Posted by djmmm on February 4, 2005, at 11:27:26
In reply to Re: Nardil maintenance dose not effective IMO » djmmm, posted by Questionmark on February 3, 2005, at 17:24:00
> > > > Since Nardil is considered an "irreversible" MAOI-- meaning it formes a permanent covalent bond to MAO enzymes-- MAO activity is consistant until new MAO is manufactured by the mitochondria of your cells.
> > > >
> > > > Parnate is not considered completely irreversible, since new MAO is produced more rapidly, due to the cohesivness of the bond Parnate forms with MAO enzymes.
> > > >
> > > > Nardil is also a hydrazine deravitive. These meds tend to "build up" in your system, often requiring liver function tests (due to potential liver toxicity). Because Nardil is truely "irreversible" and accumulates in your body, taking a "maintenance" dose of as little as 15mg every other day is possible for most people (only after maximum effect is achieved).
> > > >
> > > > Im not too familiar with "poop-out" and MAOIs. My theory is that "poop-out" is mostly a serotonin issue, excess serotonin to be specific.
> > >
> > >
> > > In my personal experience with Nardil, the concept of keeping a low maintenence dose after a short "loading" period (usually about four to six weeks i believe) at a higher dose (usu. 60-90mg) does not work at all, despite how it may look on paper. i'm on 60mg/day, and oftentimes if i reduce it to 45mg/day for a few days-- or even 30mg for a day or two-- i notice myself feeling worse... in multiple areas. And if i miss a mere day's worth of Nardil entirely, the following day i end up feeling significant differences in my mood, anxiety levels, and ability to think clearly, for example. i really wish the maintenance-dose theory worked, but i'm certain that it does not for me.
> > > Maybe new MAO enzymes are restored by the body around every 24 hours or less (almost definitely). Maybe phenelzine doesn't really render the MAO enzyme inactive for as long as is believed (doubtful). Maybe the so-called "new" formulation of Nardil is absorbed (and hence, metabolized &/or excreted) much more quickly than the "old" formulation-- so that the "old Nardil" did actually stay in the body long enough for the maintenance-dose-type-theory to hold true, and the "new Nardil" does not stay active in the body long enough for the theory to hold true. Actually, i just thought of some things that don't allow this to make sense, but it doesn't matter. My point is that i don't know, but i do know that i really don't believe the maintenance dose theory could be effective for many people at all, especially or at least on the new Nardil formulation. i would be highly interested to know why this is though (on a pharmacological or pharmakinetic level). Any thoughts?
> >
> > A maintenance dose is possible because of the amount of time it takes to manufacture new MAO. The 2 week period is simply an average (based on your metabolism)..remember, a maintence dose can be as little as 15mg, every other day, or as much as 45mg a day. Remember, MAO inhibition is not 100%, even at an effective dose, MAO enzymes are still effective, as are other metabolizing enzymes, reuptake, etc.
> >
> > As far as your theory that the "new" nardil may not remain in your system long enough to allow for a maintenance dose... even if this was true, one would only need to take a higher dose for a longer amount of time to acheive adaquate MAO inhibition. The irreversible bond has not changed, regardless of the excipients. If you are having trouble with getting a response from the "new" nardil, simply increase the dose and/or try (i know it's hard-- ive been there) to be patient.
> >
> > Playing the devils advocate...Just a thought..maybe the new excipients are somehow preventing the development of "active" metabolites..I know that the older version of the drug had a metabolite that had a strong effect on PEA levels. I'm wondering, if there IS a change in parent drug metabolism by the excipients (via absorbtion, etc), then there would certainly be a change in the formation of active metabolites (which may really be why Nardil works so well)..but this doesn't explain the many people who are happy with the "performance" of the "new" > nardil.
> >
>
> Okay, i'm still confused about the whole maintenance dose thing. i know that an effective dose of Nardil does not need to result in 100% MAO inhibition (actually most if not all of the literature concerning this says that at least an 80% level of MAO inhibition should be achieved for adequate relief of depressive symptoms, or something along those lines). But, for me at least, i *often and consistently* (so this is not in my head, figuratively speaking) notice a difference in how i feel and think and behave-- including the fact that i get more depressed and anxious, and less hopeful, etc.-- in less than 48 to 72 hours of taking one dose less than normal per day (45mg instead of 60mg)... which would mean that my MAO enzymes are being remanufactured less than every two or three days, right? Is this right or am i missing something?
> You said that the 2 week period for making new MAO is about average-- do you know if they have more-or-less proven this with any tests/studies or is this just the amount of time they (scientists; researchers) theorized it takes.
> You also mentioned that a maintenance dose can be up to 45mg a day. If that's true, i guess i'm more inclined to believe in this notion. Yeah, i guess it just does all depend on how long it takes for MAO to be regenerated. Is there really a lot of individual variation when it comes to this-- like some can take 72 hours or less and some can take up to two weeks or more? If that's true then i believe that it's possible for the maintenance dose to work in some people-- the slow metabolizers.
> i know for myself, however, if i went on a 15mg dose of Nardil for just a few days, i'd start feeling some significant withdrawal symptoms. But, yeah okay, i get it-- it all depends on that one factor.
>
> No, i hope i didn't cause confusion with people-- i was never on the "old Nardil," and am still absolutely in love with the "new Nardil;" i was just saying that maybe that's where the difference in plausibility of using the maintenance dose lies, but i don't know.
>
> Yeah, what you said in the last paragraph is a really good point and thought-- that "if there IS a change in parent drug metabolism by the excipients (via absorbtion, etc), then there would certainly be a change in the formation of active metabolites (which may really be why Nardil works so well)." And many people could still be happy with how the new Nardil works if their brains need more help in the 5-HT (and maybe NE) area than with PEA (and hence, dopamine) and/or GABA (and/or alanine?).
> Man! i rEAlly wanna know what the deal is with the new Nardil formulation though!-- the pharmacological and pharmokinetic difference(s). Someone (/some group) needs to find out.
>
> Thanks for discussing all this with me.The "new" nardil contains:
Each NARDIL film-coated tablet for oral administration contains phenelzine sulfate equivalent to 15 mg of phenelzine base and the following inactive ingredients:
mannitol,USP;
corn starch, NF;
croscarmellose sodium, NF;
povidone, USP;
edetate disodium,USP;
magnesium stearate, NF;
isopropyl alcohol, USP;
purified water, USP;
opadryorange Y30-13242A;
simethicone emulsion, USPThe "older formulation" contains:
Each Nardil tablet for oral administration contains phenelzine sulfate equivalent to 15 mg of phenelzinebase.
Inactive ingredients include:
acacia NF;
calcium carbonate;
carnauba wax, NF;
corn-starch, NF;
FDand C yellow No. 6;
gelatin, NF;
kaolin, USP;
magnesium stearate, NF;
mannitol, USP;
pharmaceuticalglaze, NF;
povidone, USP;
sucrose, NF;
talc, USP;
white wax, NF;
white wheat flour.the difference :
the old version contains 11 excipients that the new version lacks...
-acacia NF;
-calcium carbonate;
-carnauba wax, NF;
-FDand C yellow No. 6;
-gelatin, NF;
-kaolin, USP;
-pharmaceutical glaze, NF;
-sucrose, NF;
-talc, USP;
-white wax, NF;
-white wheat flourThe New version contians 6 excipients that the old version lacks:
-croscarmellose sodium, NF;
-edetate disodium,USP;
-isopropyl alcohol, USP;
-purified water, USP;
-opadryorange Y30-13242A;
-simethicone emulsion, USPThey share only 4 excipients
-mannitol, USP;
-corn-starch, NF;
-povidone, USP;
-magnesium stearate, NF;
poster:djmmm
thread:450404
URL: http://www.dr-bob.org/babble/20050202/msgs/453103.html