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Original Investigation
November 2017

Comparative Effectiveness and Safety of Cognitive Behavioral Therapy and Pharmacotherapy for Childhood Anxiety Disorders: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Mayo Clinic Evidence-Based Practice Center, Rochester, Minnesota
  • 2Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota
  • 3Division of Health Care Policy and Research, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
  • 4Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota
  • 5Mayo Clinic Libraries, Rochester, Minnesota
JAMA Pediatr. 2017;171(11):1049-1056. doi:10.1001/jamapediatrics.2017.3036
Key Points

Question  What is the comparative effectiveness of cognitive behavioral therapy and pharmacotherapy for childhood anxiety disorders?

Findings  In this systematic review and meta-analysis, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and cognitive behavioral therapy were all effective in reducing anxiety symptoms. Selective serotonin reuptake inhibitor and serotonin-norepinephrine reuptake inhibitor use were associated with various adverse events that were mostly not serious.

Meaning  The choice of treatments should be based on values, preferences, availability of services, and adverse effect profile.


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. 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.