New Antidepressant Label Addresses Suicidality

A "black box" warning about the increased risk of suicidal thoughts and behavior ("suicidality") in children and adolescents being treated with antidepressant medications will soon appear in bold type on the drugs' package inserts, but most experts agree that it should be viewed more like a caution sign than a stop sign. (See end of article for text of warning.)

The US Food and Drug Administration (FDA) decided to require the warning in October 2004 after studying data from 24 studies involving more than 4,400 patients. The FDA concluded that children and adolescents were at twice the risk of suicidality if they were taking antidepressants than if they were taking placebo pills (4% vs. 2% of the study groups). There were no actual suicides reported, however, so the FDA and others have stressed that the new label should not be viewed as prohibiting the use of antidepressants in treating young patients.

"The idea is that there has to be some warning about suicidality risk, and I don't think that's entirely a bad thing to be aware of," said Carlyle H. Chan, MD, Medical College Professor of Psychiatry and Director of the Residency Education Program in the Department of Psychiatry and Behavioral Medicine.

"Unfortunately," said Dr. Chan, "more primary care physicians and pediatricians may be less likely to prescribe antidepressants. Yet, there's a lot of depression out there and there's a lot of good that comes out of these medications."

Weighing the Pluses and Minuses
Prozac is currently the only medication approved by the FDA to treat depression in children and adolescents. Several other antidepressants are regularly prescribed "off label" for younger patients to treat depression and other psychiatric disorders and were included in the studies compiled by the FDA.

"When you're trying to weigh the pluses and minuses, not to prescribe it means that you also have the risk of more children and adolescents becoming depressed, and they're at a risk for suicide because of depression as well," said Dr. Chan. "The alert is definitely worthwhile to make people aware of the risk of suicidality, but hopefully it doesn't become an obstacle to kids getting treatment.

"The people selected were screened for not having suicidality going into the study, so this is new suicide ideation after the study began. So there's twice the risk. Why that is, I don't think you can say for certain. One possible reason is that the medication is causing it; that's obviously one thing that you'd worry about.

"But there's also the phenomenon that we've known for a long time, ever since the original antidepressants came out, that when people are severely depressed sometimes they don't have the energy or will to carry out any type of suicide attempt. Then, as they get better and as they get a little bit more mobilized, suddenly at that point they're more prone to act on some of those feelings even though they're improving. That initial improving period has always been a risky period."

Most Benefit from Antidepressants
While the "black box" is the most serious warning placed on prescription medications by the FDA, in this case the agency has made a concerted effort in news releases and other materials not to minimize the benefits of antidepressants, apparently keeping in mind the distinction between suicidality and actual suicides and other study data that shows very positive outcomes.

"Another thing to look at in terms of those studies is that the benefit out of antidepressants in general is still roughly about a 65% response rate," said Dr. Chan. "So if you take a hundred kids, you've got 65 getting better and you've got four that have potential increased risk for suicide.

"The whole point of that is that they're still an important medication to have available to treat depression. But you do have to assess the risk and you have to monitor more closely. The most important takeaway message (of the FDA decision) is that once you prescribe an antidepressant medication you have to monitor children and adolescents very closely to see if they are in that 4% group that's at a greater risk for suicidality."

Dr. Chan encouraged parents to communicate with their children's doctors openly regarding what the black box label and suicidality really mean. "First of all, you have to talk about it," he said. "Sometimes there's a fear to talk about suicidality, and I think there's a myth that by talking about it you might plant the idea, planting the seed, so to speak. The important thing is to keep it open and on the table. Part of the initial assessment that we make with patients is a suicide assessment: Have they thought about it? Have they made an attempt before? Do they have any specific plans?"

"And it's really important to keep talking about it, not just at the assessment level. I think what the warning label emphasizes is that after the assessment you have to recheck, and you have to follow them to see whether or not there's either a recurrence or an increase in their suicide thoughts and ideation, and whether they can handle them.

"The good news is that antidepressants are an effective treatment. Any medication on the market has both good effects and bad effects, and so you have to weigh the balances."

Dan Ullrich
HealthLink Contributing Writer

This article includes information from the U.S. Food and Drug Administration

What the Black Box Will Say
In a letter sent to drug manufacturers in mid-November, the FDA provided the following wording for the black box warning to be included in antidepressant package inserts:

Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of [Drug Name] or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. [Drug Name] is not approved for use in pediatric patients except for patients with [Any approved pediatric claims here]. (See Warnings and Precautions: Pediatric Use)

Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of nine antidepressant drugs (SSRIs and others) in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events on drug was 4%, twice the placebo risk of 2%. No suicides occurred in these trials.

Each year, Medical College of Wisconsin physicians care for more than 180,000 patients, representing nearly 500,000 patient visits. Medical College physicians practice at Children's Hospital of Wisconsin, Froedtert Memorial Lutheran Hospital, the Milwaukee VA Medical Center, and many other hospitals and clinics in Milwaukee and southeastern Wisconsin.