A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF FLUOXETINE INCHILDREN AND ADOLESCENTS WITH DEPRESSION

Background: Depression is a major cause of morbidity and mortality in children and adolescents. To date, randomized, controlled, double-blin d trials of antidepressants (largely tricyclic agents) have yet to rev eal that any antidepressant is more effective than placebo. This artic le is of a randomized, double-blind, placebo-controlled trial of fluox etine in children and adolescents with depression. Method: Ninety-six child and adolescent outpatients (aged 7-17 years) with nonpsychotic m ajor depressive disorder were randomized (stratified for age and sex) to 20 mg of fluoxetine or placebo and seen weekly for 8 consecutive we eks. Randomization was preceded by 3 evaluation visits that included s tructured 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 s everity depressive symptoms. Results: Of the 96 patients; 48 were rand omized to fluoxetine treatment and 48 to placebo. Using the intent to treat sample, 27 (56%) of those receiving fluoxetine and 16 (33%) rece iving placebo were rated ''much'' or ''very much'' improved on the Cli nical Global Impressions scale at study exit (chi(2)=5.1, df=1, P=.02) . Significant differences were also noted in weekly ratings of the Chi ldren's Depression Rating Scale-Revised after 5 weeks of treatment (us ing 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 i n only 31% of the fluoxetine-treated patients and 23% of the placebo p atients. Conclusion: Fluoxetine was superior to placebo in the acute p hase treatment of major depressive disorder in child and adolescent ou tpatients with severe, persistent depression: Complete remission of sy mptoms was rare.