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Q: 3-Part Q re: Venlafaxine, & Lamotrigine, Atomoxetine
Can lamotrigine, venlafaxine and atomoxetine all be taken together or would they
place too much burden on the liver's P450 enzyme system and their respective
metabolization and excretion?
Does Venlafaxine only increase serotonin at select sites like the 5HT2A receptor
or at all serotonin receptors in the brain?
Can 5-htp taken sublingually be an effective alternative to venlafaxine to
increase serotonin?
Dear AJ --
Taking your three questions in turn:
1. Can these three medications be taken together? Yes,
to our current knowledge, these enzymes are not like working parts in a car
engine -- you can't "place too much burden on them". You can try to get
too much medication through a narrow channel, such that medication levels "pile
up" behind the blockage. That's a well-recognized phenomenon called "drug-drug
interaction", when two medications compete for the same channel; or when one of
them causes changes in the level of enzyme for a particular channel. That's
generally what we're looking for when we do an interaction check.
A program that allows people to run their own checks is
linked from my
home page at the bottom right hand
corner: "Searching Medications or Interactions" (I'm linking my page
rather than the program in case their link changes in the future, or in case I
find a better such program) but caution, many of the results that come up are
not "clinically significant", meaning that we've been using the two drugs
together for years and have not seen the problem that the theory says we should
see. Doing that now for your medications, "no interactions were found for the
drugs you selected" is the computer reply. These programs are not perfect, but
they're a good way to at least take a first shot at the question you're asking.
2. I had to look this one up. One study I found
confirmed the mechanism of action of venlafaxine, in terms of its serotonergic
effects, as mediated by 5HT2A and 5HT2B (here's the very
technical report).
No, not all serotonin receptors, just those two, it is thought.
3. 5-hydroxy-trypophan is the direct precursor to
serotonin: it is a version of the amino acid tryptophan that is converted to
5-hydroxytryptamine, which is serotonin. You probably know that story
well, but for those who don't, here's a
nice diagram.
You'll recall, or see in the diagram, that the "rate-limiting step" in serotonin
synthesis takes place before 5-HTP, in the conversion of tryptophan to 5-hydoxy-tryptophan
(5-HTP). After that, the conversion of 5-HTP to serotonin (the
decarboxylase step) is more automatic, though still influenced by other factors
.
But, just as you describe, taking 5-htp will increase
serotonin -- all over the body, not just in the brain, and certainly not just at
the 5-HT2 receptors as is one mode of action of venlafaxine. So, to answer your
question, the two are definitely not equivalent. Searching for a recent
reference on the use of 5-HTP as a treatment for depression, here are a couple
of results that might be worth chasing down to further address your curiosity
about this:
In the general review, the problem of 5-HTP getting
converted into serotonin in the stomach is noted; I presume that's why you've
asked about absorption through the wall of the mouth (as for whether that works,
getting the stuff into the bloodstream, that's another question;
write me if you
have some information on that, please). The review also notes that unless
"peripheral" (everywhere except the central nervous system, i.e. the brain)
conversion of 5-HTP to serotonin is somehow blocked, much of what you ingest
will not reach the brain, requiring doses and thus much expense. If you
have any further information as to how people are using this stuff and getting
around that problem, send me that too.
The meta-analysis concludes that our research basis for
believing the stuff works is slim. For now it sounds to me as though buying
5-HTP and using it, by mouth absorption or otherwise, might be an expensive way
to get rather little? But I've not looked directly at the two studies the
Aussies thought were decent enough to evaluate.
Dr. Phelps
Published June, 2006
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