Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2009 Apr;166(4):418-26.
doi: 10.1176/appi.ajp.2008.08070976. Epub 2009 Feb 17.

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

David A Brent  1 , Graham J Emslie, Greg N Clarke, Joan Asarnow, Anthony Spirito, Louise Ritz, Benedetto Vitiello, Satish Iyengar, Boris Birmaher, Neal D Ryan, Jamie Zelazny, Matthew Onorato, Betsy Kennard, Taryn L Mayes, Lynn L Debar, James T McCracken, Michael Strober, Robert Suddath, Henrietta Leonard, Giovanna Porta, Martin B Keller
Affiliations
Randomized Controlled Trial

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

David A Brent et al. Am J Psychiatry. 2009 Apr.

Erratum in

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.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Effect of Treatment on Hazard of a Suicidal and Nonsuicidal Adverse Event
FIGURE 2
FIGURE 2
Rate of Adverse Events by Treatment Group
FIGURE 3
FIGURE 3
Clinical Ratings Over Time by Suicidal Event Status
See this image and copyright information in PMC

Comment in

References

    1. Bridge J, Iyengar S, Salary CB, Barbe RP, Birmaher B, Pincus H, Ren L, Brent D. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA. 2007;297:1683–1696. - PubMed
    1. Libby AM, Brent DA, Morrato EH, Orton HD, Allen R, Valuck RJ. Decline in treatment of pediatric depression after FDA advisory on risk of suiciality with SSRIs. Am J Psychiatry. 2007;164:884–891. - PubMed
    1. Gibbons RD, Brown CH, Hur K, Marcus SM, Bhaumik DK, Erkens JA, Herings RMC, Mann JJ. Early evidence on the effects of regulators’ suiciality warnings on SSRI prescriptions and suicide in children and adolescents. Am J Psychiatry. 2007;64:1356–1363. - PubMed
    1. Emslie G, Kratochvil C, Vitiello B, Silva S, Mayes T, McNulty S, Weller E, Waslick B, Casat C, Walkup J, Pathak S, Rohde P, Posner K, March J. Treatment of Adolescents With Depression Study (TADS): Safety results. J Am Acad Child Adolesc Psychiatry. 2006;45:1440–1455. - PMC - PubMed
    1. Apter A, Lipschitz A, Fong R, Carpenter DJ, Krulewizc S, Davies JT, Wilkinson C, Perera P, Metz A. Evaluation of suicidal thoughts and behaviors in children and adolescents taking paroxetine. J Child Adolesc Psychopharmacology. 2006:16–77. - PubMed

Publication types

MeSH terms