Pittsburgh -- An interdisciplinary team of researchers from Carnegie Mellon University and The Ohio State University has received a five-year, $1.2 million grant from the National Institute of Mental Health to investigate the link between antidepressants and suicidality -- including suicidal thoughts, attempts and suicide deaths. The researchers have previously challenged the U.S. Food and Drug Administration's (FDA) findings that antidepressants are causally linked to an increase in suicidal thoughts and behaviors in young people.
In 2004, the FDA performed a meta-analysis of the results of randomized clinical trials of antidepressants and concluded that the drugs led to increased suicidal behaviors and thoughts, which it termed "suicidality," among children and adolescents. As a result, the FDA required manufacturers to place a black box warning on the labels of antidepressants -- the strongest regulatory action the agency can take short of an outright ban. This has led to a decline in prescriptions of antidepressants for children and adolescents.
But the results of a study published in April by scientists from Carnegie Mellon and Ohio State suggest that the FDA may have overstated the actual risk to most teens and children on antidepressants. Using sophisticated statistical techniques, the researchers found an increased risk of suicidality only among adolescents who suffered from major depressive disorder, and then only among those who took a specific class of antidepressants -- selective serotonin reuptake inhibitors (SSRIs). Antidepressants are prescribed for a variety of other psychological ailments, such as obsessive-compulsive disorder and general anxiety disorder.
"Our concern was that by mixing together different diagnostic groups as well as different formulations of antidepressants, the FDA was underestimating important sources of variability that would make their results look more significant than they were," said Joel Greenhouse, professor of statistics at Carnegie Mellon and one of the study's authors.
Working with Greenhouse will be Howard Seltman, a research scientist in Carnegie Mellon's Statistics Department; Eloise Kaizar, who recently earned her Ph.D. in statistics from Carnegie Mellon and soon will join the statistics faculty at Ohio State; and Kelly Kelleher, director of the Center for Innovation in Pediatric Practice and vice president for Health Services Research in the Columbus Children's Research Institute at Columbus Children's Hospital. Kelleher is also a faculty member of Ohio State's College of Medicine.
Greenhouse said several other factors are worth noting. The clinical trials that formed the basis of the FDA's review were not designed to measure suicide; their purpose was to determine the efficacy of various antidepressants in treating mental illness among children and adolescents. None of the approximately 4,600 youth who participated in those studies committed suicide, and the number of suicide attempts was too low to be statistically significant. That prompted the FDA to broaden its primary outcome to include suicidality, even though there is no evidence of a link between suicidality and suicide itself.
The researchers will use the grant to analyze other data sources that might shed light on what relationship, if any, antidepressant use has with suicidal behavior. For example, the FDA did not take into account recent results from large observational studies that, using health administrative data, have been unable to find an increased risk of suicidal behavior among youths who use antidepressants. They will also review psychotherapy studies to see whether there is an increase in suicidality among teens who were successfully treated with methods other than antidepressants. Greenhouse said that many psychiatrists believe that as their patients' conditions improve, they are more likely to express suicidal thoughts simply because they are better able to articulate their feelings.
"As a regulatory agency, the FDA made a public health decision to issue the black box warning. From a scientific perspective, we are interested in the question, 'What evidence, if any, is out there that would convince the FDA to remove the black box warning?' We want to do this systematically and look at alternative explanations as well," Greenhouse said.