Posted by ace on May 10, 2008, at 0:57:42
In reply to nardil thoughts. why not to lower for maintenance, posted by cumulative on May 9, 2008, at 6:46:48
> I agree with ace's sentiments here.
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> Many of the people on this forum have had similar experiences -- lowering the dose (CONTRARY to the theory that the antidepressant effect from MAO inhbibition can be maintained at a lower dose which continues to get rid of MAO) has caused a loss of effect and relapse.
100% agreed upon. I think the monograph has to be amended: not just in the respect either....
I have not seen any clinical trials that support sustained therapeutic action, with subsequent lowering of dose. I actually feel this sentiment is an affront to medical logic...
> I think that the reason for this is that much of Nardil's antidepressant effect might stem from additional properties beyond MAOI:
>
> a) the gabaergic activity of Nardil and its metabolites, which is dose-dependentWhich I think accounts for accounts for not only Nardil's anxiolytic properties, but also it's AD effects. This aspect, I also feel, is very very much dose dependant....
> b) another Nardil metabolite is phenethylamine (PEA), an endogenous stimulant-type substance with effects comparable in many ways to amphetamine*. Typoically PEA is rapidly destroyed by the monoamine oxidase enzymes before it can reach blood levels of any significance -- Nardil's MAOI stops this from happening, but the metabolism to phenethylamine is still dose-dependent.> I think this theory accounts for Nardil's stimulating, prosocial, and (great stuff!)euthymic/hyperthymic (bordering on hypomanic) effects. The GABAergic properties might optimally be offseting nervousness from PEA, and also improving e.g. social phobia on their own.
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> (*alpha-methyl-phenethylamine)
>
> What's particularly interesting to me about Nardil is the very long-lasting efficacy -- it seems to me, from reading these anecdotal reports, that many of those (though not all) who do well on it can continue to do so for many years, even decades! The early hypomania seems to usually fade, but a VERY considerbale mood improvement remains.
I know what you mean. However, I notice that many patients, in addition to retaining a formidable therapetic response, also tend to cycle in and out of their initial hypomaniac-like state. Some have stated that Nardil (and Parnate) suffer from the 'poop-out' syndrome to a great degree. I disagree with this, not only on anectodal reports, but clinical evidence. When I have seen/heard of Nardil loosing efficacy over a period of time, the genesis of this seems to be in the fact that the patient becomes remiss to certain fundamental issues as taking the drug every day (as opposed to skipping doses), taking the drug at totally unregular time intervals.....tampering with the (effective) dosage etc etc etc
This to my mind is unusual among most of the antidepressant substances, especially those that seem to provide some dopaminergic effect, as Nardil to my mind does.I think, along with Nardil, Clomipramine, in particular, seems to share this trait. SSRI's, in my view, not only provide (for the most part) little efficacy, but seem to poop-out a lot, and, only have 'one-shot' efficay....
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> I wonder ... just found this. Very,very interesting in the context of memantine (a partial NMDA glutamate subtype antagonist) that some of us here have been examining both as a standalone antidepressant, and for halting the development of tolerance to psychostimulants, particularly the antidepressant, antianhedonic effects of these stimulants ...
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> http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0F-41KP985-2&_user=1537448&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000053621&_version=1&_urlVersion=0&_userid=1537448&md5=27e5d89f3df6c1d9491bb0b5e3951d21
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> One more thing. A few people have complained of cognitive issues with Nardil, especially early in treatment. I'm not sure if anticholinergic properties have been identified for this drug,This is true, and I do have papers at home that do strongly point to anticholinergic properties which account for this. Cognitive problems, usually are usually only early in treatment as you stated....I think they usually appear as the first s/effects (apart from somnolence in some) and are the first to dissipate....
but some of the possible side effects would seem to suggest possible anticholinergic activity very well. It's not hard to imagine that something like that could be occurring downstream. In this case, it may be interesting to look at the cholinergic precursor supplements Alpha-GPC and citicoline, both of which have benefits beyond cholingeric enhancement. iirc the old great poster here Chairman MAOWhere has Chairman gone!!?? He certainly knew his MAOI's!!!!
found galantamine (the combined acetylcholinesterase inhibitor/nicotinic agonist) to completely eliminate any cognitive issues from Nardil, and even help with Nardil anorgasmia ... which can also be an effect of excessive anticholinergic activity, among other things.
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> Last time I talked to Chairman some months ago he was taking 60mg dextroamphetamine (VERY cautiously titrated upwards by 2.6 mg at a time!) + 105 mg Nardil daily, and this had been successful for him for around 2 and a half years and continuing.
A very good, accurate post......Ace:)
poster:ace
thread:827439
URL: http://www.dr-bob.org/babble/20080430/msgs/828302.html