3-Part Q re: Venlafaxine, & Lamotrigine, Atomoxetine
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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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