If you’re one of the many people who takes an antidepressant to ease your depression, you might be taking a medication whose package insert carries a U.S. Food and Drug Administration (FDA) mandated “black box warning” label. This label cautions users about an increased risk of suicidal thoughts and behavior among children, teens, and young adults that’s been linked to taking the drugs.
This black box warning label has been carried on antidepressant medications in the classes known as selective serotonin or serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs) since 2004 (for children and teens) and 2006 (for young adults ages 18-25). This class of medications includes such commonly used antidepressants as Prozac, Zoloft, Celexa, and Effexor. The FDA required the warning after several industry-sponsored studies uncovered the increased risk for suicidal behavior as an ironic side effect to taking these meds to treat depression.
But now a new study by researchers at the University of Chicago is casting doubt on the studies that triggered the FDA’s warning label, saying that the first studies didn’t take into account how well the drugs were working to reduce users’ depression symptoms. If the drugs worked to relieve depression, the risk of suicidal thoughts and behaviors actually appears to decrease, they say, not increase. But if the depression is not brought under control – by the medications or other means – the risk of suicidal ideation remains elevated.
What is a “Black Box Warning” Label?
According to the Code of Federal Regulations, 21CFR201.57(e), “Special problems, particularly those that may lead to death or serious injury, may be required by the U.S. Food and Drug Administration to be placed in a prominently displayed box.” That means that if the FDA is alerted to clinical data – even animal studies – that appear to link a medication with a potentially life-threatening condition, FDA officials will require that people taking the drug be warned about this potential side effect.
A black box warning on a medication doesn’t mean patients shouldn’t take the medication or that a doctor should stop prescribing it. But it does mean that a doctor – and his or her patient, in their discussions about treatment – should consider the risks and benefits of the drug when deciding on a course of treatment.
Prozac’s Black Box Warning Label
What Triggered the Antidepressant Black Box Warning?
The FDA’s move to require a black box warning on antidepressant medications was triggered by a series of inquires that started in 2003 with an investigation into a clinical trial on the use of Paxil in children. Reports had shown that a small percentage of children in this trial had shown signs of increased suicidal behavior, and FDA officials were so concerned by this finding that they asked drugmakers of this med and eight others to look at all their pediatric drug trial data to see if there was a pattern to this suicidal behavior/antidepressant link.
In response, some drug companies, including Wyeth, voluntarily changed their labels and sent letters to doctors, urging caution about the use of the antidepressants in children. In October of that same year, the FDA sent out a public health advisory, doing the same thing. The concern became even more widespread when the FDA’s British counterpart, the Medicines and Healthcare Products Regulatory Agency, recommended against the use of all antidepressants except Prozac in children. Prozac, it stated, was the only drug whose benefits appeared to outweigh its risks.
The FDA would eventually act with the black box warning after a review of 25 pediatric clinical trials and 15 pediatric depression trials. The move was not without controversy, however, with many doctors feeling the warning label would deter parents from seeking medication for children who might desperately need it. Parents of young people who had committed suicide while on the drugs countered that they would have rather have been informed of the risks and live with that than live with the potentially preventable deaths of their children.
In 2006, similar findings about increased suicidal behavior and antidepressant use was found in young adults ages 18-25. This prompted the additional warning on antidepressant medications for people in this age group.
(For an in-depth look at this process, read John McManamy’s excellent timeline article here.)
What the New Study Found
In the new study, researchers looked at clinical data on 40 controlled trials on the antidepressants Prozac and Effexor. They found that suicidal thoughts and behaviors in adults (including the elderly) fell in those taking these two medications, and that these suicidal behaviors did not increase in children and teens taking them. Thus, the medications didn’t reduce suicidal ideation in kids and teens, but it also didn’t increase them as the previous studies had suggested.
The only patients whose suicide risk increased after taking the medications were those for whom the antidepressants didn’t appear to work to alleviate their depression. Thus, if a medication was helping to ease a patient’s overall depression, his or her risk of suicidal thoughts and behaviors also decreased. If the medication and/or other treatments were not working to reduce depression, the person’s suicide risk remained high.
Without this data factored in, the researchers say the data that the FDA used to make its recommendation for a black box warning may have been misleading. If the statistics on people for whom the medications weren’t working to control their depression were looked at differently, there may not have been the rise in suicidal behaviors among children, teens, and young adults that triggered the warning.
So why did the medications reduce suicidal behavior risk in adults and not in children and teens? The researchers aren’t certain at this point, but they say their finding suggests that other psychological factors – such as aggressive or impulsive – may play more into young people’s suicide risks than depression itself.
What This Study Could Mean for Antidepressant Users
This study could eventually have important implications for the FDA’s mandated black box warning on antidepressants. If the University of Chicago researchers are correct that the initial studies on which the FDA based its recommendation for the warning didn’t take into account how well the drugs were working in the patients to ease their depression, and if these studies are re-examined this light, it may be that the FDA decides to rethink the need for the warning.
More research is certainly needed before this move can come about. But this new study is good news for those whose doctors have elected that the benefits outweigh the potential risks of taking antidepressants.
Read the entire study here: Gibbons R, et al "Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine" Arch Gen Psychiatry 2012; 69: 580-587.
Sources: U.S. Food and Drug Administration; USA Today; MedPage Today; Wikipedia; Code of Federal Regulations; NPR.com; McManWeb.com.
Published On: June 22, 2012