Antidepressant exposure as a predictor of clinical outcomes in the Treatment of Resistant Depression in Adolescents (TORDIA) study

Dara J. Sakolsky, James M. Perel, Graham J. Emslie, Gregory N. Clarke, Karen Dineen Wagner, Benedetto Vitiello, Martin B. Keller, Boris Birmaher, Joan Rosenbaum Asarnow, Neal D. Ryan, James T. McCracken, Michael J. Strober, Satish Iyengar, Giovanna Porta, David A. Brent

Research output: Contribution to journalArticle

30 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)92-97
Number of pages6
JournalJournal of clinical psychopharmacology
Volume31
Issue number1
DOIs
StatePublished - Feb 2011

Keywords

  • adolescents
  • drug exposure
  • major depressive disorder
  • optimization
  • plasma concentration

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)

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    Sakolsky, D. J., Perel, J. M., Emslie, G. J., Clarke, G. N., Wagner, K. D., Vitiello, B., Keller, M. B., Birmaher, B., Asarnow, J. R., Ryan, N. D., McCracken, J. T., Strober, M. J., Iyengar, S., Porta, G., & Brent, D. A. (2011). Antidepressant exposure as a predictor of clinical outcomes in the Treatment of Resistant Depression in Adolescents (TORDIA) study. Journal of clinical psychopharmacology, 31(1), 92-97. https://doi.org/10.1097/JCP.0b013e318204b117