Connection between SSRIs, suicide coming under review
■ Studies will undertake a variety of approaches ranging from examining large databases to developing assessment tools.
By Susan J. Landers — Posted Dec. 18, 2006
Washington -- Five newly funded studies will soon delve into one of medicine's knottier questions: Do antidepressants, particularly the new and popular SSRIs, cause suicidal thoughts and behaviors?
The National Institute of Mental Health is betting that these studies can at least begin to unravel that mystery as the findings emerge in the coming years. The announcement provoked both praise and questions from close observers.
Balancing the risks and benefits of selective serotonin reuptake inhibitors, particularly for children and teens with depression, has emerged as a difficult call for physicians. On the one hand, studies show that the medications are helpful in treating moderate and severe depression among this group. But on the other, concerns about the drugs prompted the Food and Drug Administration to require that their labels carry black-box warnings for suicide risk.
Although there were no suicides among the nearly 2,200 children in studies reviewed by the FDA, the rate of suicidal thinking or behavior, including actual suicide attempts, was 4% for those on the medications compared with 2% for those on placebo.
"These new, multiyear projects will clarify the connection between SSRI use and suicidality," said NIMH Director Thomas Insel, MD, in a statement. "They will help determine why and how SSRIs may trigger suicidal thinking and behavior in some people but not others, and may lead to new tools that will help us screen for those who are most vulnerable."
Three of the five studies will conduct data reviews to determine risk, one is investigating the drugs' link to a set of symptoms that includes irritability and agitation and another intends to devise a computer tool to screen for suicidal behavior.
They will share an estimated $5.6 million in funding over the next five years.
Several medical societies, including the AMA, the American Psychiatric Assn., the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics, have advocated for increased research in this area, noted David Fassler, MD, clinical professor of psychiatry at the University of Vermont College of Medicine. "I expect the data will ultimately influence clinical practice and help inform future regulatory decisions."
Raising additional questions
But John S. March, MD, MPH, professor and chief of Child and Adolescent Psychiatry at Duke University in Durham, N.C., questions whether these particular studies will prove valuable. "You can look at these as an example of the field doing something but it is, to some extent, off target and not nearly enough."
He would rather see the FDA push more pharmaceutical companies to carry out so-called phase IV studies on antidepressants. Such studies continue to watch for side effects after a drug is approved for sale and taken by many more people than could possibly be included in a clinical trial.
Dr. March, who is the principal investigator of the Child and Adolescent Psychiatry Trials Network, or CAPTN, also noted that none of the funded studies is set up to determine why people react differently to the antidepressants. "Some people get remarkably well with no adverse effects, some people get somewhat better with mild side effects and a few people are harmed."
A pharmacogenetics trial is underway in CAPTN, which is a network of about 300 child and adolescent psychiatrists who participate in a variety of clinical trials, to try to determine why these individual differences should occur, he said.
Meanwhile, until study results emerge, physicians should continue to monitor closely children and adolescents who are starting SSRIs, for any worsening in depression or, in general, any changes in behavior such as sleeplessness or agitation.
That advice has been valid for all antidepressants for the past 20 years, said Gregory Simon, MD, MPH, psychiatrist and researcher at Group Health Cooperative, a nonprofit health care system in Seattle. "The quality of follow-up care for people who start an antidepressant is really appalling."
Close follow-up is important not only to detect suicide risk, but because there is good evidence that following people closely means that more people will get better, said Dr. Simon.