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 Wagner, Joan Rosenbaum Asarnow, Martin B. Keller, David Brent

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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); http://www.clinicaltrials.gov; NCT00018902.

Original languageEnglish (US)
Pages (from-to)490-498
Number of pages9
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume50
Issue number5
DOIs
StatePublished - May 2011

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Treatment-Resistant Depressive Disorder
Antidepressive Agents
Serotonin Uptake Inhibitors
Clinical Trials
Depression
Suicidal Ideation
Medication Adherence
Cognitive Therapy
Therapeutics
Pharmaceutical Preparations

Keywords

  • antidepressants
  • depression
  • medication adherence

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Developmental and Educational Psychology

Cite this

Pharmacokinetically and clinician-determined adherence to an antidepressant regimen and clinical outcome in the TORDIA Trial. / Woldu, Hiwot; Porta, Giovanna; Goldstein, Tina; Sakolsky, Dara; Perel, James; Emslie, Graham; Mayes, Taryn; Clarke, Greg; Ryan, Neal D.; Birmaher, Boris; Wagner, Karen; Asarnow, Joan Rosenbaum; Keller, Martin B.; Brent, David.

In: Journal of the American Academy of Child and Adolescent Psychiatry, Vol. 50, No. 5, 05.2011, p. 490-498.

Research output: Contribution to journalArticle

Woldu, H, Porta, G, Goldstein, T, Sakolsky, D, Perel, J, Emslie, G, Mayes, T, Clarke, G, Ryan, ND, Birmaher, B, Wagner, K, Asarnow, JR, Keller, MB & Brent, D 2011, 'Pharmacokinetically and clinician-determined adherence to an antidepressant regimen and clinical outcome in the TORDIA Trial', Journal of the American Academy of Child and Adolescent Psychiatry, vol. 50, no. 5, pp. 490-498. https://doi.org/10.1016/j.jaac.2011.01.018
Woldu, Hiwot ; Porta, Giovanna ; Goldstein, Tina ; Sakolsky, Dara ; Perel, James ; Emslie, Graham ; Mayes, Taryn ; Clarke, Greg ; Ryan, Neal D. ; Birmaher, Boris ; Wagner, Karen ; Asarnow, Joan Rosenbaum ; Keller, Martin B. ; Brent, David. / Pharmacokinetically and clinician-determined adherence to an antidepressant regimen and clinical outcome in the TORDIA Trial. In: Journal of the American Academy of Child and Adolescent Psychiatry. 2011 ; Vol. 50, No. 5. pp. 490-498.
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abstract = "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); http://www.clinicaltrials.gov; NCT00018902.",
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AU - Perel, James

AU - Emslie, Graham

AU - Mayes, Taryn

AU - Clarke, Greg

AU - Ryan, Neal D.

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N2 - 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); http://www.clinicaltrials.gov; NCT00018902.

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