I'm at a loss

I think I've mentioned before on this blog how highly skeptical I am of the antidepressants/suicide link in adolescents. No one would ever suggest an insulin/foot amputation link or an antihypertensive/stroke link because both are know adverse outcomes of the disease that those drugs treat. Why is depression different from diabetes or heart disease? I mean, for everyone other than Tom Cruise? (Who, let's face it, is in SERIOUS need of some psychiatric care...)

Anyway, the above linked article was published in today's NYT ~ something that would almost make you believe that it was recent information, not something released by the FDA nearly 6 months ago to support recommendations that were issued two years ago. WHATEVER. Maybe this news wasn't "fit to print" until now.

This is what has me thinking. In the article, Dr. Nierenberg from Harvard Medical School points out that not only is all this data based on clinical trials (which I'll get to in just a minute), but individuals with suicidal ideations were excluded from the trial.

This is where I'm at a loss. How would excluding those who were previously suicidal effect the outcome? First of all, it would make it impossible to tell if the drugs reduced suicidal ideation. Second, since being suicidal kept one out of the drug trial, we can't assume that everyone who entered the trial was honest about whether or not they were suicidal. They claimed not to be in order to get medication; an act of desperation no one could blame them for, but if they then "became" suicidal it would have nothing to do with the drug. It would just be honesty. But if we do assume that everyone was honest at the entry into the clinical trial, they were medicated for 4 to 16 weeks at a standardized dose, not necessarily a therapeutic one. Now, the placebo would assumably have no side effects, but the antidepressants would immediately start wrecking havoc on their patients ~ dry mouth, constipation, nausea, diarrhea, excessive sweating, tremor, head ache, orthostatic hypertension, syncope, urinary retention, weight gain ~ a real boatload of fun for someone who is already hating life. Now keep in mind that most antidepressants take 8 to 12 weeks to treat depression, and then only if at a therapeutic dose. Most of these folks weren't even on the drugs long enough to get any positive effects, just all the negative stuff. Meanwhile, everyone in placebo-land is hanging out, side effect free, waiting for their drugs to kick in. No one is actually getting "treated", but at least the placebo crowd isn't getting put through the side effect ringer for their efforts. Just thinking about that kind of makes me want to kill myself.

But back to the clinical trial issue. Clinical trials are not real life. They don't account for any type of non-compliance. They exclude anyone who steps outside their very strict parameters. They avoid comorbidities, they avoid difficult cases, they use small samples and they're a self selected group of people who are then cherry picked by the drug companies. Not real life. You ever wonder why we don't find out about some of the really troubling side effects until a drug has been on the market and out in the general public for a few years? Because clinical trials in no way resemble real life!!

So then what's the answer? Probably registries. Controlled data collection of real world patients that are being voluntarily treated by doctors with specific drugs. Their history, treatment and outcomes are recorded into a database along with a control group, say of adolescents being treated with only talk therapy, and after a period of time, when enough data has been collected, it can be analyzed to see if the hypothesis holds in the real world or if the anecdotal reports of treating physicians who have successfully used these medications are really the norm. Registries are the only way to identify the tetragenic properties of drugs since doing anything but observational research on pregnant women is ethically out of the question. Since there are women who need certain drugs to survive their pregnancy (and let's face it, survival of the mother through the pregnancy is crucial to survival of the baby!) there experience is invaluable for women who may have a choice or at least want to see if they do.

Am I suggesting that clinical trials are worthless? No, but I'm at a loss for a reason at the moment. I'm sure one will come to me sooner or later. They play an important role in monitoring and controlling the safety of U.S. pharmaceuticals. (That was a statement of fact, still don't have a reason....)

Perhaps I'll find one and get back to you...