title: Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial.
abstract: BACKGROUND
  Only about 60% of adolescents with depression will show an adequate clinical response to an initial treatment trial with a selective serotonin reuptake inhibitor (SSRI). There are no data to guide clinicians on subsequent treatment strategy.
  
  
  OBJECTIVE
  To evaluate the relative efficacy of 4 treatment strategies in adolescents who continued to have depression despite adequate initial treatment with an SSRI.
  
  
  METHODS
  Randomized controlled trial of a clinical sample of 334 patients aged 12 to 18 years with a primary diagnosis of major depressive disorder that had not responded to a 2-month initial treatment with an SSRI, conducted at 6 US academic and community clinics from 2000-2006.
  
  
  METHODS
  Twelve weeks of: (1) switch to a second, different SSRI (paroxetine, citalopram, or fluoxetine, 20-40 mg); (2) switch to a different SSRI plus cognitive behavioral therapy; (3) switch to venlafaxine (150-225 mg); or (4) switch to venlafaxine plus cognitive behavioral therapy.
  
  
  METHODS
  Clinical Global Impressions-Improvement score of 2 or less (much or very much improved) and a decrease of at least 50% in the Children's Depression Rating Scale-Revised (CDRS-R); and change in CDRS-R over time.
  
  
  RESULTS
  Cognitive behavioral therapy plus a switch to either medication regimen showed a higher response rate (54.8%; 95% confidence interval [CI], 47%-62%) than a medication switch alone (40.5%; 95% CI, 33%-48%; P = .009), but there was no difference in response rate between venlafaxine and a second SSRI (48.2%; 95% CI, 41%-56% vs 47.0%; 95% CI, 40%-55%; P = .83). There were no differential treatment effects on change in the CDRS-R, self-rated depressive symptoms, suicidal ideation, or on the rate of harm-related or any other adverse events. There was a greater increase in diastolic blood pressure and pulse and more frequent occurrence of skin problems during venlafaxine than SSRI treatment.
  
  
  CONCLUSIONS
  For adolescents with depression not responding to an adequate initial treatment with an SSRI, the combination of cognitive behavioral therapy and a switch to another antidepressant resulted in a higher rate of clinical response than did a medication switch alone. However, a switch to another SSRI was just as efficacious as a switch to venlafaxine and resulted in fewer adverse effects.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00018902.
authors.forename: David
authors.initials: D
authors.lastname: Brent
authors.forename: Graham
authors.initials: G
authors.lastname: Emslie
authors.forename: Greg
authors.initials: G
authors.lastname: Clarke
authors.forename: Karen Dineen
authors.initials: KD
authors.lastname: Wagner
authors.forename: Joan Rosenbaum
authors.initials: JR
authors.lastname: Asarnow
authors.forename: Marty
authors.initials: M
authors.lastname: Keller
authors.forename: Benedetto
authors.initials: B
authors.lastname: Vitiello
authors.forename: Louise
authors.initials: L
authors.lastname: Ritz
authors.forename: Satish
authors.initials: S
authors.lastname: Iyengar
authors.forename: Kaleab
authors.initials: K
authors.lastname: Abebe
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.forename: Neal
authors.initials: N
authors.lastname: Ryan
authors.forename: Betsy
authors.initials: B
authors.lastname: Kennard
authors.forename: Carroll
authors.initials: C
authors.lastname: Hughes
authors.forename: Lynn
authors.initials: L
authors.lastname: DeBar
authors.forename: James
authors.initials: J
authors.lastname: McCracken
authors.forename: Michael
authors.initials: M
authors.lastname: Strober
authors.forename: Robert
authors.initials: R
authors.lastname: Suddath
authors.forename: Anthony
authors.initials: A
authors.lastname: Spirito
authors.forename: Henrietta
authors.initials: H
authors.lastname: Leonard
authors.forename: Nadine
authors.initials: N
authors.lastname: Melhem
authors.forename: Giovanna
authors.initials: G
authors.lastname: Porta
authors.forename: Matthew
authors.initials: M
authors.lastname: Onorato
authors.forename: Jamie
authors.initials: J
authors.lastname: Zelazny
mesh_terms: D000293:Adolescent; D015283:Citalopram / Q000627:therapeutic use; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D003511:Cyclohexanols / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000628:therapy*; D004351:Drug Resistance; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D008297:Male; D017374:Paroxetine / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
chemical_list: D015283:Citalopram; D003511:Cyclohexanols; D005473:Fluoxetine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride