Ja du ber ju då läkarn att kolla rs6323 lr MAO-A, COMT 158 mutationer brukar va inblandat i problem bilden oxå. Finns studier från Karolinska på Pubmed.com...
Angående varför din Aurorix inte fungerar så klistrar jag in detta från mer än mig kunnig om MAOI
www.neiglobal.com
Is there a rationale as to why reversible MAOIs would or would not be as effective?
Yes, there are several reasons why selective and/or reversible drugs would probably be less efficacious. I think this is a question about reversible competitive inhibitors of MAO-A (RIMAs), i.e. moclobemide (MOC), but we could also compare the irreversible drugs selegiline (MAO-B selective) and tranylcypromine (MAO-A+B).
Tranylcypromine (TCP), phenelzine and selegiline form an irreversible bond with MAO and totally disable it. MAO function is then largely restored by production of new enzyme from the genetic code. RIMAs, like MOC, are competitive and reversible and are displaced from MAO-A by the endogenous substrate, in this case mainly 5-HT. Therefore, they have a natural ceiling effect, the more 5-HT is increased the more it displaces a RIMA from MAO-A (especially a weakly competitive one like MOC). That is probably why even large over-doses of MOC do not cause serotonin toxicity, and in fact usually present with minimal symptoms of any sort of toxicity.
We still do not really know how MAOIs work, but it seems probable that MAO has to be inhibited almost completely for there to be much effect on monoamine levels. That probably means around 95% inhibition.
Another important point is that metabolism of dopamine, norepinephrine and 5-HT is, to a greater or lesser extent, contributed to by both MAO-A and -B. For dopamine (DA) it is about 50:50. It is thus the case that TCP raises DA levels to a greater extent than does a slightly selective MAO-B drug like selegiline, or rasagiline (more selective). The main reason MAO-B inhibitors have been developed for Parkinson disease is the perceived importance of avoiding the tyramine-mediated pressor effect (“cheese reaction”). What the risk vs. benefit balance is of the larger increases of dopamine (and other mono-amines) produced by TCP vs. lesser increases from selective drugs remains uncertain, and untested, but it may be that TCP is more effective for depression/Parkinson’s than is rasagiline, or selegiline. RIMAs have little or no effect on dopamine.
So, yes, there are definitely very good reasons to suppose that irreversible MAOI-A/B inhibitors are likely to be more effective, and that is what experience teaches us, even if controlled trials are less helpful; compared with TCP, MOC is a weak antidepressant, if indeed it is an antidepressant that all. As far as I recall every single patient I ever cared for who tried MOC instead of TCP got worse and asked to go back to TCP.
P. Ken Gillman, MB, BS, MRC Psych.
