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4% to 8% of adolescents.1 MDD is associated with in school performance and social relationships, comorbid substance abuse, and an increased risk of suicide attempts. Pediatric MDD is a recurrent illness that usually continues into adult life. Therefore, it is important to have efficacious short and long-term treatments for both the acute management and the prevention of recurrences of this potentially life-long disorder. Selective Serotonin Reuptake Inhibitors (SSRIs) are one of the current treatments available for pediatric MDD. Recently, questions have been raised regarding their efficacy and safety in for the treatment of children and adolescents. Fluoxetine is the only SSRI approved thus far by the U.S Federal Drug Administration (FDA) for the treatment of pediatric MDD, based on consistent positive results in more than one study. In three studies of fluoxetine, two of sertraline (combined into one), and one each of citalopram and paroxetine, the proportion showing clinically significant improvement was significantly greater in medication (50-60%) than in placebo (30-50%), with the number of subjects needed to treat to observe one improvement (NNT) ranging from 4-10. A smaller proportion (30-40%) of subjects in these studies achieved full symptomatic remission,2-3 indicating that the optimal treatment for pediatric depression may involve a higher dose, a longer duration of treatment, or augmentation with other pharmacological or psychosocial treatments.4 Four unpublished, industry-sponsored studies with SSRIs (citalopram, escitalopram, and two with paroxetine) did not find differences between active medication and placebo. In these studies, subjects responded to both SSRIs and placebo, suggesting that these studies may have included subjects with mild depression, or even other methodological bias. For example, the greater the numbers of s i tes, the more challenging are the issues of quality control, and indeed, the drug-placebo difference is inversely proportional to the number of sites. Also, studies that included a placebo washout phase, a more stringent definition of MDD, and those conducted by academic centers showed larger di f ferences between antidepressants and placebo.4 A few unpublished, industry-sponsored randomized controlled trials (RCTs) have evaluated the effects of other classes of antidepressants for the treatment of depressed youth. Nefazodone was significantly better than placebo for youth with MDD, but the concern about hepatotoxicity have limited its use. Two RCTs with venlafaxine and two with mirtazepine were also negative. However, a reanalysis of the venlafaxine trials showed significant effects over placebo for adolescents, but not for children. No RCTs have been conducted in pediatric MDD with bupropion, although open trials are promising. Despite recent concern about SSRIs in pediatric populations, SSRIs have been well tolerated by both children and adolescents with few short-term side effects (e.g., gastrointestinal, headaches), although the long-term side effects of SSRIs have not been systematically evaluated. Approximately 3-8% of children and adolescents taking SSRIs for the treatment of depression or anxiety disorders develop increased impulsivity, Editorial

Should we use antidepressants for the treatment of major depressive disorder in children and adolescents?