Black Box Warnings on Antidepressants Backfires

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Image: Tom Varco

After a 2003 report linking selective serotonin reuptake inhibitors, or SSRIs, with increased suicide rates among children and teen agers was published, the use of this class of antidepressants in these age groups has decreased dramatically. This led to a change in labeling in 2003 that warned that use of the medications could increase suicidal thoughts and behavior among youths. Sadly, this 'black box' warning has caused a decrease in prescriptions for SSRI antidepressants which appears to have has triggered a sharp increase in suicide rates for these age groups, according to two papers that have recently been published.

According to a new study published recently in the American Journal of Psychiatry, SSRI prescriptions for children and teens decreased by 22% in both the United States and the Netherlands after government 'black box' warnings were issued.

As a result, in the United States, the youth suicide rates increased by 14% between 2003 and 2004, reports biostatistician Robert D. Gibbons and his colleagues at the University of Illinois at Chicago. This is the largest year-to-year change in suicide rates in this population since the Centers for Disease Control and Prevention began systematically collecting suicide data in 1979.

Additionally, between 2003 and 2005, Dutch youths experienced a 49% increase in their suicide rate and further, this increase shows a significant inverse association with SSRI prescriptions. Using these data, the team estimated that every 20% drop in antidepressant use among all ages in the US would lead to a nearly 10% increase in suicides -- an additional 3,040 deaths per year.

Another study by Greg Simon and James Savarino at Group Health Cooperative in Seattle revealed that the pattern of suicide attempts before and after starting antidepressant treatment was not specific to the type of medication used. This study found that the differences between treatments and changes over time probably reflect referral patterns and the expected improvement in suicidal ideation after the start of treatment.

SSRIs include Prozac, Zoloft and Paxil. According to Mental Health America, approximately 16 million Americans take SSRIs.

The Food and Drug Administration originally required black-box warnings on SSRIs in 2003 and 2004 because according to research, youths who took the drugs showed an increase in suicidal thinking. At that time, the warning applied specifically to patients younger than 19. But earlier this year, the warning was changed to include adults younger than 25.

However, an editorialist astutely observed that "it is much more likely that suicidal behavior leads to treatment than that treatment leads to suicidal behavior." Many experts argued that the FDA warnings would cause many patients to abandon treatment that they desperately need. Currently, at least 3 million Americans do not receive any treatment for their depression.

But these new studies provides the strongest evidence yet that SSRIs actually do prevent suicide in children and teens as well as in adults.

"If the intent of the black-box warning was to save lives, the warning failed," Gibbons' team wrote in their paper. " . . . What should be considered instead is better education and training of physicians."


"Early Evidence on the Effects of Regulators' Suicidality Warnings on SSRI Prescriptions and Suicide in Children and Adolescents" by Robert D. Gibbons, C. Hendricks Brown, Kwan Hur, Sue M. Marcus, Dulal K. Bhaumik, Joëlle A. Erkens, Ron M.C. Herings, and J. John Mann. Am J Psychiatry 2007 164: 1356-1363 [abstract] (quotes)

"Suicide attempts among patients starting depression treatment with medications or psychotherapy" by Simon GE and Savarino J. Am J Psychiatry (2007 July); 164:1029-34 [PDF]

"Emerging Perspectives: Look Again -- SSRIs and Fewer Suicide Attempts" [full article]

LATimes (quotes)

"Suicide Rates in Clinical Trials of SSRIs, Other Antidepressants, and Placebo: Analysis of FDA Reports" by Arif Khan, Shirin Khan, Russell Kolts, and Walter A. Brown. Am J Psychiatry 160:4 (April 2003) [free PDF] This is the original 2003 report.

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If the net effect of the warnings was to discourage treatment then the warnings were bad. The better option is treatment with drugs combined with a closer watch of patients.

I think anti-depressants like any psychotropic medicine are powerful tools, but the power they exert can lead to bad results. The best thing is to administer them carefully and to carefully monitor the patients.

The original report seemed pretty bunk to begin with. From what I remember it was a literature review, and several studies since have questioned its accuracy and concluded the increase, if existant, was at best nominal. How exactly do you measure increased suicide rates in a demographic already prone to suicidal ideation?


One of the biggest mistakes you can make, when trying to understand this complex topic, is to confuse suicidal ideation with completed suicides.

The biggest increase in suicide occurred in adolescent girls, and the bigget increase in method was is suicide by hanging or suffocation. There is nothing fuzzy about that math. It is kind of hard to miss.

I think the original FDA process reflected a fundamental misunderstanding of both how anti-depressants work, and how the American public and the medical profession thinks. Moving somewhat backwards:
1) American public thinking: Black Box Warning = Death is imminent. Do not take this drug unless you are terminally ill. Add this on top of the fact that most parents have been conditioned to think that drugs are BAD to give to their children under any circumstance, and you have a disaster in the making.
2) Physician thinking: Anything with a black box warning = more time (unpaid) to explain and justify decision to use medication to parents, potential malpractice liability if you prescribe the drug. Parents have little cause for action and zero hope of winning a case if you simply do not feel that any cases of depression are severe enough to risk braving the dangers of anti-depressants, especially since the FDA has determined that these drugs are so deadly dangerous as to require extra-special warnings on them.

3)Understanding depression: Suicidal ideation doesn't have to lead to suicide. It is in fact a sign that the depression is improving, in that the patient is able to think of things other than black, numbing despair. You do have to watch the patients much more closely at this stage. Treating depression is not like treating strep throat - you can't just give pills and send the patient away.

By bobzchemist (not verified) on 10 Sep 2007 #permalink