• Science Update
Certain circumstances may predict suicidal thinking or behavior among teens with treatment-resistant major depression who are undergoing second-step treatment, according to an analysis of data from an NIMH-funded study. The study was published online ahead of print February 17, 2009, in the American Journal of Psychiatry.
In the Treatment of SSRI-resistant Depression in Adolescents (TORDIA) study, 334 teens who did not get well after taking a type of antidepressant called a selective serotonin reuptake inhibitor (SSRI) before the trial were randomly assigned to one of four treatments for 12 weeks:
- Switch to another SSRI
- Switch to venlafaxine (Effexor), a different type of antidepressant
- Switch to another SSRI and add cognitive behavioral therapy (CBT), a type of psychotherapy
- Switch to venlafaxine and add CBT
Results of the trial were previously reported in February 2008. They showed that teens who received combination therapy, with either type of antidepressant, were more likely to get well than those on medication alone.
Using data from spontaneous reports by the participants and from systematic assessment by clinicians, David Brent, M.D., of the Western Psychiatric Institute and Clinic, and colleagues aimed to identify characteristics or circumstances that may predict whether a teen is likely to have suicidal thoughts or behavior during treatment. Nearly 60 percent of TORDIA participants had suicidal thinking or behavior at the beginning of the trial.
Fifty-eight suicidal events—which include serious suicidal thinking or a recent suicide attempt—occurred in 48 participants during the trial, most of which happened early in the trial. The researchers found that teens who had higher levels of suicidal thinking, higher levels of parent-child conflict, and who used drugs or alcohol at the trial's beginning were more likely to experience a suicidal event during treatment and less likely to respond to treatment. They were also less likely to have completed treatment.
"These new data may contribute to developing more targeted and individualized interventions." said NIMH co-author Benedetto Vitiello, M.D. "If we can know which teens may be more susceptible to suicidal thinking and behavior, we are better able to tailor safer treatments for them."
No statistically significant differences in suicidal events or non-suicidal self-injury were found among the treatment options. However, the use of venlafaxine was associated with a higher rate of self-injury in participants who had more severe suicidal thinking at the trial's beginning. These results suggest that SSRIs are preferred over venlafaxine in the treatment of depressed teens who are at risk for suicidal thinking or behavior, according to the researchers.
Although CBT was found to have a protective effect over the long-term among teens with depression in the NIMH-funded Treatment for Adolescents with Depression Study (TADS), it did not appear to reduce the rate of suicidal events in TORDIA. The researchers theorize that because the suicidal events tended to occur soon after treatment began, the CBT did not have enough time to deliver a protective dose.
Finally, Brent and colleagues found that the use of anti-anxiety medications called benzodiazepines was associated with a higher likelihood of, and faster time to, a suicidal event—an unexpected result not found in other similar studies. The researchers theorize that participants who were taking a benzodiazepine in addition to an antidepressant may have been much more severely ill and therefore may have been more prone to suicidal thoughts or behavior. But more study is warranted on the potential role of anti-anxiety medications in suicidal thinking and actions among patients also taking an antidepressant.
"Because the suicidal events tended to happen early in the treatment process, interventions that address safety, emotion regulation and family conflict should be some of the first to be implemented," concluded Dr. Brent. "With this data, we are in a better position to design future interventions that could lessen the risks of suicide even further among this vulnerable population."
Brent D, Emslie G, Clark G, Wagner KD, Asarnow JR, Spirito A, Ritz L, Vitiello B, Iyengar S, Birmaher B, Ryan N, Zelazny J, Onorato M, Kennard B, Mayes T, DeBar L, McCracken J, Strober M, Suddath R, Leonard H, Porta G, Keller M. Predictors of spontaneous and systematically assessed suicidal adverse events in the Treatment of SSRI-resistant Depression in Adolescents (TORDIA) study. American Journal of Psychiatry. Online ahead of print February 16, 2009.