ORIGINAL CONTRIBUTION

Plasma Fluoxetine Concentrations and Clinical Improvement in an Adolescent Sample Diagnosed With Major Depressive Disorder, Obsessive-Compulsive Disorder, or Generalized Anxiety Disorder Ana Bla´zquez, MD,* Sergi Mas, PhD,Þþ§ Maria Teresa Plana, MD,* Patricia Gasso´, PhD,Þþ§ Iria Me´ndez, MD,* Merce` Torra, PhD,|| Joan Albert Arnaiz, MD, PhD,Þþ¶ Ama`lia Lafuente, MD, PhD,Þþ§ and Luisa La´zaro, MD, PhD*þ§L

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. Aims: 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 ImpressionYImprovement 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. Key Words: fluoxetine, plasmatic concentrations, major depressive disorder, obsessive-compulsive disorder, or generalized anxiety disorder (J Clin Psychopharmacol 2014;34: 318Y326)

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 Biome`diques August Pi i Sunyer (IDIBAPS); §Centro de Investigacio´n Biome´dica en Red de Salud Mental (CIBERSAM); ||Pharmacology and Toxicology Department, CDB, Hospital Clı´nic de Barcelona; ¶Clinical Pharmacology Department, Hospital Clı´nic de Barcelona; and LDepartment of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain. Received June 13, 2013; accepted after revision December 4, 2013. Reprints: Ana Bla´zquez, MD, Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de Barcelona, Villarroel 170, Escalera 11 3a planta, 08036 Barcelona, Spain (e

Plasma fluoxetine concentrations and clinical improvement in an adolescent sample diagnosed with major depressive disorder, obsessive-compulsive disorder, or generalized anxiety disorder.

Fluoxetine (FLX) has been one of the most widely studied selective serotonin reuptake inhibitors in adolescents. Despite its efficacy, however, 30% to...
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