Findings support FDA's 'black box' warning on all SSRIs, researchers say
MONDAY, April 12 (HealthDay News) -- There appears to be no difference among antidepressants in raising a kid's risk of suicidal thoughts, a new long-term study shows.
The research supports the U.S. Food and Drug Administration's decision in 2004 to mandate a "black box" warning on all antidepressants for an increased suicidality risk in children and adolescents who go on the medications. And it answers an oft-raised question about which medications carry the most risk.
"Across the most frequently prescribed antidepressant agents, there was no difference in risk of suicide attempts and completed suicides," said lead researcher Dr. Sebastian Schneeweiss, an associate professor of epidemiology at the Harvard School of Public Health.
The FDA showed a doubling in the risk of suicidal ideation among children taking antidepressants, compared with placebo, Schneeweiss noted.
But, Schneeweiss added, the FDA analysis did not specify which medications were used. so there was no way to tell whether there were differences in risk.
"Physicians need to know if there is an agent where the risk is reduced or particularly elevated," he said. "That is important for clinical practice."
The report is published in the April 12 online edition of Pediatrics.
For the study, Schneeweiss's team collected data on 20,906 children aged 10 to 18 who had been diagnosed with depression in British Columbia. They were followed for nine years.
The children and adolescents in the study were on a variety of commonly prescribed antidepressants called selective serotonin reuptake inhibitors (SSRIs), including citalopram (Celexa), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft).
In the first year after starting treatment with antidepressants, there were 266 suicide attempts and three completed suicides. However, no significant difference in suicide attempts or completed suicides was noted based on which antidepressant the adolescent was taking, the researchers found.
Given these findings, doctors can focus their attention on which of the several SSRIs is most effective for an individual patient and not be concerned about increasing the potential risk of suicide, Schneeweiss said.
Different SSRIs act differently in individual patients, so now the doctor can find the most effective one and, because the risk is the same with all, "take safety out of the equation," he added.
"Nevertheless, you will still have to monitor the patient very carefully, because the elevated risk is still there," Schneeweiss said.
Much debate followed the FDA's decision to place a black box warning on antidepressants. One of the continuing arguments is that by imposing such a warning, clinicians will shy away from prescribing antidepressants to children and adolescents who really need them. This could in turn make their depression worse, which could lead to suicide.
Dr. David Fassler, a clinical professor of psychiatry at the University of Vermont College of Medicine, said that "the results of this study are consistent with previous reports and with general clinical experience."
The article represents a contribution to the growing literature on this complex issue, Fassler said.
"However, it does not shed much light on the larger question of whether or not the decision to impose a black box warning on these medications was correct and justified in the first place. Nor does the current analysis contribute to our understanding of the public health consequences of the FDA's action. Hopefully, subsequent large-scale, longitudinal studies will be designed, which will help us more fully address these critical, and as-yet unanswered, questions," he said.
Another expert, Dr. David A. Brent, a professor of psychiatry at the University of Pittsburgh, said that he was "not sure how they draw the conclusion that these findings support the black box warning."
The fact that those who use the drugs have similar rates of suicide does not justify the black box warning; it just indicates that whatever the warning should be, it should be similar across drugs, Brent said.
"The authors themselves say that the fivefold increased rate of suicide is probably a function of comorbidity and depression rather than drug. In fact, most psychological autopsy studies estimate the risk for suicide with depression to be 10 to 30 times higher, and most of those kids were untreated," he said. "So there may actually be a protective effect, but certainly the rate is not any higher than in depressed folks without exposure to antidepressants."
"The conclusions from the paper supporting the black box warning don't logically follow from the data that they provide," Brent added. "At a minimum, you would have to show that the incidence of suicidal acts and completions is higher in those who were treated vs. those not treated, and that was not done."
For more information on adolescent depression, visit the U.S. National Library of Medicine.
SOURCES: Sebastian Schneeweiss, M.D., associate professor, epidemiology, Harvard School of Public Health, Boston; David Fassler, M.D., clinical professor, psychiatry, University of Vermont College of Medicine, Burlington; David A. Brent, M.D., professor, psychiatry, University of Pittsburgh; April 12, 2010, Pediatrics, online
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