Is there a case for tramadol?

Tramadol is a mild opioid analgesic with weak agonist actions at the μ receptor; it also releases serotonin and inhibits the reuptake of noradrenaline. It’s scripted for moderate pain, restless legs syndrome and fibromyalgia.

Tramadol has been prescribed for refractory depression for years, overtly in the US as a last-line drug for depression and somewhat otherwise to trusted patients by intelligent doctors in other countries. Lurking around the internet however, one finds there isn’t as much love for this drug as for its opiate cousins. Because of its unusual actions, some are fairly content to use it with a few reservations, a very few love it (maybe because they have uncommon genuine serotonin issues), and most become disillusioned with it after a time (maybe because, like so many depressives, they don’t have serotonin issues); and tolerance is kind of an issue because of potential serotonin poisoning (god, I have a hate-on for serotonin), so in my opinion long-term use is not advised…

…but, and here’s the kicker, because of lack of knowledge patients who are scripted on-label for pain get caught in a trap of dependence and withdrawal hell. The net is filled with stories like these… …be aware.

Tramadol acts as a μ-opioid receptor agonist, serotonin releasing agent, norepinephrine reuptake inhibitor, NMDA receptor antagonist, 5-HT2C receptor antagonist, (α7)5 nicotinic acetylcholine receptor antagonist, TRPV1 receptor agonist, and M1 and M3 muscarinic acetylcholine receptor antagonist. This is one hell of a mechanism of action, and the very reason I’m wary of this drug. Calling it a “mild opiate” is like calling someone the world’s tallest midget… “like, so what?” Opiate withdrawal and PAWS are bad enough; now let’s combine O withdrawal with a SNRI-type withdrawal (Effexor discontinuation syndrome, anyone?), and fun and happy-happy joy times are right around the corner (I can see the balloons, confetti and flying ribbons already). I’ve been through SNRI discontinuation syndrome, and I cannot imagine dealing with, both at once, O withdrawal and SNRI withdrawal.  If one must abruptly discontinue for any reason (there are many…) and is into this stuff up to his neck, one had better get ready to take some time off work and possibly check into a medical facility; there ain’t no staying in bed with the Thomas Recipe, benzo’s and classical guitar cd’s with this stuff.

People are more and more advocating tramadol as a possibility for refractory depression, but I wonder if they’ve done their homework or don’t take seriously the potential for pain caused by this drug. Again, I have experience with these side effects and have no problem with the thought of saying “uhh… no.” Consider too, possible seizures for some, and tramadol starts to sound like not so much fun anymore. Indeed, a growing awareness regarding seizures appears to be another of tramadol’s bad raps…

…so, if one thinks combining tramadol with most mainstream antidepressants to increase efficacy might be the ticket, I would be inclined to put that thought away; maybe I’m wrong, but possible serotonin complications make this idea hard to defend.

~If your doctor is willing to script tramadol (imo, stacked with no other ADs), and you’ve done your homework and are aware of the negatives, you might be presented with an opportunity because it’s a “mild opiate” and maybe not so stigmatised by patronising (or just simply worried about a patient) doctors; maybe it is worth trying. As long as the supply doesn’t get abruptly cut off, you don’t develop a scary tolerance and this funny little opioid works as well as other “normal” opiates for refrac-depression, maybe try it out. There is evidence that tramadol binds to kappa receptors, but no evidence of wretched κ effects; so this is a big point in its favour. Just be careful and don’t beat a dead horse if it doesn’t work the way you want it to in the long-term…

…a blog-mate recently wrote that she takes a very small dose every few days to excellent effect. Maybe this is the way to go with this stuff. Little to no tolerance is built, and the potential for bad side effects is reduced big time.

I might look more into tramadol later, if my interest is piqued; but I can’t help feeling like a bit of an opie-snob with this stuff. Because of its obscure actions, this drug may be the holy grail for someone with an obscure kind of depression, but probably not much fun for most. I just don’t know if it comes close to “real” opiates for a person with EDS/refrac-depression…

…personally, I’d try LDN before tramadol.