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Anxiety in Children

Comparative Effectiveness Reviews, No. 192

Investigators: , PhD, , PhD, LP, , PhD, LP, , MBBS, , BA, , MD, MSc, , MD, , MD, , MD, , BSPH, , PhD, , MD, , MD, , MS, , MD, , MD, , PhD, , MLS, and , MD, MPH.

Author Information
Rockville (MD): Agency for Healthcare Research and Quality (US); .
Report No.: 17-EHC023-EF

Structured Abstract


To evaluate the comparative effectiveness and safety of treatments for childhood anxiety disorders, including panic disorder, social anxiety disorder, specific phobias, generalized anxiety disorder, and separation anxiety.

Data sources:

We searched MEDLINE®, Embase®, PsycINFO®, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and SciVerse Scopus through February 1, 2017, and reviewed bibliographies and the gray literature.

Review methods:

We included randomized and non-randomized comparative studies that compared psychotherapy, pharmacotherapy, or a combination in children ages 3 to 18 years with panic disorder, social anxiety disorder, specific phobias, generalized anxiety disorder, or separation anxiety. Pairs of independent reviewers selected studies using pre-specified inclusion and exclusion criteria.


We included 206 studies. Compared with pill placebo, selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors improved primary anxiety symptoms (moderate to high strength of evidence [SOE]). Tricyclic antidepressants marginally improved clinical response (low SOE). Benzodiazepines did not show significant improvement in primary anxiety symptoms (low SOE). Data on head-to-head comparisons across drugs were sparse (only 2 RCTs; low SOE). Compared with waitlisting or no treatment, cognitive behavioral therapy (CBT) improved primary anxiety symptoms (clinician, child, and parent report), function, remission, and clinical response (low to moderate SOE). Compared with other therapies (attention control or treatment as usual), CBT reduced primary anxiety symptoms (child report; moderate SOE). Compared with CBT alone, the combination of imipramine and CBT reduced primary anxiety symptoms (child report) and function (moderate SOE). The combination of sertraline and CBT reduced primary anxiety symptoms (clinician report), improved function, and increased clinical response compared with CBT alone or sertraline alone (moderate SOE). CBT reduced primary anxiety symptoms and improved function more than fluoxetine, and was more likely to increase remission than sertraline. Medications increased short-term adverse events that were mostly not serious (low or moderate SOE). Studies were too small or too short to assess suicidality with SSRI or SNRI. One trial showed a statistically nonsignificant increase in suicidal ideation with venlafaxine (low SOE).


CBT is effective in reducing anxiety symptoms and improving function. Medications, primarily those targeting serotonin, are also effective and were associated with various short-term adverse events, which were mostly not serious, but studies were too small or too short to assess suicidality with SSRI or SNRI. The combination of medications and CBT is likely more effective than either treatment alone. Comparative effectiveness evidence between various medications and comparing CBT versus medications, or the combination, is limited and represents a need for research in this field. Future research is needed to evaluate components of CBT, effect modifiers of treatment, and long-term safety of drugs, and needs to be more inclusive of underserved populations and minorities.

Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services1, Contract No. 290-2015-00013-I. Prepared by: Mayo Clinic Evidence-based Practice Center, Rochester, MN

Suggested citation:

Wang Z, Whiteside S, Sim L, Farah W, Morrow A, Alsawas M, Barrionuevo Moreno P, Tello M, Asi N, Beuschel B, Daraz L, Almasri J, Zaiem F, Gunjal S, Larrea Mantilla L, Ponce Ponte O, LeBlanc A, Prokop LJ, Murad MH. Anxiety in Children. Comparative Effectiveness Review No. 192. (Prepared by the Mayo Clinic Evidence-based Practice Center under Contract No. 290-2015-00013-I.) AHRQ Publication No. 17-EHC023-EF. Rockville, MD: Agency for Healthcare Research and Quality; August 2017. DOI:

This report is based on research conducted by the Mayo Clinic Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2015-00013-I). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.

The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.

AHRQ or U.S. Department of Health and Human Services endorsement of any derivative products that may be developed from this report, such as clinical practice guidelines, other quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied.

This report may periodically be assessed for the currency of conclusions. If an assessment is done, the resulting surveillance report describing the methodology and findings will be found on the Effective Health Care Program Web site at Search on the title of the report.


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Bookshelf ID: NBK476277PMID: 29360312


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