Efficacy and Safety of Selective Serotonin Reuptake İnhibitors in Childhood and Adolescent Depression: a Meta-Analysis

Objective:

There is no defi nite conclusion on which the best selective serotonin reuptake inhibitors (SSRI) is in the treatment of childhood and adolescents depression in terms of safety and effi cacy. The aims of this meta-analysis are to evaluate effi cacy and safety including serious adverse events, adverse events leading to discontinuation, mania, hypomania, suicide proneness and suicide attempt of (SSRIs) in children and adolescents with depressive disorder.

Method:

Using key words that include “depression”, “children”, “adolescent”, “treatment”, and “related drug name”, the PubMed was screened. In addition, the reference lists of retrieved articles and reviews were searched up to March 2011.

Results:

Thirteen randomized controlled studies of SSRIs were included, covering a total of 2608 children and adolescents. Number needed to treat for SSRIs was between 4.7 (for fl uoxetine) and 27.8 (for citalopram). The ORs of SSRIs were between 2.4 (95% CI 1.7-3.4 for fl uoxetine) and 1.3 (95% CI 0.6-2.5 for citalopram). Although fl uoksetin has the highest OR, the response rate of fl uoksetin was 63.2% whereas 68.0% for sertraline, and 63.6% for escitalopram. The response rate of plasebo was found to be 47.1%. The pooled ORs of SSRIs for suicide proneness and suicide attempt were 2.1 (95% CI 1.2 – 3.7) and 1.4 (95% CI 0.7 – 2.8), respectively. Completed suicide as a result of treatment with SSRIs was not seen. The rates of hypomania was similar to the rates of mania (0.2% vs. 0.1%; OR: 1.2; 95% CI 0.4-3.7). The pooled ORs of serious adverse events in using SSRI and adverse events leading to discontinuation were 1.7 (95% CI 1.2 – 2.4) and 1.6 (95% CI 1.1 – 2.3), respectively.

Conclusions:

The meta-analysis suggested that SSRI antidepressants have limited effi cacy on juvenile depression. The SSRI antidepressants in childhood and adolescent depression treatment may differ in therapeutic effi cacy. Although fl uoxetine seems to be more effective compared to other antidepressants (e.g. sertraline and escitalopram), diverse plasebo response rates among studies may contribute to results. The results of present meta-analysis suggested that the SSRIs may increase the rate of suicide proneness and attempt in children and adolescents. However, the methodologies of studies that included in meta-analysis were not proper for investigation of suicide proneness and attempt. Taking account potential confounding factors, methodologically suitable studies to evaluate effi cacy and safety of SSRIs in children and adolescents with depression are warranted.