A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression

Background: Depression is a major cause of morbidity and mortality in children and adolescents. To date, randomized, controlled, double-blind trials of antidepressants (largely tricyclic agents) have yet to reveal that any antidepressant is more effective than placebo. This article is of a randomized, double-blind, placebo-controlled trial of fluoxetine in children and adolescents with depression. Method: Ninety-six child and adolescent outpatients (aged 7-17 years) with nonpsychotic major depressive disorder were randomized (stratified for age and sex) to 20 mg of fluoxetine or placebo and seen weekly for 8 consecutive weeks. Randomization was preceded by 3 evaluation visits that included structured diagnostic interviews during 2 weeks, followed 1 week later by a 1-week, single-blind placebo run-in. Primary outcome measurements were the global improvement of the Clinical Global Impressions scale and the Children's Depression Rating Scale-Revised, a measure of the severity depressive symptoms. Results: Of the 96 patients; 48 were randomized to fluoxetine treatment and 48 to placebo. Using the intent to treat sample, 27 (56%) of those receiving fluoxetine and 16 (33%) receiving placebo were rated ''much'' or ''very much'' improved on the Clinical Global Impressions scale at study exit (chi(2)=5.1, df=1, P=.02). Significant differences were also noted in weekly ratings of the Children's Depression Rating Scale-Revised after 5 weeks of treatment (using last observation carried forward). Equivalent response rates were found for patients aged 12 years and younger (n=48) and those aged 13 years and older (n=48). However, complete symptom remission (Children's Depression Rating Scale-Revised less than or equal to 28) occurred in only 31% of the fluoxetine-treated patients and 23% of the placebo patients. Conclusion: Fluoxetine was superior to placebo in the acute phase treatment of major depressive disorder in child and adolescent outpatients with severe, persistent depression: Complete remission of symptoms was rare.