Because of the black box warnings (also known as boxed warnings) on antidepressants, many people believe that antidepressants cause suicidal thinking, suicidal behavior, and suicide. The black box warning for antidepressants is, after all, the strongest warning the Food and Drug Administration (FDA) can give to a drug. However, the black box warning for antidepressants was written almost 20 years ago, and we’ve learned a lot and compiled a lot of data since then. These latest data show that antidepressants increase suicide or cause suicides, and what can we learn from this new information? Should we fear the risk of suicide with antidepressants? (TL;DR here.)
What is the black box warning for antidepressants and how does it relate to suicide?
As mentioned above, a black box warning is the strongest warning the FDA can give to a drug. The warnings themselves are common, but the black box warnings are less so.
According to the Cleveland Clinic:
Black box warnings, also called boxed warnings, are required by the US Food and Drug Administration for certain drugs that pose serious safety risks. Often these warnings communicate possible rare but dangerous side effects or may be used to communicate important instructions for safe use of the drug.
They appear in bold print and surrounded by a black border on the insert inside a medicine’s package and on the medicine’s manufacturer’s website, if available.
For example, black box warning for fluoxetine (Prozac) says:
In short-term studies, antidepressants increased the risk of suicidal ideation and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorder and other psychiatric illnesses
This increase was not observed in patients >24 years of age. a slight decrease in suicidal ideation was observed in adults >65 years of age
In children and young adults, the risks must be weighed against the benefits of taking antidepressants
Patients should be closely monitored for behavioral changes, clinical deterioration, and suicidal tendencies. this should be done during the initial 1-2 months of treatment and dosage adjustments
The patient’s family should notify the health care provider of any sudden changes in behavior
Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of treatment
As you can see, the boxed warning talks about suicide with antidepressants and other important prescribing information. Black box warnings are really for doctors, but patients are generally told about them through drug leaflets (the ones you hopefully get at the pharmacy). Black box warnings tend to scare doctors and patients alike.
Antidepressants and suicidality — More recent data
The black box warning was placed on antidepressants in 2004. It made sense at the time. It is the FDA’s job to be conservative with people’s safety. Numbers, even preliminary ones, need to be taken into account when they point to something as serious as suicide.
However, now, people are questioning not only the appropriateness of the black box warning but also its benefit.
This is an excellent review (as of 2014) in Psychiatric Times on the risks of suicide, suicidal acts, and suicide after starting an antidepressant. Takeaways include the following:
- Analysis of data from the FDA’s Adverse Reaction Reporting System (MedWatch, where adverse drug reactions are reported after marketing) from 1998 to 2004 showed that, as a class, selective serotonin reuptake inhibitors (SSRIs) and serotonin reuptake inhibitors (SSRIs) -norepinephrine (SNRIs) had a lower suicide rate than tricyclic antidepressants (TCAs). (Note that TCAs are an older class of antidepressants that are no longer commonly 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 lethal in a suicide attempt.
- Increasing use of antidepressants has been shown to correlate with decreasing suicide rates over time around the world. For example, in Sweden, a doubling of SSRI prescriptions was associated with a 25% reduction in the incidence of suicide.
- US county-level data on suicide rates and antidepressant prescription rates were analyzed from 1996 to 1998. After adjustment for sex, race, age, income, and county-level unobservable effects, the analyzes revealed that increases in SSRI and SNRI prescribing were associated with decreased suicide rates both between and within counties over time.
- A cohort study of 226,866 veterans with newly diagnosed depression showed that the rate of suicide attempt was lower in those treated with an SSRI than in those not treated with an antidepressant.
What about youth suicide?
Data on suicidal thoughts and actions in youth are less conclusive. Some data show no increased risk of suicide in young people taking antidepressants. other evidence suggests there may be a small increase in risk for them under 18 (not 24). However, the risk is less than previously thought. It appears that suicidal thoughts and actions are driven by factors other than depression in youth. (The thinking is that antidepressants relieve depression in youth, but it’s not what drives their suicidal behavior.)
Even worse, found this 2020 study increases in suicide deaths among young people after black box warnings and reductions 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 professionals chose to use antidepressants less. In addition, 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 to even make a diagnosis, which is unfortunate considering the other types of help that young people could. have received if they had been diagnosed.
These reflections may have been wrong:
- Researchers looked at 845 suicides in the 10- to 19-year-old group in Sweden from 1992 to 2010. After the 2004 warning, the suicide rate increased for 5 consecutive years (60.5%), largely in those who did not take antidepressants.
As the Psychiatric Times article states:
The FDA’s implementation of a black box warning was intended to reduce suicide rates in children, adolescents, and young adults. The picture that follows the FDA warning and the implementation of the black box warning is not one of a lower suicide rate as the FDA planned or hoped. Instead, we see fewer prescriptions for antidepressants, an increase in youth suicide, and negative effects on human capital.
This report on Frontiers in Psychiatry describes the real damage a black box warning can do.
TL;DR — Do antidepressants increase suicides? Did the black box warning reduce suicide rates?
In short, it appears that antidepressants do not actually increase the risk of suicide in adults. There may be a small risk to youth (even that is uncertain), but there are significant benefits in this group that should be considered. Furthermore, it appears that issuing such a severe warning about antidepressants actually had the unfortunate effect of increasing suicides, not decreasing them.
I’m not going to say what kind of warning the FDA should put on a drug. What I would say, though, is that our concerns about suicides due to antidepressants were overblown. With incomplete information, we had to at the time, but the same level of concern doesn’t seem warranted now, given the more up-to-date data we have. We should always, always maintain increased supervision when a person starts any medication because we don’t know how they will react to it, but it is very unlikely that an antidepressant will actually cause suicide and overreacting to that possibility to the point of denying people a antidepressant or even a diagnosis is wrong.
Note: I am not a doctor and everyone’s individual risk profile varies. Always discuss all your concerns openly with your doctor.
Image by Nick Youngson via Pix4free.org.
