November 1997

A Double-blind, Randomized, Placebo-Controlled Trial of Fluoxetine in Children and Adolescents With Depression

Author Affiliations

From the Departments of Psychiatry (Drs Emslie, Rush, and Kowatch and Ms Rintelmann), Neurology (Dr Weinberg), and Academic Computing (Dr Carmody), University of Texas Southwestern Medical Center at Dallas, and Terrell State Hospital (Dr Hughes), Terrell, Tex.

Arch Gen Psychiatry. 1997;54(11):1031-1037. doi:10.1001/archpsyc.1997.01830230069010

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 (ϰ2=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 ≤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.