ARTICLES
Fluoxetine for Acute Treatment of Depression in Children and Adolescents: A Placebo-Controlled, Randomized Clinical Trial

https://doi.org/10.1097/00004583-200210000-00010Get rights and content

ABSTRACT

Background:

This report presents results from the acute treatment phase of a clinical trial designed to confirm efficacy of a fixed dose of 20 mg of fluoxetine in children and adolescents with major depressive disorder (MDD).

Method:

After a 3-week screening period, 122 children and 97 adolescents with MDD (DSM-IV) were randomly assigned to placebo or fluoxetine. After a 1-week placebo lead-in, fluoxetine-treated patients received fluoxetine 10 mg/day for 1 week, then fluoxetine 20 mg/day for 8 weeks.

Results:

Fluoxetine was associated with greater mean improvement in Children's Depression Rating Scale-Revised (CDRS-R) score than placebo after 1 week (p < .05) and throughout the study period. Significantly more fluoxetine-treated patients (41%) met the prospectively defined criteria for remission than did placebo-treated patients (20%) (p < .01). More fluoxetine- (65%) than placebo-treated (53%) patients met the prospectively defined response criterion of ≥30% decrease in CDRS-R score, but this difference was not significant (p = .093). Significantly more fluoxetine-than placebo-treated patients completed acute treatment (p = .001). There were no significant differences between treatment groups in discontinuations due to adverse events (p = .408).

Conclusions:

Fluoxetine 20 mg daily appears to be well tolerated and effective for acute treatment of MDD in child and adolescent outpatients. Fluoxetine is the only antidepressant that has demonstrated efficacy in two placebo-controlled, randomized clinical trials of pediatric depression.

Section snippets

Study Design

A multiphase study was designed to examine efficacy and tolerability of various dosing strategies for fluoxetine treatment of depressed children and adolescents. The initial phase, reported here, was designed to confirm a previous report that fluoxetine 20 mg was effective and well tolerated for acute treatment of pediatric MDD.

To obtain the most reliable assessment of patients’ condition, this study incorporated an extensive diagnostic evaluation period requiring three independent diagnostic

Baseline Patient Comparisons

After 2 weeks of evaluation, and a 1-week placebo lead-in period, 109 patients were randomly assigned to fluoxetine treatment and 110 to placebo treatment (Fig. 1). There were no statistically significant differences between treatment groups in patient demographics at baseline (Table 2). Randomization of patients resulted in treatment groups that were reasonably balanced for the current comorbid conditions attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, and

DISCUSSION

Fluoxetine was well tolerated and effective in a double-blind, placebo-controlled study evaluating 9 weeks of acute therapy with fluoxetine 20 mg daily in 219 child and adolescent outpatients with MDD. Fluoxetine 20 mg daily was more effective than placebo for the treatment of depression as demonstrated by significantly greater improvement in the CDRS-R score. During the first week of treatment, fluoxetine-treated patients received 10 mg of fluoxetine daily. Since fluoxetine was statistically

REFERENCES (34)

  • JW Rintelmann et al.

    The effects of extended evaluation on depressive symptoms in children and adolescents

    J Affect Disord

    (1996)
  • RE Roberts et al.

    Screening for adolescent depression: a comparison of depression scales

    J Am Acad Child Adolesc Psychiatry

    (1991)
  • JG Simeon et al.

    Adolescent depression: a placebo-controlled fluoxetine treatment study and follow-up

    Prog Neuropsychopharmacol Biol Psychiatry

    (1990)
  • American Academy of Child and Adolescent Psychiatry

    Practice parameters for the assessment and treatment of children and adolescents with depressive disorders

    J Am Acad Child Adolesc Psychiatry

    (1998)
  • AT Beck et al.

    Internal consistencies of the original and revised Beck Depression Inventory

    J Clin Psychol

    (1984)
  • C Boulos et al.

    An open naturalistic trial of fluoxetine in adolescents and young adults with treatment-resistant major depression

    J Child Adolesc Psychopharmacol

    (1992)
  • DA Brent

    Depression and suicide in children and adolescents

    Pediatr Rev

    (1993)
  • Cited by (495)

    • Antidepressants in children and adolescents with major depressive disorder and the influence of placebo response: A meta-analysis

      2022, Journal of Affective Disorders
      Citation Excerpt :

      Nine abstracts were excluded because they studied antidepressants as adjuncts to psychotherapy (Cornelius et al., 2010, 2009; Davey et al., 2019; Dinan, 2000; Goodyer et al., 2008; Iftene et al., 2015; Mandoki et al., 1997; Melvin et al., 2006; Riggs et al., 2007); three because they did not use the CDRS-R (Berard et al., 2006; Keller et al., 2001; Von Knorring et al., 2006); two because they did not focus on FDA or EMA-approved agents (Berk et al., 2020; Gabbay et al., 2018); one because it focused on subjects with alcohol or cannabis use disorder and depression (Findling et al., 2009); and one because it was not funded by industry (March, 2004). The remaining 15 manuscripts described eligible trials (Durgam et al., 2018) (Findling et al., 2020) (Atkinson et al., 2014) (Emslie et al., 2014) (Atkinson et al., 2018) (Weihs et al., 2018) (Emslie et al., 2007) (Emslie et al., 1997) (Emslie et al., 2002) (Wagner et al., 2003) (Emslie et al., 2006) (Wagner et al., 2004) (Emslie et al., 2009) (Wagner et al., 2006) (DelBello et al., 2014). Three additional unpublished studies, NCT02709746, NCT02431806, and NCT00812812 were identified with the use of www.clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT02709746; https://clinicaltrials.gov/ct2/show/NCT02431806; https://clinicaltrials.gov/ct2/show/NCT00812812).

    • Safety and efficacy of agomelatine in children and adolescents with major depressive disorder receiving psychosocial counselling: a double-blind, randomised, controlled, phase 3 trial in nine countries

      2022, The Lancet Psychiatry
      Citation Excerpt :

      Individual items are scored between 1 (no difficulties) and 5 or 7 (clinically severe difficulties). The CDRS-R was the primary efficacy endpoint in most published depression trials in adolescent patients, including the fluoxetine trials on which the European Medicines Agency and FDA approvals were based,18–20 and also in a 2009 study on escitalopram.21 A cutoff of 45 on the CDRS-R total score was chosen to ensure inclusion of patients with sufficiently severe major depressive disorder symptoms, and was previously used in a trial of escitalopram in adolescents.21

    View all citing articles on Scopus

    This study was funded by Eli Lilly and Company. Drs. Emslie and Wagner were paid consultants for Eli Lilly and Company for this study. Drs. Heiligenstein, Hoog, Brown, Jacobson, Mr. Ernest and Ms. Nilsson are employees of Eli Lilly and Company and may own stock in that company.

    The authors gratefully acknowledge the contributions of the Fluoxetine Treatment of Pediatric Depression Group: Dr. Ralph S. Albertini, Butler Hospital; Dr. Mark Bangs, Riley Children and Adolescent Psychiatry Clinic; Dr. Joan Busner, St. Louis University School of Medicine, Department of Psychiatry; Dr. Jeffrey Danzinger, ICSL Clinical Studies; Dr. Robert Findling, University Hospitals of Cleveland, Department of Psychiatry; Dr. Nora Galil, NeuroScience, Inc.; Dr. Thomas Gualtieri, North Carolina Neuropsychiatry; Dr. Stuart Kaplan, St. Louis University School of Medicine, Department of Psychiatry; Dr. Markus Kruesi, Institute for Juvenile Research, University of Illinois at Chicago; Dr. Samuel Kuperman, University of Iowa Hospitals and Clinics, Department of Psychiatry; Dr. Brian McConville, University of Cincinnati; Dr. James McCracken, UCLA, Neuropsychiatric University and Hospital; Dr. Daryl Nucum, Irvine Clinical Research Center; Dr. Julia Oldroyd, Irvine Clinical Research Center; Dr. Elizabeth Reeve, Regions Hospital, Child and Adolescent Psychiatry Clinic; Dr. Robert Reichler, PsychCare Northwest; Dr. David Rosenberg, University Health Center; Dr. John Sargent, The Menninger Clinic Center of Clinical Research, Topeka, KS; Dr. Phillipe Weintraub, University of Colorado Health Science Center.

    View full text