title: Pharmacokinetically and clinician-determined adherence to an antidepressant regimen and clinical outcome in the TORDIA trial.
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.
  
  
  METHODS
  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 Information-Treatment of SSRI-Resistant Depression in Adolescents (TORDIA); http://www.clinicaltrials.gov; NCT00018902.
authors.affiliation: Mt. Sinai School of Medicine, New York, USA.
authors.forename: Hiwot
authors.initials: H
authors.lastname: Woldu
authors.forename: Giovanna
authors.initials: G
authors.lastname: Porta
authors.forename: Tina
authors.initials: T
authors.lastname: Goldstein
authors.forename: Dara
authors.initials: D
authors.lastname: Sakolsky
authors.forename: James
authors.initials: J
authors.lastname: Perel
authors.forename: Graham
authors.initials: G
authors.lastname: Emslie
authors.forename: Taryn
authors.initials: T
authors.lastname: Mayes
authors.forename: Greg
authors.initials: G
authors.lastname: Clarke
authors.forename: Neal D
authors.initials: ND
authors.lastname: Ryan
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.forename: Karen Dineen
authors.initials: KD
authors.lastname: Wagner
authors.forename: Joan Rosenbaum
authors.initials: JR
authors.lastname: Asarnow
authors.forename: Martin B
authors.initials: MB
authors.lastname: Keller
authors.forename: David
authors.initials: D
authors.lastname: Brent
mesh_terms: D000293:Adolescent; D018687:Antidepressive Agents, Second-Generation / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002648:Child; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D003511:Cyclohexanols / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy*; D016903:Drug Monitoring; D004351:Drug Resistance; D057915:Drug Substitution; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D055118:Medication Adherence / Q000523:psychology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D013406:Suicide, Attempted / Q000517:prevention & control / Q000706:statistics & numerical data; D000069470:Venlafaxine Hydrochloride
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride