Imagine that your best friend is really, truly depressed. And imagine that they are given a bottle of pills with the following label: “Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders.” Pretty scary, huh? You and your friend might think that the risk (suicide) outweighs the potential benefit (some relief from that depression). At the very least, you might think about an alternative treatment plan that does not involve such scary drugs. Evidently, a lot of doctors have been thinking the same thing, because the prescription rates for antidepressants have been falling ever since the FDA started requiring those labels.
It is easy to understand why. No one, whether they are a doctor, a parent, or a best friend, wants to contribute to a suicide. Everyone wants to be cautious when they are dealing with someone who is already at risk, for fear they will make things worse. The FDA labels speak exactly to that fear.
Where does this fear come from? There have been plenty of anecdotes about people, including teens, committing suicide shortly after starting an antidepressant. These anecdotes led to studies looking closely at teens in the first months following a new prescription to SSRI (selective serotonin reuptake inhibitor) antidepressants. In requiring new labels, the FDA was responding to studies showing a link between SSRI’s and increased suicidal thoughts.
You may be wondering why these studies track suicidal thoughts, and other indexes of “suicidality” and not suicides themselves. There is a very good reason, actually. Suicides are, thank goodness, very rare events, measured in the single digits per 100,000 patients. So for a study to find a statistically significant increase in actual suicides, even among depressed patients being prescribed antidepressants, it would need millions of subjects. Can’t be done. So even though suicidal thoughts are not the same as suicides, they do provide some measure of danger signs. Which is better than no data at all.
But was the FDA response to these studies just a healthy dose of caution? Maybe not. In fact, as prescription rates for antidepressants declined, suicide rates increased.
In hindsight, this might look pretty obvious. Being depressed is obviously a risk factor for suicide, after all. In fact, some researchers have been arguing since before the FDA required the warnings that they were a bad idea. Their data showed a very different side of SSRIs – a decrease in suicides in counties in the US where SSRIs were prescribed more heavily. Although these data were correlational, they suggested a net benefit to these newer antidepressants. And although a correlation can’t tell us much about cause and effect, it is really hard to argue that SSRIs cause more suicides if higher rates of use are correlated with lower rates of suicides.
Why did the FDA focus on the studies that showed a risk to SSRIs, and not on the studies that showed a benefit. One possibility is that they fell victim to a very common bias in the way people reason about risks and benefits. We have an aversion to risks, which is disproportional to our attraction to gains. When told that a new drug might kill one patient out of a thousand, we focus on that one. This is a more powerful force in our thinking than the idea that in the other 999 patients, there might be more than one that the drug saves.
So what about that friend looking at a “black label” warning on a bottle of SSRIs? Should they avoid the SSRIs altogether? In this case, a little caution may do a lot more harm than good. On the other hand, the data showing an increased risk when first taking the drug should not be ignored. I would speculate that for some depressed teens, the SSRI may provide just enough relief to allow them to carry out a suicide they were too apathetic to manage before. The critical period of risk seems to be the first weeks and maybe months of a prescription. So that is when your friend needs your support the most.