title: Serum levels of citalopram and its main metabolites in adolescent patients treated in a naturalistic clinical setting.
abstract: The prescribing of selective serotonin reuptake inhibitors for adolescents is extensive despite the fact that there are few pharmacokinetic (PK), efficacy, safety, or tolerability studies on this group. This study reports the PK findings from two trials in adolescents treated with citalopram (CIT) in naturalistic clinical settings: one retrospective and one prospective. The aim of our study was to describe serum concentrations of CIT, desmethylcitalopram (DCIT), and didesmethylcitalopram (DDCIT) (trough values in steady state) in adolescents in relation to daily dose and clinical information obtained from therapeutic drug monitoring request forms. Altogether, 44 patients younger than 21 years were scrutinized using this combined open-label approach. The main findings were that (1) there was a pronounced interindividual variability of serum CIT, DCIT, and DDCIT concentrations in all doses prescribed, in agreement with previous studies on adults; on correcting for dose, the coefficient of variance was about 50% for CIT, DCIT, and DDCIT; (2) the transformation of CIT to DCIT and of DCIT to DDCIT was similar within the dose range 20 to 60 mg/day; (3) there was a difference between the sexes on comparing the dose-corrected concentrations of CIT and DCIT, with girls presenting significantly higher values than boys; and (4) there was a strong dose-serum concentration relationship in three identified subgroups of adolescents: (a) nonsmokers (CIT, r(2) = 0.71; DCIT, r(2) = 0.81), (b) girls not taking oral contraceptives (CIT, r(2) = 0.75; DCIT, r(2) = 0.71,), and (c) girls in the last 14 days of the menstrual cycle (CIT, r(2) = 0.68; DCIT, r(2) = 0.64). In summary, the present study tentatively supports influences of sex, oral contraceptives, and smoking habits on the disposition of CIT in younger patients. Hence, future studies on CIT should assess these parameters.
authors.affiliation: Division of Psychiatry, Department of Neuroscience and Locomotion, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Margareta
authors.initials: M
authors.lastname: Reis
authors.forename: Gunilla
authors.initials: G
authors.lastname: Olsson
authors.forename: Björn
authors.initials: B
authors.lastname: Carlsson
authors.forename: Jöns
authors.initials: J
authors.lastname: Lundmark
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Dahl
authors.forename: Jan
authors.initials: J
authors.lastname: Wålinder
authors.forename: Johan
authors.initials: J
authors.lastname: Ahlner
authors.forename: Finn
authors.initials: F
authors.lastname: Bengtsson
mesh_terms: D000293:Adolescent; D015283:Citalopram / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use; D016001:Confidence Intervals; D003276:Contraceptives, Oral / Q000097:blood; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012189:Retrospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood* / Q000627:therapeutic use; D012737:Sex Factors; D012907:Smoking / Q000097:blood
chemical_list: D015283:Citalopram; D003276:Contraceptives, Oral; D017367:Selective Serotonin Reuptake Inhibitors; C046304:desmethylcitalopram; C064735:didesmethylcitalopram