Antidepressants and Youth: A Decade since the “Black Box”

Ten years ago, the Food and Drug Administration mandated that all antidepressants carry a prominent “black box” warning to alert prescribers of the potential danger in children and adolescents of these medications leading to new suicidal thoughts or actions. The warning came in the midst of passionate debate about the potential risks and benefits of using and not using these drugs. A decade later, this discussion has largely disappeared from the public eye and evaded media headlines. Nevertheless, antidepressants continue to be prescribed and research into their use has continued.

What have we learned since then? I offer my take on some key conclusions.

1. The risk of suicide due to antidepressants was overstated. As additional information accumulated from clinical trials comparing any type of suicidal thoughts or behavior between youth taking antidepressants versus placebo, it became more and more difficult to find that “signal” related to active drug. Perhaps more importantly, several studies that did not rely on clinical trials and studied actual suicides or suicide attempts did not show links to the taking of antidepressants and, if anything, indicated the opposite: namely that untreated depression posed an even greater risk. For those teens and families where the medication may have made things worse, such knowledge holds little comfort; however, it bears repeating that there still has never been an actual suicide (knock on wood) in any of the antidepressant trials.
2. The efficacy of antidepressants was also overstated. As people scrutinized more and more closely the issue of suicidal behavior and antidepressants, it became clear that much more data were available that was not easily found in the medical literature. Many more trials of depression and antidepressants were performed and funded by pharmaceutical companies and many of these trials did not show that antidepressants were superior to placebo. The problem was that most of these negative trials weren’t published, while those that were positive were thrust into the spotlight. Overall, it seems that about 60% of depressed children and adolescents respond to antidepressants. This doesn’t sound too bad until you also learn that 50% of them respond to a sugar pill.
3. The prescribing of antidepressants has come back. Soon after the 2004 warnings, the number of antidepressant prescriptions dropped. Then, after the Centers For Disease Control reported a spike in the youth suicide rate that same year, people began to worry that we may have made things worse. Since then, however, the suicide rate has generally remained flat and antidepressant prescribing as increased once again to the relief of some and the dismay of others.
4. Antidepressants don’t work by fixing a serotonin “chemical imbalance.” While it is true that antidepressants in the short term result in more of the neurotransmitter serotonin being available in brain synapses (the space between neurons that communicate with each other), depression is not simply the result of not having enough serotonin. The medications likely work by ultimately changing the expression of certain genes that relate to how strongly certain neurons are connected. This process may explain why antidepressants take time to be effective for most people.
5. Antidepressants actually work better for youth with anxiety rather than depression. Research in child with anxiety disorders and obsessive-compulsive disorder have shown more promising results with antidepressants. While a form of therapy call cognitive-behavior therapy (CBT) is still the recommended first intervention for childhood anxiety disorders, antidepressants have been shown to be effective both alone and in combination with CBT. What is different about these studies, however, is not that antidepressants in anxiety disorders lead to higher rates of improvement but that the placebo rate is much less. It also should be noted that anxiety and depression run closely together for many.
6. We still have a lot to learn. Children and adolescents who are extremely irritable, unmotivated and at times suicidal are a diverse group whose difficulties can stem from a large number of factors. Exactly what is happening in the brain of individuals who get clinically depressed and how antidepressants work remain inadequately understood.

Overall, it appears that the amount of risk and benefit of this class of medications is less than many believed a decade ago. Antidepressants can be useful for many youth but need to be considered only as part of an overall treatment strategy that addresses the entire family environment and potential causes of the symptoms.

@copyright by David Rettew, MD

David Rettew is author of Child Temperament: New Thinking About the Boundary Between Traits and Illness and a child psychiatrist in the psychiatry and pediatrics departments at the University of Vermont College of Medicine.

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