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new to Parnate (MAOI) - Fatigue (Serotonin?)

Posted by mrSwim on December 21, 2016, at 23:15:06

Hi all
Firstly thanks for this forum and your input. Without it, I don't think I would have come across the experiences, advice, links and references that I had done in order to convince me to try Parnate (MAOI) for my situation. I lost all faith in anti-depressants and the medical system in helping my situation after only being offered SSRIs and SNRI's, (and antihistamines!), all unsuccessfully or making matters worse. I gave up for a long time. Self study led me to discover Parnate, and to push for this medication.

The benefits have been outstanding. My question is relating to the Fatigue being experienced, which I know is a common side effect. (Even with this fatigue/lethargy, I would still continue to take the medication for the time being.)

But I wonder if anyone has any information as to what may be the actual cause of this fatigue and increase in perceived weakness of my body. It's much more a physical lethargy and fatigue, than mental. Mentally there is calm and peace, but definitely not a fogginess I would associate with a mental fatigue.

I'm aware that MAO enzymes may have more functions throughout the body other than just regarding the breakdown of neurotransmitters, with perhaps more roles in the GI tract and Liver and elsewhere to a degree. But I cannot find any information about how inhibition of MAO directly can cause perceived fatigue/weakness, eg regarding muscle function or anything like that.

I have come across information suggesting that Norepinephrine can actually be reduced on MAOI's, due to higher levels of Octopamine displacing NE in synaptic vesicles - an adaption to the tyramine pressor response. So one idea is that lowered Norepinephrine may be the cause of this fatigue, however I do not fully understand the significance of this Octopamine/Norepinephrine relationship or the consequences or magnitude of reduced Norepinephrine - whether incorporating an NRI such as Reboxotine would be of benefit at all or whether this would cause unwanted/unnecessary complications. ---> Either way, I think potentially lowered Norepinephrine levels would be a longer term adaption to MAOI's (if at all) - not applicable to fatigue/lethargy experienced in early use of MAOI's.

I'm wondering about Serotonin. As expressed, I had no beneficial response to SSRI's. So I have an intuitive feeling that increased levels of Dopamine (and possibly NE, and endogenous PEA) are more helpful in this situation, and probably in many other peoples too, particularly those who don't response do SSRI's - a lot of people!) - Thus, my positive response to MAOI's and not to SSRI's. And THIS leads me to wonder whether the MAO Inhibition of the breakdown of Serotonin may be unwanted in this situation, and whether too-high (but within safe levels) of Serotonin may be the cause of fatigue and lethargy. (I don't take any 5-htp or tryptophan.).

If this could be the case, one (uneducated) concern could be the downregulation of serotonin receptors in the longer term, eg receptors adapting to the surplus of Serotonin levels available. I say uneducated, as I don't fully understand this mechanism and I'm not sure it would be guaranteed to occur. But if it is a possible outcome of having too high levels of Serotonin available then it is something I would want to take precautions to prevent.

I will probably in the future transition to L-deprenyl, if this is possible at that point in time, for it's selective MAO-B inhibition, and to explore whether this alone provides the improvements being experienced on non-selective MAOI. For now, I'm very happy to continue with things as they are and let things settle for a while, even with the fatigue and lethargy being experienced.
(I can't imagine it will be of much help, but I should be able to get a script for Modafinil in the new year to explore whether that helps, but I can imagine the benefits of this are more on cognition than on somatic - but worth a shot I reckon!)

So, sorry I wrote a lot there - to boil it down, do you think MAOI's could cause favorable neurotransmitter levels but possibly an excess of Serotonin, and that this could be the cause of fatigue and lethargy?

Thanks for your time in reading this, and for any response too :)





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