How to manage adolescent depression is a problem that has vexed clinicians and parents ever since the Food and Drug Administration issued a “black-box” warning several years ago that adolescents taking antidepressants were at a higher risk of suicidal behaviors. Following the warning, antidepressant use declined. Whether or not suicides increased as a result has been unclear.
Now, a report published in the April 2009 American Journal of Psychiatry, “Predictors of Spontaneous and Systematically Assessed Suicidal Adverse Events in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) Study,” offers preliminary data in the search to clarify this critical issue.
The multi-institutional study was led by David Brent, M.D., of Western Psychiatric Institute and Clinic of the University of Pittsburgh, a NARSAD Distinguished Investigator and winner of NARSAD’s 2006 Ruane Prize for Children and Adolescent Psychiatric Research. NARSAD Scientific Council Member Martin B. Keller, M.D., of Brown University Medical School, was among the study collaborators.
In an editorial in the journal assessing the research, NARSAD Distinguished Investigator Myrna M. Weissman, Ph.D. of Columbia University and the York State Psychiatric Institute, a leader in child psychiatry studies, hailed Dr. Brent and associates for “a report full of pearls for psychiatrists and families.”
In the TORDIA study, 334 depressed adolescents who had not responded to a previous trial with an SSRI (selective-serotonin reuptake inhibitor) antidepressant were randomized to either another SSRI or to venlafaxine (Effexor) a serotonin-norepinephrine reuptake inhibitor (SNRI), with or without cognitive behavior therapy. Self-harm events, i.e., suicidal and non-suicidal self-injuries were assessed by spontaneous report for the first 181 participants, and by systematic weekly assessment for the last 153 participants.
The results showed higher rates of suicidal (20.8 percent vs. 8.8 percent) and nonsuicidal self-injury (17.6 percent vs. 2.2 percent ), but not serious adverse events (8.4 percent vs. 7.3 percent), were detected with systematic monitoring. Median time to a suicidal event was three weeks, predicted by suicidal ideation, family conflict, and drug and alcohol use. Median time to nonsuicidal self-injury was two weeks, predicted by previous history of nonsuicidal self-injury.
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 was associated with higher rate of both suicidal and nonsuicidal self-injury adverse events.
The authors concluded: “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.”
In her editorial, Dr. Weissman remarked on the importance of the inclusion of nonsuicidal self-injury – self-harm events such as cutting, burning and skin-scratching -- which are “alarmingly prevalent” among adolescents. Complementing the authors’ conclusions, she noted “the pearl here is the value of systematic monitoring for early detection. Systematic monitoring provides more opportunities than we have had before for early intervention with high-risk adolescents, before events become serious. We need now to develop and test new psychotherapeutic and psychopharmacological strategies to react to these events in vulnerable patients.”
Dr. Weissman added that studies such as TORDIA, “can provide other evidence for guidelines for the use of antidepressants in high-risk adolescents so that treatments are not withheld for the majority who might benefit but are used more cautiously in those who are at higher risk for suicide and injury.”
(This article was adapted with permission from the American Journal of Psychiatry.)