A literature review by Safer23 examined the efficacy of SSRIs in children and adolescents with depression or anxiety disorders using published RCT data. The review demonstrated that SSRIs when compared with placebo do not significantly reduce depressive symptoms in children; however, a modest degree of efficacy was found when using SSRIs with depressed adolescents.
In contrast, published data (such as presented earlier) provide evidence that children and adolescents with anxiety disorders demonstrate significant improvements when treated with SSRIs. The review by Safer23 indicated that SSRIs are probably more effective when treating children and adolescents with anxiety disorders rather than with depression.Black box warning considerations
Although children and adolescents who participated in RCTs reported minimal adverse effects with medication, there continues to be concern regarding the use of medication to treat childhood anxiety and depressive disorders. The FDA now requires a black box warning on SSRI medications that states "antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with major depressive disorder and other psychiatric disorders."24
In a meta-analysis of 24 controlled clinical trials of antidepressants with youths, Hammad25 demonstrated that the risk of adverse suicidal events was approximately 4% for youths receiving antidepressants versus approximately 2% for those receiving placebo.
Another meta-analysis of 21 studies of antidepressants in youths, including 14 treatment trials for major depression and 7for anxiety disorders, looked at the safety of SSRIs in children and adolescents.26 These studies included the original data provided by the drug manufacturers to the FDA in 2003.
The overall findings from this meta-analysis showed that the incidence ratio for serious suicidal events (eg, suicide attempt or suicidal ideation necessitating hospitalization) was 1.89, which represents a significant difference between drug and placebo for risk of suicidal events. Results were similar when the meta-analysis was repeated using only the 14 trials of youths with major depression. The incidence ratio was 1.95, which also showed a significant difference between drug and placebo on risk of suicidality. However, when only the 7 studies of youths with anxiety disorders were included, there was no significant difference between antidepressants and placebo with regard to suicidal events (incidence ratio = 1.31).26 Since fewer studies were included in the examination of the effects of antidepressants for treating anxiety, the latter result should be viewed as preliminary.
The black box warning on increased suicidality in children and adolescents who are being treated with SSRIs has led to substantial concern from parents and health care professionals. The use of antidepressant medications in persons aged 18 years or younger declined approximately 20% after the FDA released the first public health advisory warning in March 2004 about the increased risk of suicidality associated with antidepressants in children and adolescents.27 This suggests that parents may be less likely to seek antidepressant medication treatment in a clinical setting and some physicians may be overly cautious about prescribing this type of medication for children and adolescents, which results in some children not getting needed treatment.
Another concern is that the black box warning may impact parents' willingness to allow their children with anxiety to participate in research studies that include an SSRI component. Pretreatment attrition caused by medication concerns has been a substantial problem in previous studies and limits external validity of the research results. Young and colleagues28 reported a 67% pretreatment attrition rate in their study of social phobia in children and adolescents that included behavioral therapy, fluoxetine(Drug information on fluoxetine), and placebo. The most common reason given by parents who refused to allow their children to participate was fear of possible randomization to the medication group, which accounted for 45% of refusals.
In another study, parents answered a questionnaire about whether they would allow their children to participate in a hypothetical study that included an active medication group.28 A majority (64%) said they would not allow their children to participate, with the most common reasons being potential adverse effects and dependence on the medications. These data were collected between May 2001 and September 2004; therefore, resistance to medications was present before the black box warning. It is suspected that parental concern regarding antidepressants has increased since the inclusion of the black box warning.Conclusion
Current research on the treatment of anxiety disorders in children is important for treatment in clinical settings. It is imperative that clinicians use data to develop and implement effective treatment protocols for children and adolescents with anxiety disorders.
When clinicians are developing a treatment protocol, it is vital that they assess the severity of anxiety, degree of interference, and the level of family functioning. The most effective treatment strategy will likely include a multimodal approach that comprises both psychosocial and psychopharmacological interventions.
Although knowledge about the treatment of childhood anxiety disorders has significantly progressed during the past 10 years, there are areas that need further exploration. It is crucial that future studies attempt to delineate specific treatment mechanisms of CBT and identify specific predictors of positive treatment outcome in childhood anxiety. In addition, research that examines the combined efficacy of CBT and medication versus CBT or medication alone in the treatment of anxiety disorders in children is needed to develop guidelines for combining and sequencing these effective treatments.
Currently, the Child and Adolescent Anxiety Multimodal Treatment Study is being conducted to compare several treatment modalities29: medication, CBT, medication and CBT, and pill placebo. The results from this study will provide important information regarding treatment of childhood anxiety disorders.