Predictors of spontaneous and systematically assessed suicidal adverse events in the treatment of SSRI-resistant depression in adolescents (TORDIA) study.
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.
Brent
David A
DA
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
Emslie
Graham J
GJ
Clarke
Greg N
GN
Asarnow
Joan
J
Spirito
Anthony
A
Ritz
Louise
L
Vitiello
Benedetto
B
Iyengar
Satish
S
Birmaher
Boris
B
Ryan
Neal D
ND
Zelazny
Jamie
J
Onorato
Matthew
M
Kennard
Betsy
B
Mayes
Taryn L
TL
Debar
Lynn L
LL
McCracken
James T
JT
Strober
Michael
M
Suddath
Robert
R
Leonard
Henrietta
H
Porta
Giovanna
G
Keller
Martin B
MB
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
D000928:Antidepressive Agents; D001569:Benzodiazepines; D015283:Citalopram; D003511:Cyclohexanols; D005473:Fluoxetine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride