Pharmacokinetically and clinician-determined adherence to an antidepressant regimen and clinical outcome in the TORDIA Trial

Hiwot Woldu, Giovanna Porta, Tina Goldstein, Dara Sakolsky, James Perel, Graham Emslie, Taryn Mayes, Greg Clarke, Neal D. Ryan, Boris Birmaher, Karen Dineen Wagner, Joan Rosenbaum Asarnow, Martin B. Keller, David Brent

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Objective: Nonadherence to antidepressant treatment may contribute to poor outcome and to suicidal adverse events in adolescent depression. We examine the relationship between adherence and both clinical response and suicidal events in participants in the Treatment of Resistant Depression in Adolescents (TORDIA) study. Method: The relationship between adherence to medication and clinical outcome was assessed in 190 treatment-resistant depressed adolescents who were randomized to one of four cells: switch to another selective serotonin reuptake inhibitor (SSRI), switch to venlafaxine, or either of these two medication switches plus cognitive behavioral therapy. Plasma levels of antidepressant drug and metabolites were determined after 6 and 12 weeks of treatment. A twofold or greater variation in the dose-adjusted concentration of drug plus metabolites (level/dose ratio [LDR]) was defined as nonadherence. Nonadherence was also determined by clinician pill counts (CPC) of the proportion of prescribed pills that were unused and was defined as having greater than 30% of the prescribed pills remaining. Results: LDR and CPC showed low concordance. LDR was unrelated to clinical response. CPC adherence was related to a higher response rate overall (adherent, 63.0% versus nonadherent, 47.2%, p = .03). Approximately half (50.8%) of the sample surveyed showed evidence of nonadherence by CPC. Neither measure of adherence was related to the occurrence of suicidal events or to the pace of decline in suicidal ideation. Conclusions: Clinician pill counts may be a relevant measure of adherence that is related to outcome under formal clinical trial conditions in depressed adolescents. Nonadherence appears to be a common and significant source of treatment nonresponse. Clinical Trial Registration InformationTreatment of SSRI-Resistant Depression in Adolescents (TORDIA);; NCT00018902.

Original languageEnglish (US)
Pages (from-to)490-498
Number of pages9
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Issue number5
StatePublished - May 2011


  • antidepressants
  • depression
  • medication adherence

ASJC Scopus subject areas

  • Developmental and Educational Psychology
  • Psychiatry and Mental health


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