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Because of concerns that suicidality might increase after SSRI administration, the U.S. Food and Drug Administration recommended that suicidality be systematically assessed in the federally funded randomized study, Treatment of SSRI-Resistant Depression in Adolescents (TORDIA). Researchers have now reported the suicidality findings.
Researchers randomized 334 adolescents with DSM-IV treatment-resistant major depression (≥8 weeks of SSRIs, including 4 weeks at dosing equivalent to ≥40 mg of fluoxetine) to an alternative SSRI or to venlafaxine, with or without cognitive-behavioral therapy. The study had no placebo arm. Suicidal events were identified through spontaneous reports by patients or families for the first 181 enrollees and by systematic research assessment for later enrollees. At baseline, three fifths of all participants had suicidal ideation, and one third had nonsuicidal self-injury. By 12 weeks, 14% of all patients had suicidal self-injury, and 9% had nonsuicidal self-injury.
Systematic assessments for self-harm uncovered significantly higher percentages of events than spontaneous reports did (suicidal self-injury, 21% vs. 9%; nonsuicidal self-injury, 18% vs. 2%). Systematic reporting was also associated with earlier identification of suicidal behaviors (2 weeks vs. 5 weeks with spontaneous reporting). Predictors of suicidal behavior were baseline suicidality, family conflict, and substance use. Venlafaxine was associated with suicidal behavior in patients with high baseline ideation. Use of concomitant benzodiazepines was associated with suicidality, but numbers were small.
Brent DA et al. Predictors of spontaneous and systematically assessed suicidal adverse events in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study. Am J Psychiatry 2009 Feb 17; [e-pub ahead of print]. (http://dx.doi.org/10.1176/appi.ajp.2008.08070976)
Comment
Spontaneous reporting might have been less reliable than systematic reporting because, understandably, parents often deny suicidality in their children and adolescents and because pediatric patients can be secretive about their thoughts. Regardless of the reasons, these data strongly emphasize the imperative to systematically assess for suicidality, especially in the first weeks of antidepressant treatment.