyses: Difference in outcomes for different delivery formats (child‐focused, child and parent, parent only) (Chi² = 8.14, df = 2, P = 0.02, I² = 75.4%) No difference in outcomes for individual versus group formats (Chi² = 0.35, df = 1, P = 0.56; I² = 0%) Difference in outcomes for interventions with different amounts of therapist contact (Chi² = 10.75, df = 2, P= 0.005; I² = 81.4%) Insufficient studies for subgroup analyses examining outcomes for participants with and without ASD
Reduction in anxiety symptoms (child report) post‐treatment	The mean anxiety symptoms (child report) in the CBT groups was 0.67standard deviations lower (0.88 to 0.47 lower).		Moderate effect size	2831 (45 studies)	⊕⊕⊝⊝ low⁴	Subgroup analyses: Difference in outcomes for different delivery formats (child‐focused, child and parent, parent only) (Chi² = 14.67,df = 2, P < 0.001, I² = 86.4%) Difference in outcomes for individual versus group formats (Chi² =6.47, df = 1, P = 0.01; I² = 84.5%) No difference in outcomes for interventions with different amounts of therapist contact (Chi² = 3.33, df = 2, P = 0.19; I² = 39.9%) No difference in outcomes for participants with and without ASD (Chi² = 0.02, df = 1, P = 0.88; I² = 0%)
Reduction in anxiety symptoms (parent report) post‐treatment	The mean anxiety symptoms (parent report) in the CBT groups was 0.70standard deviations lower (0.90 to 0.51 lower).		Moderate effect size	2137 (35 studies)	⊕⊕⊝⊝ low⁴	Subgroup analyses: No difference in outcomes for different delivery formats (child‐focused, child and parent, parent only) (Chi² = 3.43, df = 2, P = 0.18, I² = 41.8%) Difference in outcomes for individual versus group formats (Chi² = 6.79,df = 1, P = 0.009, I² = 85.3%) No difference in outcomes for interventions with different amounts of therapist contact (Chi² = 3.77, df = 2, P = 0.15; I² = 46.9%) No difference in outcomes for participants with and without ASD (Chi² = 1.42, df = 1, P = 0.23; I² = 29.8%)
Reduction in depressive symptoms post‐treatment	The mean depressive symptoms in the CBT groups was 0.34 standard deviations lower (0.51 to 0.17 lower).		Small effect size	1157 (17 studies)	⊕⊕⊕⊝ moderate²
Improvement in global functioning post‐treatment	The mean global functioning in the CBT groups was 1.03 standard deviations higher (0.68 to 1.38 higher).		Large effect size	557 (11 studies)	⊕⊕⊝⊝ low⁵
Adverse events (randomisation to post‐treatment)	See comment	See comment	Not estimable	‐	See comment	No study reported adverse events in both CBT and waitlist/no treatment groups
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CBT: cognitive behavioural therapy; CI: confidence interval; ITT: intention‐to‐treat; OR: odds ratio
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

CBT compared with treatment as usual for anxiety disorders in children and adolescents
Patient or population: children and adolescents with anxiety disorders Settings: outpatient clinics/schools Intervention: CBT Comparison: treatment as usual
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk¹	Corresponding risk
	Treatment as usual	CBT
Remission of primary anxiety diagnosis post‐treatment (ITT)	408 per 1000	687 per 1000 (383 to 886)	OR 3.19 (0.90 to 11.29)	487 (8 studies)	⊕⊕⊝⊝ low²	Subgroup analyses: Difference in outcomes for different delivery formats (child‐focused versus child and parent) (Chi² = 10.90, df = 1, P < 0.001, I² = 90.8%) Insufficient studies for subgroup analyses examining differences in outcomes for individual versus group formats and interventions with varyingamount of therapist contact time Difference in outcomes for participants with and without ASD (Chi² = 5.71, df = 1, P = 0.02; I² = 82.5%)
Acceptability (number of participants lost to post‐treatment assessment)	93 per 1000	124 per 1000 (70 to 209)	OR 1.37 (0.73 to 2.56)	441 (8 studies)	⊕⊕⊝⊝ low³
Remission of all anxiety diagnoses post‐treatment (ITT)	414 per 1000	660 per 1000 (451 to 820)	OR 2.74 (1.16 to 6.46)	203 (5 studies)	⊕⊕⊝⊝ low³
Reduction in anxiety symptoms (child report) post‐treatment	The mean anxiety symptoms (child report) in the CBT groups was 0.15standard deviations lower (0.78 lower to 0.48 higher).		Cross 0	214 (6 studies)	⊕⊕⊝⊝ low²
Reduction in anxiety symptoms (parent report) post‐treatment	The mean anxiety symptoms (parent report) in the CBT groups was 0.32standard deviations lower (0.70 lower to 0.06 higher).		Cross 0	228 (7 studies)	⊕⊕⊝⊝ low²
Reduction in depressive symptoms post‐treatment	See comment		Not estimable	‐	See comment	Insufficient evidence to estimate effect
Improvement in global functioning post‐treatment	See comment		Not estimable	‐	See comment	Insufficient evidence to estimate effect
Adverse events (randomisation to post‐treatment)	See comment	See comment	Not estimable	‐	See comment	No study reported adverse events in both CBT and Treatment as Usual groups
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CBT: cognitive behavioural therapy; CI: confidence interval; ITT: intention‐to‐treat; OR: odds ratio
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

CBT compared with attention control for anxiety disorders in children and adolescents
Patient or population: children and adolescents with anxiety disorders Settings: outpatient clinics/schools Intervention: CBT Comparison: attention control
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Attention control¹	CBT
Remission of primary anxiety diagnosis post‐treatment (ITT)	293 per 1000	486 per 1000 (355 to 617)	OR 2.28 (1.33 to 3.89)	822 (10 studies)	⊕⊕⊝⊝ low^2,	Subgroup analyses: Difference in outcomes for different delivery formats (child‐focused versus child and parent) (Chi² = 7.65, df = 1, P = 0.006; I² = 86.9%) No difference in outcomes for individual versus group formats (Chi² = 1.22, df = 1, P = 0.27; I² = 17.7%) Insufficient studies for subgroup analyses examining outcomes for interventions with varying amounts of therapist contact, and participants with and without ASD
Acceptability (number of participants lost to post‐treatment assessment)	201 per 1000	201 per 1000 (146 to 272)	OR 1.00 (0.68 to 1.49)	797 (12 studies)	⊕⊕⊝⊝ low³
Remission of all anxiety diagnoses post‐treatment (ITT)	185 per 1000	385 per 1000 (217 to 584)	OR 2.75 (1.22 to 6.17)	378 (5 studies)	⊕⊕⊝⊝ low²
Reduction in anxiety symptoms (child report) post‐treatment	The mean anxiety symptoms (child report) in the CBT groups was 0.31standard deviations lower (0.51 to 0.11 lower).		Small effect size	978 (15 studies)	⊕⊕⊕⊝ moderate⁴
Reduction in anxiety symptoms (parent report) post‐treatment	The mean anxiety symptoms (parent report) in the CBT groups was 0.25standard deviations lower (0.61 lower to 0.11 higher).		Cross 0	638 (8 studies)	⊕⊕⊝⊝ low⁵
Reduction in depressive symptoms post‐treatment	The mean depressive symptoms in the CBT groups was 0.18standard deviations lower (0.45 lower to 0.09 higher).		Cross 0	613 (10 studies)	⊕⊕⊝⊝ low⁵
Improvement in global functioning post‐treatment	See comment		Not estimable	‐	See comment	Insufficient evidence to estimate effect
Adverse events (randomisation to post‐treatment)	See comment	See comment	Not estimable	‐	See comment	No study reported adverse events in both CBT and attention control groups
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CBT: cognitive behavioural therapy; CI: confidence interval; ITT: intention‐to‐treat; OR: odds ratio
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

CBT compared with alternative treatment for anxiety disorders in children and adolescents
Patient or population: children and adolescents with anxiety disorders Settings: outpatient clinics/schools Intervention: CBT Comparison: alternative treatment
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Alternative treatment¹	CBT
Remission of primary anxiety diagnosis post‐treatment (ITT)	See comment	See comment	Not estimable	‐	See comment	Insufficient evidence to estimate effect or conduct subgroup analyses
Acceptability (number of participants lost to post‐treatment assessment)	115 per 1000	171 per 1000 (74 to 350)	OR 1.58 (0.61 to 4.13)	515 (7 studies)	⊕⊕⊝⊝ low²
Remission of all anxiety diagnoses post‐treatment (ITT)	607 per 1000	579 per 1000 (351 to 775)	OR 0.89 (0.35 to 2.23)	401 (4 studies)	⊕⊕⊝⊝ low²
Reduction in anxiety symptoms (child report) post‐treatment	The mean anxiety symptoms (child report) in the CBT groups was 0.09standard deviations lower (0.40 lower to 0.21 higher).		Cross 0	399 (6 studies)	⊕⊕⊝⊝ low³
Reduction in anxiety symptoms (parent report) post‐treatment	The mean anxiety symptoms (child report) in the CBT groups was 0.13standard deviations lower (0.33 lower to 0.06 higher).		Cross 0	423 (6 studies)	⊕⊕⊝⊝ low⁴
Reduction in depressive symptoms post‐treatment	Not estimable		Not estimable	‐	See comment	Insufficient evidence to estimate effect
Improvement in global functioning post‐treatment	Not estimable		Not estimable	‐	See comment	No evidence available to estimate effect
Adverse events (randomisation to post‐treatment)	See comment	See comment	Not estimable	‐	See comment	No study reported adverse events in both CBT and Treatment as Usual groups
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CBT: cognitive behavioural therapy; CI: confidence interval; ITT: intention‐to‐treat; OR: odds ratio
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Remission of primary anxiety diagnosis post‐treatment (ITT)	39	2697	Odds Ratio (IV, Random, 95% CI)	5.45 [3.90, 7.60]
1.1.1 Child focused	19	1184	Odds Ratio (IV, Random, 95% CI)	10.42 [5.84, 18.58]
1.1.2 Child and parent	19	1142	Odds Ratio (IV, Random, 95% CI)	4.08 [2.72, 6.11]
1.1.3 Parent only	4	371	Odds Ratio (IV, Random, 95% CI)	2.83 [1.12, 7.16]
1.2 Subgroup analysis: remission of primary anxiety diagnosis post‐treatment (ITT) (individual vs group)	39		Odds Ratio (IV, Random, 95% CI)	Subtotals only
1.2.1 Individual focused	17	1165	Odds Ratio (IV, Random, 95% CI)	4.53 [2.55, 8.03]
1.2.2 Group focused	25	1532	Odds Ratio (IV, Random, 95% CI)	6.25 [4.45, 8.78]
1.3 Subgroup analysis: remission of primary anxiety diagnosis post‐treatment (ITT) (amount of therapist contact time)	39		Odds Ratio (IV, Random, 95% CI)	Subtotals only
1.3.1 Therapist contact (< 10 hours)	6	513	Odds Ratio (IV, Random, 95% CI)	6.12 [2.08, 18.00]
1.3.2 Therapist contact (≥10 and < 20 hours)	23	1622	Odds Ratio (IV, Random, 95% CI)	5.85 [3.95, 8.64]
1.3.3 Therapist contact (≥ 20 hours)	13	562	Odds Ratio (IV, Random, 95% CI)	4.44 [2.26, 8.72]
1.4 Subgroup analysis: remission of primary anxiety diagnosis post‐treatment (ITT) (age)	39		Odds Ratio (IV, Random, 95% CI)	Subtotals only
1.4.1 ≤ 12 years	11	789	Odds Ratio (IV, Random, 95% CI)	3.93 [2.20, 7.02]
1.4.2 Mixed age range (< 12 and ≥ 12 years)	21	1447	Odds Ratio (IV, Random, 95% CI)	6.43 [3.90, 10.58]
1.4.3 ≥ 12 years	7	461	Odds Ratio (IV, Random, 95% CI)	5.28 [2.83, 9.86]
1.5 Subgroup analysis: remission of primary anxiety diagnosis post‐treatment (ITT) (ASD vs non‐ASD)	39		Odds Ratio (IV, Random, 95% CI)	Subtotals only
1.5.1 Sample with ASD	4	136	Odds Ratio (IV, Random, 95% CI)	1.79 [0.39, 8.16]
1.5.2 Not sample with ASD	35	2561	Odds Ratio (IV, Random, 95% CI)	5.88 [4.19, 8.24]
1.6 Remission of primary anxiety diagnosis post‐treatment (completers)	38	2406	Odds Ratio (IV, Random, 95% CI)	11.55 [8.41, 15.86]
1.7 Acceptability (number of participants lost to post‐treatment assessment)	45	3158	Odds Ratio (IV, Random, 95% CI)	1.09 [0.85, 1.41]
1.8 Remission of all anxiety diagnoses post‐treatment (ITT)	28	2075	Odds Ratio (IV, Random, 95% CI)	4.43 [2.89, 6.78]
1.8.1 Child focused	11	564	Odds Ratio (IV, Random, 95% CI)	8.52 [2.97, 24.39]
1.8.2 Child and parent	15	916	Odds Ratio (IV, Random, 95% CI)	5.19 [3.26, 8.27]
1.8.3 Parent only	7	595	Odds Ratio (IV, Random, 95% CI)	1.89 [0.98, 3.65]
1.9 Subgroup analysis: remission of all anxiety diagnoses post‐treatment (ITT) (individual vs group)	28		Odds Ratio (IV, Random, 95% CI)	Subtotals only
1.9.1 Individual focused	9	671	Odds Ratio (IV, Random, 95% CI)	3.72 [1.70, 8.12]
1.9.2 Group focused	20	1404	Odds Ratio (IV, Random, 95% CI)	4.92 [2.95, 8.20]
1.10 Subgroup analysis: remission of all anxiety diagnoses post‐treatment (ITT) (amount of therapist contact time)	28		Odds Ratio (IV, Random, 95% CI)	Subtotals only
1.10.1 Therapist contact (< 10 hours)	5	461	Odds Ratio (IV, Random, 95% CI)	1.42 [0.68, 2.96]
1.10.2 Therapist contact (≥ 10 and < 20 hours)	17	1123	Odds Ratio (IV, Random, 95% CI)	6.59 [3.62, 12.01]
1.10.3 Therapist contact (≥ 20 hours)	9	491	Odds Ratio (IV, Random, 95% CI)	5.03 [2.55, 9.93]
1.11 Subgroup analysis: remission of all anxiety diagnoses post‐treatment (ITT) (age)	28		Odds Ratio (IV, Random, 95% CI)	Subtotals only
1.11.1 ≤ 12 years	10	950	Odds Ratio (IV, Random, 95% CI)	3.59 [1.97, 6.56]
1.11.2 Mixed age range (< 12 years and ≥ 12 years)	15	980	Odds Ratio (IV, Random, 95% CI)	4.87 [2.58, 9.21]
1.11.3 ≥ 12 years	3	145	Odds Ratio (IV, Random, 95% CI)	8.48 [0.79, 91.08]
1.12 Remission of all anxiety diagnoses post‐treatment (completers)	27	1871	Odds Ratio (IV, Random, 95% CI)	9.13 [5.78, 14.41]
1.13 Reduction in anxiety symptoms (child report) post‐treatment	45	2831	Std. Mean Difference (IV, Random, 95% CI)	‐0.67 [‐0.88, ‐0.47]
1.13.1 Child focused	24	1239	Std. Mean Difference (IV, Random, 95% CI)	‐1.04 [‐1.41, ‐0.67]
1.13.2 Child and parent	20	1285	Std. Mean Difference (IV, Random, 95% CI)	‐0.45 [‐0.67, ‐0.23]
1.13.3 Parent only	5	307	Std. Mean Difference (IV, Random, 95% CI)	0.04 [‐0.38, 0.46]
1.14 Sensitivity analysis: reduction in anxiety symptoms (child report) post‐treatment (broad anxiety measures)	38	2459	Std. Mean Difference (IV, Random, 95% CI)	‐0.41 [‐0.57, ‐0.25]
1.15 Subgroup analysis: reduction in anxiety symptoms (child report) post‐treatment (individual vs group)	45		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
1.15.1 Individual focused	21	1203	Std. Mean Difference (IV, Random, 95% CI)	‐0.39 [‐0.64, ‐0.15]
1.15.2 Group focused	27	1628	Std. Mean Difference (IV, Random, 95% CI)	‐0.91 [‐1.22, ‐0.60]
1.16 Subgroup analysis: reduction in anxiety symptoms (child report) post‐treatment (amount of therapist contact time)	45		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
1.16.1 Therapist contact (< 10 hours)	9	587	Std. Mean Difference (IV, Random, 95% CI)	‐0.36 [‐0.75, 0.03]
1.16.2 Therapist contact (≥ 10 and < 20 hours)	29	1840	Std. Mean Difference (IV, Random, 95% CI)	‐0.81 [‐1.09, ‐0.52]
1.16.3 Therapist contact (≥ 20 hours)	10	404	Std. Mean Difference (IV, Random, 95% CI)	‐0.62 [‐1.06, ‐0.18]
1.17 Subgroup analysis: reduction in anxiety symptoms (child report) post‐treatment (age)	45		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
1.17.1 ≤ 12 years	11	663	Std. Mean Difference (IV, Random, 95% CI)	‐0.23 [‐0.54, 0.08]
1.17.2 Mixed age range (< 12 years and ≥ 12 years)	28	1834	Std. Mean Difference (IV, Random, 95% CI)	‐0.62 [‐0.83, ‐0.41]
1.17.3 ≥ 12 years	6	334	Std. Mean Difference (IV, Random, 95% CI)	‐1.78 [‐3.01, ‐0.56]
1.18 Subgroup analysis: reduction in anxiety symptoms (child report) post‐treatment (ASD vs non‐ASD)	45		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
1.18.1 Sample with ASD	5	181	Std. Mean Difference (IV, Random, 95% CI)	‐0.61 [‐1.54, 0.33]
1.18.2 Not sample with ASD	40	2650	Std. Mean Difference (IV, Random, 95% CI)	‐0.68 [‐0.90, ‐0.47]
1.19 Reduction in anxiety symptoms (parent report) post‐treatment	35	2137	Std. Mean Difference (IV, Random, 95% CI)	‐0.70 [‐0.90, ‐0.51]
1.19.1 Child focused	13	734	Std. Mean Difference (IV, Random, 95% CI)	‐0.87 [‐1.21, ‐0.53]
1.19.2 Child and parent	17	1031	Std. Mean Difference (IV, Random, 95% CI)	‐0.69 [‐0.98, ‐0.39]
1.19.3 Parent only	5	372	Std. Mean Difference (IV, Random, 95% CI)	‐0.37 [‐0.77, 0.04]
1.20 Sensitivity analysis: reduction in anxiety symptoms (parent report) post‐treatment (broad anxiety measures only)	32	1952	Std. Mean Difference (IV, Random, 95% CI)	‐0.59 [‐0.77, ‐0.41]
1.21 Subgroup analysis: reduction in anxiety symptoms (parent report) post‐treatment (individual vs group)	35		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
1.21.1 Individual focused	17	858	Std. Mean Difference (IV, Random, 95% CI)	‐0.43 [‐0.65, ‐0.21]
1.21.2 Group focused	21	1279	Std. Mean Difference (IV, Random, 95% CI)	‐0.92 [‐1.21, ‐0.62]
1.22 Subgroup analysis: reduction in anxiety symptoms (parent report) post‐treatment (amount of therapist contact time)	35		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
1.22.1 Therapist contact (< 10 hours)	4	336	Std. Mean Difference (IV, Random, 95% CI)	‐0.36 [‐0.81, 0.10]
1.22.2 Therapist contact (≥ 10 and < 20 hours)	22	1402	Std. Mean Difference (IV, Random, 95% CI)	‐0.66 [‐0.89, ‐0.43]
1.22.3 Therapist contact (≥ 20 hours)	10	399	Std. Mean Difference (IV, Random, 95% CI)	‐1.03 [‐1.55, ‐0.52]
1.23 Subgroup analysis: reduction in anxiety symptoms (parent report) post‐treatment (age)	35		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
1.23.1 ≤ 12 years	11	750	Std. Mean Difference (IV, Random, 95% CI)	‐0.40 [‐0.63, ‐0.17]
1.23.2 Mixed age range (< 12 years and ≥ 12 years)	18	1057	Std. Mean Difference (IV, Random, 95% CI)	‐0.76 [‐1.04, ‐0.49]
1.23.3 ≥ 12 years	6	330	Std. Mean Difference (IV, Random, 95% CI)	‐1.07 [‐1.78, ‐0.37]
1.24 Subgroup analysis: reduction in anxiety symptoms (parent report) post‐treatment (ASD vs non‐ASD)	35		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
1.24.1 Sample with ASD	7	244	Std. Mean Difference (IV, Random, 95% CI)	‐1.12 [‐1.91, ‐0.34]
1.24.2 Not sample with ASD	28	1893	Std. Mean Difference (IV, Random, 95% CI)	‐0.63 [‐0.82, ‐0.44]
1.25 Reduction in depressive symptoms post‐treatment	17	1157	Std. Mean Difference (IV, Random, 95% CI)	‐0.34 [‐0.51, ‐0.17]
1.26 Improvement in global functioning post‐treatment	11	557	Std. Mean Difference (IV, Random, 95% CI)	1.03 [0.68, 1.38]
1.27 Remission of primary anxiety diagnosis at follow‐up (ITT)	5		Odds Ratio (IV, Random, 95% CI)	Subtotals only
1.27.1 Follow‐up (≤ 6 months)	4	153	Odds Ratio (IV, Random, 95% CI)	10.94 [2.33, 51.41]
1.27.2 Follow‐up (> 6 and ≤ 12 months)	3	166	Odds Ratio (IV, Random, 95% CI)	2.80 [0.24, 33.19]
1.28 Remission of primary anxiety diagnosis at follow‐up (completers)	5		Odds Ratio (IV, Random, 95% CI)	Subtotals only
1.28.1 Follow‐up (≤ 6 months)	4	151	Odds Ratio (IV, Random, 95% CI)	11.46 [2.40, 54.67]
1.28.2 Follow‐up (> 6 and ≤ 12 months)	3	161	Odds Ratio (IV, Random, 95% CI)	4.04 [0.77, 21.20]
1.29 Remission of all anxiety diagnoses at follow‐up (ITT)	5		Odds Ratio (IV, Random, 95% CI)	Subtotals only
1.29.1 Follow‐up (≤ 6 months)	3	130	Odds Ratio (IV, Random, 95% CI)	8.25 [0.69, 98.10]
1.29.2 Follow‐up (> 6 and ≤ 12 months)	3	166	Odds Ratio (IV, Random, 95% CI)	3.75 [0.25, 56.88]
1.29.3 Follow‐up (> 12 months)	2	131	Odds Ratio (IV, Random, 95% CI)	0.48 [0.17, 1.38]
1.30 Remission of all anxiety diagnoses at follow‐up (completers)	5		Odds Ratio (IV, Random, 95% CI)	Subtotals only
1.30.1 Follow‐up (≤ 6 months)	3	128	Odds Ratio (IV, Random, 95% CI)	8.68 [0.72, 104.46]
1.30.2 Follow‐up (> 6 and ≤ 12 months)	3	161	Odds Ratio (IV, Random, 95% CI)	5.01 [0.70, 35.87]
1.30.3 Follow‐up (> 12 months)	2	114	Odds Ratio (IV, Random, 95% CI)	1.25 [0.36, 4.34]
1.31 Reduction in anxiety symptoms (child report) at follow‐up	5		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
1.31.1 Follow‐up (≤ 6 months)	5	179	Std. Mean Difference (IV, Random, 95% CI)	‐1.92 [‐2.95, ‐0.89]
1.32 Sensitivity analysis: remission of primary anxiety diagnosis post‐treatment (ITT) (only studies where sequence generation is clear)	20	1476	Odds Ratio (IV, Random, 95% CI)	4.84 [3.03, 7.73]
1.33 Sensitivity analysis: remission of primary anxiety diagnosis post‐treatment (ITT) (only studies where blind assessors used)	31	2037	Odds Ratio (IV, Random, 95% CI)	5.54 [3.76, 8.18]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Remission of primary anxiety diagnosis post‐treatment (ITT)	8	487	Odds Ratio (IV, Random, 95% CI)	3.19 [0.90, 11.29]
2.1.1 Child focused	3	315	Odds Ratio (IV, Random, 95% CI)	0.61 [0.18, 2.01]
2.1.2 Child and parent	5	172	Odds Ratio (IV, Random, 95% CI)	8.56 [3.10, 23.66]
2.2 Subgroup analysis: remission of primary anxiety diagnosis post‐treatment (ITT) (ASD vs non‐ASD)	8		Odds Ratio (IV, Random, 95% CI)	Subtotals only
2.2.1 Sample with ASD	4	142	Odds Ratio (IV, Random, 95% CI)	11.25 [3.11, 40.79]
2.2.2 Not sample with ASD	4	345	Odds Ratio (IV, Random, 95% CI)	1.14 [0.29, 4.47]
2.3 Remission of primary anxiety diagnosis post‐treatment (completers)	8	440	Odds Ratio (IV, Random, 95% CI)	4.87 [1.51, 15.72]
2.4 Acceptability (number of participants lost to post‐treatment assessment)	8	441	Odds Ratio (IV, Random, 95% CI)	1.37 [0.73, 2.56]
2.5 Remission of all anxiety diagnoses post‐treatment (ITT)	5	203	Odds Ratio (IV, Random, 95% CI)	2.74 [1.16, 6.46]
2.6 Remission of all anxiety diagnoses post‐treatment (completers)	5	201	Odds Ratio (IV, Random, 95% CI)	2.78 [1.18, 6.55]
2.7 Reduction in anxiety symptoms (child report) post‐treatment	6	214	Std. Mean Difference (IV, Random, 95% CI)	‐0.15 [‐0.78, 0.48]
2.8 Sensitivity analysis: reduction in anxiety symptoms (child report) post‐treatment (broad anxiety measures only)	5	187	Std. Mean Difference (IV, Random, 95% CI)	0.07 [‐0.54, 0.68]
2.9 Reduction in anxiety symptoms (parent report) post‐treatment	7	228	Std. Mean Difference (IV, Random, 95% CI)	‐0.32 [‐0.70, 0.06]
2.10 Sensitivity analysis: reduction in anxiety symptoms (parent report) post‐treatment (broad anxiety measures only)	6	202	Std. Mean Difference (IV, Random, 95% CI)	‐0.16 [‐0.44, 0.11]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Remission of primary anxiety diagnosis post‐treatment (ITT)	10	822	Odds Ratio (IV, Random, 95% CI)	2.28 [1.33, 3.89]
3.1.1 Child focused	7	509	Odds Ratio (IV, Random, 95% CI)	3.58 [1.92, 6.65]
3.1.2 Child and parent	4	313	Odds Ratio (IV, Random, 95% CI)	1.12 [0.65, 1.92]
3.2 Subgroup analysis: remission of primary anxiety diagnosis post‐treatment (ITT) (individual vs group)	10		Odds Ratio (IV, Random, 95% CI)	Subtotals only
3.2.1 Individual focused	5	469	Odds Ratio (IV, Random, 95% CI)	2.04 [1.06, 3.91]
3.2.2 Group focused	5	353	Odds Ratio (IV, Random, 95% CI)	3.10 [1.14, 8.45]
3.3 Remission of primary anxiety diagnosis post‐treatment (completers)	10	752	Odds Ratio (IV, Random, 95% CI)	3.88 [2.52, 5.97]
3.4 Acceptability (number of participants lost to post‐treatment assessment)	12	797	Odds Ratio (IV, Random, 95% CI)	1.00 [0.68, 1.49]
3.5 Remission of all anxiety diagnoses post‐treatment (ITT)	5	378	Odds Ratio (IV, Random, 95% CI)	2.75 [1.22, 6.17]
3.6 Remission of all anxiety diagnoses post‐treatment (completers)	5	359	Odds Ratio (IV, Random, 95% CI)	3.88 [1.58, 9.51]
3.7 Reduction in anxiety symptoms (child report) post‐treatment	15	978	Std. Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.51, ‐0.11]
3.8 Sensitivity analysis: reduction in anxiety symptoms (child report) post‐treatment (broad anxiety measures only)	11	685	Std. Mean Difference (IV, Random, 95% CI)	‐0.18 [‐0.34, ‐0.02]
3.9 Reduction in anxiety symptoms (parent report) post‐treatment	8	638	Std. Mean Difference (IV, Random, 95% CI)	‐0.25 [‐0.61, 0.11]
3.10 Sensitivity analysis: reduction in anxiety symptoms (parent report) post‐treatment (broad anxiety measures only)	4	345	Std. Mean Difference (IV, Random, 95% CI)	‐0.04 [‐0.26, 0.18]
3.11 Reduction in depressive symptoms post‐treatment	10	613	Std. Mean Difference (IV, Random, 95% CI)	‐0.18 [‐0.45, 0.09]
3.12 Remission of primary anxiety diagnosis at follow‐up (ITT)	4		Odds Ratio (IV, Random, 95% CI)	Subtotals only
3.12.1 Follow‐up (≤ 6 months)	4	341	Odds Ratio (IV, Random, 95% CI)	3.06 [1.22, 7.65]
3.13 Remission of primary anxiety diagnosis at follow‐up (completers)	4		Odds Ratio (IV, Random, 95% CI)	Subtotals only
3.13.1 Follow‐up (≤ 6 months)	4	302	Odds Ratio (IV, Random, 95% CI)	6.52 [2.58, 16.43]
3.14 Remission of all anxiety diagnoses at follow‐up (ITT)	3		Odds Ratio (IV, Random, 95% CI)	Subtotals only
3.14.1 Follow‐up (≤ 6 months)	3	205	Odds Ratio (IV, Random, 95% CI)	5.44 [1.00, 29.60]
3.15 Remission of all anxiety diagnoses at follow‐up (completers)	3		Odds Ratio (IV, Random, 95% CI)	Subtotals only
3.15.1 Follow‐up (≤ 6 months)	3	182	Odds Ratio (IV, Random, 95% CI)	11.19 [1.94, 64.51]
3.16 Reduction in anxiety symptoms (child report) at follow‐up	6		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
3.16.1 Follow‐up (≤ 6 months)	6	434	Std. Mean Difference (IV, Random, 95% CI)	‐0.44 [‐0.79, ‐0.08]
3.17 Reduction in anxiety symptoms (parent report) at follow‐up	6		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
3.17.1 Follow‐up (≤ 6 months)	6	434	Std. Mean Difference (IV, Random, 95% CI)	‐0.63 [‐1.33, 0.08]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Acceptability (number of participants lost to post‐treatment assessment)	7	515	Odds Ratio (IV, Random, 95% CI)	1.58 [0.61, 4.13]
4.2 Remission of all anxiety diagnoses post‐treatment (ITT)	4	401	Odds Ratio (IV, Random, 95% CI)	0.89 [0.35, 2.23]
4.3 Remission of all anxiety diagnoses post‐treatment (completers)	4	348	Odds Ratio (IV, Random, 95% CI)	1.52 [0.70, 3.27]
4.4 Reduction in anxiety symptoms (child report) post‐treatment	6	399	Std. Mean Difference (IV, Random, 95% CI)	‐0.09 [‐0.40, 0.21]
4.5 Sensitivity analysis: reduction in anxiety symptoms (child report) post‐treatment (broad anxiety measures only)	5	378	Std. Mean Difference (IV, Random, 95% CI)	‐0.00 [‐0.21, 0.20]
4.6 Reduction in anxiety symptoms (parent report) post‐treatment	6	423	Std. Mean Difference (IV, Random, 95% CI)	‐0.13 [‐0.33, 0.06]

*Study characteristics*
Methods	Study design: randomised controlled trial Total duration of study: 10‐ to 12‐week treatment, 3‐month follow‐up Number of study centres and location: 1, Iran Study setting: private clinic Date of study: October 2011 to August 2012
Participants	N = 34 (CBT: N = 12; CBT (emotion‐focused): N = 12; no treatment control: N = 10) Mean age (SD): 10.57 (2.27) Age range: 9 to 13 years Inclusion criteria: separation anxiety disorder diagnosis (based on the ADIS‐C/P), not receiving medication or stopped using drugs for at least 1 month before pretest Exclusion criteria: IQ < 80, learning disorders, psychosis, serious mental or physical problems, low interest in continuing the study
Interventions	CBT Intervention: Coping Cat Concomitant/excluded medications: no medication or stopped for at least 1 month before pretest Delivery format: child‐only sessions, does not specify if parent sessions included; group format Therapist contact time: 10 hours (10 x 1 hour) Who delivers the intervention: advanced PhD students in psychology CBT (emotion‐focused) Intervention: emotion‐focused CBT (ECBT) (Suveg 2006) Concomitant/excluded medications: no medication or stopped for at least 1 month before pretest Delivery format: child‐only sessions, and 2 parent sessions; group format Therapist contact time: 12 hours (child: 10 x 1; parent: 2 x 1) Who delivers the intervention: advanced PhD students in psychology Wait list/no treatment Intervention: no treatment Concomitant/excluded medications: no medication or stopped for at least 1 month before pretest
Outcomes	Reduction in anxiety symptoms (child report) post‐treatment and 3‐month follow‐up: SCARED‐C Reduction in anxiety symptoms (parent report) post‐treatment and 3‐month follow‐up: SCARED‐P
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Judgement Comment: No detail given
Allocation concealment (selection bias)	Unclear risk	Judgement Comment: No detail given
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Judgement Comment: Even though blinding was not possible, we judged that it was unlikely this led to a departure from the intended intervention
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Judgement Comment: No detail given but child/parent report questionnaires only
Incomplete outcome data (attrition bias) All outcomes	High risk	Judgement Comment: Reason for missing outcome data (low interest in attending sessions) likely to be related to outcome
Selective reporting (reporting bias)	Low risk	Judgement Comment: Outcomes for each measure reported
Other source of bias ‐ Therapy integrity	Unclear risk	Judgement Comment: Therapists PhD students. No detail on any attempt to maintain or measure therapy integrity
Other bias	Unclear risk	Judgement Comment: Timings for post‐treatment assessment not detailed. Treatment period different for 2 treatment groups

*Study characteristics*
Methods	Study design: cluster‐randomised controlled trial Total duration of study: 6‐, 12‐, and 24‐month follow‐up Number of study centres and location: 8 primary schools in Australia Study setting: primary schools
Participants	N = 128 randomised (CBT: N = 61; active control: N = 68) (NB: N = 64 met diagnostic criteria for an anxiety disorder and were included here (based on ADIS‐P)) Age range: 7 to 14 years Inclusion criteria: children met diagnostic criteria for anxiety disorder or features of anxiety disorder. We only included those who met diagnostic criteria (based on ADIS‐P, CSR = 4+) Exclusion criteria: Clinical Severity Rating 6 to 8
Interventions	CBT Intervention: Coping Koala (Australian modification of Coping Cat) Concomitant/excluded medications: Delivery format: child only, parent only; group Therapist contact time: 10 to 23 hours (10 x 1 to 2 hours, plus 3 parent sessions) Who delivers the intervention: clinical psychologists Waitlist/no treatment Intervention: monitoring, no intervention
Outcomes	Remission of primary anxiety disorder diagnosis post‐treatment and 6‐, 12‐, and 24‐month follow‐up: ADIS‐P Remission of all anxiety disorder diagnoses post‐treatment and 6‐, 12‐, and 24‐month follow‐up: ADIS‐P Reduction in anxiety symptoms (child report) post‐treatment and 6‐, 12‐, and 24‐month follow‐up: RCMAS
Notes	Author provided data on outcomes for participants who met diagnostic criteria for an anxiety disorder (CSR 4+) at baseline. Cluster trial ‐ adjustments for analysis as per protocol
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Judgement Comment: Schools matched for size, sociodemographics, and were randomly allocated to condition. No further detail
Allocation concealment (selection bias)	Unclear risk	Judgement Comment: No detail
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Judgement Comment: Even though blinding was not possible, we judged that it was unlikely this led to a departure from the intended intervention
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Judgement Comment: Blind assessors
Incomplete outcome data (attrition bias) All outcomes	Low risk	Judgement Comment: Author provided data
Selective reporting (reporting bias)	Low risk	Judgement Comment: Outcomes reported/provided
Other source of bias ‐ Therapy integrity	Low risk	Judgement Comment: Regular supervision, integrity monitored, and no significant departures from protocol reported
Other bias	Low risk	Judgement Comment: The study appears to be free of other sources of bias

*Study characteristics*
Methods	Study design: factorial randomised controlled trial Number of study centres and location: Brazil Date of study: recruitment from July 2011 to September 2012 Withdrawals: N = 96 originally randomised, but 17 withdrew before first session and were not aware of allocation ‐ not included
Participants	N = 79 (CBT + Attention Bias Modification N = 21; CBT + Attention Control Training: N = 21; active control therapy + Attention Bias Modification: N = 17; active control therapy + Attention Control Training: N = 20) Age range: 7 to 11 Inclusion criteria: primary diagnosis of generalised anxiety disorder, separation anxiety disorder, or social anxiety disorder (based on K‐SADS) Exclusion criteria: (i) other psychiatric disorder judged by the clinician to cause more impairment or distress than GAD, separation anxiety disorder, or social anxiety disorder; (ii) any history of mental health treatment; (iii) IQ lower than 70
Interventions	CBT (CBT + Attention Bias Modification) Intervention: Friends for Life (group CBT) + Attention Bias Modification (160 trials) Delivery format: child and parent sessions; group Therapist contact time: 15 hours (10 x 90 minutes) Who delivers the intervention: trained psychologists CBT (CBT + Attention Control Training) Intervention: Friends for Life (group CBT) + Attention Control Training (160 trials) Delivery format: child and parent sessions; group Therapist contact time: 15 hours (10 x 90 minutes) Who delivers the intervention: trained psychologists Active control (control therapy + Attention Bias Modification) Intervention: control therapy ‐ educational tasks and psychoeducation + Attention Bias Modification (160 trials) Delivery format: child and parent sessions; group Therapist contact time: 15 hours (10 x 90 minutes) Who delivers the intervention: trained psychologists Active control (control therapy + Attention Control Training) Intervention: control therapy ‐ educational tasks and psychoeducation + Attention Control Training (160 trials) Delivery format: child and parent sessions; group Therapist contact time: 15 hours (10 x 90 minutes) Who delivers the intervention: trained psychologists
Outcomes	Reduction in anxiety symptoms (child report) post‐treatment: SCAS‐C Reduction in anxiety symptoms (parent report) post‐treatment: SCAS‐P Reduction in depressive symptoms post‐treatment: CDI
Notes	Comparisons: CBT + Attention Bias Modification vs active control therapy + Attention Bias Modification CBT + Attention Control Training vs active control therapy + Attention Control Training Active control therapy + Attention Bias Modification = alternative treatment Active control therapy + Attention Control Training = attention control
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Judgement Comment: Computer‐generated numbers used to allocate participants to each group
Allocation concealment (selection bias)	Low risk	Quote: "Allocation to groups was concealed, so therapists did not know the participant’s group allocation until the delivery of the ﬁrst therapy session." Judgement Comment: Independent
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Judgement Comment: Participants and investigators were blind
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Judgement Comment: Independent assessors
Incomplete outcome data (attrition bias) All outcomes	High risk	Judgement Comment: Attrition detailed, and ITT reported. However, there was a large number of dropouts (23/79), and dropouts were related to CBT + Attention Bias Modification.
Selective reporting (reporting bias)	Low risk	Judgement Comment: Outcomes reported
Other source of bias ‐ Therapy integrity	Low risk	Judgement Comment: Trained therapists. Fidelity monitored in supervision.
Other bias	Low risk	Judgement Comment: The study appears to be free of other sources of bias

Study	Reason for exclusion
Asbrand	Data not analysable
Asbrand 2019	Data not analysable
Baer 2005	Data not analysable
Beidel 2000	Not manualised/modular CBT
Beidel 2007	Not manualised/modular CBT
Bergman 2013	Not manualised/modular CBT
Bernstein 2005	Participants did not all meet diagnostic criteria for an anxiety disorder.
Bodden 2008a	Not an RCT
Clementi 2019	No non‐CBT control/comparator
Cobham 2012	Not an RCT
Cotton 2019	Not manualised/modular CBT
Ebrahiminejad 2016	Not manualised/modular CBT
Flatt 2010	Data not analysable
Gil Bernal 2009	No baseline structured diagnostic assessment/participants did not meet diagnostic criteria for anxiety disorder
Ginsburg 2019b	Participants did not all meet diagnostic criteria for an anxiety disorder.
Hayward 2000	Not an RCT
Jansen 2012	No baseline structured diagnostic assessment/participants did not meet diagnostic criteria for anxiety disorder
Kerns 2016	No baseline structured diagnostic assessment/participants did not meet diagnostic criteria for anxiety disorder
Kujawa 2019	Not an RCT
Lyneham 2006	No direct contact with parent/child/not face‐to‐face
Mendlowitz 1999	Not an RCT
Nauta 2003	Not an RCT
NCT00576719	Data not analysable
Oerbeck 2014	Not manualised/modular CBT
Ollendick 2018	Not manualised/modular CBT
Ost 2015	Not manualised/modular CBT
Ozyurt 2018	Not manualised/modular CBT
Pereira 2014	Participants did not all meet diagnostic criteria for an anxiety disorder.
Rudy 2017	Not manualised/modular CBT
Salzer 2018	Adults (≥ 19 years) (includes 20‐year‐olds)
Sevi Tok 2016	No baseline structured diagnostic assessment/participants did not meet diagnostic criteria for anxiety disorder
Storch 2019	Not manualised/modular CBT
Sung 2011	No baseline structured diagnostic assessment/participants did not meet diagnostic criteria for anxiety disorder
Weisz 2012	Participants did not all meet diagnostic criteria for an anxiety disorder.

Methods	RCT
Participants	Inclusion criteria: age 12 to 19, clinical levels of anxiety acquired brain injury
Interventions	CBT
Outcomes	Primary: SCAS, SCARED, ADIS
Notes

Methods	RCT. CBT vs waitlist
Participants	Inclusion criteria: anxiety disorder, sleep problems Age: 13 to 17
Interventions	Cognitive behaviour therapy for adolescents with anxiety and sleep‐related problems
Outcomes	Primary: ADIS (anxiety). Insomnia (Insomnia Severity Index)
Notes	Status: not yet recruiting

Methods	RCT
Participants	Target: N = 80 Inclusion criteria: age 10 to 14; diagnosed with diabetes, clinical or subclinical anxiety
Interventions	CBT Waitlist
Outcomes	Primary: YAM‐5
Notes	Not yet recruiting

Methods	RCT
Participants	Target: N = 420 Inclusion criteria: depressive disorder or anxiety disorder; age 6 to 18
Interventions	CBT Psychodynamic psychotherapy
Outcomes	Primary: number of psychiatric diagnoses
Notes

Methods	RCT
Participants	Inclusion criteria: female; age 8 to 12; anxiety symptoms (SCAS cut‐off), mild to moderate anxiety disorder not requiring drug therapy
Interventions	CBT: group, based on Coping Cat Control: group, storytelling
Outcomes	SCAS, SDQ, CDI
Notes	Complete

Methods	RCT
Participants	Target: N = 228 Inclusion criteria: aged 8 to 12; Attention Deficit Hyperactivity Disorder; anxiety disorder (generalised anxiety disorder, social anxiety disorder, separation anxiety disorder)
Interventions	CBT Treatment As Usual
Outcomes	Remission of anxiety disorder (GAD, social anxiety disorder, separation anxiety disorder)
Notes	Complete

Methods	RCT
Participants	Inclusion criteria: age 7 to 18; anxiety disorder (based on ADIS); discontinue other psychotherapy for the trial
Interventions	CBT Control (no treatment)
Outcomes	Primary: ADIS
Notes

Methods	RCT
Participants	Inclusion criteria: age 9 to 15; clinical or subclinical diagnosis of anxiety disorder or depressive disorder
Interventions	CBT Control: no treatment
Outcomes	Primary: ADIS
Notes

PERMALINK

Cognitive behavioural therapy for anxiety disorders in children and adolescents

Anthony C James

Tessa Reardon

Angela Soler

Georgina James

Cathy Creswell

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Participant characteristics

Diagnosis

Comorbidity

Settings

Exclusion criteria

Types of interventions

Experimental intervention

Comparator interventions

Where CBT was delivered alone

Where CBT was delivered in combination with medication for the treatment of anxiety

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Grey literature

Reference lists

Correspondence

Data collection and analysis

Selection of studies

Data extraction and management

Main comparisons

Assessment of risk of bias in included studies

Measures of treatment effect

Dichotomous data

Continuous data

Unit of analysis issues

Cluster‐randomised trials

Cross‐over trials

Studies with multiple treatment groups

Continuous data

Dichotomous data

Dealing with missing data

Missing statistics

Missing participants

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Dichotomous data

Continuous data

Tables and figures

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

GRADE and ‘Summary of findings' table

Results

Description of studies

1. Summary of characteristics of included studies.

Results of the search

1.

Included studies

Design

Sample size

Methods	RCT
Participants	Target: N = 60 Inclusion criteria: age 10 to 16; IQ in average range; Autism Spectrum Disorder diagnosis; clinical level of anxiety (semi‐structured interview)
Interventions	CBT Active control
Outcomes	Primary: anxiety symptoms
Notes	No longer recruiting

Methods	RCT
Participants	Target: N = 280 Inclusion: age 7 to 17; clinically significant anxiety as determined by structured clinical interview; anxiety primary concern
Interventions	CBT Relaxation Therapy
Outcomes	Primary: brain function/structure Secondary: Pediatric Anxiety Rating Scale
Notes	Started December 2016

Methods	RCT
Participants	Target: N = 44 Inclusion criteria: age 16 to 21; ASD; diagnosis of 1 of the following anxiety disorders: separation anxiety disorder, specific phobia, panic disorder, generalised anxiety disorder, social phobia, or obsessive compulsive disorder, and minimum score of 14 on the Hamilton Anxiety Scale
Interventions	CBT TAU
Outcomes	Primary: Hamilton Anxiety Scale (change from baseline)
Notes	Not all participants would be eligible.

Methods	RCT
Participants	Target: N = 200 Inclusion criteria: age 9 to 17; primary DSM‐5 anxiety disorder or depressive disorder
Interventions	Individual Behavioral Activation Therapy (IBAT) The PASCET Program for Youth Depressive Disorders Coping Cat (CBT) Waitlist
Outcomes	Primary: Clinical Global Impression Severity (CGIS) scale (change)
Notes

Methods	RCT
Participants	Target N = 135 Inclusion criteria: attend elementary school, elevated anxiety symptoms and Clinical Severity Rating 3+ on ADIS
Interventions	Teacher Anxiety Program for Elementary Students (TAPES) Teacher Anxiety Training (TAT)
Outcomes	Secondary: change on modified ADIS
Notes	Anxiety diagnosis not required.

Study name	Effectiveness of school group‐based acceptance and commitment therapy for children with anxiety: a randomised controlled trial
Methods	RCT
Participants	Target N = 130 Inclusion criteria: 1. Aged between 7 and 17 years. 2. Meet criteria for a primary diagnosis of an anxiety disorder. 3. Available/able to attend The Children’s Hospital at Westmead for pretreatment, immediate post‐treatment, and 6‐month post‐treatment assessments as well as attending a minimum of 80% of therapy sessions. 4. Have a parent/caregiver who is willing to attend and participate in the assessment as well as 2 parent sessions
Interventions	Proactive (Acceptance and Commitment Therapy group‐based manualised therapy programme delivered by school counsellors) vs waitlist (10 weeks)
Outcomes	Primary outcomes: Change in score on the Pediatric Anxiety Rating Scale (PARS) ‐ clinician, child, and parent rated (pre‐, post‐treatment and 6 months post‐treatment) Change in the Spence Anxiety Scale for Children (SCAS) ‐ child and parent rated (pre‐, post‐treatment and 6 months post‐treatment)
Starting date	28 September 2016
Contact information	Dr Karen Hancock SCHN, CHW Department of Psychological Medicine Locked Bag 4001 Westmead NSW 2145 Australia karen.hancock@health.nsw.gov.au
Notes	www.who.int/trialsearch/Trial2.aspx?TrialID=ACTRN12616001552471 anzctr.org.au/ACTRN12616001552471.aspx

Study name	Neural mechanisms of CBT for anxiety in children with autism: randomized controlled trial
Methods	RCT
Participants	Target N = 150 Inclusion criteria: aged 8 to 14; diagnosis of autism spectrum disorder; diagnosis of anxiety disorder and clinically significant level of anxiety; full‐scale IQ and verbal IQ > 70; unmedicated or on stable medication with no planned changes for duration of study; able to meet MRI safety (e.g. no metal medical implants) and data quality requirements (e.g. able to keep head still during scanning)
Interventions	CBT vs Psychoeducation and Supportive Therapy (PST)
Outcomes	Primary outcomes: Pediatric Anxiety Rating Scale (PARS) (change from baseline ‐ midpoint; change from baseline ‐ endpoint) Clinical Global Impression‐Improvement (CGI‐I) scale (change from baseline ‐ midpoint; change from baseline ‐ endpoint) Blood oxygenation level dependent signal (BOLD) during down‐regulation versus passive viewing of affective images (change from baseline ‐ midpoint; change from baseline ‐ endpoint)
Starting date	April 2016
Contact information	Denis Sukhodolsky Yale Child Study Center New Haven, Connecticut, USA denis.sukhodolsky@yale.edu
Notes	clinicaltrials.gov/show/nct02725619

Study name	Specifying and treating the anxiety phenotype in autism spectrum disorder
Methods	RCT
Participants	Target N = 132 Inclusion criteria: age 8 to 14; meets criteria for a diagnosis of ASD; clinically significant anxiety symptoms (minimum score of 8 on the Pediatric Anxiety Rating Scale); clinically significant anxiety symptoms as defined by qualifying for a diagnosis on 1 or more non‐phobia items on the ADIS; full‐scale and verbal comprehension IQ greater than 50; anxiety symptoms are considered the primary mental health problem (i.e. most impairing/distressing); stable medication, non‐psychotherapy and psychosocial regimen
Interventions	CBT vs drug (sertraline) vs pill placebo
Outcomes	Primary outcome: change in Pediatric Anxiety Rating Scale (pretreatment, post‐treatment, 3‐month follow‐up)
Starting date	1 November 2017
Contact information	Brianna Health, PhD UC Davis MIND Institute Sacramento, California, USA, 95817 bheath@ucdavis.edu
Notes	clinicaltrials.gov/ct2/show/nct03279471

Study name	Brain response associated with parent‐based treatment for childhood anxiety disorders
Methods	RCT
Participants	Target N = 226 Inclusion criteria: prepubertal; clinical diagnosis of primary anxiety disorder; must not have another mental illness more impairing than the most impairing anxiety disorder; IQ of at least 80
Interventions	Supportive Parenting for Anxious Child Emotions vs CBT vs parent educational support
Outcomes	Primary outcome: Pediatric Anxiety Rating Scale (PARS) (12 weeks) Secondary outcome: Multidimensional Anxiety Scale for Children (MASC) parent and child report (12 weeks)
Starting date	1 September 2018
Contact information	Eli R Lebowitz, PhD Yale University Child Study Center New Haven, Connecticut, USA, 06519 eli.lebowitz@yale.edu
Notes	clinicaltrials.gov/ct2/show/NCT03585010