A Review of Pharmacotherapy of Major Depression in Children and Adolescents

OBJECTIVE: The review examined the historical progression and current status of pharmacotherapy of child and adolescent major affective disorder. METHODS: A MEDLINE search was used to identify double-blind, placebo-controlled studies of child and adolescent major depression. Only studies that used reliable diagnostic and recovery parameters were included. RESULTS: Few well-designed studies have compared placebo and tricyclic antidepressants in the treatment of major depressive disorder in children and adolescents. However, results consistently suggest that tricyclic antidepressants are not efficacious. Early results of double-blind placebo-controlled trials with fluoxetine and paroxetine have shown a significant drug effect. However, the results are inconsistent, which could reflect the ways that response to medication is defined, the ways that rating scales measure recovery, and uncertainties of dosing strategies with second-generation antidepressants. Hypothesized reasons for the unique response pattern in youths include the changing hormonal status of children, the differential maturation of the noradrenergic versus serotonergic neurotransmitter systems, and the possibility that a large proportion of depressed youths are in the early stages of bipolar disorder, which is not effectively treated by these medications. CONCLUSIONS: Tricyclic antidepressants are not superior to placebo for the treatment of child and adolescent major depressive disorder. Although two of three trials of second-generation antidepressants in this age group have had negative results, data suggest that these drugs may be more promising. It is too early in our investigation to know whether these agents will be effective in treating major depressive disorder in children and adolescents.