FDA’s continuing use of ‘black box’ for antidepressants ignores the harms of this warning

The Food and Drug Administration’s “black box” warnings and advisories give important safety information about drugs. But they can sometimes go too far and harm more people than they help.

Take the FDA’s highly publicized warnings that taking antidepressants increases the risk of suicidality (defined as serious thoughts about taking one’s own life or planning or attempting suicide) among children, adolescents, and young adults. We have evidence, as do many others, that these warnings have decreased youths’ access to mental health care and increased suicide attempts. So far, the FDA has refused to accept this evidence.

Depression in young people is a disabling and stigmatizing illness, both in the U.S. and around the world. It is the leading cause of suicide, which climbed by about 50 percent among adolescents between 2003 and 2016.

Antidepressants help many people fight depression. But based on a controversial review of industry studies, beginning in October 2003 the FDA issued a series of health advisories warning that children and adolescents taking antidepressants were at increased risk of suicidality.

In October 2004, the FDA required a so-called “black box warning” of this risk to be printed on the labels of all antidepressant drugs. It was implemented in January 2005. Two years later, the FDA extended the same warning to include young adults, again based on industry studies. Each announcement was accompanied by a slew of media reports about the link between antidepressant use and suicide that exaggerated the danger message.

All antidepressant prescriptions still contain this frightening black box warning, and the message is repeated in TV ads.

In an effort to monitor and reduce suicidality — including suicide attempts — among young people, the FDA also urged clinicians to ask about suicidal thoughts every time they prescribed antidepressants to a young person.

The FDA was undoubtedly acting with good intentions. But the warnings reduced the use of both antidepressants and talk therapy among young persons with depression, with the unwanted consequences of reducing its diagnosis and treatment. This was followed rapidly by an increase in suicidal behavior.

There’s no question that antidepressants can cause harm if used inappropriately. But the FDA failed to recognize — and still won’t acknowledge — that the harms of its public advisories and black box warning on antidepressants for young people more than outweigh the benefits. The evidence is strong that:

• the warnings stopped many adolescents and young adults from seeking care for depression
• many of those with depression didn’t seek help and so did not receive effective drug treatment
• psychotherapy and other mental health visits declined
• suicide attempts increased

We used a simple and clear way to measure the effects of these antidepressant warnings. Called the interrupted-time-series design, this rigorous method graphically displays how the warnings resulted in sudden and harmful breaks from existing trends.

Decline in diagnoses of major depressive disorder

Up to half of people with depression are not treated for it; some commit suicide as a result. In a study of 55 million managed care enrollees, the FDA warnings led to an almost 40 percent reduction in the identification of adolescent patients with major depressive disorder, an important predictor of suicide. The researchers also saw a significant reduction in diagnoses among young adults.

This began soon after the first FDA advisory in October 2003. It continued after the FDA black box warning for children and adolescents started in 2005 and the one for young adults began in 2007.

Decline in antidepressant use

In the years following the FDA’s first antidepressant warning in October 2003, there was a sudden, nearly 50 percent decline in the use of antidepressants among more than 400,000 poor children and adolescents in Tennessee who were covered by Medicaid. It’s hard to believe that this was not an unintended result of the warnings.

Reduction in psychotherapy

Mental health advocates hoped that any decline in antidepressant use following the FDA’s warnings would be matched by increases in face-to-face psychotherapy to treat depression and improve detection of suicidal behavior. But that didn’t happen. Psychotherapy among all patients with major depression declined after the warnings. The reduction was almost identical in adolescents and young adults.

Clearly, the FDA’s recommendation that clinicians increase monitoring of patients for suicidal thoughts and behaviors did not occur.

Increase in psychotropic drug poisonings

Based on data from 11 health plans with more than 7 million people, a study we published in BMJ demonstrated two dramatic outcomes of the FDA’s antidepressant warnings and the associated publicity over a 10-year period: a sudden 31 percent reduction in antidepressant use among adolescents and a 24 percent reduction in young adults, with a simultaneous increase in poisonings due to the use of psychoactive drugs such as tranquilizers like Valium and antipsychotic drugs, a method that adolescent girls often use to attempt suicide.

These were the consequences not only of reductions in medication, but also of reductions in diagnosis, psychotherapy, and monitoring, as well as a general chilling atmosphere for depression treatment created by overblown media reports of a link between antidepressant use and suicide.

Additional data

Researchers have been evaluating the impact of the FDA’s antidepressant warnings for years. A 2008 study, for example, documented possible increases in completed suicides as a result of the warnings. Earlier this year, the Centers for Disease Control and Prevention confirmed that suicide attempts among teenagers have doubled in the last decade. While this research wasn’t intended to isolate the effects of the warnings, it suggests that suicide deaths increased simultaneously with the continuation of the black box warnings.

There are now even more high-quality studies, some up to a decade long, from diverse environments and involving tens of millions of individuals, showing increased harm following the warnings, sometimes almost immediately.

It’s time to rethink the warning

The FDA knows that drug warnings are seldom totally harmless, and it carefully weighs the tradeoffs. The antidepressant warnings may have made sense to the FDA at the time, though critics have long charged that the data on which the FDA based the warnings are flawed. But the body of evidence that has been accumulated since then overwhelms the analysis that prompted the FDA’s decisions.

The risk of suicidal thoughts and behaviors and suicide attempts among youths, adolescents, and young adults due to taking antidepressants was never as high as the risk due to untreated depression.

Yet just this spring, an FDA representative, rather than admitting the error, dismissed the effects of the warnings on antidepressant use in an article in the journal Medical Care, ignoring the threat to the mental health of young people.

It’s time for the FDA to acknowledge this miscalculation. Going forward, FDA policymakers should consider working with researchers who study the antidepressant black box warning about suicide. Because it continues to dampen effective drug and non-drug treatment and monitoring for depression — and because teen suicide attempts are accelerating — it’s appropriate to think about removing this warning.

Stephen Soumerai is professor of population medicine, founding and former director of the Division of Health Policy and Insurance Research, and teaches research methods at Harvard Medical School. Ross Koppel is adjunct professor of sociology at the University of Pennsylvania, where he is also a senior fellow at the Leonard Davis Institute, the Institute of Biomedical Informatics, and the Center for Public Health Initiatives. Caitlin Lupton, an administrative specialist for the Division of Health Policy and Insurance Research, created the graphs for this article.