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Effective Health Care Program

Anxiety in Children

Systematic Review

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Purpose of Review

To evaluate the comparative effectiveness and harms of psychotherapy and medications for childhood anxiety disorders (panic disorder, social anxiety disorder, specific phobias, generalized anxiety disorder, and separation anxiety).

Key Messages

  • Cognitive behavioral therapy reduces anxiety symptoms based on child, parent, and clinician reports, improves functioning, and leads to clinical response.
  • Medications (selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors) are also effective in reducing anxiety symptoms but not based on all three reporters (child, parent, and clinician) and are more likely to cause short-term adverse events. Long-term adverse events require further study.
  • Cognitive behavioral therapy reduced primary anxiety symptoms and improved function more than fluoxetine and increased remission more than sertraline.
  • The combination of medications and cognitive behavioral therapy is more effective than either treatment alone, but the benefits and risks of each need to be considered.
  • Future research should address treatment of children who have other psychiatric conditions in addition to anxiety, evaluate the effectiveness of the components of cognitive behavioral therapy, compare drugs head to head, and study the long-term adverse effects of medications.

Structured Abstract

Objectives

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.

Results

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).

Conclusions

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.

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. www.effectivehealthcare.ahrq.gov/reports/final.cfm. DOI: https://doi.org/10.23970/AHRQEPCCER192.

Journal Publication

Wang Z, Whiteside SPH, Sim L, et al. Comparative effectiveness and safety of cognitive behavioral therapy and pharmacotherapy for childhood anxiety disorders: a systematic review and meta-analysis. JAMA Pediatr. 2017 Aug 31. Epub ahead of print. DOI: 10.1001/jamapediatrics.2017.3036.