Comparative effectiveness and safety of cognitive behavioral therapy and pharmacotherapy for childhood anxiety disorders

A systematic review and meta-analysis

Zhen Wang, Stephen Perry Whiteside, Leslie Sim, Wigdan Farah, Allison S. Morrow, Mouaz Alsawas, Patricia Barrionuevo, Mouaffaa Tello, Noor Asi, Bradley Beuschel, Lubna Daraz, Jehad Almasri, Feras Zaiem, Laura Larrea-Mantilla, Oscar J. Ponce, Annie LeBlanc, Larry J. Prokop, Mohammad H Murad

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

IMPORTANCE: Childhood anxiety is common. Multiple treatment options are available, but existing guidelines provide inconsistent advice on which treatment to use. OBJECTIVES: To evaluate the comparative effectiveness and adverse events of cognitive behavioral therapy (CBT) and pharmacotherapy for childhood anxiety disorders. DATA SOURCES: We searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and SciVerse Scopus from database inception through February 1, 2017. STUDY SELECTION: Randomized and nonrandomized comparative studies that enrolled children and adolescents with confirmed diagnoses of panic disorder, social anxiety disorder, specific phobias, generalized anxiety disorder, or separation anxiety and who received CBT, pharmacotherapy, or the combination. DATA EXTRACTION AND SYNTHESIS: Independent reviewers selected studies and extracted data. Random-effects meta-analysis was used to pool data. MAIN OUTCOMES AND MEASURES: Primary anxiety symptoms (measured by child, parent, or clinician), remission, response, and adverse events. RESULTS: A total of 7719 patients were included from 115 studies. Of these, 4290 (55.6%) were female, and the mean (range) age was 9.2 (5.4-16.1) years. Compared with pill placebo, selective serotonin reuptake inhibitors (SSRIs) significantly reduced primary anxiety symptoms and increased remission (relative risk, 2.04; 95% CI, 1.37-3.04) and response (relative risk, 1.96; 95% CI, 1.60-2.40). Serotonin-norepinephrine reuptake inhibitors (SNRIs) significantly reduced clinician-reported primary anxiety symptoms. Benzodiazepines and tricyclics were not found to significantly reduce anxiety symptoms. When CBT was compared with wait-listing/no treatment, CBT significantly improved primary anxiety symptoms, remission, and response. Cognitive behavioral therapy reduced primary anxiety symptoms more than fluoxetine and improved remission more than sertraline. The combination of sertraline and CBT significantly reduced clinician-reported primary anxiety symptoms and response more than either treatment alone. Head-to-head comparisons were sparse, and network meta-analysis estimates were imprecise. Adverse events were common with medications but not with CBT and were not severe. Studies were too small or too short to assess suicidality with SSRIs or SNRIs. One trial showed a statistically nonsignificant increase in suicidal ideation with venlafaxine. Cognitive behavioral therapy was associated with fewer dropouts than pill placebo or medications. CONCLUSIONS AND RELEVANCE: Evidence supports the effectiveness of CBT and SSRIs for reducing childhood anxiety symptoms. Serotonin-norepinephrine reuptake inhibitors also appear to be effective based on less consistent evidence. Head-to-head comparisons between various medications and comparisons with CBT represent a need for research in the field.

Original languageEnglish (US)
Pages (from-to)1049-1056
Number of pages8
JournalJAMA Pediatrics
Volume171
Issue number11
DOIs
StatePublished - Nov 1 2017

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Cognitive Therapy
Anxiety Disorders
Meta-Analysis
Anxiety
Safety
Drug Therapy
Serotonin Uptake Inhibitors
Separation Anxiety
Sertraline
Placebos
Databases
Suicidal Ideation
Fluoxetine
Panic Disorder
Therapeutics
Benzodiazepines
MEDLINE
Guidelines

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Comparative effectiveness and safety of cognitive behavioral therapy and pharmacotherapy for childhood anxiety disorders : A systematic review and meta-analysis. / Wang, Zhen; Whiteside, Stephen Perry; Sim, Leslie; Farah, Wigdan; Morrow, Allison S.; Alsawas, Mouaz; Barrionuevo, Patricia; Tello, Mouaffaa; Asi, Noor; Beuschel, Bradley; Daraz, Lubna; Almasri, Jehad; Zaiem, Feras; Larrea-Mantilla, Laura; Ponce, Oscar J.; LeBlanc, Annie; Prokop, Larry J.; Murad, Mohammad H.

In: JAMA Pediatrics, Vol. 171, No. 11, 01.11.2017, p. 1049-1056.

Research output: Contribution to journalArticle

Wang, Z, Whiteside, SP, Sim, L, Farah, W, Morrow, AS, Alsawas, M, Barrionuevo, P, Tello, M, Asi, N, Beuschel, B, Daraz, L, Almasri, J, Zaiem, F, Larrea-Mantilla, L, Ponce, OJ, LeBlanc, A, Prokop, LJ & Murad, MH 2017, 'Comparative effectiveness and safety of cognitive behavioral therapy and pharmacotherapy for childhood anxiety disorders: A systematic review and meta-analysis', JAMA Pediatrics, vol. 171, no. 11, pp. 1049-1056. https://doi.org/10.1001/jamapediatrics.2017.3036
Wang, Zhen ; Whiteside, Stephen Perry ; Sim, Leslie ; Farah, Wigdan ; Morrow, Allison S. ; Alsawas, Mouaz ; Barrionuevo, Patricia ; Tello, Mouaffaa ; Asi, Noor ; Beuschel, Bradley ; Daraz, Lubna ; Almasri, Jehad ; Zaiem, Feras ; Larrea-Mantilla, Laura ; Ponce, Oscar J. ; LeBlanc, Annie ; Prokop, Larry J. ; Murad, Mohammad H. / Comparative effectiveness and safety of cognitive behavioral therapy and pharmacotherapy for childhood anxiety disorders : A systematic review and meta-analysis. In: JAMA Pediatrics. 2017 ; Vol. 171, No. 11. pp. 1049-1056.
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abstract = "IMPORTANCE: Childhood anxiety is common. Multiple treatment options are available, but existing guidelines provide inconsistent advice on which treatment to use. OBJECTIVES: To evaluate the comparative effectiveness and adverse events of cognitive behavioral therapy (CBT) and pharmacotherapy for childhood anxiety disorders. DATA SOURCES: We searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and SciVerse Scopus from database inception through February 1, 2017. STUDY SELECTION: Randomized and nonrandomized comparative studies that enrolled children and adolescents with confirmed diagnoses of panic disorder, social anxiety disorder, specific phobias, generalized anxiety disorder, or separation anxiety and who received CBT, pharmacotherapy, or the combination. DATA EXTRACTION AND SYNTHESIS: Independent reviewers selected studies and extracted data. Random-effects meta-analysis was used to pool data. MAIN OUTCOMES AND MEASURES: Primary anxiety symptoms (measured by child, parent, or clinician), remission, response, and adverse events. RESULTS: A total of 7719 patients were included from 115 studies. Of these, 4290 (55.6{\%}) were female, and the mean (range) age was 9.2 (5.4-16.1) years. Compared with pill placebo, selective serotonin reuptake inhibitors (SSRIs) significantly reduced primary anxiety symptoms and increased remission (relative risk, 2.04; 95{\%} CI, 1.37-3.04) and response (relative risk, 1.96; 95{\%} CI, 1.60-2.40). Serotonin-norepinephrine reuptake inhibitors (SNRIs) significantly reduced clinician-reported primary anxiety symptoms. Benzodiazepines and tricyclics were not found to significantly reduce anxiety symptoms. When CBT was compared with wait-listing/no treatment, CBT significantly improved primary anxiety symptoms, remission, and response. Cognitive behavioral therapy reduced primary anxiety symptoms more than fluoxetine and improved remission more than sertraline. The combination of sertraline and CBT significantly reduced clinician-reported primary anxiety symptoms and response more than either treatment alone. Head-to-head comparisons were sparse, and network meta-analysis estimates were imprecise. Adverse events were common with medications but not with CBT and were not severe. Studies were too small or too short to assess suicidality with SSRIs or SNRIs. One trial showed a statistically nonsignificant increase in suicidal ideation with venlafaxine. Cognitive behavioral therapy was associated with fewer dropouts than pill placebo or medications. CONCLUSIONS AND RELEVANCE: Evidence supports the effectiveness of CBT and SSRIs for reducing childhood anxiety symptoms. Serotonin-norepinephrine reuptake inhibitors also appear to be effective based on less consistent evidence. Head-to-head comparisons between various medications and comparisons with CBT represent a need for research in the field.",
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T1 - Comparative effectiveness and safety of cognitive behavioral therapy and pharmacotherapy for childhood anxiety disorders

T2 - A systematic review and meta-analysis

AU - Wang, Zhen

AU - Whiteside, Stephen Perry

AU - Sim, Leslie

AU - Farah, Wigdan

AU - Morrow, Allison S.

AU - Alsawas, Mouaz

AU - Barrionuevo, Patricia

AU - Tello, Mouaffaa

AU - Asi, Noor

AU - Beuschel, Bradley

AU - Daraz, Lubna

AU - Almasri, Jehad

AU - Zaiem, Feras

AU - Larrea-Mantilla, Laura

AU - Ponce, Oscar J.

AU - LeBlanc, Annie

AU - Prokop, Larry J.

AU - Murad, Mohammad H

PY - 2017/11/1

Y1 - 2017/11/1

N2 - IMPORTANCE: Childhood anxiety is common. Multiple treatment options are available, but existing guidelines provide inconsistent advice on which treatment to use. OBJECTIVES: To evaluate the comparative effectiveness and adverse events of cognitive behavioral therapy (CBT) and pharmacotherapy for childhood anxiety disorders. DATA SOURCES: We searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and SciVerse Scopus from database inception through February 1, 2017. STUDY SELECTION: Randomized and nonrandomized comparative studies that enrolled children and adolescents with confirmed diagnoses of panic disorder, social anxiety disorder, specific phobias, generalized anxiety disorder, or separation anxiety and who received CBT, pharmacotherapy, or the combination. DATA EXTRACTION AND SYNTHESIS: Independent reviewers selected studies and extracted data. Random-effects meta-analysis was used to pool data. MAIN OUTCOMES AND MEASURES: Primary anxiety symptoms (measured by child, parent, or clinician), remission, response, and adverse events. RESULTS: A total of 7719 patients were included from 115 studies. Of these, 4290 (55.6%) were female, and the mean (range) age was 9.2 (5.4-16.1) years. Compared with pill placebo, selective serotonin reuptake inhibitors (SSRIs) significantly reduced primary anxiety symptoms and increased remission (relative risk, 2.04; 95% CI, 1.37-3.04) and response (relative risk, 1.96; 95% CI, 1.60-2.40). Serotonin-norepinephrine reuptake inhibitors (SNRIs) significantly reduced clinician-reported primary anxiety symptoms. Benzodiazepines and tricyclics were not found to significantly reduce anxiety symptoms. When CBT was compared with wait-listing/no treatment, CBT significantly improved primary anxiety symptoms, remission, and response. Cognitive behavioral therapy reduced primary anxiety symptoms more than fluoxetine and improved remission more than sertraline. The combination of sertraline and CBT significantly reduced clinician-reported primary anxiety symptoms and response more than either treatment alone. Head-to-head comparisons were sparse, and network meta-analysis estimates were imprecise. Adverse events were common with medications but not with CBT and were not severe. Studies were too small or too short to assess suicidality with SSRIs or SNRIs. One trial showed a statistically nonsignificant increase in suicidal ideation with venlafaxine. Cognitive behavioral therapy was associated with fewer dropouts than pill placebo or medications. CONCLUSIONS AND RELEVANCE: Evidence supports the effectiveness of CBT and SSRIs for reducing childhood anxiety symptoms. Serotonin-norepinephrine reuptake inhibitors also appear to be effective based on less consistent evidence. Head-to-head comparisons between various medications and comparisons with CBT represent a need for research in the field.

AB - IMPORTANCE: Childhood anxiety is common. Multiple treatment options are available, but existing guidelines provide inconsistent advice on which treatment to use. OBJECTIVES: To evaluate the comparative effectiveness and adverse events of cognitive behavioral therapy (CBT) and pharmacotherapy for childhood anxiety disorders. DATA SOURCES: We searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and SciVerse Scopus from database inception through February 1, 2017. STUDY SELECTION: Randomized and nonrandomized comparative studies that enrolled children and adolescents with confirmed diagnoses of panic disorder, social anxiety disorder, specific phobias, generalized anxiety disorder, or separation anxiety and who received CBT, pharmacotherapy, or the combination. DATA EXTRACTION AND SYNTHESIS: Independent reviewers selected studies and extracted data. Random-effects meta-analysis was used to pool data. MAIN OUTCOMES AND MEASURES: Primary anxiety symptoms (measured by child, parent, or clinician), remission, response, and adverse events. RESULTS: A total of 7719 patients were included from 115 studies. Of these, 4290 (55.6%) were female, and the mean (range) age was 9.2 (5.4-16.1) years. Compared with pill placebo, selective serotonin reuptake inhibitors (SSRIs) significantly reduced primary anxiety symptoms and increased remission (relative risk, 2.04; 95% CI, 1.37-3.04) and response (relative risk, 1.96; 95% CI, 1.60-2.40). Serotonin-norepinephrine reuptake inhibitors (SNRIs) significantly reduced clinician-reported primary anxiety symptoms. Benzodiazepines and tricyclics were not found to significantly reduce anxiety symptoms. When CBT was compared with wait-listing/no treatment, CBT significantly improved primary anxiety symptoms, remission, and response. Cognitive behavioral therapy reduced primary anxiety symptoms more than fluoxetine and improved remission more than sertraline. The combination of sertraline and CBT significantly reduced clinician-reported primary anxiety symptoms and response more than either treatment alone. Head-to-head comparisons were sparse, and network meta-analysis estimates were imprecise. Adverse events were common with medications but not with CBT and were not severe. Studies were too small or too short to assess suicidality with SSRIs or SNRIs. One trial showed a statistically nonsignificant increase in suicidal ideation with venlafaxine. Cognitive behavioral therapy was associated with fewer dropouts than pill placebo or medications. CONCLUSIONS AND RELEVANCE: Evidence supports the effectiveness of CBT and SSRIs for reducing childhood anxiety symptoms. Serotonin-norepinephrine reuptake inhibitors also appear to be effective based on less consistent evidence. Head-to-head comparisons between various medications and comparisons with CBT represent a need for research in the field.

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