title: Escitalopram in the treatment of adolescent depression: a randomized, double-blind, placebo-controlled extension trial.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the extended efficacy, safety, and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder (MDD).
  
  
  METHODS
  Adolescents (12-17 years) who completed an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in study of escitalopram 10-20 mg versus placebo could enroll in a 16-24-week, multisite extension trial; patients maintained the same lead-in randomization (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo) during the extension. The primary efficacy was Children's Depression Rating Scale-Revised (CDRS-R) change from the lead-in study baseline to treatment week 24 (8-week lead-in study plus 16-week extension); the secondary efficacy was Clinical Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses used the last observation carried forward (LOCF) approach; sensitivity analyses used observed cases (OC) and mixed-effects model for repeated measures (MMRM). Safety was evaluated via adverse event (AE) reports and the clinician-rated Columbia-Suicide Severity Rating Scale (C-SSRS).
  
  
  RESULTS
  Following lead-in, 165 patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40 (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R total score improvement was significantly greater for escitalopram than for placebo (p=0.005, LOCF; p=0.014; MMRM). Response rates (CDRS-R ≥ 40% reduction from baseline [adjusted and unadjusted] and CGI-I ≤ 2) were significantly higher for escitalopram than for placebo (LOCF); remission rates (CDRS-R ≤ 28) were 50.6% for escitalopram and 35.7% for placebo (p=0.002). OC analyses were not significantly different between groups. The most frequent escitalopram AEs (≥ 5% and more frequent than placebo) were headache, nausea, insomnia, vomiting, influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were mild/moderate and not related to the study drug. AEs suggestive of self-harm occurred in 5.7% and 7.1% of placebo and escitalopram patients. Occurrence of suicidal behavior and/or suicidal ideation assessed by C-SSRS was 10.9% (14/128) for placebo and 14.5% (19/131) for escitalopram.
  
  
  CONCLUSIONS
  Extended use of escitalopram was generally safe and resulted in modest improvement in efficacy in adolescents with MDD.
authors.affiliation: 1 Johns Hopkins University and the Kennedy Krieger Institute , Baltimore, Maryland.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.forename: Adelaide
authors.initials: A
authors.lastname: Robb
authors.forename: Anjana
authors.initials: A
authors.lastname: Bose
mesh_terms: D000293:Adolescent; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D015283:Citalopram / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D059020:Suicidal Ideation; D013405:Suicide
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram
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