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

Abstract

Major depressive disorder (MDD) affects 2% of children and 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 lifelong 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dose, a longer duration of treatment, or augmentation with other pharmacological or psychosocial treatments. 4 Four unpublished, industry-sponsored studies with SSRIs (citalopram, escitalopram, and two with paroxetine) did not find differences between active medication and placebo.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 sites, 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of MDD, and those conducted by academic centers showed larger differences between antidepressants and placebo. 4 A few unpublished, industry-sponsored randomized controlled trials (RCTs) have evaluated the effects of other classes of antidepressants for the treatment of depressed youth.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, headac...

Symptom Persistence in Seriously Emotionally Disordered Children: Findings of a Two-Year Follow-up after Residential Treatment

“…A convergence of results suggests however, that for internalizing disorders such as anxiety (Albano et al 2003) and depression (Hammen and Rudolph 2003), symptoms are relatively stable over time for a substantial number of youth. For example, in a group of prepubertal children and post-pubertal youth, Birmaher and Brent (2005) reported that adolescents assessed for psychopathology every two years over a five-year period had similar internalizing symptomatology, severity of index episodes, and rate of recurrence (40%). Other researchers report a 50% persistence rate for major depressive disorder (Goodyer et al 1997).…”

Antidepressants and suicide in adolescents

“…Tem sido defendido que um dos mecanismos que poderia explicar este aumento de risco seria o da activação comportamental, o aumento da impulsividade, agitação, irritabilidade, acatísia, ansiedade e insónia que aproximadamente 3 a 8% das crianças e adolescentes que tomam SSRIs desenvolvem, sintomas que devem ser diferenciados da mania ou da hipomania 62 .…”

“…Outras explicações para o comportamento suicidário com os antidepressivos passariam pela não adesão ao tratamento, resultando em ausência de resposta, pelos sintomas de descontinuação e pelas variações de polimorfismos genéticos, com aumento da susceptibilidade aos efeitos adversos 62 .…”

“…Num ensaio clínico com a paroxetina surgiram resultados positivos, mas sem diferença estatisticamente significativa. Foram conduzidos outros dois ensaios clínicos, que não encontraram diferença em relação ao placebo 62 .…”