Brief, intensive and concentrated cognitive behavioral treatments for anxiety disorders in children: A systematic review and meta-analysis

Accepted Manuscript Brief, intensive and concentrated cognitive behavioral treatments for anxiety disorders in children: A systematic review and meta-analysis Lars-Göran Öst, Thomas H. Ollendick PII:

S0005-7967(17)30142-0

DOI:

10.1016/j.brat.2017.07.008

Reference:

BRT 3167

To appear in:

Behaviour Research and Therapy

Received Date: 20 December 2016 Revised Date:

14 June 2017

Accepted Date: 15 July 2017

Please cite this article as: Öst, Lars.-Gö., Ollendick, T.H., Brief, intensive and concentrated cognitive behavioral treatments for anxiety disorders in children: A systematic review and meta-analysis, Behaviour Research and Therapy (2017), doi: 10.1016/j.brat.2017.07.008. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

Brief, intensive and concentrated cognitive behavioral treatments for anxiety disorders in children: a systematic review and meta-analysis Lars-Göran Öst1, 2, * & Thomas H. Ollendick3 Department of Psychology, Stockholm University, Sweden

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Department of Clinical Neuroscience, Psychology section, Karolinska Institutet, Sweden

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Child Study Center, Department of Psychology, Virginia Polytechnic Institute and State

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University, Blacksburg, VA, USA

*Corresponding author at Department of Psychology, Stockholm University, S-106 91 Stockholm, Sweden. e-mail address: [email protected] (L-G Öst), Phone: +46-737 121 285 1

ACCEPTED MANUSCRIPT Abstract Anxiety disorders are among the most common disorders affecting youths in the general population, with up to 10% of children and 20% of adolescents meeting criteria for an anxiety disorder at any one point in time. Cognitive-behavior therapies (CBT), varying between 9 and

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18 weeks of treatment, are considered evidence-based for the treatment of anxiety disorders in youth. During the last two decades treatments that are brief, intensive, or concentrated (BIC) have been developed and this meta-analysis includes 23 RCTs of these new approaches across

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the anxiety disorders. BIC yielded a lower attrition (2.3%) than standard CBT (6.5%). The effect sizes (ES) for comparison of BIC with waiting-list (1.47) and placebo (0.91) were

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significant, whereas that with standard CBT (0.01) was not. Regarding remission at post/recovery at follow-up BIC (54%/64%) and standard CBT (57%/63%) were comparable and both were significantly higher than placebo (26%/35%), which was higher than WLC (7%/9%). Within-group ES at post and follow-up were 1.50 and 1.53 for BIC, and 0.98 and

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1.05 for standard CBT, indicating maintenance of the effects up to 12 months after therapy. Advantages and disadvantages of BIC are discussed and we suggest that BIC-interventions

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represent a paradigm shift in the delivery of services for youth with anxiety disorders.

Keywords: children, anxiety disorders, cognitive-behavioral treatment, meta-analysis,

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systematic review

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ACCEPTED MANUSCRIPT Introduction Anxiety disorders are among the most common disorders affecting children and adolescents in the general population, with up to 10% of children and 20% of adolescents meeting criteria for an anxiety disorder at any one point in time (Essau & Gabbidon, 2013).

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Moreover, a recent finding from the National Comorbidity Survey Replication – Adolescent Supplement (NCS-A) found that 31.9% of the adolescents met a lifetime prevalence of any anxiety disorder (Merikangas, He, Burstein et al., 2010). These disorders typically emerge in

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mid- to late-childhood, result in considerable distress, and have an adverse impact on

academic, social, and familial aspects of the growing child (Grills-Taquechel & Ollendick,

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2012), resulting in an overall compromised quality of life (Liberman, Larsson, Altuzarra, Öst, & Ollendick, 2015). Furthermore, they frequently persist into adulthood and are oftentimes associated with other negative mental health (e.g., major depression, substance abuse) and adverse outcomes across the lifespan (Creswell, Waite, & Cooper, 2016). The societal costs of

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these disorders are considerable, both in the short-term and the long-term (Lynch & Dickerson, in press). Despite the significant costs and public health burden of these disorders, they remain largely untreated in youth with a majority of youth either not having access to or

2016).

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not receiving evidence-based treatments (Higa-McMillan, Francis, Rith-Najarian, & Chorpita,

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In recent years, considerable evidence has accumulated that documents the efficacy

and effectiveness of cognitive-behavior therapy (CBT) for the treatment of anxiety disorders in youth (see Higa-McMillan et al., 2016; James, James, Cowdrey, Soler & Choke, 2013; and Reynolds, Wilson, Austin, & Hooper, 2012 for recent reviews). For the most part, this evidence has been derived from “standard” CBT interventions: treatments that typically consist of 11 – 18 sessions delivered weekly by highly trained and supervised therapists. For the most part, these treatments have included two primary components: cognitive

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ACCEPTED MANUSCRIPT restructuring/challenging of catastrophic thinking and graduated exposure to the feared, anxiety-producing stimuli (enacted in-vivo, imaginally, or virtually). These components are evident in treating youth with all of the major anxiety disorders including generalized anxiety disorder, social anxiety disorder, separation anxiety disorder, panic disorder with or without

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agoraphobia, specific phobia, obsessive-compulsive disorder, and post-traumatic stress disorder. Although standard CBT interventions have been shown to be effective for a

majority of youth in these studies, between 25% and 40% of youth do not remit (Higa-

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McMillan et al., 2016; James et al., 2013; Ollendick & King, 2012; Reynolds et al., 2012). Against this backdrop, recent trends in psychotherapy research have witnessed the

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development and use of brief and more intensive approaches that are designed to reach more patients, to be more efficient, and to be more cost-effective. CBT, given its evidentiary support and its sound underlying therapeutic principles, is uniquely positioned to be in the foreground of this movement.

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In general, these approaches have modified more traditional or conventional CBT approaches by reducing either the number of sessions or the time period over which the sessions are delivered. Importantly, however, they still utilize the two primary therapeutic

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components of standard CBT: cognitive restructuring/challenging of catastrophic thinking and graduated exposure. Like traditional CBT, these approaches are typically delivered face-to-

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face and in a clinic setting. For the most part, the therapists who deliver these intensive interventions are also highly trained and closely supervised. Thus, these approaches require considerable “specialist therapist time,” and constitute a revolution in delivery of mental health services in that they provide intervention in a non-traditional format outside the typical “therapy hour” and in fewer than the 11 - 18 sessions that characterize traditional CBT. Some patients may prefer more intense intervention such as these. These alternative interventions, of course, can best be viewed as part of a stepped-care approach – some patients will prefer

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ACCEPTED MANUSCRIPT and benefit from them whereas others will likely desire and perhaps require more standard interventions of a longer duration. Anxiety disorders in particular would seem to be ideal targets for these interventions. Based on learning theory, Bouton (1993) showed that original feared associations (CS-US

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pairings) that characterize anxiety can be inhibited by newly formed CS-non-US pairings. Although fear memories are not erased, they are inhibited and “contextualized” by the newly acquired pairings. Bouton’s seminal work was conducted in the non-human, animal

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laboratory. However, over the past 20 – 25 years, much research has been conducted in

human laboratories and similar findings have been obtained. Craske and her colleagues, for

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example, have recently summarized this research and demonstrated its applicability to the treatment of anxiety disorders (see Craske, Liao, Brown, & Vervliet, 2012, for review). In as much as standard CBT, relies upon cognitive change and exposure as critical components of treatment, the relevance of these findings is evident. In the child and adolescent arena, for

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example, In-Albon and Schneider (2007) reported that systematic exposure techniques were applied in over 90% of the clinical trials that showed standard CBT to be more effective than other interventions. Craske et al. (2012) suggest that for exposure to be maximally effective, it

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should be delivered in sessions that are close in proximity and that involve multiple situations for the new pairings to be formed. We believe these brief and intensive approaches provide

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the necessary conditions for these pairings to occur. In a recent set of papers published in Psychopathology Review (see Ollendick, 2014),

the potential applicability of these interventions were briefly examined in the treatment of six of the major anxiety disorders in childhood and adolescence: specific phobia, social anxiety disorder, separation anxiety disorder, generalized anxiety disorder, panic disorder with and without agoraphobia, and obsessive compulsive disorder. Although all papers in this review suggested the potential cost-effectiveness of these brief interventions and that they may be the

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ACCEPTED MANUSCRIPT treatment of choice for some youth and their families, these papers did not examine the effectiveness of these approaches for the various anxiety disorders. Here, we define three types of these new approaches that we label brief, intensive, and concentrated (BIC), respectively. We define brief as those interventions that have a markedly reduced number of

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sessions compared to standard CBT, concentrated as those interventions that are carried out with more than one session/week during a fairly short time period, and intensive as those interventions that are both brief and concentrated, e.g. the one-session treatment for specific

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phobias developed by Öst (1989). We specifically exclude studies that Bennett-Levy and Farrand (2010) refer to as brief, low intensity interventions. A variety of low intensity

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interventions exist ranging from guided or unguided internet-based interventions and self-help books to 30-minute advice clinics delivered by family physicians and mental health professionals in primary care settings. They are not examined in this review. The aims of the present meta-analysis are to address the following questions:

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1. Are BIC acceptable to youth with anxiety disorders? This will be explored by analyzing declining rate and attrition rate.

2. Are BIC effective for youth anxiety disorders? Comparison with waitlist control

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conditions will address this question.

3. Are BIC specific, i.e. better than a condition controlling for nonspecific factors, in

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youth anxiety disorders? To examine this question placebo comparisons will be used. 4. Are the effects of BIC maintained at follow-up? Within-group effect sizes at post- and follow-up assessment will explore this question. 5. Do BIC lead to remission and recovery? Proportion of patients achieving clinically significant improvement at post- and follow-up assessment will address this question.

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ACCEPTED MANUSCRIPT 6. How does BIC compare with standard CBT? This question will be examined by analyzing declining rate, attrition rate, effect size (ES) post and follow-up, ES within,

Method 2.1. Literature search

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remission (post), and recovery (at follow-up).

PsycINFO and PubMed were searched from the start of the data bases to May 1st 2016

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with the following search words: anxiety disorder OR OCD OR PTSD AND randomized controlled trial OR RCT OR random* AND youth OR child* OR adolescent OR pediatric.

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All abstracts were read and when there was an indication of a group of patients receiving any type of cognitive-behavioral treatment being compared with another condition in a RCT the full-text was retrieved. Studies using single case designs were excluded since there is no consensus yet regarding the calculation of effect sizes for these designs. The reference lists in

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the retrieved articles were then checked against the database search and any other articles that might fulfil the inclusion criteria were retrieved. We also included two studies we had

publication.

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knowledge about after presentations at CBT-congresses and that were submitted for

2.1.1. Inclusion criteria

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In order to be included in the review and meta-analysis a study had to: (1) Be published in an English language journal or presented at a CBT-congress and submitted for publication. (2) Randomly allocate participants to either treatment or control, or to two or more active treatments. (3) Have at least one brief, intensive or concentrated treatment condition as defined by us above, (4) Have one or more therapists providing the treatment, (5) Have participants who were diagnosed with a specific anxiety disorder according to DSM or ICD, and had a maximum age of 18. This latter criterion was used for all studies with the exception

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ACCEPTED MANUSCRIPT of an early study conducted by Sheslow, Bondy, and Nelson (1983) that carefully enrolled children between the ages of 4 and 5 who evidenced extreme fear of the dark based on a behavioral avoidance test. 2.1.2. Exclusion criteria

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The following exclusion criteria were used. (1) Anxiety disorders not being the principal

diagnosis. (2) The study is not a RCT. (3) The study is not testing a form of CBT. (4) The study is a secondary analysis of a previously published RCT.

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Figure 1 shows a flowchart of the inclusion of studies in the present meta-analysis,

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which was conducted according to the PRISMA criteria (Liberati et al., 2009).

2.2. Categorization of potential moderators 2.2.1. Conditions

We define the various treatment formats in the following way. A Brief treatment is

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one where total number of sessions is reduced by at least 50% compared to standard treatment. It may be carried out over the same number of weeks as standard treatment or over a shorter period of time. A Concentrated treatment means that total number of sessions

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is the same as standard treatment but it is carried out over a much shorter time period, e.g. daily sessions over three weeks instead of weekly sessions over 15 weeks. Finally, in an

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Intensive treatment, both the total number of sessions and weeks of treatment are greatly reduced compared to standard treatment, e.g. the one-session treatment for specific phobias, which is maximized to 3 hours and carried out during a morning or an afternoon. We refer to these three types of treatments using the acronym BIC. Based on various meta-analyses Table 1 summarizes the mean (and range) number of sessions and weeks of treatment for CBT-methods applied for different anxiety disorders. In order for an intervention to be classified as brief or concentrated it has to be ≤ 50% of the

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ACCEPTED MANUSCRIPT mean number of sessions or weeks of treatment, respectively, for the disorder in question. The exception is the Deblinger et al. (2011) study on PTSD in which the brief treatment is 8 sessions, which does not fulfill the ≤ 50% criterion, but it was compared to 16 sessions. A treatment is classified as Standard CBT if it has weekly sessions to a number as devised by

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the originators of that treatment. In the present meta-analysis there were three studies having a standard CBT-condition; Bolton et al. (2011) 12 sessions, Deblinger et al. (2011) 16 sessions, and Storch et al. (2007) 14 weeks.

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2.2.2. Declining participation

Patients who fulfilled diagnostic criteria and were offered participation but then

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declined and those who accepted participation but did not show up for the first session were counted as decliners. 2.2.3. Attrition

Patients who participated in at least one session but failed to complete the agreed upon

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number of sessions were counted as dropouts. People who completed therapy but did not show up for the post-treatment assessment were not included in this category. 2.2.4. Format and parental involvement

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Format of therapy was classified as individual, group, or family treatment. Degree of parental involvement was classified as low if parents were not present during sessions but

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informed about progress of the therapy, moderate if parents were present full-time during some therapy sessions or only part-time during all sessions, and high if parents were present full-time during all therapy sessions. 2.2.5. Statistical analysis and type of comparison Statistical analyses were categorized as intent-to-treat (ITT) if all randomized participants were included in the statistical analysis and completers if dropouts were deleted. Comparison condition was classified as active treatment, placebo, or waitlist control.

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ACCEPTED MANUSCRIPT 2.2.6. Pre-treatment severity In order to analyze whether the severity of the sample before treatment influenced the effect size the pre-treatment score on the primary measure was recoded as the percentage of the maximum score possible on that measure. For example; if a study used the Clinician Severity

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Rating (0-8) and the sample mean was 6.0 the percentage would be 75.0 (6/8). If studies had more than one type of measure we selected the measure to use in the following order: (1) Independent assessor rating, (2) Behavioral approach test, and (3) Self-report measure.

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2.2.7. Other potential moderators

We also extracted data on number of participants in the study, proportion of females, mean

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age, proportion currently receiving drug treatment for their anxiety disorder, and treatment variables such as duration (in days), number of sessions, total hours of therapy, and intensity (hours/week). As categorical variables we also included type of anxiety disorder, profession

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of therapist, and continent where the study was performed.

2.3. Methodological quality

2.3.1. The psychotherapy outcome study methodology rating scale (POMRS)

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The scale consists of 22 items covering various important aspects of the methodology in psychotherapy outcome research (see Öst, 2008):1. Clarity of sample description, 2.

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Severity/chronicity of the disorder, 3. Representativeness of the sample, 4. Reliability of the diagnosis in question, 5. Specificity of outcome measures, 6. Reliability and validity of outcome measures, 7. Use of blind evaluators, 8. Assessor training, 9. Assignment to treatment, 10. Design, 11. Power analysis, 12. Assessment points, 13. Manualized, replicable, specific treatment programs, 14. Number of therapists, 15. Therapist training/experience, 16. Checks for treatment adherence, 17. Checks for therapist competence, 18. Control of concomitant treatments, 19. Handling of attrition, 20. Statistical analyses and presentation of

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ACCEPTED MANUSCRIPT results, 21. Clinical significance, 22. Equality of therapy hours (for non-WLC designs only). Each item is rated as 0 = poor, 1 = fair, and 2 = good, and each step has a verbal description of one or more sentences. The internal consistency of the scale was good with a Cronbach’s α of .82. The inter rater reliability for the total score of the scale, based on 25% randomly

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selected studies, was ICC(3, 1) = .91 (between the first author and a second rater trained to criterion). 2.3.2. Risk of bias

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The first author used the Cochrane Collaboration tool for assessing risk of bias

(Higgins, Altman, & Sterne, 2011). The following domains were rated: random sequence

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generation, allocation concealment, blinding of outcome assessment, incomplete outcome data, and selective reporting. Blinding of participants and personnel was deleted since it cannot be achieved in RCTs of psychotherapy. Each domain was rated as high (-), unclear (?), or low (+) risk of bias. These ratings were then given a score of 1, 0.5, and 0,

2.4. Meta-analysis

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respectively, and the total score ranged from 0-5 regarding overall risk of bias.

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2.4.1. Primary outcome measure

The primary outcome measure for this meta-analysis is some kind of continuous

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measure of anxiety severity, since all RCTs have that. This could be an independent assessor rating of severity, e.g. the Clinician Severity Rating or Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS), a behavioral approach test, or a self-rating of anxiety, e.g. Spence Child Anxiety Scale or Social Phobia and Anxiety Inventory for Children.

2.4.2. Secondary outcome measure

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ACCEPTED MANUSCRIPT As secondary outcome measure we used dichotomous measures applied to evaluate proportion of patients achieving remission at post-treatment and recovery at follow-up (Frank et al., 1991). The reason for using this as a secondary measure, even if an individual RCT may have designed it as primary, is that only 11 of the studies (48%) included this type of measure.

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It was loss of the primary anxiety diagnosis in all but three studies. Öst et al. (2001) and

Muris et al. (2002) used clinically significant change (Jacobson & Truax, 1991) and Storch et

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al. (2007) used loss of diagnosis and a CY-BOCS score of < 11.

2.4.3. Statistical analysis

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In the present meta-analysis the primary outcome measure in each study was used to calculate effect size for that study. When a study presented intent-to-treat (ITT) data, these were used for analyses, if not, completer data were used. The effect size (ES) was calculated as: (MBIC – Mcomparison)/SDpooled, separately for post- and follow-up assessment. The mean ES

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was computed by weighting each ES by the inverse of its variance. Before pooling the effect sizes we screened for statistical outliers, defined as being outside M ± 2SD. Four (4.8%) of the ESs were outliers, and winsorising (Lipsey & Wilson,

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2001) was used by reducing outliers to the exact value of M+2SD. The software Comprehensive Meta-Analysis, version 2.2.057 (CMA; Biostat Inc., 2006) was used for all

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analyses and to correct for small sample sizes Hedges’s g was calculated. A random effects model was used since it could not be assumed that the ESs came from the same population as studies comparing CBT conditions with waitlist, placebo, and other forms of CBT were included in the meta-analysis. Heterogeneity among ES’s was assessed with the Q- and the I-square statistic. The possibility of publication bias was analyzed with the trim-and-fill method of Duval and Tweedie (2000) as well as Egger’s regression intercept (Egger, Davey Smith, Schneider, &

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ACCEPTED MANUSCRIPT Minder, 1997). Moderator analyses of continuous variables were carried out with metaregression and for categorical variables with sub-group analysis using the mixed effect model. In order to analyze a potential moderator variable we determined that at least 75% of the

Results 3.1. Description of the studies

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3.1.1. Background data

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studies should have information on the variable in question.

Background data of the included studies are presented in Table 2. Thirteen of the studies

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were on specific phobias, three on OCD, three on PTSD, and one each on social anxiety disorder, separation anxiety disorder, panic disorder with agoraphobia, and mixed anxiety. The studies used DSM-III-R (APA, 1987) or DSM-IV (APA, 1994) criteria to diagnose the participants. Only 10 (43%) of the studies reported proportion declining to participate in the

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study and the mean rate was 6.1% (Mdn 4.0%). Note that this figure pertains to the RCT as such, not the BIC-condition in particular. There was a majority of girls in the RCTs (M 66.2%, Mdn 60%, range 38-100%). Children aged 4-18 were treated in the studies with a

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mean age of 10.9 years (Mdn 11.2). Only 10 studies (43%) reported proportion of comorbid disorders in the samples and the mean was 69.3% (Mdn 75.5%, range 12-100%). Finally,

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proportion of participants on concurrent drug treatment was reported in 16 studies (70%) with a mean of 7.5% (Mdn 0%, range 0-60%).

3.1.2. Treatment data Treatment data of the studies are presented in Table 3. In 19 (83%) of the studies the primary treatment used an individual format whereas in the remaining four studies a group format was used. The degree of parental involvement was low in 18 (78%) studies,

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ACCEPTED MANUSCRIPT moderate in two, and high in three. The type of BIC-treatment was brief in seven (30%), intensive in 11 (48%), and concentrated in five (22%). The means regarding duration of treatment was 16.4 days (Mdn 3.0, range 1-84), number of sessions 4.2 (Mdn 3.0, range 1-

3.0, range 4-23).

3.1.3. Comparison of the BIC-treatments

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14), total number of hours 7.0 (Mdn 4.0, range 1-23), and intensity (hours/week) 4.3 (Mdn

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The results of the comparisons of three BIC-conditions on treatment data are shown in Table 4. One way ANOVAs yielded significant F-values for all variables tested. Subsequent post-

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hoc test (Scheffé) showed that intensive treatment differed significantly from brief and concentrated treatment as could be expected (based on the classification) on treatment duration and number of sessions, and from concentrated on total hours of treatment and

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intensity.

3.1.4. Attrition

All studies provided information on attrition and 17 of the 23 studies (74%) had no dropout

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at all. Mean attrition in the various RCTs was only 2.3% (Mdn 0%, range 0-13.7%). In the BIC-conditions it was 2.3% (Mdn 0%), in Standard CBT 6.5% (Mdn 7.8%), in Placebo-

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conditions 1.4% (Mdn 0%), and in WLC 2.4% (Mdn 0%). These conditions did not differ significantly. However, a one-way ANOVA on just the BIC-conditions yielded a significant F(2, 29) = 9.37, p<0.001. Intensive treatment (M 0%) was significantly lower than Brief treatment (M 6.3%), whereas Concentrated treatment (M 2.3%) did not differ from either of the other conditions.

3.2. Methodological data

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ACCEPTED MANUSCRIPT 3.2.1. Methodology ratings The total mean (SD) scores on the Psychotherapy outcome study methodology rating scale were as follows: Brief 21.3 (4.4), Intensive 21.8 (7.8), and Concentrated treatment 21.8 (7.4). These means are somewhat lower than what we found in previous meta-analyses on OCD in

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adults (23.3; Öst, Havnen, Hansen & Kvale, 2015) and children (24.6; Öst, Riise,

Wergeland, Hansen & Kvale, 2016), but somewhat higher than in the meta-analysis on

Acceptance and Commitment Therapy (18.6; Öst, 2014). One-way ANOVA yielded a non-

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significant F(2, 20) = 0.01. Comparisons on the individual items also yielded non-significant differences between the three types of BIC-treatments. Data are displayed in Table S1 in the

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Supplement.

3.2.2. Risk of bias

The total scores on risk-of-bias were 1.36 (0.48) for Brief, 1.09 (0.58) for Intensive, and 1.50

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(0.61) for Concentrated treatment, and the one-way ANOVA yielded a non-significant F(2, 20) = 1.07. Data for the individual studies are shown in Table S2 in the Supplement.

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3.3. Meta-analysis

3.3.1. Primary outcome measure

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The effect sizes on the primary outcome measure at post-treatment assessment are displayed in Table 5. The overall ES across all comparisons was g = 0.68, which is significant and moderate. When BIC was compared to waitlist control the ES was very large, g = 1.47, and in comparison with placebo conditions it was large, g = 0.97. Interestingly, the comparison of BIC and standard CBT yielded no difference at all, g = 0.01. In four of these comparisons the ES turned out to be significantly heterogeneous with I2-values between 56 and 82, which suggest the need for moderator analyses (see below).

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ACCEPTED MANUSCRIPT At follow-up (Table 6) it was only possible to analyze 12 comparisons. The overall ES across comparisons (g = 0.18) and BIC vs. WLC (g = 0.69) were significant. Of interest is also that in comparison with standard CBT the BIC-conditions were still not different (g =

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0.10).

3.3.2. Exploratory moderator analyses

Moderator analyses were undertaken to explore BIC characteristics (e.g., number of

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sessions), patient characteristics that have been associated with outcomes for standard CBT (e.g., sex and age), and characteristics of our meta-analytic procedures (e.g., risk of bias).

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The results of the moderator analyses on the continuous variables are displayed in Table 7. Number of participants in the study was a negative moderator, i.e., a lower ES was associated with higher N. Proportion of girls and mean age of the sample were both positive moderators, i.e., higher ES as proportion of girls and mean age increased. Methodological

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quality, risk-of-bias, and percent concurrently on drug treatment were not significant moderators of the ES. Regarding treatment variables both days of treatment length and number of sessions were significant negative moderators, i.e., a higher ES was associated

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with shorter treatment period and fewer sessions. Total hours of treatment was not significant but the intensity of treatment (hours/week) was a positive moderator. Both

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attrition and pre-treatment severity were non-significant moderators. The results of the sub-group analyses of categorical variables are shown in Table 8.

Type of disorder was significant with specific phobia and mixed anxiety yielding high and significant ESs, whereas the remaining disorders had non-significant ESs. Therapist profession was also significant with studies using clinical psychologists yielding higher effects than studies having counselors (Qbeetween = 4.41, p<0.05) or various other mental health professions (Qbeetween = 17.38, p<0.0001) as therapists. Another significant variable

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ACCEPTED MANUSCRIPT was degree of parental involvement in the treatment. Somewhat unexpectedly, conditions with low involvement yielded significantly higher ES (Qbeetween = 15.92, p<0.0001) than those with high parental involvement. An expected result is that type of comparison condition was a significant predictor with WLC-comparisons yielding higher ES than

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Placebo-comparisons (Qbeetween = 6.21, p<0.05) and Active treatment comparisons (Qbeetween = 26.10, p<0.0001). Placebo-comparisons were also higher than active treatment

comparisons (Qbeetween = 9.63, p<0.01). Type of BIC-treatment, treatment format, type of

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data analysis, and continent where the study was carried out were all non-significant

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moderators.

3.3.3. Publication bias

The analysis of possible publication bias for all studies using Egger’s regression intercept yielded a significant t(30) = 2.89, p<0.01. Duval and Tweedie’s trim and fill method

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indicated 8 trimmed studies. For the BIC vs. WLC comparisons there was also an indication of publication bias; Egger’s regression intercept yielded a significant t(9) = 2.70, p< .05. Duval and Tweedie’s trim and fill method indicated 4 trimmed studies. The outcome was the

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same for the BIC vs. Placebo comparisons with Egger’s regression intercept yielding a significant t(4) = 6.05, p< .01. Duval and Tweedie’s trim and fill method indicated 3

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trimmed studies. Finally, the BIC vs. other CBT comparisons did not display any significant evidence of publication bias.

3.3.4. Remission at post-treatment Eleven of the 23 studies (48%) reported data on remission. Nine of these studies used loss of principal diagnosis as the measure of remission, whereas two applied Jacobson and Truax (1991) criteria for clinically significant change. The remission rates at post-treatment are

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ACCEPTED MANUSCRIPT displayed in Table 9. A subgroup analysis yielded a significant Qbetween = 20.5 (df 3), p < 0.001. BIC (54.2%) and standard CBT (57.1%) did not differ but both had significantly higher remission rate than placebo (26.0%), which in turn was significantly higher than

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WLC (6.9%). The three BIC-treatments did not differ significantly on this measure.

3.3.5. Recovery at follow-up

Recovery rates at follow-up are also shown in Table 9. For all conditions these were

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somewhat higher than the remission rates at post-treatment, indicating not only maintenance of the treatment effects but some further improvement. The subgroup analysis yielded a

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significant Qbetween = 23.2 (df 3), p < 0.001. BIC (64.1%) and standard CBT (63.4%) did not differ but both were significantly higher than placebo (34.5%), which was higher than WLC (9.1%).

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3.3.6. Within-group effect size

Table 10 displays the within-group (pre-post) effect size for the different conditions. At posttreatment BIC had a very large ES (g = 1.50), followed by Standard CBT (g = 0.98), Placebo

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(g = 0.56), and waitlist control (g = 0.21). A subgroup analysis yielded a significant difference between these conditions (Qbetween = 54.9 (df 3), p < 0.0001). Subsequent pairwise

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comparisons showed that BIC did not differ from Standard CBT but was significantly better than Placebo (Qbetween = 23.6 (df 1), p < 0.001) and WLC (Qbetween = 51.9 (df 1), p < 0.0001). At follow-up assessment BIC had a very large ES (g = 1.53) followed by Standard

CBT (g = 1.05), Placebo (g = 0.90), and WLC (g = -0.06). The subgroup analysis was once again significant (Qbetween = 20.5 (df 3), p < 0.001), and the pairwise comparisons showed that BIC did not differ from Standard CBT but was significantly higher than Placebo (Qbetween = 6.4 (df 1), p < 0.05) and WLC (Qbetween = 19.8 (df 1), p < 0.001).

18

ACCEPTED MANUSCRIPT A subgroup analysis of the three BIC-conditions at post-treatment yielded a significant difference (Qbetween = 6.5 (df 3), p < 0.05). Pairwise comparisons showed that Intensive treatment had a higher ES than Brief (Qbetween = 4.1 (df 1), p < 0.05), as did Concentrated treatment (Qbetween = 6.2 (df 1), p < 0.05). At follow-up assessment the BIC-conditions did not

Discussion

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differ significantly from each other (Qbetween = 3.2 (df 2), p = 0.18).

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Our findings are relatively straightforward and provide initial support for Brief, Intensive, and Concentrated (BIC) interventions in treating youth with various anxiety

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disorders. First, these approaches were acceptable to youth and their parents as only about 6% of families declined to enter into RCTs of these interventions and only about 2% withdrew once the treatment had actually begun. Second, these approaches were effective in comparison to wait-list control conditions with an average effect size of 1.47. Moreover, and

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third, these treatments were effective when compared to placebo control conditions such as education/support and non-directive therapy (average effect size = 0.97). Fourth, the effects were maintained up to 1-year following treatment with within group effect sizes averaging

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1.50 at post-treatment and 1.53 at follow-up. Fifth, these interventions not only led to treatment response but also to 54% remission rates and 64% recovery rates. Sixth, and

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finally, BIC interventions compared favorably on all of the above indices to standard, full dose CBT interventions (see Tables 5-6 and 9-10). This was true for all three types of BIC interventions (i.e., brief, intensive, and concentrated as defined by us). As noted in Table 2, support for these interventions comes from 23 randomized clinical controlled trials that have been conducted in Australia, Europe, and North America. As is evident in Table 2, the support is greater for specific phobias with 13 of the 23 studies (56.5%) examining exposure-based treatments for this disorder and smaller percentages

19

ACCEPTED MANUSCRIPT examining other disorders such as PTSD, OCD, panic disorder, social anxiety disorder, and separation anxiety disorder. No studies examined the efficacy of these approaches with generalized anxiety disorder or the newly admitted anxiety disorder of selective mutism (DSM-5. APA, 2013; Muris & Ollendick, 2015). Indeed, the support might be considered

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strong for specific phobia (13 studies), modest for PTSD and OCD (3 studies each), and

minimal for panic disorder, social anxiety disorder, separation anxiety disorder, and mixed anxiety disorders (1 study each). Clearly, more trials need to be conducted with youth with

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these latter anxiety diagnoses before we can conclude that BIC approaches are effective with them. Nonetheless, the current findings are suggestive of positive outcomes.

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Interestingly, within the above limitation regarding the number of studies for certain anxiety disorders, support for the BIC interventions was greater for girls than boys and for older than younger children. Similar outcomes have been reported in recent meta-analytic reviews of standard CBT approaches (Higa-McMillan et al., 2016; James et al., 2013).

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Surprisingly, our findings indicated that the degree of parent involvement was inversely related to treatment outcomes. In our review, degree of parental involvement was classified as low if parents were not present during sessions, moderate if parents were present during

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some but not all therapy sessions, and high if parents were present throughout the therapy sessions. This finding was most likely associated with the treatment of specific phobias in

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which moderate to high parental involvement was rare (only 2 of 13 studies). Although the role of parental involvement has been mixed with standard CBT approaches, major metaanalytic reviews tend to report similar overall findings to what we found here (see HigaMcMillan et al., 2016; In-Albon & Schneider, 2007; Reynolds et al., 2012; Thulin, Svirsky, Serlachius, Andersson & Öst, 2014). Recently, Ollendick et al. (2015) suggested that such seemingly paradoxical effects might be related to how parents potentially serve as a “safety”

20

ACCEPTED MANUSCRIPT function and how children, in turn, might fail to develop personal self-efficacy in mastering their fears when parents are present. From a methodological point of view it is encouraging that the overall effect size was not moderated by the studies’ methodological quality, risk-of-bias, attrition, pre-treatment

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severity of the patients, percent concurrently on drug treatment, and type of data-analysis. On the other hand, the treatment variables therapy length and number of sessions were significant negative moderators, and intensity of treatment was a positive moderator.

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Together, these findings can be seen as strengths of our meta-analysis and the overall effectiveness of BIC interventions.

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How do BIC interventions fare in comparison with standard CBT reported in previous meta-analyses? Reynolds et al. (2012) analyzed between-group ES and reported an overall g = 0.66, a CBT vs. WLC g = 0.77, and a CBT vs. active control g = 0.39. We found a similar overall g = 0.68, but higher BIC vs. WLC g = 1.47, and BIC vs. active control g =

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0.97. There is an overlap between our and Reynolds meta-analyses of four studies (Gallagher et al., 2004: Muris et al., 2002; Ollendick et al., 2009; Öst et al., 2001). These studies yielded a mean g of 0.75, very similar to the overall g of 0.68, and we believe that the

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comparison remains valid. Higa-McMillan et al. (2016) analyzed within-group ES and found a g = 1.19 for all CBT-conditions and g = 1.05 for exposure treatments. We found a g

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= 1.50 for all BIC-conditions and g = 1.57 for Intensive treatments. The overlap with the Higa-McMillan meta-analysis is six studies (Dewis et al., 2001; Muris et al., 1998: Muris et al., 2002; Ollendick et al., 2009; Öst et al., 2001; Sheslow et al., 1983) and these yielded a mean g-value of 1.87, somewhat higher than the overall of 1.50. This indicates possibly higher effects for BIC than standard CBT and higher for Intensive treatment than traditional exposure treatments.

21

ACCEPTED MANUSCRIPT A meta-analysis is never better than the included studies and we cannot conclude how effective BIC is for generalized anxiety disorder (no study), social anxiety disorder, panic disorder, and separation anxiety disorder (one study each). However, in adults there are a number of BIC-studies for social anxiety and panic disorder showing as good effects as

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standard CBT (Öst, 2016) and it is probable that the same will be found in forthcoming child studies on these disorders, since our findings on specific phobias, OCD and PTSD mirror those in adult studies. Another limitation might be our classification of treatments as Brief,

SC

Intensive, and Concentrated. However, there are clear differences between the categories and the classification is easy to make by trained raters, even if there are examples in the literature

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where the authors call a treatment intensive (Storch et al., 2007) when it was classified by us as concentrated.

With these limitations in mind what can we conclude from our meta-analysis? Why might BIC treatments be advantageous and what limitations are associated with their use?

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We believe there are a number of advantages associated with BIC approaches. (1) The youth and his or her parents do not have to come in for therapy once a week but the treatment can be carried out in one day, one weekend, or one week. (2) BIC approaches fill a need for

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families who live far away from a therapist who is trained in these treatments. They can travel to the therapist’s place of practice and stay for a brief period while receiving therapy.

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(3) These approaches represent an alternative for those who have not responded to standard CBT or other treatments with weekly 50-minute sessions. (4) BIC approaches might be more cost-effective on a long-term basis; an advantage for those individuals, insurance companies, or other organizations paying for the therapy. (5) Such approaches reduce the risk of attrition. A large meta-analysis (Swift & Greenberg, 2012) showed that attrition increased with the length of therapy. Here, too, our attrition rates were extremely low. (6) BIC approaches may yield increasing effects through maximizing learning via massed

22

ACCEPTED MANUSCRIPT practice, as suggested by Craske et al. (2012). (7) They might help the child and her or his family to focus their attention, energy, and time on the therapy itself. There may be fewer other life circumstances and distractions that interfere with treatment, as there can be in more standard treatments delivered on a once per week basis. (8) BIC approaches might also

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reduce functional impairment and distress faster than standard treatments since they are

carried out in a shorter period of time. (9) They may facilitate the therapist’s monitoring of progress and the therapist’s ability to adjust the treatment and “personalize” it to the needs of

SC

the youth and her or his family. (10) BIC approaches reduce the time that the child and his or her family have to be away from home, school, work and friends. (11) Finally, they might

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facilitate dissemination of evidence-based treatment (EBT) since many psychiatric outpatient centers report economical and other barriers to allow for and provide the number of sessions the standard treatments were originally developed to deliver (i.e., 11 – 18 sessions). Of course, there are also a number of disadvantages associated with these treatments.

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(1) If the family needs to travel to another city there is the cost not only of travel but also temporary living where therapy takes place. (2) The child and her or his parents need to be absent from work and school during a certain time period of consecutive days – perhaps up

EP

to a week in time – unless, therapy can be delivered during vacation times. (3) BIC approaches might be less suitable for disorders that require a lot of exposure in various

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natural situations in order to test the patient’s catastrophic beliefs and assumptions such as in the generalized type of social anxiety disorder. (4) A potential administrative or reimbursement problem might be that some insurance systems do not ”accept” intensive treatments (e.g., therapists can only book 1 hour per patient per day, which prevents onesession treatment or multiple sessions in any one day). Although these limitations are present, we believe that the advantages of BIC approaches far outweigh the disadvantages and, if the clinical effectiveness is not inferior to

23

ACCEPTED MANUSCRIPT that of standard treatment, BIC should be considered as the treatment of choice when devising a treatment plan for youth with anxiety disorders. We believe these approaches and the advances associated with them represent a paradigm shift in the delivery of clinical services for the anxiety disorders. It may be time to re-examine the standard delivery of 50-

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minute sessions that are spread out over 9-18 weeks, if not longer. Brief, intensive, and concentrated treatments appear to work as well.

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Funding No external funding was obtained for this meta-analysis. Contributors

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LGÖ designed the meta-analysis, wrote the coding schema, rated the studies, metaanalyzed the included studies, and wrote the first draft of method and results. THO wrote the first draft of introduction and discussion. Both authors participated in the revision and approved the final manuscript.

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Conflict of interest

None of the authors have any conflict of interest to report.

Appendix A. Supplementary data

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Supplementary data related to this article can be found at

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Öst, L-G., Riise, E., Wergeland G.J., Hansen, B., & Kvale, G. (2016). Cognitive behavioral and pharmacological treatments of OCD in children: A systematic review and metaanalysis. Journal of Anxiety Disorders, 43, 58-69. DOI: 10.1016/j.janxdis.2016.08.003 *Öst, L-G., Svensson, L., Hellström, K., & Lindwall, R. (2001). One-session treatment of specific phobias in youths: A randomized clinical trial. Journal of Consulting and Clinical Psychology, 69, 814-924. DOI: 10.1037/0022-006X.69.5.814 Pincus, D. B., Ehrenreich May, J., Whitton, S. W., Mattis, S. G., & Barlow, D. H. (2010). Cognitive.behavioral treatment of panic disorder in adolescence. Journal of Clinical Child & Adolescent Psychology, 39, 638–649. DOI: 10.1080/15374416.2010.501288 *Pincus, D. B., Gallo, K., Hardway, C., Angelosante, A., & Whitton, S. W. (2012). Intensive treatment of adolescents with panic disorder and agoraphobia. Presentation at the ABCT annual meeting. Reynolds, S., Wilson, C., Austin, J., & Hooper, L. (2012). Effects of psychotherapy for anxiety in children and adolescents: A meta-analytic review. Clinical Psychology Review, 32, 251–262. DOI: 10.1016/j.cpr.2012.01.005 *Santucci, L. C.; & Ehrenreich-May, J. (2013). A randomized controlled trial of the Child Anxiety Multi-day Program (CAMP) for separation anxiety disorder. Child Psychiatry and Human Development, 44, 439-451. DOI: 10.1007/s10578-012-0338-6 Schneider, S., Blatter-Meunier, J., Herren, C., Adornetto, C., In-Albon, T., & Lavallee, K. (2011). Disorder-specific cognitive-behavioral therapy for separation anxiety disorder in young children:A randomized waiting-list controlled trial. Psychotherapy & Psychosomatics, 80, 206–215. DOI: 10.1159/000323444 *Sheslow, D. V., Bondy, A. S., & Nelson, R. O. (1982). A comparison of graduated exposure, verbal coping skills, and their combination in the treatment of children’s fear of the dark. Child & Family Behavior Therapy, 4, 33-45. DOI: 10.1300/J019v04n02_03 *Storch, E. A., Geffken, G. R., Merlo, L. J., Mann, G., Duke, D., , , Goodman, W. K. (2007). Family-based cognitive-behavioral therapy for pediatric obsessive-compulsive disorder: Comparison of intensive and weekly approaches. Journal of the American Academy of Child & Adolescent Psychiatry, 46, 469-478. DOI: 10.1097/chi.0b013e31803062e7 Thulin, U., Svirsky, L., Serlachius, E., Andersson, G., & Öst, L-G. (2014). The effect of parent involvement in the treatment of anxiety disorders in children: A meta-analysis. Cognitive Behaviour Therapy, 43, 185-200. DOI: 10.1080/16506073.2014.923928 *Waters, A. M., Farrell, L. J., Zimmer-Gembeck, M. J., Milliner, E., Tiralongo, E., , , Ollendick, T H. (2014). Augmenting one-session treatment of children's specific phobias with attention training to positive stimuli. Behaviour Research and Therapy, 62, 107-119. DOI: 10.1016/j.brat.2014.07.020

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Table 1

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Mean (range) number of sessions and weeks of treatment for standard CBT divided on the respective anxiety disorder. Studies in the present meta-analysis are excluded. Weeks of treatment

Reference

7 (3-10)

6 (3-10)

Öst (2017)

Social phobia

18 (12-36)

13 (12-20)

Öst (2017)

Panic disorder

11a

10a

Pincus et al. (2010)

OCD

12 (9-14)

13 (6-20)

Öst et al. (2016)

Separation anxiety

16b

12b

Schneider et al. (2011)

PTSD

12 (6-20)

12 (6-20)

Morina et al. (2016)

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Specific phobia

SC

Number of sessions

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Disorder

Only one study. b Only two studies having the same number of sessions and weeks.

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a

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Mixed anxiety 13 (8-20) 13 (9-20) James (2015) ___________________________________________________________

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Table 2. Background data for the included studies. Severity inclusion criterion

Diagnostic system

Percent declining Tx

Percent Mean Comorage bidity

Percent previous Tx

Percent current drug Tx

N

Percent females

Age range

32

50

4-5

4.5

0

Country

Disorder

Sheslow (1983)

USA

SPE (darkness)

Muris (1997)

Holland

SPE (spider)

DSM-III-R

22

100

9-14

11.6

0

Muris (1998)

Holland

SPE (spider)

DSM-III-R

26

100

8-17

12.6

0

28

64

10-17

13.2

60

61

7-17

11.7

42

0

196

54

6-17

11.0

68

0

43

60

7-17

11.2

12

0

BAT step

RI PT

Study

Australia

SPE (spider)

DSM.IV

BAT step

Öst (2001)

Sweden

SPE (mixed)

DSM-IV

CSR 4+

0

Ollendick (2009)

Swe/USA SPE (mixed)

DSM-IV

CSR 4+

0

Flatt (2010)

Australia

SPE (mixed)

DSM-IV

Leutgeb (2012a)

Austria

SPE (spider)

DSM-IV

BAT/SPQ

30

100

8-14

11.5

0

Leutgeb (2012b)

Austria

SPE (spider)

DSM-IV

BAT

32

100

8-13

11.3

0

Waters (2014)

Australia

SPE (mixed)

DSM.IV

CSR 4+

37

57

6-17

10.6

Byrne (2015)

Australia

SPE (spider, dogs)

DSM-IV

Marked fear

35

60

6-14

8.8

Ollendick (2015)

USA

SPE (mixed)

DSM-IV

CSR 4+

9.3

97

52

6-15

8.9

93

0

Farrell (2016)

Australia

SPE (mixed)

DSM-IV

CSR 4+

20.5

35

71

7-14

10.4

100

6

Gallagher (2004)

USA

SOP

DSM-IV

23

52

8-11

10.0

Pincus (2012)

USA

PDA

DSM-IV

63

57

11-17

15.2

78 73

73

60

90

11

11

14

29

3 32.7 35.0

16 7.5 15.9

USA

OCD

DSM-IV

TE D

M AN U

Storch (2007) Merlo (2010)

USA

OCD

DSM-IV

≥16 CY-BOCS

Bolton (2011)

England

OCD

DSM-IV

Santucci (2013)

USA

SAD

DSM-IV

DSM-IV

USA

PTSD

Catani (2009)

Germany

PTSD

Deblinger (2011)

USA

PTSD

Muris (2002)

Holland

Mixed

Information given M SD

9.8

≥13 SPAI-C

CSR 4+

7.4

≥16 CY-BOCS

4.8

55

7-17

13.3

6-17

13.3

96

59

10-18

14.5

CSR 4+

29

100

7-12

9.2

94th perc.

248

61

6-12

8.2

31

45

8-14

11.9

5.0

210

61

4-11

7.7

0

20

65

9-12

10.0

40

23 63.0 65.4

23 66.2 19.4

23 10.9 2.4

10 69.3 29.2

4.0

5 symptoms

17

10 6.1 6.3

5 9

38

DSM-III-R

22

97

40

DSM-IV

DSM-IV

0

16

EP

AC C

Chemtob (2002)

SC

Dewis (2001)

ACCEPTED MANUSCRIPT

Table 3. Treatment data for the included studies.

Comparison group

Sheslow (1983)

Exp

Placebo

Therapy format I

Degree of parental involvement None

DuraType tion of Tx days C

3

0

1

1.5

1.5

0

0

0

0

1

2.5

2.5

0

0

0

0

3

2.3

1.2

10.7

11.1

10.5

1

1

1

3.0

3.0

0

0

0

12

None

I

1

None

I

1

Dewis (2001)

Exp

VRE/WLC

I

None

B

14

Öst (2001)

Exp

ExpP/WLC

I

None/High

I

None

I

None

I

Leutgeb (2012a)

Exp

WLC

I

None

Leutgeb (2012b)

Exp

WLC

I

None

Exp+ATP

Exp+Pla

I

None

Byrne (2015)

Exp+DCS

Exp+Pla

I

None

Ollendick (2015)

Exp

Augm. Exp

I

Farrell (2016) ms.

Exp+DCS

Exp+Pla

I

CBT

WLC

G

Pincus (2012)

PCT

PCT+FAM/WLC

I

Storch (2007)

ERP+CT

ERP int.

I

Merlo (2010)

ERP+CT

CBT+MI

F

Bolton (2011)

CT brief

CT/WLC

Santucci (2013)

CBT

WLC

Chemtob (2002)

CBTind

CBTgroup

Catani (2009)

Narr exp

Placebo

CBT8

CBT16

Muris (2002)

CBT

Placebo

M SD

3.0

0

0

0

6

3.0

3.0

0

0

0

12

I

1

1

4

4

0

0

0

0

I

1

1

4

4

0

0

0

0

1

1

3.0

3

0

0

0

3

1

1

1

1

0

0

0

0

None/High

I

1

1

3.0

3.0

0

0

0

6

Moderate

I

1

1

3.0

3.0

0

0

0

3

None

B

21

3

9

3.0

0

0

0

1

None/Mod.

C

6

6

20

18.0

9.5

9.1

8.7

12

High

C

21

14

21

7.0

5.0

0

10.0

3

High

C

21

14

22.5

7.5

0

0

0

0

I

Low

B

84

5

5

0.4

7.3

5.6

5.6

G

Moderate

C

7

7

23

23.0

0

0

0

1.5

I

None

B

28

4

4

1.0

13.7

14.6

5.1

12

I

None

B

14

6

7.5

3.8

0

0

0

6

I

High

B

56

8

12

1.5

7.1

9.6

4.7

0

G

None

B

42

12

6

1.0

0

0

0

0

7.0 7.3

4.3 5.4

2.3 4.3

2.3 4.4

AC C

Deblinger (2011)

3.0

1

I

EP

Gallagher (2004)

1

I

TE D

Waters (2014)

1

1

M AN U

I

SC

I I

I

F-up months

0

EMDR

Pla/WLC

Attrition comp.

0

EMDR/Pla

Pla/WLC

Attrition BIC

0

Exp

Exp

Attrition total

1.5

Exp

Exp

Intensity hrs/week

1.5

Muris (1997)

Ollendick (2009)

Total time in hours

3

Muris (1998)

Flatt (2010)

No. of Sessions

RI PT

Study

Method of CBT

16.4 22.8

4.2 4.3

3

1.8 3.6 3.8 4.5

ACCEPTED MANUSCRIPT Table 4 Comparison of BIC-therapies on treatment variables [M (SD)]. Brief

Intensive

Concentr.

F-value

Tx duration (days)

Difference

37.0 (25.8)

1.0 (0.0)

21.6 (20.9)

9.97a

# of sessions

5.9 (3.2)

1.0 (0.0)

8.0 (5.0)

14.70b

I>B=C

Total time (hrs)

6.4 (3.3)

2.7 (1.0)

17.4 (9.2)

17.83b

I=B>C

I>B

RI PT

Variable

Intensity (hrs/week) 1.7 (1.2) 2.8 (0.9) 11.4 (8.8) 9.87a I=B>C __________________________________________________________________________

AC C

EP

TE D

M AN U

SC

Note: a p<0.001, b p<0.0001. > significantly different than, = no significant difference.

ACCEPTED MANUSCRIPT Table 5 Effect sizes (Hedges’ g) for all BIC RCTs divided on comparison conditions for posttreatment assessments. g-value

95% CI

All BIC studies

32

0.68

0.43-0.94

5.26d

BIC vs. WLC

11

1.47

1.00-1.95

6.06d

BIC vs. Placebo

6

0.97

0.53-1.41

4.29d

BIC vs. Active

15

0.05

-0.15;0.25

0.48

12

0.01

BIC vs. Other CBT

M AN U

Tx

z-value

-0.21-0.23

Q-value

I2

169.5d

82

46.6d

79

9.0

45

27.9a

50

24.7b

56

RI PT

k

SC

Comparison

0.09

AC C

EP

TE D

________________________________________________________________________________________ Note: k = number of comparisons, CI = confidence interval. A positive g-value means that the first treatment in the comparison is better and a negative that the second is better. a p<0.05, b p<0.01, c p<0.001, d p<0.0001

ACCEPTED MANUSCRIPT Table 6 Effect sizes (Hedges’ g) for all BIC RCTs divided on comparison conditions for follow-up assessments. g-value

95% CI

z-value

All BIC studies

12

0.18

0.03-0.33

2.29a

BIC vs. WLC

2

0.69

0.09-1.30

2.24a

BIC vs. Placebo

2

0.36

-0.12-0.83

1.46

BIC vs. Other Tx

8

0.08

-0.12-0.27

0.76

BIC vs. Other

7

0.10

M AN U

CBT

Q-value

-0.10-0.31

1.00

I2

RI PT

k

10.3

0

0.1

0

1.5

32

4.4

0

3.4

0

SC

Comparison

AC C

EP

TE D

________________________________________________________________________________________ Note: k = number of comparisons, CI = confidence interval. A positive g-value means that the first treatment in the comparison is better and a negative that the second is better. a p<0.05.

ACCEPTED MANUSCRIPT Table 7 Meta-regression analyses of the overall effect size of BIC RCTs at post-treatment.

k 32

Point estimate -0.0020

z-value -3.16

p-value 0.0016

Percent females

32

0.0196

4.66

0.0001

Mean age at treatment

32

0.0443

2.09

Methodology scores

32

-0.0061

-0.68

Risk of bias

32

0.0244

0.32

Percent on current drug Tx

16

.0.0060

Days of treatment

32

-0.0093

Number of sessions

32

Total hours of Tx

32

Intensity

32

Attrition

32 29

SC

0.036

0.495

0.747

0.0907

-4.66

0.0001

-0.0492

-3.15

0.0016

-0.0093

-1.08

0.280

0.0360

4.77

0.0001

-0.0155

-1.53

0.127

1.12

0.262

M AN U

-1.69

TE D

Pre-treatment severity

RI PT

Variable Number of participants

0.0006

_________________________________________________________________

AC C

EP

Note; k = number of comparisons,

ACCEPTED MANUSCRIPT Table 8

k

g

95% CI

Disorder Mixed anxiety OCD PDA PTSD SPE

2 4 3 4 19

1.17 0.57;1.76 0.16 -0.56;0.88 1.08 -0.16;2.32 -0.02 -0.50;0.45 0.88 0.54;1.22

Type of BIC Brief Intensive Concentrated

10 14 8

0.29 0.84 0.93

-0.08;0.66 0.44;1.25 0.33;1.52

Treatment format Individual Group

27 4

0.73 0.64

0.43;0.72 0.18;1.10

Therapist profession Clin. psychologist Counselor Student Various

13 2 9 2

0.89 0.53;1.25 0.35 -0.01;0.71 0.62 0.26;0.98 -0.30 -0.74;0.13

Qb-value

p-value

14.46

0.006

5.18

SC

Variable

RI PT

Subgroup analyses of the overall effect size of BIC RCTs at post-treatment.

M AN U

0.10

0.82 0.54;1.10 0.67 -0.50;1.83 -0.16 -0.54;0.23

Type of comparison Active treatment Placebo WLC

15 5 11

0.10 0.73 1.47

-0.12;0.32 0.40;1.07 1.00;1.95

6 26

0.81 0.65

0.05;1.57 0.38;0.93

AC C

EP

TE D

Degree of parental involvement Low 26 Moderate 2 High 4

Type of data analysis Completer Intent-to-treat

0.075

0.758

18.68

0.0001

16.01

0.001

29.90

0.0001

0.15

0.701

Continent 0.26 0.877 North America 12 0.58 0.20;0.96 Europe 9 0.71 0.33;1.10 Australia 5 0.72 0.14;1.29 _______________________________________________________________________ Note: k = number of comparisons, CI = confidence interval, Qb = Q between subgroups.

ACCEPTED MANUSCRIPT Table 9 Proportions of remission at post-treatment and recovery at follow-up. Mea-

k

sure

Placebo

WLC

z-value*

Q-value

I2

tion

Rem.

14

54.2%

43.5;64.5

0.77

46.7d

72

Rec.

12

64.1%

55.1;72.2

3.02b

28.2b

61

Rem.

2

57.1%

43.8;69.4

1.05

0.6

0

Rec.

2

63.4%

41.3;81.0

1.19

1.8

43

Rem.

2

26.0%

13.3;44.6

-2.47a

1.7

41

Rec.

1

34.5%

25.3;45.0

-2.84b

0.0

0

Rem.

5

6.9%

1.8;23.4

-3.60d

1.6

0

Rec.

1

9.1%

1.3;43.9

-2.20a

0.0

0

RI PT

Standard CBT

95% CI

SC

BIC

Propor-

M AN U

Comparison

AC C

EP

TE D

_______________________________________________________________________________________ Note: k = number of comparisons, CI = confidence in terval. *Test if significantly different from 50%, Rem. = remission, Rec. = recovery. a p<0.05, b p<0.01, c p<0.001, d p<0.0001.

ACCEPTED MANUSCRIPT Table 10 Within-group effect sizes (Hedges’ g) for all treatment conditions at post-treatment and follow-up assessments. Time point

k

g-value

95% CI

z-value

Q-value

I2

BIC

Post

25

1.50

1.21;1.79

10.19d

105.8d

77

F-up

16

1.53

1.16;1.91

8.08d

99.3d

85

Post

5

0.89

0.34;1.44

3.17b

16.5b

76

F-up

4

0.98

0.25;1.70

2.62b

20.2d

85

d

d

75

Standard CBT

Placebo

WLC

12

1.57

1.20;1.95

8.18

F-up

8

1.78

1.33;2.22

7.85d

34.5d

80

Post

8

1.75

1.35;2.15

8.59d

10.3

32

F-up

4

1.62

1.26;1.98

8.78d

1.4

0

Post

3

0.98

0.00:1.95

1.97a

27.4d

93

F-up

3

1.05

0.16;1.94

2.30d

22.5d

91

0.29;0.84

4.03

d

1.8

0

SC

Concentrated

Post

44.8

Post

4

0.56

F-up

2

0.90

M AN U

Intensive

0.57;1.22

5.44d

0.2

0

Post

9

0.21

0.00;0.43

1.97a

2.3

0

2

-0.06

-0.65;0.54

-0.19

0.0

0

F-up

TE D

Brief

RI PT

Comparison

_________________________________________________________________________________________

AC C

EP

Note: k = number of comparisons, CI = confidence interval. a p<0.05, b p<0.0001, c p<0.0001, d p<0.0001.

ACCEPTED MANUSCRIPT

References identified by literature search: 875

RI PT

After removal of duplicates: 659 abstracts

Excluded based on abstract: 601

SC

Full-text articles retrieved: 58

M AN U

Excluded: 35 -Anxiety not the principal diagnosis: 7 -Not using a BIC-condition: 7 -Not a RCT: 6 -Secondary analysis: 6 -Not testing CBT: 4 -Not only treating youth: 3 -Various: 2

TE D

Included: 23 RCTs

AC C

EP

Fig. 1. Flowchart of the inclusion of studies.

ACCEPTED MANUSCRIPT Highlights Brief, intensive, and concentrated (BIC) treatments were reviewed.

•

BIC yielded very large effect sizes compared to wait list and placebo.

•

There was no significant difference between BIC and standard length CBT.

•

The effects of BIC and standard CBT were maintained at follow-up.

•

BIC represents a paradigm shift in treating youth anxiety disorders.

AC C

EP

TE D

M AN U

SC

RI PT

•