title: An open-label safety and pharmacokinetics study of duloxetine in pediatric patients with major depression.
abstract: OBJECTIVE
  This preliminary, 32-week study assessed the safety, tolerability, and pharmacokinetics of duloxetine in pediatric patients (aged 7-17 years) with major depressive disorder.
  
  
  METHODS
  Patients received flexible duloxetine doses of 20-120 mg once daily, with dose changes made based on clinical improvement and tolerability. Pharmacokinetic samples were collected across all duloxetine doses, and data were analyzed using population modeling. Primary outcome measures included treatment-emergent adverse events (TEAEs), vital signs, and Columbia-Suicide Severity Rating Scale (C-SSRS).
  
  
  RESULTS
  Of the 72 enrolled patients, 48 (66.7%) completed acute treatment (18 weeks) and 42 (58.3%) completed extended treatment. Most patients (55/72; 76%) required doses ≥ 60 mg once daily to optimize efficacy based on investigator judgment and Clinical Global Impressions-Severity score. Body weight and age did not significantly affect duloxetine pharmacokinetic parameters. Typical duloxetine clearance in pediatric patients was ≈ 42%-60% higher than that in adults. Four patients (5.6%) discontinued due to TEAEs. Many (36/72, 50%) patients experienced potentially clinically significant (PCS) elevations in blood pressure, with most cases (21/36, 58%) being transient. As assessed via C-SSRS, one nonfatal suicidal attempt occurred, two patients (2.8%) experienced worsening of suicidal ideation, and among the 19 patients reporting suicidal ideation at baseline, 17 (90%) reported improvement in suicidal ideation.
  
  
  CONCLUSIONS
  Results suggested that pediatric patients generally tolerated duloxetine doses of 30 to 120 mg once daily, although transient PCS elevations in blood pressure were observed in many patients. Pharmacokinetic results suggested that adjustment of total daily dose based on body weight or age is not warranted for pediatric patients and different total daily doses may not be warranted for pediatric patients relative to adults.
authors.affiliation: Lilly Corporate Center, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. prakash@lilly.com
authors.forename: Apurva
authors.initials: A
authors.lastname: Prakash
authors.forename: Evelyn
authors.initials: E
authors.lastname: Lobo
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kratochvil
authors.forename: Roy N
authors.initials: RN
authors.lastname: Tamura
authors.forename: Beth A
authors.initials: BA
authors.lastname: Pangallo
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Bullok
authors.forename: Tonya
authors.initials: T
authors.lastname: Quinlan
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 / Q000493:pharmacokinetics; D001794:Blood Pressure / Q000187:drug effects; D002648:Child; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D059020:Suicidal Ideation; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride