Posted by Tomatheus on December 27, 2005, at 21:02:56
In reply to Re: What to do if Nardil and Parnate were discontinued » Tomatheus, posted by ed_uk on December 27, 2005, at 12:11:34
Ed,
See below for my responses to parts of your post.
> >But let me make it clear that for some Nardil responders, none of options the that you listed below will be adequate substitutes.
> I agree. I was just making a few suggestions.
I know. I wasn't trying to suggest that you were guaranteeing that your suggestions would be effective substitutes for all Nardil and/or Parnate responders. As unconscionable as it would be for Pfizer, for example, to discontinue Nardil, there is a real possibility that this might happen. If it does indeed happen, those without the means to order Nardil from outside the United States are going need to resort to trying to find a medication or med combo that's the "next best thing" to Nardil. Based on the limited amount of research I've done, I do think that the "next best thing" will hardly be a sufficient option for many Nardil responders. But nevertheless, Nardil users are going to need to know what their options are if Pfizer ends up doing the unthinkable. And so it's great that you're decided to suggest some alternatives. I do think that the options you recommended are the best alternatives to consider in the absence of Nardil and/or Parnate, and I'm truly glad that you made the suggestions that you did. I just think that for many patients, there will be no substitute for Nardil, and I wanted to make it clear that the availability of meds that *might* be decent alternatives for some Nardil responders can in no way be used to justify discontinuing the medication -- just in case anybody gets that idea. I think that there is definitely some evidence to suggest that some Nardil users will not achieve clinically significant remission with any other medication, and I intend to continue my hunt for more evidence for my own personal reasons.
But anyway, I think we're on the same wavelength on this issue. I just wanted to explain that I did find your suggestions helpful, but I was concerned that others might make the false assumption that Nardil and Parnate responders should have no problem finding another medication (or med combo) that effectively treats their psychiatric condition.
> >Unfortunately, the only commercially available MAO-inhibiting mediction in the world is moclobemide
>
> I think pirlindole is still available in Russia (as Pyrazidol) and Portugal (as Implementor). Pirlindole seems to have been studied mainly in Russia.Oops. I clearly wasn't thinking right when I wrote that statement ("Unfortunately, the only commercially available MAO-inhibiting mediction in the world is moclobemide"). What I wanted to say was that moclobemide is the only commercially available medication available anywhere in the world that is highly preferential to MAO-A over MAO-B. But based on your response, it actually seems that you somehow understood what I was meaning to say, which I am thankful for.
I have never come across any information concerning the availability of pirlindole in any of the MAOI review articles I've read, but then again, most of the research articles I've read are at least a few years old, so maybe the information I have is dated. Either that or I overlooked something, which is possible.
But anyway, thanks for the info on pirlindole. Of course, moclobemide is still the only medication available in most Western countries that is highly preferential to MAO-A over MAO-B. And it's not even available in the United States. So, even though most Americans should have the means to obtain moclobemide from an overseas pharmacy, there are a few who won't be able to afford it. And of course, Pfizer will never be able to seriously suggest taking moclobemide (either as monotherapy or in combination with a drug that's preferential in its inhibition of MAO-B) as an alternative to Nardil unless the FDA approves moclobemide. In terms of the Nardil alternatives that Pfizer can legally suggest, all of them are more preferential to MAO-B than Nardil is, which would be a problem for the subset of Nardil responders who receive their primary benefits from the drug's inhibition of MAO-A.
> >it is not uncommon or unreasonable to hypothesize that moclobemide is less effective than MAOIs such as Nardil and Parnate because moclobemide only inhibits MAO-A without inhibiting MAO-B
>
> I think it's highly likely.
>
>...
>
>
> It is my belief that the co-administration of moclobemide with a low dose of rasagiline (eg. 1mg/day) might produce a substantial anxiolytic/antidepressant effect in some patients.I think there's a good chance that your belief may be correct. I wasn't meaning to suggest that the suggestions you made won't work for anybody. This is just my opinion, of course, but yeah, I do think that selegiline+moclobemide and rasagiline+moclobemide would likely be effective combos for some patients.
And I do think that for some patients, the therapeutic benefits of inhibiting both MAO-A and MAO-B are definitely more pronounced than the benefits of solely inhibiting MAO-A. The abstract that you provided clearly suggests that the combined inhibition of MAO-A and MAO-B is more effective at reducing anxiety or fear (as measured in terms of "freezing behavior") than the inhibition of either just MAO-A or just MAO-B.
So for some patients, the difference in efficacy between moclobemide and Nardil (and moclobemide and Parnate) may partially be due to the fact that moclobemide only inhibits MAO-A, while Nardil and Parnate inhibit both MAO-A and MAO-B. As I said, I do think that is a reasonable hypothesis, and I see now that there is some evidence to support it. At the same time, I do think that there is some evidence to suggest that moclobemide's inhibition of MAO-A is not equipotent to Nardil's inhibition of MAO-A. So, I do think that the difference in efficacy between moclobemide and Nardil (as well as moclobemide and Parnate) is at least partially due the strong possibility that moclobemide does not produce the "true" benefits of sustained MAO-A inhibition.
> >is typically described in the scientific literature as being a highly effective antidepressant
>
> The scientific literature has a tendency to describe most drugs as 'potent' ;-)True, but I don't think I've ever come across a reseach article that has described moclobemide as "potent." I can't say with 100 percent certainty that clorgyline is more potent than moclobemide because the two drugs have never been compared in any published studies (at least not in any that I'm aware of), but everything I've read suggests that it's a strong possibility.
> > But if anybody gets the idea from reading your post that a vast majority of Nardil responders will be able to find effective alternatives, then they better think again.
>
> Ouch, that hurt.Sorry, I didn't mean to be hurtful, but I don't think that there's enough evidence to suggest that a "vast majority" of Nardil responders will be able to find another medication or med combo that provides clinically significant relief from the symptoms of their psychiatric illnesses. I think this is especially true in the United States, where (from a legal standpoint), moclobemide is not available. Although the number of patients who have reported being responsive to the "old" Pfizer Nardil but not the "new" Pfizer Nardil (or any other medicatinon or med combo) is not incredibly huge, I wouldn't say that these patients represent a small minority, either (especially considering that there are probably a significant number of "new" Nardil non-responders who never realized that their problem with Nardil was due to the change in their medication's formulation). In light of the fact that there are still some "old" Nardil responders who have not been able to achieve a clinically significant remission with another medication, it is likely that many of those who have been responsive to both the "old" Nardil and the "new" Nardil will also not be able to find an effective substitute for Nardil.
Tomatheus
poster:Tomatheus
thread:591969
URL: http://www.dr-bob.org/babble/20051221/msgs/592609.html