Many parents have said yes. David Healy, a Scottish psychiatrist, prompted by those stories, did a small experiment in which undepressed persons took anti-depressants. About 10% of them started having suicidal thoughts. Drug companies and the University of Toronto (where Healy had been offered a job) reacted very badly to this information, as Healy describes in Let Them Eat Prozac. An article in the latest issue of the American Journal of Psychiatry by David Leon, a biostatistician on the FDA oversight panel, describes why he voted to extend a warning about this from children (< 18 years old) to young adults (18-24 years old). This was the main data:
What’s shown is the odds ratio for a report of suicide ideation or behavior, comparing those who got anti-depressants with those who got placebos. An odds ratio of more than 1 means greater risk in those who got anti-depressants. The red bar is from a different study. When different ages are lumped together there is no increase in risk but that hides opposing tendencies at high and low ages.
The article contains this curious sentence: “The results did not provide definitive evidence of risk, yet they failed to demonstrate an absolute absence of risk.” No possible results could “demonstrate an absolute absence of risk” so it is unclear what Dr. Leon meant. Later he writes: “My vote to extend the black box warning to young adults was based on concern that risk of suicidality could not be ruled out and, given the widespread antidepressant use, even a small risk must not be ignored.” Yes, he has it backwards: The data do not “fail to rule out” suicide risk (no possible data could “rule out” such risk, i.e., show the risk is zero); they manage to overcome a barrier to show it’s there. And yes, he’s congratulating himself (”even a small risk must not be ignored”) for doing his job.
Uh-oh. That someone — a biostatistician, no less — in such a powerful regulatory position fails to understand basic concepts is bad enough; to make things worse, Dr. Leon has received money from three of the companies (Eli Lilly, Organon, and Pfizer) he oversees.
Related post by Andrew Gelman.
Finding ratios 5 sigma below 1 (for a well-reasoned study) would easily satisfy my definition for “absolute absence of risk”. It means in a large sample of people, the risk just doesn’t occur. The results do not provide definitive evidence of risk because… the value isn’t 3 sigma above 1. What’s hard about this?
I don’t doubt that anti-depressants help many people.
But the question on if anti-depressants are necessary and if they are, in fact, better than other less abrasive treatment methods is still questionable to me.
Messing around with one’s brain chemistry does strike me as potentially dangerous. It might subdue the depression, but the side effects are unknown.
If more organic means can provide the same benefits as the abrasive means, then it’s an easy decision. Yet psychiatrist don’t seem to be open to the organic means.
NE1, what is the numerical value of a risk ratio “5 sigma below 1″? And why 5? why not 20? or 3?
Seth, you must be joking. A value 5 sigma below 1.0 means that if we were able to commission 4000 independent studies like this, we would expect to find an increase in ideation over placebo in just about one. So that, unless this is *that* one horribly biased study, we can be pretty certain that the risk does not exist (and is most likely reversed!).
Now, if you want to turn that around and say that’s still not enough, that 2 excess children having suicidal ideas is too many, then sure, price in some reasonable precautions. The odds against a 20 sigma study would be so great as to require the inadequacy of the study on other grounds (systematic error).
But no, at some point you have to say: These 3999 positively (!) reacting teens are good evidence for me, and the 1 other could very well be the product of some other unfortunate circumstance. This isn’t even in the realm of this Commentary, though. The value is within 1sigma of 1 here, so there isn’t sufficient evidence to draw any hard conclusion. He also explicitly says that the black box warning is not about discouraging use, but warning about the danger of not monitoring; the reality is unknown, doctors are encouraged to be perceptive.
You say: “The data do not “fail to rule out” suicide risk (no possible data could “rule out” such risk, i.e., show the risk is zero); they manage to overcome a barrier to show it’s there.
This is certainly not true. I have been willing to give you the benefit of the doubt on many things, as this is not my field, but one thing I have learned is an appreciation for the depth of people such as Leon. I may not understand the analyses he walks us through, but I do know that such processes are created for a reason. I am amazed that you feel capable of dismissing them without any reasoning yourself. You must think he has not gone far enough in restricting these drugs, but the evidence you seek does not seem to be in this report.
Lasser: it’s not hard to imagine that some people have inappropriate levels of the basic neurotransmitters in the brain, a natural “chemical imbalance”. In that case it seems perfectly reasonable to me to plan on replacing those chemicals with a pill, as opposed to suggesting they exercise or eat more ice cream. To insist otherwise, as say the Scientologists might, is to turn one’s back on centuries of confidence building in science. I know you’re not taking this stance, but I think much of the public is still attached to the stigma against anti-depressants.