Researchers: FDA Warnings Associated With Decreases in Treatment

Teen mental health is everywhere in the news right now.

There’s one aspect of teen mental health dominating the headlines: the increase in teen suicide risk and suicide deaths.

It’s not a new story.

Between 2007 and 2018, teen suicide rates increased almost sixty percent. In 2014, suicide became the second leading cause of death for people age 10-24.

Alongside these increases in rates of suicide and suicidality – thoroughly documented between 2007 and 2019 – rates of mental health disorders such as depression and anxiety increased at the same time. The coronavirus pandemic exacerbated this trend.

Laypeople and experts alike offered a host of explanations, including these three:

1. Computers

The increasing presence of home computers was often connected to negative/declining teen mental health. Many people cited an increase in screen time as a reason for the deteriorating mental health of teens. Online video games garnered negative attention from parents and professionals

2. Smartphones

The invention and use of smartphones was also often connected to negative/declining teen mental health. The first smartphone appeared around 2007, which correlates with an increase in mental health issues among teens that accelerated between 2007 and 2014.

3. Social Media

Finally, the appearance and widespread use of social media was also connected to negative/declining teen mental health. This is connected to both smartphone use and computer use, both of which fall under the umbrella of screen time.

When a former Facebook employee testified before Congress last year, Instagram (owned by Facebook) came under fire for downplaying data that indicated specific groups of teens – younger adolescent females with low self-esteem, pre-existing mental health disorders, who spend more than an hour a day on social media – were at increased risk of depression and anxiety as a result of their social media use.

While most people agree that it’s logical to connect social media use and increased screen time with the increase in mental health problems among adolescents, research does not necessarily confirm this position. It appears that where social media is concerned, what causes problems is how teens use social media, not that they use social media.

Last year, however, new research appeared that identifies another possible explanation for the overall decrease in mental health among adolescents and young adults and the increase in suicide rates: warnings form the Food and Drug Administration (FDA) on the potential of increased suicidal thoughts or suicidality as a documented side-effect of some anti-depressant medications.

The FDA Warnings: Antidepressants Prescribed for Depressive Disorders

In 2004, the FDA added a Black Box Warning to the packaging of serotonin reuptake inhibitors (SSRIs), which are common anti-depressant medications used to treat major depressive disorder (MDE) and various other mental health conditions.

Here’s what the warning said:

“Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of [SSRIs] or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need…patients of all ages on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior.”

For someone with MDD, or the parent of a teen with MDD, this warning probably came as a shock. From a laypersons point of view, the entire point of antidepressants is to help manage the symptoms of depression. Most people also understand that extreme, severe depressive symptoms include suicidal thoughts and can lead to the worst conceivable outcome, a suicide attempt.

The news that a medication prescribed to help people with MDD might include suicidal thoughts or suicidality as a side effect is perplexing at best.

Perplexing, confounding, contradictory, and hard to make sense of, for anyone. And the sentence ending with “…must balance this risk with clinical need…” does not help.

The research we share in this article, from a paper called “Increases in Suicide Deaths Among Adolescents and Young Adults Following US Food and Drug Administration Antidepressant Boxed Warnings and Declines in Depression Care” published in October 2020, offers evidence that – in addition to being confusing for regular people – the addition of this warning may have led to the following unintended consequences:

• Decrease in antidepressant treatment for depression among teens (medications)
• Decrease in treatment for depression among teens (psychotherapy)
• Increase in suicides among adolescents and young adults

In the context of a treating a mental health condition, these consequences – if this research is accurate – are not good news at all.

Let’s take a look at the data researchers used to reach these conclusions.

Three Decades of Data: Did the FDA Warning Help or Harm?

The research team, made up of scientists from Harvard University and the University of Washington, examined all validated U.S. death certificates registered between 1990 and 2017 in order to “estimate changes in trends of US suicide deaths per 100,000 adolescents (ages 10–19) and young adults (ages 20–24) after the [FDA] warnings, controlling for baseline trends.”

We’ll now share the general trends they observed, based on the death certificate data they collected, which they cross-referenced with prevalence data on treatment for depressive disorders with medication and/or psychotherapy.

Researchers identified:

• Significant decreases in diagnosis of depressive disorders among adolescents, young adults, and adults
• A sudden decline in psychotherapy for depressive disorders immediately following the FDA warning
• An increase – 20% to 60% – in the percentage of youth with a depressive disorder who did not receive antidepressant treatment
• Significant declines of 30% – 50% declines in the use of antidepressant medication among teens and young adults
• Continued lower antidepressant use for over 7 years after the first FDA warning

That’s not at all what they FDA intended. Their goal was to help people with depression by preventing the development of side effects by warning people of their possibility. However, several factors – including sensationalist media coverage – may have contributed to these unintended consequences.

Now let’s look at what researchers found for adolescents (age 10-19) and young adults (age 20-24), specifically. We’ll start with the data on adolescents.

Adolescents: Before and After the Warnings

• The 13 years before the warnings showed a downward trend in suicide deaths:
  • 1990: 6.4 suicide deaths per 100,000 adolescents
  • 2002: 4.2 suicide deaths per 100,000 adolescents
• The 12 years after FDA warnings showed are reversal in this trend:
  • 2005: 4.4 suicide deaths per 100,000 adolescents
  • 2017: 7.2 suicide deaths per 100,000 adolescents
• Suicide deaths separated from the baseline trend immediately:
  • An increase of 0.49 suicide deaths per 100,000 adolescents and a trend increase of 0.03 suicide deaths per 100,000 adolescents per year

According to the researchers, this data suggests the warnings may have contributed to 2365 excess suicide deaths among adolescents between 2005 to 2010.

Now let’s look at the data on young adults.

Young Adults: Before and After the Warnings

• The 13 years before the warnings showed a downward trend in suicide deaths:
  • 1990: 15.1 suicide deaths per 100,000 young adults
  • 2002: 12.3 suicide deaths per 100,000 young adults
• The 12 years after FDA warnings showed are reversal in this trend:
  • 2005: 12.4. suicide deaths per 100,000 young adults
  • 2017: 17.0 suicide deaths per 100,000 young adults

According to the researchers, this data suggests the warnings may have contributed to 3593 excess suicide deaths among young adults between 2005 to 2010.

That’s serious data – and those are alarming conclusions, which we will discuss next.

How to Interpret This Data

It’s imperative to interpret this data with perspective and caution, while recognizing its validity within parameters determined and defined by the nature of the study.

We’ll quote the study authors:

“A single quasi‐experimental study cannot establish causality. However, the boxed warnings and associated reductions in depression care were further associated with a significant increase in suicide deaths among adolescents and young adults.”

The mechanism they describe for the increased suicide deaths includes the following features:

• The FDA warning
• Exaggerated media coverage of the FDA warning, which:
  • Stigmatized depression in general for young people
  • Stigmatized treatment for depression
• A reluctance on the part of providers to prescribe anti-depressants, which:
  • Reduced rates of diagnosis of depressive disorders among adolescents and young adults
  • Reduced rates of psychotherapy for depressive disorders among adolescents and young adults
  • Decreased prescriptions for SSRIs for adolescents and young adults diagnosed with depressive disorders

In addition, other unintentional injury deaths, which researchers used for comparison, did not increase after the FDA warnings. This strengthened the case for the association between the FDA warnings and the increase in suicide deaths.

Again, this study presents correlative data, which is different than causative data. A quick reminder about what those terms mean:

Correlation:

This is a statistical measure that describes the relationship between two or more variables. Correlation between variables does not mean a change in one variable causes the change in the other variable.

Causation:

This indicates that one variable or event is the result of the other variable or event. This is simple cause and effect.

Therefore, what this research presents is a very strong correlation between the FDA Black Box warnings and the various negative consequences listed above, up to and including the most serious negative consequence of all, death. Their estimate on excess suicide death is the result of mathematical modeling, not a causative relationship between variables. Based on available population data, they calculated the percentage reduction in diagnosis and treatment (medication and/or therapy) with the increase in suicide rates and determined the FDA warning may have been associated with close to six thousand excess deaths by suicide among adolescents and young adults between 2005 and 2010.

What Are the Next Steps?

Parents of teenagers with a depressive disorder need to understand one very important thing:

Treatment for depression works, and can prevent exacerbation of depressive symptoms, which can include thoughts that lead to suicidal ideation and suicide attempts.

Here’s another thing parents of teenagers with a depressive disorder should understand:

Some data indicates a weak correlation between increased suicidal ideation among teens who take antidepressants for depressive disorders.

A re-analysis of the FDA data shows an increased odds ratio of 1.5-2 for increased suicidal ideation and suicidal behavior among teens who take SSRIs for depression. This means that of 100 teens who use SSRIs for depression, 1-2 may experience suicidal thoughts or behavior a because of SSRIs.

This is a serious side-effect that parents and teens should know about before beginning a course of treatment that involves SSRIs. The study authors agree, and recommend that the FDA replace their black box warning with a warning that does not elicit fear and reluctance to seek treatment.

We agree. That’s a reasonable, evidence-based compromise.

With that said, we’ll end this article with a third thing parents of teens with a depressive disorder should know. For most people with depression – including children, adolescents, and young adults – the most effective treatment is a combination of cognitive behavioral therapy (CBT) and medication, which, in some cases, include SSRIs.

Parents, teens, and their healthcare providers should discuss the relative risks and benefits of any course of treatment for depression before initiating that treatment. This discussion should be based on the foundational awareness that depressive disorders rarely resolve without appropriate professional support and care.