Different Types and Acceptability of Psychotherapies for Acute Anxiety Disorders in Children and Adolescents

Key Points Question What is the best psychotherapeutic approach for anxiety disorders in children and adolescents in terms of efficacy and acceptability? Findings This network meta-analysis included 101 unique trials with 6625 unique participants who received 11 different psychotherapies and 4 control conditions. Only group cognitive behavioral therapy was significantly more effective in reducing anxiety symptoms than other psychotherapies and all control conditions posttreatment and at short-term follow-up. Meaning Group cognitive behavioral therapy may be the initial choice of psychotherapy for anxiety disorders in children and adolescents, after replication in future research with focus on disorder-specific psychotherapies and identification of moderators of treatment effect.


eMethods 1. Published Protocol and Changes Made to the Protocol
The protocol has been registered in PROSPERO (No. CRD42015016283) and published in BMJ Open -available at http://bmjopen.bmj.com/content/5/10/e008572.full.pdf+html Here below some changes and clarifications to the published protocol: 1. In order to obtain more exact results from databases, we adjusted some of the text words in search strategy. For example, we added the words "phobias", "CBT", "systematic desensitization", "eye movement desensitization and reprocessing", "EMDR", "self-talk", "self talk", "emotive imagery", "contingency management", "preschool, and "pre-school". Besides, we also searched additional sources of clinical trials, including Trial Register (Netherlands) and ISRCTN registry (UN).
2. We added the assessment of the quality of evidence of network estimates for primary outcomes by using the GRADE framework, which characterizes the quality of a body of evidence on the basis of the study limitations, imprecision, inconsistency, indirectness, and publication bias. 3. We had planned to conduct subgroup analyses, sensitivity analyses and meta-regressions. While given the limitation of the number of trials in some subgroups, we adjusted some analyses with changing the cut-off point of duration of psychotherapy in subgroups (short-term treatment of 10 or fewer weeks vs. long-term treatment of more than 10 weeks). In addition, we added to perform two sensitivity network meta-analyses for primary outcomes by omitting the trial with maternal anxiety disorder, and omitting the trial with rated as high risk studies. Since most of trials recuited patients with comorbid general psychiatric disorders, we did not perform the subgroup analyses and meta-regression analyses (with or without comorbid general psychiatric disorders). #2 anxiety or anxious or phobic or fear or fears or phobia or phobias or "panic disorder*" or "overanxious disorder*" or "avoidant disorder*" or agoraphobia or "selective mutism" or "panic attack specifier" or "combat disorder*" or "mixed disorder*" or neurosis or neuroses or neurotic or "school refusal":ti (Word variations have been searched) #3 anxiety or anxious or phobic or fear or fears or phobia or phobias or "panic disorder*" or "overanxious disorder*" or "avoidant disorder*" or agoraphobia or "selective mutism" or "panic attack specifier" or "combat disorder*" or "mixed disorder*" or neurosis or neuroses or neurotic or "school refusal":ab (Word variations have been searched) #4 #1 or #2 or #3 #5 MeSH descriptor: [Psychotherapy] explode all trees #6 psychother* or behavio* or cogniti* or CBT or interpersonal or relaxation or bibliotherap* or counsel* or "family treatment" or supportive or problem-solving or "problem solving" or psychodynamic or exposure or modeling or "reinforced practice" or "systematic desensitization" or "eye movement desensitization and reprocessing" or EMDR or self-talk or "self talk" or "emotive imagery" or "contingency management" or therapy:ti (Word variations have been searched) #7 psychother* or behavio* or cogniti* or CBT or interpersonal or relaxation or bibliotherap* or counsel* or "family treatment" or supportive or problem-solving or "problem solving" or psychodynamic or exposure or modeling or "reinforced practice" or "systematic desensitization" or "eye movement desensitization and reprocessing" or EMDR or self-talk or "self talk" or "emotive imagery" or "contingency management" or therapy:ab (Word variations have been searched) #8 #5 or #6 or #7 #9 adolesc* or child* or boy* or girl* or juvenil* or minors or paediatri* or pediatri* or pubescen* or school* or student* or teen* or young or youth* or class* or preschool or pre-school:ti (Word variations have been searched) #10 adolesc* or child* or boy* or girl* or juvenil* or minors or paediatri* or pediatri* or pubescen* or school* or student* or teen* or young or youth* or class* or preschool or pre-school:ab (

OVID (Embase and PsycINFO)
1 exp anxiety disorder/ 2 (anxiety or anxious or phobic or fear or fears or phobia or phobias or panic disorder$ or overanxious disorder$ or avoidant disorder$ or agoraphobia or selective mutism or panic attack or combat disorder$ or mixed disorder$ or neurosis or neuroses or neurotic or school refusal).ti.
3 (anxiety or anxious or phobic or fear or fears or phobia or phobias or panic disorder$ or overanxious disorder$ or avoidant disorder$ or agoraphobia or selective mutism or panic attack or combat disorder$ or mixed disorder$ or neurosis or neuroses or neurotic or school refusal).ab. 4 1 or 2 or 3 5 exp psychotherapy/ 6 (psychother$ or behavio$ or cogniti$ or CBT or interpersonal or relaxation or bibliotherap$ or counsel$ or family treatment$ or supportive or problem-solving or problem solving or psychodynamic or exposure or modeling or reinforced practice or systematic desensitization or (eye movement desensitization and reprocessing) or EMDR or self-talk or self talk or emotive imagery or contingency management or therapy).ti 7 (psychother$ or behavio$ or cogniti$ or CBT or interpersonal or relaxation or bibliotherap$ or counsel$ or family treatment$ or supportive or problem-solving or problem solving or psychodynamic or exposure or modeling or reinforced practice or systematic desensitization or (eye movement desensitization and reprocessing) or EMDR or self-talk or self talk or emotive imagery or contingency management or therapy).ab 8 5 or 6 or 7 9 (adolesc$ or child$ or boy$ or girl$ or juvenil$ or minors or paediatri$ or pediatri$ or pubescen$ or school$ or student$ or teen$ or young or youth$ or class$ or preschool or pre-school).ti.
10 (adolesc$ or child$ or boy$ or girl$ or juvenil$ or minors or paediatri$ or pediatri$ or pubescen$ or school$ or student$ or teen$ or young or youth$ or class$ or preschool or pre-school).ab. Web of Science #1 TS=(anxiety OR anxious OR phobic OR fear OR fears OR phobia OR phobias OR "panic disorder*" OR "overanxious disorder*" OR "avoidant disorder*" OR agoraphobia OR "selective mutism" OR "panic attack specifier" OR "combat disorder*" OR "mixed disorder*" OR neurosis OR neuroses OR neurotic OR "school refusal") Indexes=SCI-EXPANDED, SSCI, CPCI-S, CPCI-SSH Timespan=All years #2 TS=(psychother* OR behavio* OR cogniti* OR CBT OR interpersonal OR relaxation OR bibliotherap* OR counsel* OR "family treatment" OR supportive OR problem-solving OR "problem solving" OR psychodynamic OR exposure OR modeling OR "reinforced practice" OR "systematic desensitization" OR "eye movement desensitization and reprocessing" OR EMDR OR self-talk OR "self talk" OR "emotive imagery" OR "contingency management" OR therapy) Indexes=SCI-EXPANDED, SSCI, CPCI-S, CPCI-SSH Timespan=All years #3 TS=(adolesc* OR child* OR boy* OR girl* OR juvenil* OR minors OR paediatri* OR pediatri* OR pubescen* OR school* OR student* OR teen* OR young OR youth* OR class* OR preschool OR pre-school) Indexes=SCI-EXPANDED, SSCI, CPCI-S, CPCI-SSH Timespan=All years #4 TS=(random* OR allocate* OR assign* OR "cross over*" OR crossover* OR controlled) S2 TI (anxiety OR anxious OR phobic OR fear OR fears OR phobia OR phobias OR "panic disorder*" OR "overanxious disorder*" OR "avoidant disorder*" OR agoraphobia OR "selective mutism" OR "panic attack specifier" OR "combat disorder*" OR "mixed disorder*" OR neurosis OR neuroses OR neurotic OR "school refusal") S3 AB (anxiety OR anxious OR phobic OR fear OR fears OR phobia OR phobias OR "panic disorder*" OR "overanxious disorder*" OR "avoidant disorder*" OR agoraphobia OR "selective mutism" OR "panic attack specifier" OR "combat disorder*" OR "mixed disorder*" OR neurosis OR neuroses OR neurotic OR "school refusal") S4 S1 or S2 or S3 S5 MH "Psychotherapy+" S6 TI (psychother* OR behavio* OR cogniti* OR CBT OR interpersonal OR relaxation OR bibliotherap* OR counsel* OR "family treatment" OR supportive OR problem-solving OR "problem solving" OR psychodynamic OR exposure OR modeling OR "reinforced practice" OR "systematic desensitization" OR "eye movement desensitization and reprocessing" OR EMDR OR self-talk OR "self talk" OR "emotive imagery" OR "contingency management" OR therapy ) S7 AB (psychother* OR behavio* OR cogniti* OR CBT OR interpersonal OR relaxation OR bibliotherap* OR counsel* OR "family treatment" OR supportive OR problem-solving OR "problem solving" OR psychodynamic OR exposure OR modeling OR "reinforced practice" OR "systematic desensitization" OR "eye movement desensitization and reprocessing" OR EMDR OR self-talk OR "self talk" OR "emotive imagery" OR "contingency management" OR therapy ) S8 S5 or S6 or S7 S9 TI (adolesc* OR child* OR boy* OR girl* OR juvenil* OR minors OR paediatri* OR pediatri* OR pubescen* OR school* OR student* OR teen* OR young OR youth* OR class* OR preschool OR preschool ) S10 AB (adolesc* OR child* OR boy* OR girl* OR juvenil* OR minors OR paediatri* OR pediatri* OR pubescen* OR school* OR student* OR teen* OR young OR youth* OR class* OR preschool OR pre-school ) S11 (MM "Child") OR (MM "Adolescence") S12 S9 or S10 or S11 S13 MH "Clinical Trials+" S14 TI (random* OR allocate* OR assign* OR "cross over*" OR crossover* OR controlled ) S15 AB (random* OR allocate* OR assign* OR "cross over*" OR crossover* OR controlled ) S16 S13 or S14 or S15 S17 S4 and S8 and S12 and S16 ProQuest Dissertations S1 TI,AB(anxiety OR anxious OR phobic OR fear OR fears OR phobia OR phobias OR "panic disorder*" OR "overanxious disorder*" OR "avoidant disorder*" OR agoraphobia OR "selective mutism" OR "panic attack speci?er" OR "combat disorder*" OR "mixed disorder*" OR neurosis OR neuroses OR neurotic OR "school refusal") S2 TI,AB(psychother* OR behavio* OR cogniti* OR CBT OR interpersonal OR relaxation OR bibliotherap* OR counsel* OR "family treatment" OR supportive OR problem-solving OR "problem solving" OR psychodynamic OR exposure OR modeling OR "reinforced practice" OR "systematic desensitization" OR "eye movement desensitization and reprocessing" OR EMDR OR self-talk OR "self talk" OR "emotive imagery" OR "contingency management" OR therapy) S3 TI(adolesc* OR child* OR boy* OR girl* OR juvenil* OR minors OR paediatri* OR pediatri* OR pubescen* OR school* OR student* OR teen* OR young OR youth* OR class* OR preschool OR preschool) S4 TI,AB(random* OR allocate* OR assign* OR "cross over*" OR crossover* OR controlled) S5 S1 AND S2 AND S3 AND S4 LILACS #1 (anxiety or anxious or phobic or fear or fears or phobia or phobias or "panic disorder$" or "overanxious disorder$" or "avoidant disorder$" or agoraphobia or "selective mutism" or "panic attack specifier" or "combat disorder$" or "mixed disorder$" or neurosis or neuroses or neurotic or "school refusal") and (psychother$ or behavio$ or cogniti$ or CBT or interpersonal or relaxation or bibliotherap$ or counsel$ or "family treatment" or supportive or problem-solving or "problem solving" or psychodynamic or exposure or modeling or "reinforced practice" or "systematic desensitization" or "eye movement desensitization and reprocessing" or EMDR or self-talk or "self talk" or "emotive imagery" or "contingency management" or therapy) and (adolesc$ or child$ or boy$ or girl$ or juvenil$ or minors or paediatri$ or pediatri$ or pubescen$ or school$ or student$ or teen$ or young or youth$ or class$ or preschool or pre-school) [Title words] or (anxiety or anxious or phobic or fear or fears or phobia or phobias or "panic disorder$" or "overanxious disorder$" or "avoidant disorder$" or agoraphobia or "selective mutism" or "panic attack specifier" or "combat disorder$" or "mixed disorder$" or neurosis or neuroses or neurotic or "school refusal") and (psychother$ or behavio$ or cogniti$ or CBT or interpersonal or relaxation or bibliotherap$ or counsel$ or "family treatment" or supportive or problem-solving or "problem solving" or psychodynamic or exposure or modeling or "reinforced practice" or "systematic desensitization" or "eye movement desensitization and reprocessing" or EMDR Bibliotherapy BIB BIB is an unstructured therapy in which parents are provided with a self-help book to be used for guided parent-delivered psychotherapy.

Control conditions:
No-treatment NT NT is a control condition in which the participants receive no active treatment during the study and in which they do not expect to receive such after the study is over.
Psychological placebo PBO PBO is a control condition that was regarded as inactive by the researchers but was presented to the participants as being an active therapy.
Treatment-as-usual TAU TAU is not considered to be structured psychotherapy but may have some treatment effects.
Waitlist WL WL is a control condition in which the participants receive no active treatment during the study but are forewarned that they can receive one after the study period is over.

Hierarchy of anxiety symptom severity measurement scales
Hierarchy Anxiety symptom severity rating scales Abbreviation Pediatric Anxiety Rating Scale PARS Note: where different anxiety symptom severity rating scales were used, for the purpose of pooling results, we chose the single best available outcome measure according to a hierarchy based on psychometric properties and appropriateness for use with children and adolescents.

Hierarchy of quality of life and functional improvement measurement scales
Hierarchy Anxiety symptom severity rating scales Abbreviation  y=a table of the arm-means, sd=a table of the arm sd, n=a table of the arm sample size, t=a table with r= a table of the number of events, n=a table of the arm sample size, t=a table with

Risk of bias graph: it is a plot of the distribution of judgments (Yes, No, Unclear) across studies for each risk of bias entry
Each domain in the tool includes one or more specific entries in a 'Risk of bias' table. Within each entry, the first part of the tool describes what was reported to have happened in the study, in sufficient detail to support a judgement about the risk of bias. The second part of the tool assigns a judgement relating to the risk of bias for that entry. This is achieved by assigning a judgement of 'Low risk' of bias, 'High risk' of bias, or 'Unclear risk' of bias.
The domains of sequence generation, allocation concealment and selective outcome reporting should each be addressed in the tool by a single entry for each study. For blinding of participants and personnel, blinding of outcome assessment and for incomplete outcome data, two or more entries may be used because assessments generally need to be made separately for different outcomes (or for the same outcome at different time points).

Hasse diagram for mean overall change in anxiety symptoms at post-treatment and follow-up
Upper treatments represent higher ranks. BIB-CBT =bibliotherapy cognitive-behavioral therapy, G-BT=group behavioral therapy, G-CBT=group cognitive-behavioral therapy, G-CBT+P=group cognitive-behavioral therapy with parental involvement, I-BT+P=individual behavioral therapy with parental involvement, I-CBT=individual cognitive-behavioral therapy, I-CBT+P=individual cognitive-behavioral therapy with parental involvement, I+G-BT=individual and group behavioral therapy, I+G-CBT=individual and group cognitive-behavioral therapy, Int-CBT=internet-assisted cognitive-behavioral therapy, NT=no-treatment, PBO=psychological placebo, P-CBT=parent-only cognitive-behavioral therapy, TAU=treatment as usual, WL=waitlist.

eTable 1. Subgroup Network Meta-analyses and Network Metaregression for Efficacy Outcomes
Subgroup network meta-analyses and network meta-regression of each condition for mean improvement in symptoms at post-treatment compared with psychological placebo by standardized mean difference (95% CrI)*  BIB-CBT=bibliotherapy cognitive-behavioral therapy, CrI=credibility interval, G-BT=group behavioral therapy, G-CBT=group cognitive-behavioral therapy, G-CBT+P=group cognitivebehavioral therapy with parental involvement, I-BT+P=individual behavioral therapy with parental involvement, I-CBT=individual cognitive-behavioral therapy, I-CBT+P=individual cognitivebehavioral therapy with parental involvement, I+G-BT=individual and group behavioral therapy, I+G-CBT=individual and group cognitive-behavioral therapy, Int-CBT=internet-assisted cognitive-behavioral therapy, NT=no-treatment, P-CBT=parent-only cognitive-behavioral therapy, TAU=treatment as usual, WL=waitlist.         I-CBT+P  G-CBT+P vs Int-CBT  G-CBT+P vs PBO  I+G-BT vs PBO  I-BT+P vs I-CBT  I-BT+P vs I-CBT+P  I-BT+P vs PBO  I-CBT vs I-CBT+P  I-CBT vs Int-CBT  I-CBT vs PBO  I-CBT vs TAU  I-CBT+P vs Int-CBT  I-CBT+P vs PBO  I-CBT+P vs TAU  Int-CBT vs P-CBT  BIB-CBT vs G-CBT+P  BIB-CBT vs I-CBT  BIB-CBT vs I-CBT+P  P-CBT vs G-CBT+P  G-BT vs G-CBT  G-CBT vs G-CBT+P  G-CBT vs I-CBT  G-CBT vs NT  G-CBT vs PBO  G-CBT vs TAU  G-CBT+P vs PBO  I-BT+P vs I-CBT+P  I-BT+P vs PBO  I-CBT vs I-CBT+P  I-CBT vs Int-CBT  I-CBT vs PBO  I-CBT vs TAU  I-CBT+P          * Salanti G, Del Giovane C, Chaimani A, Caldwell DM, Higgins JP. Evaluating the quality of evidence from a network meta-analysis. PLoS One. 2014 Jul 3;9(7):e99682. a The consideration for study limitations was based on the relative contributions of risk of bias in direct evidence. We downgraded by one level for moderate risk, and two levels for high risk of bias. b The consideration for imprecision was based on the width of the confidence interval. c The consideration for heterogeneity and inconsistency was based on the corresponding p value. We downgraded by one level for significant heterogeneity and inconsistency, respectively. d The consideration for indirectness was based on the results of subgroup analysis. We downgraded by one level if the confidence interval between the two subroups is not overlap. In some cases, there are both statistically significant differences for the nonoverlapping two subgroups, we didn't downgrade these cases. e The consideration for publication bias was based on the comparison-adjusted funnel plot and Egger's test. Abbreviation: BIB-CBT=bibliotherapy