title: Long-term outcome of adolescent depression initially resistant to selective serotonin reuptake inhibitor treatment: a follow-up study of the TORDIA sample.
abstract: BACKGROUND
  We examined the long-term outcome of participants in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study, a randomized trial of 334 adolescents (aged 12-18 years) with DSM-IV-defined major depressive disorder initially resistant to selective serotonin reuptake inhibitor (SSRI) treatment who were subsequently treated for 12 weeks with another SSRI, venlafaxine, another SSRI + cognitive-behavioral therapy (CBT), or venlafaxine + CBT. Responders then continued with the same treatment through week 24, while nonresponders were given open treatment.
  
  
  METHODS
  For the current study, patients were reassessed 48 (n = 116) and 72 (n = 130) weeks from intake. Data were gathered from February 2001 to February 2007. Standardized diagnostic interviews and measures of depression, suicidal ideation, related psychopathology, and level of functioning were periodically administered. Remission was defined as ≥ 3 weeks with ≤ 1 clinically significant symptom and no associated functional impairment (score of 1 on the adolescent version of the Longitudinal Interval Follow-Up Evaluation [A-LIFE]), and relapse, as ≥ 2 weeks with probable or definite depressive disorder (score of 3 or 4 on the A-LIFE). Mixed-effects regression models were applied to estimate remission, relapse, and functional recovery.
  
  
  RESULTS
  By 72 weeks, an estimated 61.1% of the randomized youths had reached remission. Randomly assigned treatment (first 12 weeks) did not influence remission rate or time to remission, but the group assigned to SSRIs had a more rapid decline in self-reported depressive symptoms and suicidal ideation than those assigned to venlafaxine (P < .03). Participants with more severe depression, greater dysfunction, and alcohol or drug use at baseline were less likely to remit. The depressive symptom trajectory of the remitters diverged from that of nonremitters by the first 6 weeks of treatment (P < .001). Of the 130 participants in remission at week 24, 25.4% relapsed in the subsequent year.
  
  
  CONCLUSIONS
  While most adolescents achieved remission, more than one-third did not, and one-fourth of remitted patients experienced a relapse. More effective interventions are needed for patients who do not show robust improvement early in treatment.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00018902.
authors.affiliation: Division of Services and Intervention Research, National Institute of Mental Health, Room 7147, 6001 Executive Blvd, Bethesda, MD 20892-9633, USA. bvitiell@mail.nih.gov
authors.forename: Benedetto
authors.initials: B
authors.lastname: Vitiello
authors.forename: Graham
authors.initials: G
authors.lastname: Emslie
authors.forename: Gregory
authors.initials: G
authors.lastname: Clarke
authors.forename: Karen Dineen
authors.initials: KD
authors.lastname: Wagner
authors.forename: Joan R
authors.initials: JR
authors.lastname: Asarnow
authors.forename: Martin B
authors.initials: MB
authors.lastname: Keller
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.forename: Neal D
authors.initials: ND
authors.lastname: Ryan
authors.forename: Betsy
authors.initials: B
authors.lastname: Kennard
authors.forename: Taryn L
authors.initials: TL
authors.lastname: Mayes
authors.forename: Lynn
authors.initials: L
authors.lastname: DeBar
authors.forename: Frances
authors.initials: F
authors.lastname: Lynch
authors.forename: John
authors.initials: J
authors.lastname: Dickerson
authors.forename: Michael
authors.initials: M
authors.lastname: Strober
authors.forename: Robert
authors.initials: R
authors.lastname: Suddath
authors.forename: James T
authors.initials: JT
authors.lastname: McCracken
authors.forename: Anthony
authors.initials: A
authors.lastname: Spirito
authors.forename: Matthew
authors.initials: M
authors.lastname: Onorato
authors.forename: Jamie
authors.initials: J
authors.lastname: Zelazny
authors.forename: Giovanna
authors.initials: G
authors.lastname: Porta
authors.forename: Satish
authors.initials: S
authors.lastname: Iyengar
authors.forename: David A
authors.initials: DA
authors.lastname: Brent
mesh_terms: D000203:Activities of Daily Living; D000293:Adolescent; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D003511:Cyclohexanols / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D059020:Suicidal Ideation; D013997:Time Factors; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride