Major Depressive Disorder in Children and Adolescents: Clinical Trial Design and Antidepressant Efficacy

Major depressive disorder is a common, chronic, recurring, and disabling illness in children and adolescents.Epidemiologic data suggest that the mean age at onset for depression is becoming younger. Antidepressantsare widely used in pediatric patients despite a relatively small evidence base from randomized,controlled studies. Compared with the adult population, there are very few controlled studies of antidepressantsin children and adolescents, and the studies that have been conducted do not unambiguously demonstrateefficacy. These findings in general are contrary to clinicians’ experiences with antidepressants in thispopulation. The different factors associated with the outcome of antidepressant studies in children and adolescentsare reviewed. Developmental issues in pediatric patients, such as age of puberty and maturity ofneural circuitry, are considered in the context of failed clinical trials. Review of existing controlled trialsdemonstrates a wide variety in study methodology. Factors such as the study location, methods of patientrecruitment, small sample sizes, inclusion/exclusion criteria, study design, and choice of outcome measuresall influence the ability of a study to detect differences between an antidepressant and placebo. In the currentatmosphere of increased concern about antidepressant side effects, including suicidality, it is increasinglyimportant that clinicians who treat depressed children and adolescents make informed therapeutic decisionsbased on data from well-controlled clinical trials.