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.