Cognitive-behavioral therapy (CBT), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs) are all effective for childhood anxiety, a new systematic review and meta-analysis suggests.
In light of these findings, study investigator Zhen Wang, PhD, of the Mayo Clinic, Rochester, Minnesota, told Medscape Medical News the choice of treatment for pediatric anxiety should be based on “values, preferences, availability of services, and adverse effect profile.”
The study was published online August 31 in JAMA Pediatrics.
Anxiety Rising
Childhood anxiety disorders are the most common mental health diagnoses, with prevalence rates of 15% to 20%. They are associated with significant impairment, the researchers note.
“Rates of anxiety and depression seem to be increasing in youth, although we don’t know this with certainty. But it has been hypothesized to be related to the challenges of modern society, especially fewer opportunities to connect with others,” said Dr Wang.
The investigators note that although multiple treatment options are available, existing guidelines provide inconsistent advice on which to use.
The meta-analysis and systematic review included 115 randomized as well as nonrandomized comparative trials. The trials included a total of 7719 patients with a diagnosis of an anxiety disorder who received CBT, pharmacotherapy, or a combination of the two. The mean age of the patients was 9.2 years, and 4290 (55.6%) were female.
Anxiety disorders included separation anxiety disorder, generalized anxiety disorder, and social anxiety disorder. Other sources of childhood anxiety included panic disorder or a specific phobia.
Outcomes of interest were primary anxiety symptoms, treatment response, and clinical remission.
The investigators found that compared with placebo, SSRIs were significantly more effective at reducing primary anxiety symptoms, with increased remission (relative risk [RR], 2.04; 95% confidence interval [CI], 1.37 – 3.04) and response (RR, 1.96; 95% CI, 1.60 – 2.40).
They also found that SNRIs significantly reduced clinician-reported primary anxiety symptoms. In contrast, benzodiazepines and tricyclics had no significant effect on anxiety systems.
Compared to wait-list/no treatment, CBT significantly improved primary anxiety symptoms, remission, and response. Combination treatment with sertraline (Zoloft, Pfizer) and CBT significantly reduced clinician-reported primary anxiety symptoms and response more than either treatment alone.
In addition, the investigators found that CBT reduced primary anxiety symptoms more than fluoxetine did and improved remission more than sertraline did.
SSRIs and SNRIs were often associated with adverse events, but these events were generally not serious and typically did not lead to discontinuance of treatment. However, the investigators note that the studies were either too small or too short to allow assessment of suicidality that may have been associated with these medications.
Few adverse events were reported for CBT, but Dr Wang noted that most CBT studies did not evaluate the study participants for the occurrence of adverse events.
“Head-to-head comparisons between various medications and comparing with CBT represent a need for research in the field,” the investigators conclude.
Full Remission Remains Elusive
In an accompanying editorial, Joan Rosenbaum Asarnow, PhD, David Geffen School of Medicine, University of California, Los Angeles, and colleagues also note the high prevalence of anxiety in youth and the fact that these disorders can become more severe in adulthood.
“From a clinical perspective, the key issues are how many children will recover, how much recovery is expected, and how rapidly will recovery occur,” the editorialists write.
The most rigorous of the randomized trials reviewed by Dr Wang and colleagues was the Child/Adolescent Anxiety Multimodal Study, which included patients aged 7 to 17 years who had been diagnosed with separation anxiety, generalized anxiety, or social phobia.
Among the cohort who received the combination of a SSRI and CBT, more than 80% showed “much or very much” clinical improvement at the end of 12 weeks of treatment, compared with 55% for those receiving an SSRI alone and 60% for those receiving CBT alone.
Patients treated with the SSRI plus CBT, as well as those treated with an SSRI alone, also improved more quickly, with patients showing signs of symptom alleviation relative to placebo by 4 weeks.
“Therefore, current evidence indicates that treatment with demonstrated efficacy in the reviewed trials can yield substantial improvements in anxiety symptoms within a relatively brief period,” the editorialists write.
On the other hand, they also note that it is “equally and arguably more important” to take into account the effect treatment has on school attendance and overall social performance.
Dr Asarnow and colleagues point out that relatively few of the studies that were included in the meta-analysis provide any indication of the durability of the effects of treatment on anxiety symptoms.
“This important limitation is underscored by the Child/Adolescent Anxiety Multimodal Study findings that approximately half of youth receiving gold-standard CBT, SSRI, or CBT plus SSRI treatments experienced diagnostic recurrence within 6 years of initial treatment,” they write.
“[T]his means that full remission is not expected for many children, even with our best treatments,” they conclude.
The study was funded by the Agency for Healthcare Research and Quality. The authors and editorialists have disclosed no relevant financial relationships.
JAMA Pediatr. Published online August 31, 2017. Abstract, Editorial
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