Talk:Tramadol

Serotonin (SERT) action pharmocologically relevant ??

The article should probably caveat the action on increasing serotonin as not pharmocologically relevant. The SERT dissociation constant is very large. SSRIs have much smaller ones, by 1-2 orders of magnitude. I think the serotonin effects are too small to be practically relevant. Danski14^(talk) 01:13, 16 September 2018 (UTC)

With some SSRIs it doesn't matter. It has a black box warning interaction with Zoloft, Paxil, and some other SSRIs, Zoloft for example has a lower 5HT2C binding affinity than tramadol and O-DSMT, while tramadol can potentially compete at NET but they're pretty similar there. Anecdotally I was accidentally prescribed both at the same time once and by the 2nd day was noticing early effects of serotonin syndrome and went back to the doctor in a fairly "cracked out" state and white-boarded the whole mess of why it was a problem to mix them for the poor orthopedic specialist who followed most of it and switched me over to vicodin at equivalent dose.

It's been about 6 years since I was up all night studying it but the problem seemed to mainly exist with SSRIs that had some binding affinity lower than tramadol at certain 5HT subtypes... Sadly I can't recall the specific problem that caused. Tramadol is also a serotonin releasing agent and relatively potent for what it is, with possibly stronger SRA effects from metabolites since they all do different stuff and have their own affinities / dissociation constants everywhere. Full-concentration / thereapeutic dose SSRIs after a month don't reach full SERT occupancy (or they'd probably just kill people, really) so there's still a chance for more reuptake inhibition to stack on top of that the SSRI is producing regardless of the higher Kd and full inhibition isn't something wanted. I think 5-HT3 and 7 were major issues since antidepressants aren't normally agonists at those receptors and released serotonin will preferentially bind to the non-occupied ones, depending on the antidepressant 1A and 1B might be left alone too, although I recall it having less problems with those. Zoloft was a specific black box warning at the time.

The exact quote from this ref is --

5.9 Serotonin Syndrome Risk

Cases of serotonin syndrome, a potentially life-threatening condition, have been reported with the use of tramadol, including ULTRACET, during concomitant use with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) [see Drug Interactions (7)]. This may occur within the recommended dosage range.

Honestly that's all the evidence I need, since prescribing warnings are too sparse for many drugs, if anything. Removing something specifically warned about because of interpretation of limited receptor binding affinities isn't proper.

A Shortfall Of Gravitas (talk) 14:57, 22 May 2023 (UTC)

If you have adequate sources to support this claim, feel free to add content Caitlin.swartz (talk) 08:50, 30 March 2019 (UTC)

Typo in lede

It says "may be sold in combined with paracetamol" which is ungrammatical. it should be changed, maybe to say "in combination with" or "with xxx in combined form" morsontologica (talk) 08:06, 7 January 2019 (UTC)

I have fixed it. Thanks for catching the error and reporting it here. -- Ed (Edgar181) 13:27, 7 January 2019 (UTC)

For future reference (though this particular user was apparently experienced with Wikipedia), all readers are encouraged to jump in and correct these sorts of errors. Copyediting is an essential part of Wikipedia :) Caitlin.swartz (talk) 08:59, 30 March 2019 (UTC)

Outdated reference?

• I apologize in advance if this is a dumb question.*

Reference 17 (Lee CR, McTavish D, Sorkin EM (1993)) is ~26 years old and contains outdated information, as our understanding of Tramadol has changed significantly. However, the cited information presented in this Wiki page appears to be currently accurate. Furthermore, there's only one sentence which appears to rely on this citation (the one regarding morphine equivalents). Is it necessary to update the source in this specific example? Thank you. 2603:301E:103:8200:58F9:50A5:F1AA:DEFD (talk) 09:19, 30 March 2019 (UTC)

Btw, I'm in the process of a name change. Hence the string username. 2603:301E:103:8200:58F9:50A5:F1AA:DEFD (talk) 09:21, 30 March 2019 (UTC)

Better withdrawal info?

I'm not a doctor so don't know what may be available in the medical literature, and wish someone with the resources would look at this. I do not believe the statement that dependence only occurs at high doses and/or after extended periods of time is at all accurate. I took codeine at high doses every day for over a year for severe dental pain (actually, dihydrocodeine DF-118, c. 150-240 mg. per day), withdrew cold turkey, and had no withdrawal symptoms other than cold feet (literally) for a week or so. Fast forward another year and I start getting joint pain in my fingers (and I'm a musician). Can't take NSAIDs b/c I'm on blood thinners and paracetamol is worthless. Take tramadol instead. Take it LESS THAN TWO WEEKS at c. 200 mg a day (100 mg. bid) then stop b/c the pain is better. In 24 hours, I have severe chills and feel like I've come down with a bad flu (not fun in COVID time). Decide to take tramadol to see if it stops the chills ... it does. So a man who had no problems withdrawing from long-term, high dose codeine use becomes dependent on tramadol after two weeks. There are thousands of similar anecdotal reports. Anyone on the medical side who can validate this, please update the section on addiction/dependence. ___HB — Preceding unsigned comment added by 61.15.225.100 (talk) 03:46, 1 November 2020 (UTC)

It's probably dependent on the person. Codeine is incredibly weak for one but I doubt that's the issue. I had no problems with cold turkey withdrawal from O-DSMT (the active, stronger metabolite) after taking around 1g of it in a month. In comparison 15mg of it was as much as I could handle without "nodding" and I always stuck to the same dose. It's roughly 6x stronger supposedly (felt more like 15mg = 4mg hydromorphone to me, whereas tramadol does almost nothing to me, so I may be a poor metabolizer) so it should have been equivalent to about the same dose per day you were on, just lower doses by weight. I had no problems stopping it immediately. Tramadol is much dirtier than its main active metabolite on its own though, hitting GABA receptors, SERT, NET, DAT, and a mess of other crap. I'd expect it to be a sort of mild opioid withdrawl combined with a antidepressant withdrawal (especially if you weren't on them) combined with a mild benzo withdrawal combined with... you get the point. You don't see a receptor activity profile that random / scattershot outside of antipsychotic pages, normally. It usually indicates a really poorly designed dirty drug that just happened to work and managed to get approved.

The antipsychotics tend to be antagonists almost everywhere because a) the doctors have no clue whatsoever what will actually work because of lack of understanding of mental disorders involving hallucination and b) slowing down that much of the brain shuts the crazies up so everybody can just ignore them and pretend like they're ok. Ironically I was given anti-psychotics for sleep once, which is a fairly new and incredibly stupid practice, and found out that they cause me to hallucinate horribly, often for weeks after I stop taking them. Apparently doctors are just now figuring this out. It happens when they give them to people without psychotic disorders, and they usually try to treat the hallucinations with higher doses of stronger anti-psychotics. They also give you parkinsons symptoms that can last forever but that's just part of the magic of mental health care.

OTOH I seem to be immune to addiction from any normal pain relieving doses of opioids too. I think it's probably fairly common, if you don't get obsessed with the drug and it's only acting fairly weakly on MOR and KOR rebound is quick (it's just that people only post their life-wrecking horror story of hitting the needle and blowing businessmen in alleys for $5 to get their next hit). I'm fairly sure people who get addicted to something like vicodin TRY to get addicted to it. Stronger stuff like hydromorphone and fentanyl are a different story obviously. I've only had withdrawal from 8mg daily of buprenorphine for over a month and it was relatively short. — Preceding unsigned comment added by A Shortfall Of Gravitas (talk • contribs) 15:34, 22 May 2023 (UTC)

Mix with Benzos

Why is there no warning about mixing a narcotic with Benzodiazepines?? Or did I miss it?? Lady Meg (talk) 05:26, 27 July 2023 (UTC)