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The Antidepressant Black Box Warning: Is It Necessary? Did It Backfire?

Do antidepressants cause suicide

The FDA issued a black box warning for antidepressants and suicide risk in 2004, and expanded it three years later. Ten years after, was it – is it – necessary? Did it backfire? How ’bout we take a look?

Is it possible that patients might have become reluctant to disclose symptoms of depression that could lead to a firm diagnosis and antidepressant treatment? Sure. And physicians may easily have become shy about prescribing.

A mother of a 15-year-old recently commented on a Chipur article, expressing concern about the side effects of the antidepressant Viibryd. Seems her son was transitioning from another antidepressant, Lexapro.

To help her out, I began researching the usual suspects – weight gain, GI issues, fatigue, blurred vision. But then it dawned on me – antidepressants and a 15-year-old. Needless to say, my research took a much different turn.

In 2004 the US Food and Drug Administration (FDA) issued a black box warning on antidepressants because of increased risk of suicidal thought, feeling, and behavior in young people.

So here we are, 10 years later. How’d that work-out?

My research led me to a great article on The New England Journal of Medicine website, posted October 2014. Written by Richard A. Friedman, MD, it’s entitled “Antidepressants’ Black-Box Warning — 10 Years Later.”

This piece is based 100% upon that piece…

Setting the Table

Dr. Friedman kicks-things-off by detailing the black box warning issuance in 2004, and emphasizes the decision was controversial from the get-go. Yep, members of the medical community were concerned the warning would do more harm than good.

How could that be? Well, depressed folk would be discouraged from seeking help, and docs would be looking over their shoulders every time they wrote an antidepressant (AD) scrip.

Friedman says – 10 years later – there are buckets of epidemiologic data to address concerns from all angles.

Still, for our purposes…

What effect has the black box warning had on rates of detection and treatment of depression? And is there evidence that rates of suicide, or attempts, have changed?

The Stats

According to Friedman, who can really blame the FDA for issuing the warning? I mean, they’d conducted a series of meta-analyses of close to 400 randomized clinical trials of ADs involving nearly 100,000 participants.

Revealed: the rate of suicidal thinking or behavior was 4% among patients assigned to receive an AD, compared to 2% among those assigned to receive placebo. Of note, none of the documented suicide attempts were fatal (for whatever that’s worth, right?).

Age was later factored into the equation and it was noted the increased suicide risk was significant among children and adolescents under the age of 18 – exclusively. Further, no increased risk was noted for adults over age 24. In fact, among adults 65 and older, ADs had a clear protective effect against suicidal ideation and behavior.

In 2007 the FDA upped the ante by mandating an expanded AD black box warning citing increased risk of suicidal thinking and behavior in young adults ages 18-24 during initial treatment (generally the first one to two months).

Was It Worth It?

Dr. Friedman proposes the FDA was obviously mindful of the need to balance the small risk associated with AD treatment against its proven benefits. However, 10 years later, he asks if the well-intended warning accomplished its mission. And that would be to educate clinicians about risk, without discouraging appropriate treatment of depression. (And let’s not forget about saving lives.)

Friedman leans toward the answer being no.

He cites a mega-huge cohort study with data gathered between 2000 and 2010. The results showed major reductions in AD use by adolescents and adults of all ages within two years of the black box warning. And although the downward trend in adolescent AD use somewhat reversed in 2008, it was still below 2004 rates.

Friedman points-out that though the FDAs black box warning was intended to impact children and adolescents, it likely had an effect on treatment of adults with depression. Not only were they not the intended target, there’s compelling evidence that ADs have a positive effect on older adult suicide risk.

But there’s more…

In addition to AD prescriptions plummeting post-black box warning, the rate of diagnosis of new cases of depression significantly dropped, as well. And, by the way, as AD prescribing fell, there was no compensatory increase in other forms of depression treatment – psychotherapy, other psychotropic drugs.

(Now in all fairness, Friedman points-out that the data used in drawing the above conclusions only show that they happen to correlate with the black box warning issuance. A causal link between the warnings and changes in depression diagnosis and treatment can’t be established.)

Still, the black box warning could well have had an impact upon both users and physicians in the face of warning controversy and media coverage. Is it possible that patients might have become reluctant to disclose symptoms of depression that could lead to a firm diagnosis and AD treatment? Sure. And physicians may easily have become shy about prescribing.

Yet more…

Post-black box warning, a significant increase in psychotropic drug poisoning presented in adolescents and young adults. Were these suicide attempts caused by the downward trend in AD use?

Who knows for sure; however, it’s a call to prescribing clinicians to understand the risks of untreated depression, in terms of morbidity and mortality, have always been far greater than the very small risk associated with AD treatment. Friedman believes that calls for education, especially for primary care physicians.

What Next?

In wrapping-up his article, Dr. Friedman questions what the FDA should do in light of the observational data. He argues the black box warning should be removed entirely. At the very least, he challenges the medical profession to engage in discussion regarding removal.

Friedman believes the medical profession can’t ignore the weight of available epidemiologic data, or the very real possibility that the FDA warning has unintentionally discouraged depressed patients from seeking treatment – and doctors from prescribing antidepressants.

Your Opinion?

If you’re reading this article, there’s a pretty good chance you have some experience with depression – maybe antidepressants. So what do you think?

Does the black box warning stay or go? Would you express your opinion in a comment?

Hey! Want to read the original article, as well as all of Dr. Friedman’s stats? Here ya’ go.

More about the mood and anxiety disorders? The Chipur titles.

  • Patricia Miller

    Due to the black box warnings issued in 2004 specific to pregnant women, there were some increased suicide attempts in antenatal women and increased severity in postpartum depression in that depression predisposed subset population who had gone off their medication. By 2007 that black box label was removed. The damage remains still in that many obstetricians are slow to treat antenatal depression for fear of damage to the growing baby. The mental health prescribers are more likely to believe that the mother’s mental health is going to be predictive of a healthy child, delivery, and mother/child bonding. There may need to be a modification of medication during the pregnancy or lactation, but mental health issues truly matter.

    That was a very LONG answer to say that I believe the black box warnings have over generalized and do not provide accurate information for any consumer. Individual risk factors will always matter when it comes to suicide as will access to a lethal means. Thanks for a great topic.

    • Well, Hi, Patricia! Glad you stopped-by and commented.

      Good catch and share on the 2004 bb warning directed at pregnant women – I was not aware of it. Not surprising, is it, that the “hangover” remains. No doubt, a delicate balancing act of issues; however, yes, “mental health issues truly matter.”

      I’m with you (and Dr. Friedman) on the AD bb warnings – over-generalization, with some unfortunate fallout. (Yet I can still understand why the FDA felt compelled to issue.)

      Thank you, Patricia…