Posted by TH on April 23, 2019, at 17:20:42
In reply to tolerance to maois - peter kramer, posted by rose45 on April 23, 2019, at 9:17:45
While there does seem to be documented evidence of MAOIs losing their effectiveness, I'm not sure there is enough evidence to say for sure that it is a tolerance.
If the phenomenon is in fact a tolerance, would it be a decreased sensitivity to the MAOI drug, an increased expression of MAO, or an upregulation in serotonin / norepinephrine / dopamine receptors?
This is all research that could be done, but as there is no money in prescribing MAOIs it seems unlikely that it will be performed. At this point in time, MAOI users tend to be playing guinea pig with themselves.
This does however give you a unique opportunity to do valuable self-experimentation that others may be able to benefit from.
The fact that you were able to switch from one MAOI to another and get an improved response casts doubt on the idea of an increased expression of MAO, or on upregulated serotonin / norepinephrine / dopamine receptors.
If the cause of such a tolerance was an increase in MAO expression, you should have been able to increase the dose of Nardil to "mop up" any extra MAO. In this scenario, the switch to Parnate in theory could only have helped if your new Parnate dose provided a higher level of MAO inhibition than your old Nardil dose.
If the cause of such a tolerance was a down-regulation of serotonin / norepinephrine / dopamine receptors, no level of MAO inhibition should have provided relief, nor should changing to Parnate.
If this tolerance is indeed the result of increased MAO expression, the first experiment should probably be to continue increasing the dose of Parnate, and deal with the side effects.
If this does not provide relief, it would leave many other possible causes for this phenomenon.
If we are indeed assuming that the antidepressant effects of an MAOI come as a consequence of MAO inhibition, and Parnate worked at a low dose even after a tolerance to Nardil developed, it seems reasonable to consider that for some reason, Nardil, specifically, was no longer able to inhibit MAO. I don't have nearly enough knowledge to speculate on what could cause that, but it certainly would match your experience.
If this is the case, maybe whatever caused Nardil to be ineffective has reversed, and you may get the same results you once did by switching back?
If the cause does turn out to be down-regulation of serotonin / norepinephrine / dopamine receptors, I don't know of anything that could likely help other than pausing treatment and waiting for the receptors to readjust. As I posted in a previous thread, there is some evidence of the kappa opioid receptors mediating dopamine down-regulation, but this is extremely experimental and really a long shot.
In all honesty, much of this is a shot in the dark. Just about any change here could potentially bring some relief, and all you can really do is cross your fingers and try the most plausible options first.
Don't forget that there is probably no value in trying to figure this out while still withdrawing from benzos. The discomfort from that would more than drown out any potential positive effects.
Good luck Rose, I hope you can find something.
poster:TH
thread:1104119
URL: http://www.dr-bob.org/babble/20190206/msgs/1104122.html