Posted by Chairman_MAO on June 20, 2005, at 15:23:24
In reply to What AD most like Tramadol???, posted by ace on June 19, 2005, at 1:54:23
Drug-induced euprhoria ALWAYS fades to some degree. ALWAYS. You will NEVER be able to recapture the initial euphoria you felt on Nardil; this is simply the nature of the brain, mind, and LIFE. Moreover, increased 5-HT is NOT what you need for this euphoria. Indeed, unless you can convince me otherwise using a rational argument, I will maintain that your reasoning is based upon a dangerously flawed understanding of neuropsychopharm and the mechanism of action of the drugs in question here. DO NOT mix a potent serotonergic with an MAOI! ____*****YOU WILL NOT GET THE RESULTS YOU ARE SEEKING, AND WILL LIKELY END UP DELIRIOUS, IN THE E.R., OR EVEN DEAD!*****______ Try l-tryptophan if you wish to test out this hypothesis. However, even that combination can result in serotonin syndrome; it simply has SOME track record of safety, and was popular in the 70s and early 80s, AFAIK.
That said, there are ways to make your response to phenelzine more "robust", which is the closest thing you're going to get to eurphoria, IMO. Please believe me that what you liked about tramadol was the mu-opioid stimulation. Get on an opioid (buprenorphine, tramadol, morphine, etc)! Tramadol's effects on 5-ht are weak, and yet you report that it "brings back the Nardil euphoria". If that's so, then why do you draw the conclusion that a more potent serotonergic agent is what you need? That seems illogical to me.
If you cannot get on an opioid, you need something to enhance activity in the nucleus accumbens. Opioids inhibit GABAnergic activity in the NAc, thereby enhancing dopaminergic tone there, which gives a sense of well-being. Moreover, they inhibit NE release in the locus coeruleus, which gives a sense of serenity and calm (the "real" picture is way more complex, but this is the level that I understand). It is likely, however, that the Nardil is already fulfilling this function, so it is not as important.
Thus, you need an agent to increase DA tone in the NAc. You can go with a direct DA agonist: use either cabergoline up to ~8mg/day (one case study had success at 2.5mg), or pramipexole/ropinirole. Your pdoc should be able to go over the differences with you, and if you ask me I can go into it further. Tolerance will develop to the feeling of well-being you get from that, however, due to DA autoreceptor desensitization leading to decreased DA release. Thus, you need a DA autoreceptor antagonist (amisulpride, which may work alone in this application) or a DA releaser (amantadine, memantine). In fact, tramadol/buprenorphine + memantine would be an excellent combination, because memantine (ideal dose for this 60mg/day) is known to attenuate opioid tolerance.
For the biggest "punch", try Nardil + cabergoline 1-8mg/day + buprenorphine 0.3mg-0.6mg sublingual (or whatever dose works for you). Bupe is arguably the best antidepressant opioid because of kappa antagonism. Its limited abuse potential also makes it attractive to pdocs. On top of that, add memantine, 10-30mg bid, and you have a regimen that basically will give you as much "euphoria" as you reasonably can expect long-term.
Caveat emptor: euphoria is much more enjoyable when the drugs make it possible to get it from REAL-LIFE experiences as opposed to getting it from the drugs directly. Think about it this way: The weather on some islands in the South Pacific is beautiful. However, many of those islands are crappy places to live because there is no economy. The relation between mood (euphoria) and your life is the same: No matter how great your mood, if you don't have content in your life that matches it, no amount of euphoria will ever be satisfying enough.
PLEASE heed my warnings and do not add a potent serotonergic agent to Nardil! The fact that you keep contemplating this despite what we're saying here worries me. I empathize with your quest for well-being in more ways than you likely imagine, and what may seem like harsh criticism is actually my trying to bequeath to you wisdom that I learned the hard way--so you don't have to.
Please keep us posted on what you decide to do, and best of luck.
--cm
poster:Chairman_MAO
thread:515368
URL: http://www.dr-bob.org/babble/20050617/msgs/516066.html