Posted by Adam on April 6, 2002, at 12:59:27
In reply to Re: Selegiline MAOI patch rejected by FDA, posted by Elizabeth on April 4, 2002, at 19:22:58
This does not suprise me at all.
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. Still, if I recall correctly, there was statistically significant improvement overall in depressive symptoms in these studies. None of us have seen all the data, though; but I very much doubt it could be argued that the STS would not have helped many people.
Elizabeth may be right, and more time and more studies will lead to approval. My guess is there were still safety concerns, given that selegiline is a non-specific MAOI when delivered transdermally at 10 and 20mg/patch. No new MAOI of that type could get approval these days, with the alternatives now available, unless there were something special about it. 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. However, the potential for deadly drug interactions remains. There is also little flexibility, as the purported protection of alimentary MAO-A may be compromised at doses higher than 20mg/day, transdermally.
Anyway, that's my guess: Selegiline, after all, performs no better than any other antidepressant, and because it has some troubling safety issues, the FDA decided it wasn't worth the risks. The hurdle is just higher for the STS, and unless it can get over that, it's simply out of the running.
It's too bad. From my own personal experience, the STS can work wonders. 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 bet if trials could be designed more intelligently, the STS would look like the knock-'em-dead medicine the earlier, optimistic claims, made it out to be. 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. 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.
Imagine giving tamoxifen to someone with prostate cancer. Wouldn't make a lot of sense, would it? 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.
There may still be hope: The STS is being tested for other indications. If it gets approved for one of those, it may be possible to use it off-label for depression. That has seemed to me for some time to be the most likely scenerio, if it gets approved at all.
poster:Adam
thread:100963
URL: http://www.dr-bob.org/babble/20020402/msgs/102142.html