Antidepressant Medications for Kids and the Law of Unintended Consequences

Act 1:
The black box warning in 10/04

In October of 2004, the Federal Drug Administration (FDA) mandated that a "black box" warning be put on all antidepressant (SSRI) medications prescribed for youths, age 17 years and younger. A "black box warning" is a black-bordered warning accompanying prescription medications that serves to inform about possible serious adverse side effects.

Here's what it looks like. Please click on it and read it. What is your reaction to it? How would you feel if your depressed teen was prescribed one of these medications and this is what you read? What might you do (or not do) about it?

Black Box Warning

As this is the most serious warning that can be given to a medication (the next step is to pull the drug off the market), it's instructive to ask what prompted it.

Thirty one experts had reviewed all of the available scientific information and held a two day hearing about the possible increased risk of suicide in youths when taking antidepressant medications. They found double the rate (4%) of teens reporting suicidal thoughts but - and this is important - zero cases of actual suicide in teens who took these medications.

Based on this analysis - in a divided vote - the committee recommended the black box warning you see above.

* * * *

Act 2:
Headlines on 9/6/07: "Youth suicides increased as antidepressant use fell"

This was based on an epidemiological study* which showed the following:

Use of SSRIs

Suicide Rates for Victims Less Than 20 Years Old

Suicide Rate - U.S.

Suicide Rate - Holland

Forget the statistical analyses; it's pretty easy for you to see that the drop in SSRI use in kids (green and blue lines) is mirrored by the increase in suicide rate in the U.S. and in Holland. This, of course, raises the concern that there has been an under-treatment of depression with medications, resulting in more actual suicides. The authors wonder if the FDA warning "may have left some of the most vulnerable youths untreated."

* * * *

Are you convinced that the black box warning led to an increased suicide rate? You shouldn't be. Here's why:

• An apparent association (correlation) does not prove causation. (In fact, this is the problem with all such "epidemiological" studies). The increase in suicides could be a coincidence, due to completely different factors (I, for one, am quite depressed about the Detroit Tigers this year, not my lack of Prozac).


• The reported increase represented just 248 additional deaths of the 62 million youths in the U.S. And 1/2 of those were 18 -19 years old and therefore not included in the black box warning. The actual numbers are very small.


• The data only represents one year (two in Holland) and that is insufficient time to determine if it is truly an enduring trend.
  

So, yes, the black box warning could be the bad guy, but until there are further studies, we can't and shouldn't say with any certainty.

* * * *

Thoroughly confused? Good, you should be. It's too soon to tell.

But it also was too soon to tell three years ago, when the experts decided to issue their black box warning. One of them said: "I anticipate there will be alarm from parents and the child. I think that's worth that complication, because it will raise the threshold" for prescribing the drugs to children.

I find this viewpoint - which somehow captured the day - curious at best. Estimates of the lifetime risk of suicide attempts in depressed persons range from 2-15% (depending on the population studied). In contrast, the FDA analyses suggested an absolute risk of suicide in patients taking antidepressants as 0.01%. To me this suggests we should have a black box warning stating: "Caution, under-treatment of your child's depression could be hazardous to his/her health."

In medicine, alas, our Hippocratic Oath to "Do no harm" has been trumped by the more urgent and self-serving "Don't get sued." (The irony now is that grieving parents can and will sue for malpractice if their suicidal child had received antidepressant medications or if s/he had not.)

Additionally, the FDA had been rightly criticized for ignoring serious side effects in some popular medications and they were not going to make the same mistake again - data or no data. Finally, underlying this misguided decision, I believe, was a bias against using any psychoactive medications in children. This was a heavy-handed attempt by some to counter the trend of their use in kids.

* * * *

Beware the law of unintended consequences.

Go back and read the black box warning again. Who could not be frightened by it? If your teen is extremely depressed, better the devil you know (depression) than the one you don't (SSRI medications).

Frankly, most parents probably don't even read this dense, poorly written, and confusing warning. But the media dutifully (and, as usual, inadequately) did their job, hyping the possible link of medications and suicide without a careful critical analysis. You didn't need to read the warning - you were scared from the get-go at the thought of your kid taking an SSRI.

Are we now reaping the consequences of that rush to judgment by experts and lackadaisical critical analysis by the media? It's premature to say whether the black box warning has actually harmed children. But, I'll tell you this, in my opinion it hasn't done a bit of good.

* * * *

*Article cited:
"Early Evidence of the Effects of Regulators' Suicidality Warnings on SSRI Prescriptions and Suicide in Children and Adolescents"
Gibbons R, et al.
American Journal of Psychiatry, September 2007
ajp.psychiatryonline.org

Related Topics:

• Depression in Children
• Preventing Teen Suicide

Technorati Tags: teen suicide, depression, antidepressants, SSRI, black box>, health and wellness