title: Plasma fluoxetine concentrations and clinical improvement in an adolescent sample diagnosed with major depressive disorder, obsessive-compulsive disorder, or generalized anxiety disorder.
abstract: Fluoxetine (FLX) has been one of the most widely studied selective serotonin reuptake inhibitors in adolescents. Despite its efficacy, however, 30% to 40% of patients do not respond to treatment.
  
  
  OBJECTIVE
  The aim of this study was to evaluate whether clinical improvement or adverse events are related to the corrected dose of FLX at 8 and 12 weeks after starting treatment in a sample of adolescents diagnosed with major depressive disorder, obsessive-compulsive disorder, or generalized anxiety disorder.
  
  
  METHODS
  Seventy-four subjects aged between 10 and 17 years participated in the study. Clinical improvement was measured with the Clinical Global Impression-Improvement Scale, whereas the UKU (Udvalg for Klinske Undersogelser) scale was administered to assess adverse effects of treatment.
  
  
  RESULTS
  Fluoxetine per kilograms of body weight was related to serum concentration of FLX, NORFLX (norfluoxetine), FLX + NORFLX, and FLX/NORFLX. No relationship was found between dose-corrected FLX levels and therapeutic or adverse effects. No differences in serum concentrations were found between responders and nonresponders to treatment. Sex differences were observed in relation to dose and FLX serum concentration. The analysis by diagnosis revealed differences in FLX dose between obsessive-compulsive disorder patients and both generalized anxiety disorder and major depressive disorder patients.
  
  
  CONCLUSIONS
  Fluoxetine response seems to be influenced by factors such as sex, diagnosis, or certain genes that might be involved in the drug's pharmacokinetics and pharmacodynamics. Clinical and pharmacogenetic studies are needed to elucidate further the differences between treatment responders and nonresponders.
authors.affiliation: From the *Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de Barcelona; †Department of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona; ‡Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); §Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM); ∥Pharmacology and Toxicology Department, CDB, Hospital Clínic de Barcelona; ¶Clinical Pharmacology Department, Hospital Clínic de Barcelona; and #Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Blázquez
authors.forename: Sergi
authors.initials: S
authors.lastname: Mas
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Plana
authors.forename: Patricia
authors.initials: P
authors.lastname: Gassó
authors.forename: Iria
authors.initials: I
authors.lastname: Méndez
authors.forename: Mercè
authors.initials: M
authors.lastname: Torra
authors.forename: Joan Albert
authors.initials: JA
authors.lastname: Arnaiz
authors.forename: Amàlia
authors.initials: A
authors.lastname: Lafuente
authors.forename: Luisa
authors.initials: L
authors.lastname: Lázaro
mesh_terms: D000293:Adolescent; D001008:Anxiety Disorders / Q000188:drug therapy*; D002648:Child; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy*; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors