Large Study Reveals Insights on Suicides in Teens

The risk of suicide in adolescents taking antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), has been a subject of intense debate in recent years. A large, government-sponsored clinical trial has provided a wealth of new insights to illuminate this complex issue and clinical guidance on suicide prevention in seriously depressed youths.

The Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study was a randomized, controlled clinical trial of several treatments for 334 adolescents who were between 12 and 18 years old, had been diagnosed with major depressive disorder, and had failed to respond to an adequate course of SSRI antidepressant. Four treatment options, all given for 12 weeks, were compared for efficacy and safety: an SSRI different from the drug the patient had been taking; venlafaxine, which acts on both serotonin and norepinephrine receptors; the different SSRI plus cognitive-behavioral therapy (CBT); and venlafaxine plus CBT (Psychiatric News, March 21, 2008). Not surprisingly, the medication-plus-CBT groups had a significantly greater response than the medication-alone group; another SSRI and venlafaxine were similar in effectiveness.

The new analysis, published online in AJP in Advance on February 16, focuses on analyses of the frequencies of reported suicidal thoughts, behaviors, and attempts and associated risk factors in this particularly vulnerable population. The study will appear in print in the April American Journal of Psychiatry.

Because depression is the most prominent psychiatric risk factor for suicidal behavior, suicidal ideation and behaviors in children and adolescents often prompt physicians in the community to prescribe antidepressants, noted the team led by David Brent, M.D., a professor of psychiatry at the University of Pittsburgh School of Medicine. However, industry-sponsored clinical trials of antidepressant drugs, intended to gain regulatory approval, routinely exclude patients with a history of suicide attempts or suicidal ideation, making it difficult for clinicians to draw relevant real-life conclusions.

The TORDIA study was funded by the National Institute of Mental Health and conducted at six academic centers across the United States. A valuable feature of the protocol was that patients were not excluded if they had suicidal thoughts at the time of entering the study. Indeed, nearly 60 percent of study participants had suicidal ideation, and over one-third had a history of nonsuicidal self-injury at baseline. Another feature of the study was that the first 181 participants were monitored for suicidal thoughts and behaviors based on patients' spontaneous reports, while the latter 153 participants were questioned by the researchers every week using a standardized scale that rated the severity of the suicidal ideation and behaviors on a scale of 0 to 5.

During the 12 weeks of the study, 48 of the 334 patients had at least one suicidal event, defined as a new or worsening suicidal ideation, a suicidal threat, or a suicide attempt. The systematic assessment method identified a 20.8 percent rate of suicidal events in the second half of the study, significantly higher than the 8.8 percent rate identified by spontaneous reporting during the first half of the study.

The study also analyzed nonsuicidal self-injury events, defined as“ self-injurious behavior resulting in physical damage with no explicit or implicit intent to die” such as cutting, scratching, and burning. The rate of nonsuicidal self-injuries detected by systematic assessment was 17.6 percent and by spontaneous reporting, 2.2 percent.

Although not as sensitive as systematic assessment in less severe self-injuries, spontaneous reporting was effective in picking up serious events, defined as an event that “led to hospitalization [or] was life-threatening, disabling, or resulted in death.” The rates of all serious events detected by both methods did not differ significantly.

The most significant predictors for suicidal events were strong suicidal ideation and more severe depression at baseline, family conflict, and drug use or alcohol use. The median time to the occurrence of a suicidal event was three weeks after the treatment was initiated. A poorer response to treatment was significantly associated with suicidal events but not nonsuicidal self-injuries.

In patients with a higher-than-average baseline suicidal ideation, treatment with venlafaxine was associated with a higher likelihood of suicidal or nonsuicidal self-injury than another SSRI. CBT did not significantly affect the rate of suicidal events, which, the authors explained, may be due to the early onset of most events (on average at three weeks after the start of the study), and CBT takes a longer time to be effective.

“This study is a report full of pearls for psychiatrists and families,” said Myrna Weissman, Ph.D., in an interview with Psychiatric News. She is a professor of epidemiology and psychiatry at the College of Physicians and Surgeons and the School of Public Health at Columbia University and chief of the Department in Clinical-Genetic Epidemiology at New York State Psychiatric Institute. Her editorial on the study will appear in the April AJP. “It is very elegantly designed.”

“It's an important paper because it addressed many problems that people have been concerned about in suicidal ideation in adolescents,” Weissman said.

She noted the importance of data on nonsuicidal self-injuries. “There have been suggestions that these events may be increasing among adolescents, which is alarming.” The findings in the study can be valuable to clinical practice, she said.

“Predictors of Spontaneous and Systematically Assessed Suicidal Adverse Events in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) Study” is posted at<http://ajp.psychiatryonline.org/cgi/reprint/appi.ajp.2008.08070976v1>.▪