Pharmacological treatment of depression in children and adolescents

Major depression is a common disorder during childhood and adolescence. Over the past decade, many new antidepressants have been marketed in the US. In adults, these newer agents have been shown to be as effective as the prototypic tricyclic antidepressants (TCAs). Further, when compared with the TCAs these medications are better tolerated and are safer in overdose. Although TCAs are effective in the treatment of depressed adults, controlled clinical trials have not demonstrated their efficacy in either children or adolescents. In addition, concerns about the safety of TCAs and the monoamine oxidase inhibitors has left disappointingly few pharmacological treatment options available for depressed children and adolescents. For this reason, clinicians have begun to prescribe the newer agents for this population, despite the fact that relatively little is known about their disposition, safety or effectiveness in the young. Investigators have begun to examine whether the use of newer antidepressant medications such as fluoxetine, sertraline, paroxetine, fluvoxamine, nefazodone, and venlafaxine is truly indicated for children and adolescents with major depression. Pharmacokinetic studies of sertraline, paroxetine and nefazodone have been performed in depressed youths. The results of these studies have provided data for rational administration strategies for these agents. They have also provided evidence that these agents may be well tolerated in children and adolescents. Further evidence that these agents are often well tolerated when prescribed to depressed youths has been obtained from both open-label and double-blind studies. Published studies have generally shown that open-label treatment with these newer agents often leads to symptom amelioration in paediatric patients with major depression. Since high rates of placebo response are often seen in depressed children and adolescents, results from these studies cannot be interpreted to suggest that these medications have true antidepressant efficacy in this population. At present, the results of only two such studies have been published. The results of one of these trials are difficult to interpret because of methodological considerations. The other study reported that treatment with fluoxetine was superior to placebo. This paper critically reviews what has been published about the pharmacological treatment of depressed paediatric patients and provides some guidance to the use of antidepressants in this patient population, paying particular attention to what is known about the newer antidepressants as well as considering directions for future research.