Posted by cumulative on May 9, 2008, at 6:46:48
In reply to Nardil- The best AD ever......., posted by ace on May 5, 2008, at 23:36:34
I agree with ace's sentiments here.
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.
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-dependent
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.
(*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. 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 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 ...
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, 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 MAO 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.
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.
poster:cumulative
thread:827439
URL: http://www.dr-bob.org/babble/20080430/msgs/828104.html