title: A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the efficacy and safety of duloxetine flexible dose in children (7-11 years) and adolescents (12-17 years) with major depressive disorder (MDD).
  
  
  METHODS
  Patients (n=337) in this 36 week study (10 week acute and 26 week extension treatment) received duloxetine (60-120 mg once daily [QD], n=117), fluoxetine (20-40 mg QD, n=117), or placebo (n=103). Measures included: Children's Depression Rating Scale-Revised (CDRS-R), treatment-emergent adverse events (TEAEs), and Columbia-Suicide Severity Rating Scale (C-SSRS).
  
  
  RESULTS
  Neither active drug (duloxetine or fluoxetine) separated significantly (p<0.05) from placebo on mean change from baseline to end-point (10 weeks) on the CDRS-R total score. There were no significant differences between the duloxetine or fluoxetine groups compared with placebo on serious AEs (SAEs), total TEAEs, or discontinuation for AE during acute treatment. There were no completed suicides or deaths, and no clinically significant electrocardiogram (ECG) abnormalities observed during the study. One fluoxetine and one duloxetine patient experienced alanine aminotransferase (ALT) three or more times the upper limit of normal, which resolved during the study. A total of 8 (7.1%) duloxetine patients, 7 (6.8%) placebo patients, and 9 (8.0%) fluoxetine patients had worsening of suicidal ideation from baseline during acute treatment. Of the patients with suicidal ideation at baseline, 15/19 (79%) duloxetine, 19/19 (100%) placebo, and 16/19 (84%) fluoxetine had improvement in suicidal ideation at end-point during acute treatment. One duloxetine and two fluoxetine patients had treatment-emergent suicidal behavior during the 36 week study.
  
  
  CONCLUSIONS
  Trial results were inconclusive, as neither the investigational drug (duloxetine) nor the active control (fluoxetine) separated from placebo on the CDRS-R at 10 weeks. No new duloxetine safety signals were identified relative to those seen in adults. Clinical Trial Registry Number: NCT00849901.
authors.affiliation: 1 Finger Lakes Clinical Research , Rochester, New York.
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Atkinson
authors.forename: Apurva
authors.initials: A
authors.lastname: Prakash
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Beth A
authors.initials: BA
authors.lastname: Pangallo
authors.forename: Mark E
authors.initials: ME
authors.lastname: Bangs
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Emslie
authors.forename: John S
authors.initials: JS
authors.lastname: March
mesh_terms: D000293:Adolescent; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000068736:Duloxetine Hydrochloride; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012720:Severity of Illness Index; D059020:Suicidal Ideation; D013405:Suicide; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D000068736:Duloxetine Hydrochloride; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes