Posted by Elizabeth on April 7, 2002, at 21:11:14
In reply to Re: Selegiline MAOI patch rejected by FDA, posted by Adam on April 6, 2002, at 12:59:27
> My understanding of the results of some of the clinical trials is that STS efficacy for MDD, in the larger studies, was less easily and/or spectacularly demonstrated as it was in the earlier, smaller studes.
That still surprises me. I thought that high-dose selegiline was about as effective as the other nonselective, irreversible MAOIs (although it didn't do anything for me). It's hard to imagine that a large clinical trial (or a whole bunch of small ones) of selegiline for MDD wouldn't have clear-cut positive results. Does anyone have a clue what caused this result? A fluke seems unlikely....
> My guess is there were still safety concerns, given that selegiline is a non-specific MAOI when delivered transdermally at 10 and 20mg/patch.
Do you know what the ratio of oral dose to equivalent transdermal dose is?
> No new MAOI of that type could get approval these days, with the alternatives now available, unless there were something special about it.
Yeah, if the FDA had existed when the first MAOIs were discovered, they probably wouldn't have been approved. Kind of sad; they're really safe drugs as long as you take a few simple precautions.
> In the case of the STS, that something special was the lack of dietary restrictions, at least up to 20mg per patch per day, and rapid onset of effect.
The rapid effect is the part that has me interested. About how fast did it work, typically? And how long did the trial last?
> There is also little flexibility, as the purported protection of alimentary MAO-A may be compromised at doses higher than 20mg/day, transdermally.
Why would it?
> Anyway, that's my guess: Selegiline, after all, performs no better than any other antidepressant,
AFAIK, *no* antidepressant performs any better than any other antidepressant (overall, that is). The point of offering different options -- really different ones, not Just Another SSRI -- is to give a few more people the chance of finding something that works and is tolerable, IMO.
> and because it has some troubling safety issues, the FDA decided it wasn't worth the risks.
That is a good point; the FDA is very, uh, conservative about approving new drugs. (It's also very corrupt, of course.)
> The hurdle is just higher for the STS, and unless it can get over that, it's simply out of the running.
That would be unfortunate. It's had a lot of publicity, and a lot of people have been hoping for it. Still, oral selegiline is always an option. (That's why I was wondering about the relative dose.) It's always a shame that so many people have these (mostly irrational) fears of food-drug interactions. The drug-drug interactions are more dangerous, but they're easy to avoid too (thanks to poor Libby Zion, doctors are well aware of them).
> That it isn't for everone is not all that startling. Neither are the other MAOIs, which, overall, perform no better than other antidepressants.
I'm puzzled by that, actually. I'd expect them to have higher success rates than the other ADs.
> If my experience is at all representative, perhaps many people who tried the STS and experienced great benefit had nearly exhausted the other options. An MAOI was the next step.
I think it's pretty absurd how people think MAOIs are a last resort -- a lot of doctors, not just patients. When I was in college, I was informed by the student health center that they "don't use MAOIs." I knew several other students who were taking Nardil or Parnate, so it's not as if college kids don't need them. A lot of patients are scared of MAOIs, too -- often because they've been misinformed about potential interactions. A lot of doctors and pharmacists tell patients that they can't eat chocolate or drink any alcoholic drink, which naturally doesn't sound too great to some patients. Some people go to extreme lengths to avoid trying an MAOI, even trying things that aren't likely to work (obscure augmentation strategies, TCAs for atypical depressions, etc.). There's really no reason to avoid MAOIs so desperately...unless you're addicted to banana peels.
> To me, this looks like a self-selecting pool poised for success. For larger "better" designed studies, maybe the pool is more representative of the "general" depressive population. In such a pool, the effect of near-outliers like myself on the statistics can be diluted considerably.
That's not a very representative sample! I'm surprised they set it up that way -- if all the subjects are people who deliberately sought out a clinical trial, a lot of them are bound to be "treatment-resistant." The designers of the study must have known this.
> Imagine giving tamoxifen to someone with prostate cancer. Wouldn't make a lot of sense, would it?
I have trouble just imagining what tamoxifen would do to a man.
> Imagine giving selegiline to someone with the "wrong kind" of depression. If only we knew how to administer psycophamacoligic treatments more selectively, like we can for some cancers.
...but we don't. Even weirder, nobody seems interested in solving this problem.
-elizabeth
poster:Elizabeth
thread:100963
URL: http://www.dr-bob.org/babble/20020402/msgs/102317.html