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Nardil & Marplan

mitragyna

mitragyna

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Joined
Dec 7, 2006
Messages
242
I've been on Nardil now for about 4 months. It has worked pretty well for my social anxiety (not as much for my depression), but has cause extreme weight gain. Right before I first started taking the Nardil, I weighed 164 lb. Now, 4 months after I weight 184 lb! I don't mind gaining a few pounds, but 20 pounds is just too much.

So I went to my Psychiatrist and told him about this, and how I wanted to try Parnate instead. He insisted that I try Marplan because it has a low weight-gain side-effect profile. I said whatever, I'll give it a try.

Of course, he tells me that I need to wait two weeks after stopping the Nardil to start the Marplan. So at this very moment, I'm on day three since the cessation. I'm starting to feel real shitty again since I don't have the MAOI in me. I'm so fucking tired and can hardly muster enough energy to walk up the stairs!

I really want to start taking the Marplan to relieve these shitty symptoms from not being on the Nardil. So my question is: how dangerous would it really be if I started taking the Marplan just three days after stopping the Nardil? Marplan and Nardil are both Hydrazine derivatives, and it's not like I'm trying to take Selegiline or Parnate which I know could cause problems from their metabolites.

What do you guys think? Any help would be really appreciated, as I feel like whale shit at the bottom of the ocean. Thanks!


P.S. Does anyone know which one (Nardil or Marplan) is "stronger" or more effective for depression/anxiety?
 
Can anyone help?

It's been four days now since I've been off the Nardil. I never thought that the withdrawl from an MAOI would be so bad. It almost feels like withdrawling from speed and an SSRI at the same time...ugh!
 
I wouldn't think there would be a problem with taking the Marplan now. If fact, I would imagine that one would be able to safely replace his dose of Nardil with Marplan immediately without any tapering, cessation, or delay. The fact that you are experiencing a crash right now makes me credit all the more this assertion of mine.

It seems to me that if Marplan and Nardil are very similar in terms of potency, then the idea that immediately replacing the Nardil with the Marplan would cause a hypertensive crisis or something of that sort is as ridiculous as the idea that continuing to take one's Nardil would do so, if taken as prescribed.

Do you see what I mean? Since the medications are so similar in terms of mechanism of action, the Marplan can be thought of, for most intents and purposes (or at least for yours), to be the very same substance as Nardil, so that if taking the Nardil on a daily basis didn't cause problems, we should wonder why it would produce an untoward reaction to start the Marplan having just stopped the Nardil... Right?

But that's just my intuition. Taking it into consideration that I really know next to nothing on this subject and that it would therefore be irresponsible for me to interject my advice and put your health at risk, I resolved to say nothing at all, but since no one else seems to have any words of advice or wisdom for you, I thought to betake myself to proffer my suppositions, be they of what worth as they may. Take them with a grain of salt.
 
This is a good example of why logic and reason is pretty much useless (especially when there is actual evidence on the subject). A simple lit search in Pubmed turns up lots of reasons relying on reason is a particularly bad idea. Doing so is what caused the Peripatetics to believe earth was the center of the universe, heavier objects would fall faster and that the heavens were eternal and fixed. They, however, did not have the benefit of more than a century's worth of well documented academic research.

This is why I've always liked William Gilberd and Galileo.
Stroke resulting from a Rapid Switch from Phenelzine to Tranylcypromine. Single case report. Mattes J. J Clin Psychiatry 1998 Jul;59(7):382.

Switch MAOIs Less Than 14 Days Done Cautiously With Minor Difficulty: Report of 8 in-patient cases. Only one had a minor problem, either minor serotonergic syndrome or tranylcypromine withdrawal. Rapid conversion from one monoamine oxidase inhibitor to another. Szuba MP, et al. University of Pennsylvania. J Clin Psychiatry 1997 Jul;58(7):307-10.

Problems with switching rapidly from one MAOI to another. J Clin Psychiatry 1998 Feb;59(2):87

Drug Intell Clin Pharm. 1986 Dec;20(12):954-6.Links
Sudden death associated with switching monoamine oxidase inhibitors.Bazire SR.
A drug-free interval is often recommended when switching monoamine oxidase inhibitors, although the evidence firmly supporting this caution has been minimal. A case is reported where an abrupt change in monoamine oxidase inhibitor was followed by the death of a patient.

PMID: 3816543 [PubMed - indexed for MEDLINE]
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Edit: Did you quit abruptly? Everything I find says that a very slow withdrawal is indicated, taking up to as many as four weeks.
 
Hammilton said:
A drug-free interval is often recommended when switching monoamine oxidase inhibitors, although the evidence firmly supporting this caution has been minimal. A case is reported where an abrupt change in monoamine oxidase inhibitor was followed by the death of a patient.
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There are so many confounds here and such a paucity of information by which to untangle and resolve them. Do we know that this patient didn't take the two different MAOIs on the very same day? Do we know that the patient wasn't a dumbass who assumed that his shiny new MAOI didn't have concomitant the need for the dietary restrictions of his busted and hoary MAOI?
 
mitragyna said:
how dangerous would it really be if I started taking the Marplan just three days after stopping the Nardil?
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As far as my limited knowledge stretches, I don't think it'd be dangerous. All the drugs do is inhibit MAO, so it doesn't particularly matter whether you take Nardil or Marplan when they both do the same thing. That is, assuming they don't have any pharmacological quirks that make them more complex than a simple MAO inhibitor, as I've heard Parnate does.

The "washout period" is perfectly justified when switching between MAOIs and SSRIs, but not between MAOIs (at least those you mentioned).

P.S. Does anyone know which one (Nardil or Marplan) is "stronger" or more effective for depression/anxiety?
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Nardil is usually considered better for anxiety, due to one of its metabolites being a GABA-transaminase-inhibitor. I could definitely feel the GABA effects from Nardil when I took it. I don't know much about Marplan, but I do know Parnate is considered more for depression than anxiety due to its stimulating properties.
 
I thank you all for the helpful replies.

Well I decided to just go ahead and take the Marplan. I'm prescribed 40 mg daily, so I just started off with 5 mg to be safe. I'm up to 20 mg now, and will wait a few days to go any higher.

To whoever asked if I quit abrubtly: I did. I was taking (4) 15 mg tablets of Nardil daily. And I went from 4 tablets to 3 to 2 to 1 to 0 all in four days. So I definitley should have tapered longer. My doc did tell me to do it this way, but I should have known better...I really didn't think it would have those kind of effects from getting off of the Nardil.

Thanks again guys, I really appreciate the help! :)
 
wreckhead said:
Nardil is usually considered better for anxiety, due to one of its metabolites being a GABA-transaminase-inhibitor. I could definitely feel the GABA effects from Nardil when I took it. I don't know much about Marplan, but I do know Parnate is considered more for depression than anxiety due to its stimulating properties.
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That's what I told the fucker (my doc)! I said I'd rather switch to Parnate since the Nardil wasn't helping a whole lot with depression. But he insisted that I go on Marplan since it's known to cause less weight gain. I don't even think that's true?!

Now I need to wait another three fucking months before my doc will let me switch. Oh well, at least I'm on an MAOI...they all seem to help at least somewhat.

EDIT: Just wondering if anyone has any sources and link that show that Parnate is better for depression than Nardil. Or that Parnate is the best MAOI for depression (if it is). Or if there is any studies that show Marplan is weak compared to other MAOIs, etc etc. I'm looking too, just wondering if anyone had any on hand. Thanks!
 
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shibireru said:
There are so many confounds here and such a paucity of information by which to untangle and resolve them. Do we know that this patient didn't take the two different MAOIs on the very same day? Do we know that the patient wasn't a dumbass who assumed that his shiny new MAOI didn't have concomitant the need for the dietary restrictions of his busted and hoary MAOI?
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I don't mean to be rude... but that is SUCH a cop-out, instead of just saying 'Oh... I guess there's a chance that my advice was dangerous. Be a good bluelighter and play better safe than sorry!'.

Yes, we do know that the patient didn't take both, and yes they followed a tyrosine-restricted diet... and you could have known that also with a quick scan of the document! I mean, you could use your same 'over-complicated' argument to support NOT taking the risk... it's too complicated to untangle and be sure!

And sure it's good to make your guesses, but you did not even take a GLANCE at the plasma protein binding+displacement (a good candidate for the sudden death), apparent volume of distribution, water/octanol co-efficient, P450 changes, etc and said they'd be effectively the same compound. Very few structural modifications can make huge changes in these (and other important) pharmacokinetic properties.
 
rocknroll714 said:
Parnate is a good deal more effective than nardil or marplan for treating anxiety as it's both more selective for MAO-B inhibition (more dopamine), and it also works as a mild stimulant with 1/10th the potency of amphetamine, though certainly boosted a bit with the MAO inhibition I'd imagine. The only problem is that it tends to stop working rather quick for many.
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Do we know that MAO-B inhibition is better for anxiety than MAO-A? I always thought that MAO-B inhibition would be better for depression, whereas MAO-A inhibition would be better for anxiety...
 
rocknroll: Thanks for fixing my typo... I've been reading 'bout meta-tyrosine as a treatment for neurodegenerative disorders, and I guess my fingers just shot it out instead. (I gotta explain pathogenesis and treatment of Parkinsonism to biochem students, so I though to throw in a compound that they actually know a structural relative of... ie- meta-tyrosine).

Either way my point still stands, but a typo can be a dangerous thing
 
leungkachong said:
I don't mean to be rude... but that is SUCH a cop-out, instead of just saying 'Oh... I guess there's a chance that my advice was dangerous. Be a good bluelighter and play better safe than sorry!'.

Yes, we do know that the patient didn't take both, and yes they followed a tyrosine-restricted diet... and you could have known that also with a quick scan of the document! I mean, you could use your same 'over-complicated' argument to support NOT taking the risk... it's too complicated to untangle and be sure!

And sure it's good to make your guesses, but you did not even take a GLANCE at the plasma protein binding+displacement (a good candidate for the sudden death), apparent volume of distribution, water/octanol co-efficient, P450 changes, etc and said they'd be effectively the same compound. Very few structural modifications can make huge changes in these (and other important) pharmacokinetic properties.
Click to expand...

You misunderstood my purpose. I wrote what I wrote not so much to defend my position and advice that I issued, but to point out how meaningless those pieces of data provided by Hammilton were (or so they seemed to me.) That is to say, it wasn't "I'm right, because that information isn't detailed enough to recommend to us any course of action" but "that information you have provided isn't quite proof that what I have said is wrong, although it may very well be wrong." There is a subtle but important difference between the two.

If you will notice, I added a caveat and disclaimer at the bottom of my first post, duly drawing attention to the fact that I know little on this subject and that the OP should tread with caution. This was not added after Hammilton's post nor yours, but was a part of my original post. I was trying to reduce the OP's harm, although perhaps not with the zeal and attention to detail that you would like.

For what its worth, I'm sorry for putting Mitragyna in harm's way to whatever extent I did.
 
Rocknroll: I'm very short on time, but logic can say a lot of things if your body of information is incomplete (and I don't know what it is about pure autodidacts and giant holes in scope of knowledge... but whatever). I'll use one of the same quick example as before:

Subbing 1 drug for another, in an otherwise reasonable dosing schedule can cause severe complications. Drug X is bound to plasma proteins (a1-glycoprotein or albumin for simplicities sake), keeping the 'diffusable' plasma concentrations at y... then you introduce a CLOSELY related drug (x2) that binds wayyyy stronger to the same plasma proteins, and the 'diffusable' plasma concentration of x goes up to 50*y. You die.

If that's hard to understand, think of it in terms of apparent volume of distribution. Because there's no competition for plasma protein, you're Vd is VERY high and the effective concentration at site of action is very low. Then you introduce the closely-related strongly-protein-binding drug, and the apparent Vd for the first drug plummets. It's like the 100 'apparent liters' that the drug was diluted in of body water has become 5 'apparent liters'. And you're f*#&d. (If you actually have an understanding of pharmacology, please pretend I was talking about tissue drug binding in this second related example.)

I'm sorry, but you can't just guess on the effect of drug interactions without checking pharmacokinetic values for the drugs. If you have even a meager understanding of pharmacokinetics (or even just principles of drug distribution), then you would think assuming there'd be no problem with no protein affinities is completely illogical! It's like making a guess at action without any affinity values or even a basic SAR.

I'm not trying to be harsh, sorry if it comes across that way (hell, you've made great progress in your short time here)... I just think that your 'logic' is based on a lack of understanding w.r.t. pharmacokinetics (or even just drug distribution).
 
^ that's a good explanation of the "why" but reading the articles cited would have told him that they provided very good reason not to do such a thing even if he wouldn't have understood the mechanism behind it.
 
I was thinking of this in terms of competitive inhibition, which it isn't. Still though, if drug A irreversibly deactivates enzyme X, and drug B affects the enzyme in a different way (different site or whatever), wouldn't drug B still be "used up" on already-inactive enzyme Xs, thus not leaving enzyme X's substrate to build up to any greater extent than 2x drug A would have done...?

There's so much I don't know about biology. When phenelzine (or other irreversible inhibitor) binds to MAO, does it remain bound there indefinitely? What I mean is, does phenelzine need to be physically connected to MAO to deactivate it, or does it just break bonds once then move on to another MAO molecule?
 
wreckhead: The competitive inhibition case doesn't work here... If you were talking about my description above, it doesn't apply because these plasma/tissue proteins that cause the large increase in 'available' drug are not the actual site(s) of pharmacodynamic action.

If you weren't talking about my example... it still doesn't work. In the case of phenelzine the NH-NH2 covalently binds to MAO's active site, and yes.. stays there. Both of these MAOIs do this... they can't screw with the same enzyme molecule. Now in your case of combining a irreversible inhibitor with a non-competitive/allosteric modulator... you come to an interesting example where we find in vitro results support your 'reduced effect of the allosteric drug' idea, but in the body it doesn't seem to be measured. This is probably because of the relatively small amount of drug-to-target necessary for eliciting most therapeutic responses. Even in the in-vitro case, it only appears in-so-much as it isn't muted by the whole 'spare receptor theory' thing (a horrid model IMO, but the easiest way to explain)
 
awesome posts from hammilton and leungkachong

I guess this is almost certainly too late-coming to be helpful, mitragyna, but my friend who took* Nardil suspected that a good deal of the weight gain was due to water retention, and took a low dose of hydrochlorothiazide with success.

* he still takes it; for about five years now in combination with dextroamphetamine @ 40mg daily split into four doses (a dose that was sloowwwly titrated up 1.25 mg at a time with the care of the doctor and rescue medications on hand) it's the best thing he found for his long sufferings with treatment-resistant depression, anhedonia, inattention and social anxiety.

mileages will vary, but keep your head up.
 
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