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.


Post-acute withdrawal syndrome & EDS: a PAWS for thought

When one hears vanilla horror stories about opiate addiction, the talk usually targets abrupt withdrawal following a tolerance level developed over time; this is a nasty state immediately following cold-turkey that lasts from a few days to, uncommonly, many weeks depending on the opiate involved and the person kicking (age, length of addiction, tolerance and amount, etc). However, most don’t realise that kicking is the easy part; who but the experienced has heard of post-acute withdrawal syndrome? Who but the experienced understands that PAWS, not the initial painful kick, is the reason why the ex-user becomes a re-user? Hell, even the oft-referenced and usually quite accurate Wikipedia when perused doesn’t really get into it until specifically unearthed, as a kind of aside, or curiosity.

PAWS has implications for the EDS depressed. Because depression during PAWS is increased to levels not experienced pre-opiated, one must make a difficult and informed decision. I can understand that it is better to be judged by twelve than to be carried out by six if antidepressants just don’t do it and existential despair is the only road ahead; but a possible lifetime of dependence is a frightening investment because, though the brain usually goes back to its pre-opiate state subsequent to kicking after some time… there is evidence that a somewhat unretracted state is possible…

…do you wanna roll the dice?

I suppose if I was a sixty year old man the decision to become dependent would be a no-brainer, provided I had permanent access to product. But a young person has more to think about… looking at a future married with kids and a lifetime of potential difficulties because of opiates, even if small non-abusive doses are taken. As well as PAWS, complications like hypogonadism and adrenal dysfunction, though usually reversible, are possible, and enough to scare any young person away from potential refractory depression relief via opiates (but that’s another post).

~The crux of the issue is that EDS depression can be controlled or eliminated with rational opiate therapy; but… a lifetime of opiate use will probably be necessary and, who knows, might in the long run make depression worse with decades of use or when one is forced by circumstances to quit dosing… and the future is filled with circumstances…

…but then again, what about decades of “legitimate” antidepressant use?

No one said making this choice would be easy.

Are you sure you want to do this? A list of cons

There is a price to pay for opiate therapy. Opiates are not like other drugs. Yes, pharma antidepressants have uncomfortable withdrawal symptoms if stopped abruptly, SNRIs like Effexor being exceptionally nasty little bastards; but not much compares to opiate withdrawal. There may be a special temporary hell waiting for you if you go travelling and forget or lose your medicine.

…which brings me to my Special List of Questions for those contemplating O dependence.

~Do you have experience with withdrawals? Do you understand exactly what you’re getting into if you succumb and build a difficult tolerance? heh… virgin. Just wait…

~Are you aware of and prepared for the pain of dope sickness if circumstances don’t allow you access to opiates (eg. lack of access to product, loss while travelling)?

~Will you always be able to afford your habit?

~If carrying contraband, how will you deal with border crossings into other countries with draconian laws? Are you prepared to take dangerous chances? Will having to cancel your plans because of a physical dependence on drugs disgust you?

~When travelling around, will the fact that you’re (possibly) inevitably carrying illegal product weigh on your mind and detract from a positive experience?

~Are you the type who can’t stop at your alloted daily “lifting” dose, and obsesses into euphoric doses?

~ are you ready and willing to possibly entangle yourself with a drug?

~Have you thought about the social stigma around opiate use? Will you have to hide your use from the people around you; your family/significant other/friends/work mates? If so, how will you work out the logistics, or worse, your guilty conscience?

~Does your occupation require occasional drug testing, understanding that it can take four months or more to taper off?

~Have you educated yourself about and understand the possibly very serious post-acute withdrawal syndrome (PAWS)? If you must stop therapy, are you aware that PAWS can leave you much more depressed than you were before you started opiates, and can keep a very few in its grip for years?

These are a few queries that require contemplation before embarking on this opiated journey.

Ponder them well. Make your choice with eyes wide open.