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Dr. Bob is Robert Hsiung, MD,
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Posted by Tomatheus on December 28, 2005, at 14:46:22
In reply to Re: What to do if Nardil and Parnate were discontinued » Tomatheus, posted by ed_uk on December 28, 2005, at 13:54:06
> >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.
>
> Like moclobemide, pirlindole is considered to be a RIMA.Ed,
Thanks for the clarification. Like I said in the last post I wrote to you, I was not aware of pirlindole from the research studies that I had read, and I thank you for making me aware of the presence of pirlindole. I was just trying to restate what I was meaning to write in my *first* post because my statement in that first post accidentally ended up being erroneously wrong (I think I said that moclobemide was the only commercially available *MAOI* available anywhere in the world).
Thanks,
Tomatheus
Posted by ed_uk on December 28, 2005, at 15:23:07
In reply to Re: What to do if Nardil and Parnate were discontinued » linkadge, posted by Tomatheus on December 28, 2005, at 14:38:54
Hi T
Thanks for the interesting post :)
>there is little doubt in my mind that there are some individuals (note: I'm not saying *all* individuals) who would benefit from a potent selective inhibitor of MAO-A
I agree, very much so.
I've often wondered whether p-babble has created an unrealistically negative impression of moclobemide. Most babblers who've taken moclobemide have been very treatment resistant (they have generally imported it into the US following multiple unsuccesful trials of other ADs). Moclobemide has, after all, proved to be an effective antidepressant in numerous clinical trials.
Moclobemide's official maximum dose is 600mg/day (300mg bid). Nevertheless, some sources have suggested that doses up to 1200mg/day might be necessary. Given moclobemide's reversibility and short duration of action, some patients might benefit from taking it in multiple divided doses eg. 150-300mg four times a day. Having said that, I'm sure other people can benefit from much less!
Ed
Posted by zeugma on December 28, 2005, at 16:26:16
In reply to Moclobemide vs P-babble » Tomatheus, posted by ed_uk on December 28, 2005, at 15:23:07
Moclobemide has, after all, proved to be an effective antidepressant in numerous clinical trials. >>
So has reboxetine, but I have not seen a single positive post about this AD.
How could numerous antidepressant trials be so wrong?
-z
Posted by Tomatheus on December 28, 2005, at 17:00:35
In reply to Moclobemide vs P-babble » Tomatheus, posted by ed_uk on December 28, 2005, at 15:23:07
Ed,
I think you made some valid points concerning moclobemide. As you mentioned, moclobemide has demonstrated clinical efficacy in several clinical trials. In a meta-analysis of moclobemide and brofaromine, Lotufo-Neto et al. (1999) found that moclobemide tends to be significantly more effective than placebo, about as effective as the SSRIs, and slightly less effective than the irreversible MAOIs.
And I agree that the Babblers who have taken moclobemide for depression are most likely not representative of the depressed population as a whole. Many of us here are relatively treatment resistant, so if we're more likely to be unresponsive to most drugs than most depressed patients, the same likely holds true for moclobemide. I will say that I've read that moclobemide tends to be less effective in practice than the research studies suggest. Unfortunately, I can't seem to find the source that suggested that right now, so I can't say for sure how valid that point was. I also recall reading that moclobemide was once used as a first-line treatment in New Zealand but has since dropped to second or third-line use because of its lack of efficacy. So, I think the evidence concerning moclobemide's efficacy is mixed, but I still think that the most valid sources would have to be the clinical trials, which (as you mentioned), have shown moclobemide to be relatively effective.
I also recall reading in a research study (but I can't remember which one) that some patients might benefit from doses higher than 600mg/day. And I definitely agree that the moclobemide dosing schedule likely to produce the most benefits would be the one you suggested -- dividing the dose so its taken several times a day at regular intervals. I personally tried that strategy without any success, but just because I didn't respond to moclobemide obviously doesn't mean that others won't. As I've hypothesized in other posts (see http://www.dr-bob.org/babble/20051221/msgs/591806.html if you're interested), I think that an MAOI's ability to inhibit the MAO enzymes consistently has a lot to do with the drug's efficacy. Or it's at least one important factor, IMHO. So, for some patients, it does make sense that taking moclobemide several times a day at regular intervals might be enough to do the trick.
Tomatheus
==
REFERENCE
Lotufo-Neto, F., Trivedi, M., & Thase, M. E. (1999). Meta-analysis of the reversible inhibitors of monoamine oxidse type A moclobemide and brofaromine for the treatment of depression. Neuropsychopharmacology, 20, 226-47.
Posted by linkadge on December 28, 2005, at 18:09:31
In reply to Re: What to do if Nardil and Parnate were discontinued » linkadge, posted by ed_uk on December 28, 2005, at 13:35:23
Interesting. I have a feeling then, that MAO inhibitors may affect the system slightly differently than mice with a genetic absence of MAO
http://www.nichd.nih.gov/autism/abstracts/holschneider.htm
http://biopsychiatry.com/mao.htmlThe above seems to suggest that genetic absence of MAO-A in mice is sufficant to markedly increase serotonin.
Linkadge
Posted by linkadge on December 28, 2005, at 18:33:24
In reply to Re: What to do if Nardil and Parnate were discontinued » linkadge, posted by Tomatheus on December 28, 2005, at 14:38:54
The really dumb thing, is that if the drug companies want to target as many people as possable, they might almost want to try the MAO inhibitor route.
SSRI's don't routeenly or consistantly make the average person better than well. MAO's on the other hand, were discovered based on their propenisty to make normal people feel better than well.
MAO's could also be targeted towards the cigarette smokers. Parnate could probably get more people off the cigarettes than could say wellbutrin, since smoking is not purely dopaminergic. Tobacco inhibits both MAO A, and B.
I know that the drug companies have marketed the SSRI's for everything upto and including a bad hair day, mainly because they can. I don't think they have that option with MAOIs. Also a lot of people's depression is not so bad that they would have to give up on sausage.
If MAOI's were not as "dangerous", the drug companies could probably do the same with the MAOI's that they did with the SSRI's.
I would argue that the only reason the SSRI's are so widely distributed is reated to their presumed safety. I think that even the notion that MAOI's "only help a small subset of depressed people", is just a drug company attempt to direct us towards the newer SSRI drugs. How do we know that they only help a small subset of the depressed population? They've only been given to a small subset of depressed people. Maybe if they were used first line, remission rates would be higher.
For all the placebo's I have ingested over the years, parnate was really the only "active drug".
I won't likely get another shot at an MAOI. No doctor wants to take the "risk"
Linkadge
Posted by linkadge on December 28, 2005, at 18:47:20
In reply to Re: Moclobemide vs P-babble » ed_uk, posted by zeugma on December 28, 2005, at 16:26:16
I agree that the preception of a drug can dramatically affect its use. How many people are on a particular drug these days because their doctor told them it worked better?
There are a lot of unsubstantiated opinions out there that frame the way doctors approach drugs.
How do you get people on drugs? The more people who simply try the drug, the more people who will continue taking it. As long as a drug is better than nothing, and widely distributed, it could become sucessfull.
I think that moclobemide is probably not prescribed that much, because it just seems like the "odd one out", with all of the SSRI's about.
Prozac has a name for itself.
Linkadge
Posted by Tomatheus on December 28, 2005, at 21:14:16
In reply to Re: What to do if Nardil and Parnate were discontinued, posted by linkadge on December 28, 2005, at 18:33:24
Linkadge,
My responses are below...
> MAO's could also be targeted towards the cigarette smokers. Parnate could probably get more people off the cigarettes than could say wellbutrin, since smoking is not purely dopaminergic. Tobacco inhibits both MAO A, and B.That might not be such a bad idea. The only problem I see with it is that some smokers might not be willing to give up the forbidden tyramine-containing foods if they're not willing to give up smoking.
> If MAOI's were not as "dangerous", the drug companies could probably do the same with the MAOI's that they did with the SSRI's.
I think you're absolutely right.
> I would argue that the only reason the SSRI's are so widely distributed is reated to their presumed safety. I think that even the notion that MAOI's "only help a small subset of depressed people", is just a drug company attempt to direct us towards the newer SSRI drugs. How do we know that they only help a small subset of the depressed population? They've only been given to a small subset of depressed people. Maybe if they were used first line, remission rates would be higher.
It looks like I wrote my statement regarding the drug companies' lack of interest in helping a small subset of depressed people without thinking of the context I was putting it in. I do think that the drug companies are more interested in making drugs that they can market to large numbers of people than they are in making drugs that would likely only be prescribed to a relatively small number of depressed individuals. And I think you're absolutely correct in stating that MAOIs would help more people if more doctors were to prescribe them.
With respect to the idea that MAOIs only help a small subset of depressed patients, I would actually argue (or perhaps I should say "speculate") that most, if not all, antidepressants only help relatively small percentages of patients -- at least when factors such as the placebo effect and the lack of long-term studies are taken into account. As critics of psychiatry often argue, it's difficult to determine whether or not any given antidepressant actually "helps" depressed patients based on clinical trials that only last four to six weeks. I know that I'm just speculating here, but my guess is that all antidepressants would actually turn out to be effective in less than 50 percent of those with endogenous depressive disorders if an "effective" drug were to be defined as one that produces a clinically significant response in a patient over an extended period of time.
So, I'm not really trying to say that the MAOIs only help a small number of depressives in comparison to the SSRIs. I haven't personaly come across any reserch studies that have directly compared an MAOI with an SSRI, but I would be surprised if such a study hasn't been done. Based on the limited amount of research material that I've read, it seems that the MAOIs would be at least comparable to the SSRIs in terms of their efficacy. After all, judging from meta-analysis data that moclobemide tends to be about equally as effective as the SSRIs but less effective than the irreversible MAOIs (Lotufo-Neto et al., 1999), it would seem that MAOIs might actually be more effective than the SSRIs. So, even though I think that the notion of the MAOIs only being effective in a small subset of depressed patients is somewhat problematic (mostly because a "small subset" can mean a minority as small as 1 percent or something more like 30 percent), I think the bigger problem is the tendency of the drug companies to create the impression that SSRIs are highly effective.
> For all the placebo's I have ingested over the years, parnate was really the only "active drug".
> I won't likely get another shot at an MAOI. No doctor wants to take the "risk"I'm sorry to hear that. :(
Tomatheus
==
REFERENCE
Lotufo-Neto, F., Trivedi, M. Thase, M. E. (1999). Meta-analysis of the reversible inhibitors of monoamine oxidase type A moclobemide and brofaromine for the treatment of depression. Neuropsychopharmacology, 20, 226-47.
Posted by linkadge on December 29, 2005, at 10:31:45
In reply to Re: What to do if Nardil and Parnate were discontinued » linkadge, posted by Tomatheus on December 28, 2005, at 21:14:16
No I know what you are saying.
Not so much based on what you said.
I remember reading about the definition of an MAO inhibitor on a SSRI website (can't recall which one). Basically it tried to give the idea that they were old fashoned drugs, and that the newer SSRI's were safer and more effective.
Linkadge
Posted by ed_uk on December 29, 2005, at 16:49:31
In reply to Re: Moclobemide vs P-babble » ed_uk, posted by zeugma on December 28, 2005, at 16:26:16
Hi Z
>So has reboxetine, but I have not seen a single positive post about this AD.
Meri-Tuuli found it good initially - but then her periods stopped and she developed acne (I think).
>How could numerous antidepressant trials be so wrong?
One could argue that the 'depression rating scales' used to assess antidepressant efficacy in clinical trials are invalid. Perhaps?
On the other hand, (relatively) few babblers have tried reboxetine........and some of them were very treatment resistant.
Regards
Ed
Posted by ed_uk on December 29, 2005, at 16:52:21
In reply to Re: What to do if Nardil and Parnate were discontinued, posted by linkadge on December 28, 2005, at 18:33:24
>a lot of people's depression is not so bad that they would have to give up on sausage.
LOL
I got a really good laugh out of that
Ed
Posted by Chairman_MAO on January 2, 2006, at 12:12:11
In reply to Re: What to do if Nardil and Parnate were discontinued » linkadge, posted by ed_uk on December 29, 2005, at 16:52:21
Indeed! I never understood how someone who got to the point where they wished to take medication for psychological reasons would be aversive to following a diet that's easier than the diabetic diet, for example. Hmm, being unable to walk from my desk to the cafeteria at work without feeling waves of terror as all of the people are "staring" at me and running back to my desk after I get my food...or don't eat high tyramine foods? Lay about my apartment, depressed, lethargic, paralyzed with doubt, my mind spinning endless web of thoughts about what could go wrong with every choice or move I make or could make, or give up fine, air-dried sausage? Not be able to sustain enough attention to read through a book I earnestly want to read and find interesting because I have to keep rereading every paragraph five or more times just to feel as if I'm "getting it", or forego soy sauce on my sushi?
HAAAHAHAHAHAHAHAHHAAHHAHAHAHHAHHAHAHA, MAN, THE LAUGHING HURTS!
And let us not forget that 10mg of nifedipine, phentolamine, or 0.1-0.3mg clonidine will rapidly ameliorate the hypertensive crisis.
Posted by ed_uk on January 2, 2006, at 12:47:50
In reply to Re: What to do if Nardil and Parnate were discontinued » ed_uk, posted by Chairman_MAO on January 2, 2006, at 12:12:11
Hi Chair
I'm not sure why you posted that to me :-S
You sound angry.Anyway......
>don't eat high tyramine foods?
The problem is, many people who suffer from anxiety are likely to be frightened of having a hypertensive crisis. I don't think this is unrealistic. 'Brain selective' MAOIs could offer an important medical advance.
Regards
Ed
Posted by sdb on January 2, 2006, at 13:51:49
In reply to Re: What to do if Nardil and Parnate were discontinued » Chairman_MAO, posted by ed_uk on January 2, 2006, at 12:47:50
Hopefully phenelzine will be continued for all responders. During my trial I took the concord one (uk), unfortunately an import because here is only the moclobemide sold which does not work for most but makes more money for Roche pharmaceuticals.
Happy new year anyway!
Posted by ed_uk on January 2, 2006, at 14:00:15
In reply to Re: What to do if...good thread ed (nm), posted by sdb on January 2, 2006, at 13:51:49
Hi S
So you think the UK version is good? It certainly smells interesting LOL, I've never taken it though.
>good thread ed
Thanks S, but people keep misunderstanding me :(
Ed
Posted by zeugma on January 2, 2006, at 14:58:55
In reply to Re: What to do if Nardil and Parnate were discontinued » Chairman_MAO, posted by ed_uk on January 2, 2006, at 12:47:50
Hi Ed,
The problem is, many people who suffer from anxiety are likely to be frightened of having a hypertensive crisis. I don't think this is unrealistic. 'Brain selective' MAOIs could offer an important medical advance.>>
As an anxious person (especially about food, becoming sick after eating, etc.) I don't think this is unrealistic either. I, personally, would be even more afraid of what the cholinomimetic component of the drug would do to me (perhaps the only thing I fear more than food-related problems are severe episodes of sleep paralysis, cataplexy, etc., which such drugs have been known to produce), but the fear of a hypertensive crisis, even if it can be easily managed, is still going to give physicians and anxious patients pause.
I posted this a long time ago, but this MAO-B inhibitor is intriguing:
ABSTRACT
Caffeine and more specific antagonists of the adenosine A2A receptor recently have been found to be neuroprotective in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease. Here we show that 8-(3-chlorostyryl)caffeine (CSC), a specific A2A antagonist closely related to caffeine, also attenuates MPTP-induced neurotoxicity. Because the neurotoxicity of MPTP relies on its oxidative metabolism to the mitochondrial toxin MPP+, we investigated the actions of CSC on striatal MPTP metabolism in vivo. CSC elevated striatal levels of MPTP but lowered levels of the oxidative intermediate MPDP+ and of MPP+, suggesting that CSC blocks the conversion of MPTP to MPDP+ in vivo. In assessing the direct effects of CSC and A2A receptors on monoamine oxidase (MAO) activity, we found that CSC potently and specifically inhibited mouse brain mitochondrial MAO-B activity in vitro with a Ki value of 100 nM, whereas caffeine and another relatively specific A2A antagonist produced little or no inhibition. The A2A receptor independence of MAO-B inhibition by CSC was further supported by the similarity of brain MAO activities derived from A2A receptor knockout and wild-type mice and was confirmed by demonstrating potent inhibition of A2A receptor knockout-derived MAO-B by CSC. Together, these data indicate that CSC possesses dual actions of MAO-B inhibition and A2A receptor antagonism, a unique combination suggesting a new class of compounds with the potential for enhanced neuroprotective properties.>>
http://www.jbc.org/cgi/content/full/277/39/36040Perhaps this caffeine derivative combined with moclobemide? :-)
-z
Posted by sdb on January 2, 2006, at 15:05:39
In reply to Re: What to do if...good thread ed » sdb, posted by ed_uk on January 2, 2006, at 14:00:15
Ed!
I have never taken another phenelzine than this from concorde pharmaceuticals. And you're 100% right about the smell; when I forgot to close the bottle the whole chamber had a strange but actually not bad perfume...
I cannot compare any forms of Nardil but form me there was a clear efficacy but you know some very unpleasant sideeffects, I think even stronger than weaker ssris (citalopram).
I am interested what company concorde pharmaceuticals is; I guess a generic supplier. It is possible that they will discontinue phenelzine(?). I have heard of other suppliers, even pfizer but the formulation seems to be more bad than the old thus less effective for some people. Maybe I am not right. I very dislike the "making money" behavior of pharmaceutical industry.
I am not sure if the Nardil would work for OCD.
~sdb
Posted by forgetful mary on January 2, 2006, at 15:22:56
In reply to Re: What to do if...good thread ed, posted by sdb on January 2, 2006, at 15:05:39
Story in the Boston Globe Sunday...effectively states ssri's ineffective for many....It's a crying shame that new Pdocs scare people away from Mao's......instead many will instead commit suicide...wonder if that Tampa teen who's dad is a coach was on anti depressants??
Posted by sdb on January 2, 2006, at 15:25:19
In reply to Re: What to do if...good thread ed, posted by forgetful mary on January 2, 2006, at 15:22:56
>>Thanks S, but people keep misunderstanding me :(
I did not read the whole thread but could you precise that :-) ???
Posted by ed_uk on January 2, 2006, at 15:44:01
In reply to Re: What to do if...good thread ed, posted by sdb on January 2, 2006, at 15:05:39
Hi S
>I am interested what company concorde pharmaceuticals is; I guess a generic supplier. It is possible that they will discontinue phenelzine(?)
I think they're a very small company but I'm not sure. You can email them if you like!
Nardil keeps getting passed from one manufacturer to an other in the UK. Concord is the latest.
Ed
Posted by ed_uk on January 2, 2006, at 16:08:08
In reply to Re: What to do if...good thread ed }} ed_uk, posted by sdb on January 2, 2006, at 15:25:19
>I did not read the whole thread but could you precise that :-) ???
It's difficult to explain S, you'll have to read the thread! :)
Ed
Posted by sdb on January 2, 2006, at 16:08:11
In reply to Re: What to do if...good thread ed » sdb, posted by ed_uk on January 2, 2006, at 15:44:01
:-)
Posted by sdb on January 2, 2006, at 16:09:54
In reply to Re: What to do if...ed thanks for the info! (nm), posted by sdb on January 2, 2006, at 16:08:11
reading...
Posted by ed_uk on January 2, 2006, at 16:34:52
In reply to Re: What to do if...ed will read the whole thread, posted by sdb on January 2, 2006, at 16:09:54
I just read your post about moclobemide. It's funny what you said about sleeping - moclobemide often causes insomnia.
Ed
Posted by cecilia on January 3, 2006, at 1:03:12
In reply to Re: What to do if Nardil and Parnate were discontinued, posted by linkadge on December 29, 2005, at 10:31:45
I've been taking Marplan for about 7 weeks-hasn't done a thing for me yet, but I"m increasing the dose very slowly since I had such horrible reactions to Nardil and Parnate. I agree that the fear of a hypertensive reaction is far more of a problem than the diet itself. The foods you have to give up for a MAO diet are insignificant compared to the foods I've given up trying to lose weight. But there is one thing about the MAO diet that terrifies me-other people finding out. That's the one thing that's always terrified me about the side effects of any med-when I tried Cymbalta I was terrified that someone would notice my dilated pupils. But I've been in a state of pure panic since I discovered my sister will be giving a family dinner for a visiting relative next week. I keep thinking what if she serves something like lasagna. Christmas dinner was okay, because there's so much food that nobody notices what you eat, though the salad, I discovered after I'd put a big portion on my plate, had cheese and the stuffing sausage. But what if everything on the plate has cheese? I guess I could say I'm feeling sick and don't want to eat anything. But that seems so rude to show up with something potentially contagious. Anyone have any suggestions? Just don't say I shouldn't be ashamed of taking AD's. Because I'd rather die than have them find out. Yes, I know, for all I know they could all be taking them. I still don't want to talk about it. Cecilia
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