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

David A. Brent, 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 PortaMartin B. Keller

Research output: Contribution to journalArticle

138 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)418-426
Number of pages9
JournalAmerican Journal of Psychiatry
Volume166
Issue number4
DOIs
StatePublished - Apr 2009

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Treatment-Resistant Depressive Disorder
Suicidal Ideation
Wounds and Injuries
Family Conflict
Benzodiazepines
Therapeutics
Cognitive Therapy
Pharmaceutical Preparations
Antidepressive Agents
Alcohols
Depression
Incidence
Venlafaxine Hydrochloride

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Medicine(all)

Cite this

Predictors of spontaneous and systematically assessed suicidal adverse events in the treatment of SSRI-resistant depression in adolescents (TORDIA) study. / Brent, David A.; Emslie, Graham J.; Clarke, Greg N.; Asarnow, Joan; Spirito, Anthony; Ritz, Louise; Vitiello, Benedetto; Iyengar, Satish; Birmaher, Boris; Ryan, Neal D.; Zelazny, Jamie; Onorato, Matthew; Kennard, Betsy; Mayes, Taryn L.; DeBar, Lynn L.; McCracken, James T.; Strober, Michael; Suddath, Robert; Leonard, Henrietta; Porta, Giovanna; Keller, Martin B.

In: American Journal of Psychiatry, Vol. 166, No. 4, 04.2009, p. 418-426.

Research output: Contribution to journalArticle

Brent, DA, Emslie, GJ, Clarke, GN, Asarnow, J, Spirito, A, Ritz, L, Vitiello, B, Iyengar, S, Birmaher, B, Ryan, ND, Zelazny, J, Onorato, M, Kennard, B, Mayes, TL, DeBar, LL, McCracken, JT, Strober, M, Suddath, R, Leonard, H, Porta, G & Keller, MB 2009, 'Predictors of spontaneous and systematically assessed suicidal adverse events in the treatment of SSRI-resistant depression in adolescents (TORDIA) study', American Journal of Psychiatry, vol. 166, no. 4, pp. 418-426. https://doi.org/10.1176/appi.ajp.2008.08070976
Brent, David A. ; Emslie, Graham J. ; Clarke, Greg N. ; Asarnow, Joan ; Spirito, Anthony ; Ritz, Louise ; Vitiello, Benedetto ; Iyengar, Satish ; Birmaher, Boris ; Ryan, Neal D. ; Zelazny, Jamie ; Onorato, Matthew ; Kennard, Betsy ; Mayes, Taryn L. ; DeBar, Lynn L. ; McCracken, James T. ; Strober, Michael ; Suddath, Robert ; Leonard, Henrietta ; Porta, Giovanna ; Keller, Martin B. / Predictors of spontaneous and systematically assessed suicidal adverse events in the treatment of SSRI-resistant depression in adolescents (TORDIA) study. In: American Journal of Psychiatry. 2009 ; Vol. 166, No. 4. pp. 418-426.
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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.",
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AU - Clarke, Greg N.

AU - Asarnow, Joan

AU - Spirito, Anthony

AU - Ritz, Louise

AU - Vitiello, Benedetto

AU - Iyengar, Satish

AU - Birmaher, Boris

AU - Ryan, Neal D.

AU - Zelazny, Jamie

AU - Onorato, Matthew

AU - Kennard, Betsy

AU - Mayes, Taryn L.

AU - DeBar, Lynn L.

AU - McCracken, James T.

AU - Strober, Michael

AU - Suddath, Robert

AU - Leonard, Henrietta

AU - Porta, Giovanna

AU - Keller, Martin B.

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N2 - 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.

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