title: Predictors of spontaneous and systematically assessed suicidal adverse events in the treatment of SSRI-resistant depression in adolescents (TORDIA) study.
abstract: OBJECTIVE
  The authors sought to identify predictors of self-harm adverse events in treatment-resistant, depressed adolescents during the first 12 weeks of treatment.
  
  
  METHODS
  Depressed adolescents (N=334) who had not responded to a previous trial with an SSRI antidepressant were randomized to a switch to either another SSRI or venlafaxine, with or without cognitive behavior therapy. Self-harm events, i.e., suicidal and non-suicidal self-injury adverse events were assessed by spontaneous report for the first 181 participants, and by systematic weekly assessment for the last 153 participants.
  
  
  RESULTS
  Higher rates of suicidal (20.8% vs. 8.8%) and nonsuicidal self-injury (17.6% vs. 2.2%), but not serious adverse events (8.4% vs. 7.3%) were detected with systematic monitoring. Median time to a suicidal event was 3 weeks, predicted by high baseline suicidal ideation, family conflict, and drug and alcohol use. Median time to nonsuicidal self-injury was 2 weeks, predicted by previous history of nonsuicidal self-injury. While there were no main effects of treatment, venlafaxine treatment was associated with a higher rate of self-harm adverse events in those with higher suicidal ideation. Adjunctive use of benzodiazepines, while in a small number of participants (N=10) was associated with higher rate of both suicidal and nonsuicidal self-injury adverse events.
  
  
  CONCLUSIONS
  Since predictors of suicidal adverse events also predict poor response to treatment, and many of these events occurred early in treatment, improving the speed of response to depression, by targeting of family conflict, suicidal ideation, and drug use may help to reduce their incidence. The relationship of venlafaxine and of benzodiazepines to self-harm events requires further study and clinical caution.
authors.affiliation: University of Pittsburgh School of Medicine, Western University School of Medicine, Western Psychiatric Institute and Clinic, 3811 O'Hara St., Suite 112, Pittsburgh, PA 15213-2593, USA. brentda@upmc.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Brent
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Emslie
authors.forename: Greg N
authors.initials: GN
authors.lastname: Clarke
authors.forename: Joan
authors.initials: J
authors.lastname: Asarnow
authors.forename: Anthony
authors.initials: A
authors.lastname: Spirito
authors.forename: Louise
authors.initials: L
authors.lastname: Ritz
authors.forename: Benedetto
authors.initials: B
authors.lastname: Vitiello
authors.forename: Satish
authors.initials: S
authors.lastname: Iyengar
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.forename: Neal D
authors.initials: ND
authors.lastname: Ryan
authors.forename: Jamie
authors.initials: J
authors.lastname: Zelazny
authors.forename: Matthew
authors.initials: M
authors.lastname: Onorato
authors.forename: Betsy
authors.initials: B
authors.lastname: Kennard
authors.forename: Taryn L
authors.initials: TL
authors.lastname: Mayes
authors.forename: Lynn L
authors.initials: LL
authors.lastname: Debar
authors.forename: James T
authors.initials: JT
authors.lastname: McCracken
authors.forename: Michael
authors.initials: M
authors.lastname: Strober
authors.forename: Robert
authors.initials: R
authors.lastname: Suddath
authors.forename: Henrietta
authors.initials: H
authors.lastname: Leonard
authors.forename: Giovanna
authors.initials: G
authors.lastname: Porta
authors.forename: Martin B
authors.initials: MB
authors.lastname: Keller
mesh_terms: D000293:Adolescent; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D015283:Citalopram / Q000009:adverse effects* / Q000627:therapeutic use; D015928:Cognitive Behavioral Therapy; D003430:Cross-Sectional Studies; D003511:Cyclohexanols / Q000009:adverse effects* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004347:Drug Interactions; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D017374:Paroxetine / Q000009:adverse effects* / Q000627:therapeutic use; D016728:Self-Injurious Behavior / Q000139:chemically induced* / Q000453:epidemiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D013405:Suicide / Q000523:psychology / Q000706:statistics & numerical data*; D013406:Suicide, Attempted / Q000523:psychology / Q000706:statistics & numerical data*; D000069470:Venlafaxine Hydrochloride
chemical_list: D000928:Antidepressive Agents; D001569:Benzodiazepines; D015283:Citalopram; D003511:Cyclohexanols; D005473:Fluoxetine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride