Predictors of spontaneous and systematically assessed suicidal adverse events in the treatment of SSRI-resistant depression in adolescents (TORDIA) study

Am J Psychiatry. 2009 Apr;166(4):418-26. doi: 10.1176/appi.ajp.2008.08070976. Epub 2009 Feb 17.

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.

Method: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use
  • Benzodiazepines / adverse effects
  • Benzodiazepines / therapeutic use
  • Citalopram / adverse effects*
  • Citalopram / therapeutic use
  • Cognitive Behavioral Therapy*
  • Cross-Sectional Studies
  • Cyclohexanols / adverse effects*
  • Cyclohexanols / therapeutic use
  • Depressive Disorder, Major / drug therapy*
  • Drug Interactions
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Fluoxetine / adverse effects*
  • Fluoxetine / therapeutic use
  • Humans
  • Male
  • Paroxetine / adverse effects*
  • Paroxetine / therapeutic use
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Self-Injurious Behavior / chemically induced*
  • Self-Injurious Behavior / epidemiology
  • Suicide / psychology
  • Suicide / statistics & numerical data*
  • Suicide, Attempted / psychology
  • Suicide, Attempted / statistics & numerical data*
  • Venlafaxine Hydrochloride

Substances

  • Antidepressive Agents
  • Cyclohexanols
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Citalopram
  • Benzodiazepines
  • Paroxetine
  • Venlafaxine Hydrochloride