Do Antidepressants Increase Suicidality? Does The Black Box Warning Help or Hurt People? – Bipolar Burble Blog

Because of the black box warnings (also known as boxed warnings) on antidepressants, many people think that antidepressants cause suicidal thinking, suicidal behavior, and suicide. The black box warning on antidepressants is, after all, the strongest warning the Food and Drug Administration (FDA) can place on a medication. However, the black box warning on antidepressants was authored almost 20 years ago, and we have learned a lot and have synthesized a lot of data since then. Does this more recent data indicate that antidepressants increase suicidality or cause suicides, and what can we learn from this new information? Should we be scared of the risk of suicidality with antidepressants? (TL;DR here.)

What Is the Black Box Warning on Antidepressants, and How Does It Relate to Suicidality?

As mentioned above, a black box warning is the strongest warning the FDA can place on a drug. Warnings themselves are common, but black box warnings are less so.

According to the Cleveland Clinic:

Black box warnings, also called boxed warnings, are required by the U.S. Food and Drug Administration for certain medications that carry serious safety risks. Often these warnings communicate potential rare but dangerous side effects, or they may be used to communicate important instructions for safe use of the drug.

They appear printed in bold font surrounded by a black border on the insert that comes inside a medication’s packaging, and on the drug manufacturer’s website, if it has one.

As an example, the black box warning for fluoxetine (Prozac) says:

In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses

This increase was not seen in patients >24 years; a slight decrease in suicidal thinking was seen in adults >65 years

In children and young adults, the risks must be weighed against the benefits of taking antidepressants

Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during the initial 1-2 months of therapy and dosage adjustments

The patient’s family should communicate any abrupt changes in behavior to the health-care provider

Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy

As you can see, the boxed warning talks about suicidality with antidepressants and other important pieces of prescribing information. Black box warnings are really for doctors, but patients are generally made aware of them also through medication handouts (the ones you’re hopefully getting at the pharmacy). Black box warnings tend to scare both doctors and patients.

Antidepressants and Suicidality — More Recent Data

The black box warning was placed on antidepressants back in 2004. It made sense at the time. It’s the FDA’s job to be conservative with people’s safety. Numbers, even preliminary ones, should be heeded when they show something as serious as suicidality.

However, now, people are questioning not only the appropriateness of the black box warning but also its benefit.

This is an excellent review (from 2014) in Psychiatric Times of the risks of suicidality, suicidal actions, and suicides after starting an antidepressant. The takeaways include the following:

• Analyzing the data from the FDA Adverse Event Reporting System (MedWatch; where adverse events are reported after the drug is on the market) from 1998 to 2004 showed that, as a class, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) had a suicide rate that was lower than that of tricyclic antidepressants (TCAs). (Note that TCAs are an older class of antidepressants that is no longer frequently used.)
• In some cases, higher TCA prescription rates are actually associated with higher suicide rates. This may be due to the toxicity of TCA drugs, making them more deadly in the event of a suicide attempt.
• An increase in antidepressant use has been shown to be correlated with a decrease in suicide rates over time across the world. For example, in Sweden, the doubling of prescriptions for SSRIs was correlated with a 25% decrease in the incidence of suicide.
• US county-level data on suicide rates and antidepressant prescription rates were analyzed from 1996 to 1998. After adjusting for sex, race, age, income, and unobservable county-level effects, the analyses revealed that increases in SSRI and SNRI prescriptions were associated with decreases in suicide rates both between and within counties over time.
• A cohort study of 226,866 veterans with newly diagnosed depression indicated that the attempted suicide rate was lower in those treated with an SSRI than in those who did not receive an antidepressant.

What About Suicide in Youth?

The data on suicidal thoughts and actions in youth is less conclusive. Some data shows that there is no increased risk of suicide in youth treated with antidepressants; other data shows there may be a small increase in risk for those under the age of 18 (not 24). However, the risk is less than previously thought. It appears that suicidal thoughts and actions are driven by factors outside of depression in youth. (The thought is that the antidepressants are alleviating the depression in youth, but that’s not what’s driving their suicidal behavior.)

Even worse, this 2020 study found increases in suicide deaths among youth following the black box warnings and declines in depression care.

After the Black Box Warning, Did Suicide Increase?

Unfortunately, the initiation of the black box warning on antidepressants may have increased suicides as practitioners chose to use antidepressants less. Moreover, in youth, less depression was diagnosed after the black box warning — suggesting that not only were doctors less willing to prescribe antidepressants, but they were less willing even to make a diagnosis, which is unfortunate considering the other types of help the youth could have received if they had of been diagnosed.

These reflectances may have been a mistake:

• Researchers looked at 845 suicides in the 10- to 19-year-old group in Sweden from 1992 through 2010. After the 2004 warning, the suicide rate increased for 5 consecutive years (60.5%), largely in those who were not treated with antidepressants.

As the Psychiatric Times article puts it:

The FDA implementation of a black box warning had the purpose of reducing suicide rates in children, adolescents, and young adults. The picture following the FDA warning and implementation of the black box warning is not that of a lower suicide rate as intended or hoped for by the FDA. Instead, we see fewer antidepressant prescriptions, an increase in youth suicides, and negative effects on human capital.

This report in Frontiers in Psychiatry outlines the real-world harm the black box warning can do.

TL;DR — Do Antidepressants Increase Suicides? Did the Black Box Warning Decrease Suicide Rates?

Long story short, it looks like antidepressants do not actually raise the risk of suicide in adults. There may be a small risk for youth (even that is uncertain), but there are significant benefits in that group to be considered. Additionally, it looks like putting out such a severe warning on antidepressants actually had the unfortunate effect of increasing suicides, not decreasing them.

I’m not about to say what kind of warning the FDA should put on a medication. What I would say, though, is that our concerns over suicides due to antidepressants were exaggerated. With incomplete information, we needed to do that at the time, but the same level of concern doesn’t seem to be warranted now, given the more up-to-date data we have. We should still always, always maintain elevated oversight when a person starts any medication because we don’t know how they will react to it, but it’s highly unlikely that an antidepressant will actually cause a suicide, and overreacting to this possibility to the point of denying people an antidepressant or even a diagnosis is a mistake.

Note: I am not a doctor, and everyone’s individual risk profile varies. Always discuss all your concerns with your doctor openly.

Image by Nick Youngson via Pix4free.org.

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