title: Antidepressant exposure as a predictor of clinical outcomes in the Treatment of Resistant Depression in Adolescents (TORDIA) study.
abstract: This paper examines the relationship between plasma concentration of antidepressant and both clinical response and adverse effects in treatment-resistant depressed adolescents. Adolescents (n = 334) with major depression who had not responded to a selective serotonin reuptake inhibitor (SSRI) were randomized to 1 of 4 treatments: switch to another SSRI (fluoxetine, citalopram, or paroxetine), switch to venlafaxine, switch to SSRI plus cognitive behavior therapy, or switch to venlafaxine plus cognitive behavior therapy. Adolescents who did not improve by 6 weeks had their dose increased. Plasma concentrations of medication and metabolites were measured at 6 weeks in 244 participants and at 12 weeks in 204 participants. Adolescents treated with citalopram whose plasma concentration was equal to or greater than the geometric mean (GM) showed a higher response rate compared to those with less than the GM, with parallel but nonsignificant findings for fluoxetine. A dose increase of citalopram or fluoxetine at week 6 was most likely to result in response when it led to a change in concentration from less than the GM at 6 weeks to the GM or greater at week 12. Plasma levels of paroxetine, venlafaxine, or O-desmethylvenlafaxine were not related to clinical response. Exposure was associated with more cardiovascular and dermatologic side effects in those receiving venlafaxine. Antidepressant concentration may be useful in optimizing treatment for depressed adolescents receiving fluoxetine or citalopram.
authors.affiliation: Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA.
authors.forename: Dara J
authors.initials: DJ
authors.lastname: Sakolsky
authors.forename: James M
authors.initials: JM
authors.lastname: Perel
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Emslie
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Clarke
authors.forename: Karen Dineen
authors.initials: KD
authors.lastname: Wagner
authors.forename: Benedetto
authors.initials: B
authors.lastname: Vitiello
authors.forename: Martin B
authors.initials: MB
authors.lastname: Keller
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.forename: Joan Rosenbaum
authors.initials: JR
authors.lastname: Asarnow
authors.forename: Neal D
authors.initials: ND
authors.lastname: Ryan
authors.forename: James T
authors.initials: JT
authors.lastname: McCracken
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Strober
authors.forename: Satish
authors.initials: S
authors.lastname: Iyengar
authors.forename: Giovanna
authors.initials: G
authors.lastname: Porta
authors.forename: David A
authors.initials: DA
authors.lastname: Brent
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000097:blood*; D015283:Citalopram / Q000008:administration & dosage / Q000097:blood; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000097:blood; D006801:Humans; D008297:Male; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D005473:Fluoxetine; D015283:Citalopram