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Warning - possible SNRI and codeine reaction UPDATE: loratadine and SNRI interaction?

effie

effie

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I had a strange reaction today after taking codeine and venlafaxine (a SNRI antidepressant). It felt like a mild serotonin syndrome type reaction.

I will describe what happened and let others make their mind up - I'm really not sure what it was, and can't find much in the literature!

Last night I had about 500mg codeine - I had got hold of straight 30mg tablets and I usually CWE two boxes, so I assumed it'd be about the same. Turned out to be a lot stronger - I guess I usually lose a lot in the CWE!

Had massive histamine release, bright red with white blotches all over, intense itching lasting far longer than normal. Had two loratadines which did fuck all. Was not much fun..

Eventually it wore off and I went to bed (still itchy). In the morning I took 150mg venlafaxine, which is my standard antidepressant. Felt fine initially, but as the morning went on I started to get really hot and developed a horrible headache. By lunchtime I was pouring with sweat and felt like my heart was racing. I was told I looked awful and had to go home - checked my temp and it was 38.1 (normal is below 37, that is def classed as high).

I didn't feel like I had a cold or flu or anything - just hot and agitated and headachey. My face was really blotchy too and I felt like my eyes were swelling. It gradually wore off as the day went on (had a diaz to calm myself down) and now I've just got some residual facial redness and a little agitation..

It did felt like a mild serotonin syndrome to me, from reading about it. All I can imagine is that the codeine plus SNRI was not a good combo.. Can't find much about codeine being serotinergic, but quite a few other opiates are.. maybe it was due to a codeine metabolite.. I really don't know.

Anyway - was really scary at the time, and obviously serotonin syndrome can be fatal if it is severe so wanted to warn people about combining SSRIs or SNRIs with opiates.

I've had it with oxy before (which is def serotinergic) and been fine so it seems random - but it really scares me that the combination of SSRI/SNRI plus codeine or other opiates could potentially be dangerous!
 
You're among the most helpful bluelighters. Thanks for the information :)
 
This isn't my area at all so I don't know the details, but there are for sure reciprocal interactions between the serotonergic and histaminergic transmitter systems

If I were to guess, I don't think codeine itself is a risk for SS. I'm assuming you've taken codeine in combo with SNRI's before?

The histamine reaction could have been a problem though - massive release of H coupled with potentiation of the serotonergic system could be bad juju...

Thats all speculative though, like I said this isn't my area. Glad to hear you're OK though, must of been a pretty shite time
 
This is a bit of a surprise (and now a mild concern) to me as I'm prescribed both codeine and tramadol daily and have never had a problem with the combo. Some potentiation at first which meant lower codeine doses were needed initially but never any SS-type reactions other than when I took LSD on top of them one time.

Utterly bizarrely I had another run-in with SS just yesterday and am only just starting to feel okay again now. Thankfully way less intense than the first time it happened albeit with a longer duration. Can't really add any tips on what to avoid there cos I'm not sure what exactly caused it cos people don't tend to advertise what they cut stuff with (was meant to be MXE (from an "unofficial" vendor) but was heavily cut with *something* else that was also active).

Fuck SNRIs and fuck tramadol, in particular. Was tapering anyway but won't be refilling that script next week at all if possible. The potential for horrific drug interactions is just way too high :|

Sorry to slightly derail, Effie. Was actually just coming here to mention my own SS surprise when I saw your thread. Guess that makes us Serotonin Sisters or summat :D

Most importantly - glad you're okay now <3
 
Chemical Samile said:
This isn't my area at all so I don't know the details, but there are for sure reciprocal interactions between the serotonergic and histaminergic transmitter systems

If I were to guess, I don't think codeine itself is a risk for SS. I'm assuming you've taken codeine in combo with SNRI's before?

The histamine reaction could have been a problem though - massive release of H coupled with potentiation of the serotonergic system could be bad juju...

Thats all speculative though, like I said this isn't my area. Glad to hear you're OK though, must of been a pretty shite time
Click to expand...

That's really interesting. I thought it was copletely bizarre too as I couldn't find an literature about codeine being risk for SS. The histamine thing definitely needs looking into - was the worst histamine release I've ever had definitely.

The thing that really confused me was that I'd had oxy + SNRI before and been fine - and oxy definitly does have serotinergic properties. So, logically, the histamine release was the one unusual thing about the situation.

Thanks for all the well wishes - luckily it subsided just as I was starting to get worried, otherwise it'd have been a fun trip to hospital for me!!

Don't want to make peope too scared to have codeine with SSRI/SNRI in the future, just wanted people to be aware of my odd reaction in case anything similar happens to them...
 
Shambles said:
This is a bit of a surprise (and now a mild concern) to me as I'm prescribed both codeine and tramadol daily and have never had a problem with the combo. Some potentiation at first which meant lower codeine doses were needed initially but never any SS-type reactions other than when I took LSD on top of them one time.

Utterly bizarrely I had another run-in with SS just yesterday and am only just starting to feel okay again now. Thankfully way less intense than the first time it happened albeit with a longer duration. Can't really add any tips on what to avoid there cos I'm not sure what exactly caused it cos people don't tend to advertise what they cut stuff with (was meant to be MXE (from an "unofficial" vendor) but was heavily cut with *something* else that was also active).

Fuck SNRIs and fuck tramadol, in particular. Was tapering anyway but won't be refilling that script next week at all if possible. The potential for horrific drug interactions is just way too high :|

Sorry to slightly derail, Effie. Was actually just coming here to mention my own SS surprise when I saw your thread. Guess that makes us Serotonin Sisters or summat :D

Most importantly - glad you're okay now <3
Click to expand...

No worries with derailing, tis all important! Sorry to hear you had a bad experience recently too, tis not much fun at all :( I'm going to have to trhink carefully about all sorts of serotinergic drugs now - obv mdma is out but things like acid + SNRI may not = good. Dammit.

I like Serotonin Sisters. Would be an ace name for a band %)
 
Having just recently being put back on Venlafaxine, ( I didn't take drugs the last time I was prescribed it) this is really interesting reading. Thank you.

Obviously I've been on different types Anti-depressants since I started taking drugs, and know the drugs and know the ones to avoid, but not with an SNRI.
 
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In the past, I've had large doses of codeine, say in the morning, then MDMA at night - with no issues. I reckon we'd have heard about that being a dangerous combo, by now, if it was.
 
I think that really, for most intents and purposes SNRIs can be viewed as SSRIs in terms of drugs to avoid - MDMA does not work, and I would generally avoid hugely serotinergic drugs.. didn't occur to me that opiates might be included and I probably am going to try a sensible dose of codeine with it again as I've had CWEs plus SNRI and been fine, and as I keep saying oxycodone has also been fine. Maybe it was random, maybe it was the high codeine dosage, or maybe it was the histamine.. who knows.

SNRI + tramadol certainly looks like a recipe for disaster, Shammy!

I'll be wary of things like acid too, will do some research - be gutted if I can't have that either.. so many fun drugs are serotinergic, gah.

Still, venlafaxine works really well for me so tis worth a bit of bother.

Edit: yeah, treacle, am not saying codeine is a risk for SS and should not be taken with MDMA. Just reporting a very strange reaction I had between SNRI and codeine. Everyone at work today kept telling me how ill and hot and agitated I looked yesterday, was pretty horrible! Am 100% fine today though. All very odd.
 
Shit Effie! That's harsh :\ Glad yer alright now.
The only things I can think of is that Venlafaxine is where Tramadol came from (they're structurally related), the Histamine-Serotonin interlink that Chem Smile mentioned, possibly the Loratadine (which is also related to Trycyclic Antideps but has no other MOAs other than Histamine Antagonism)..
But I really don't know..

I take an SNRI (Dosulepin) and Codeine and have never suffered such a reaction. Very strange indeed..
 
How does this sound? Loratadine and SNRIs both have anticholingeric properties. This could result in anticholinergic toxicity syndrome:

Remember common signs and symptoms with the mnemonic, "red as a beet, dry as a bone, blind as a bat, mad as a hatter, and hot as a hare." The mnemonic refers to the symptoms of flushing, dry skin and mucous membranes, mydriasis with loss of accommodation, altered mental status (AMS), and fever, respectively.
Additional manifestations include sinus tachycardia, decreased bowel sounds, functional ileus, urinary retention, hypertension, tremulousness, and myoclonic jerking.
Patients with central anticholinergic syndrome may present with ataxia, disorientation, short-term memory loss, confusion, hallucinations (visual, auditory), psychosis, agitated delirium, seizures (rare), coma, respiratory failure, and cardiovascular collapse.

http://emedicine.medscape.com/article/812644-overview
 
effie said:
SNRI + tramadol certainly looks like a recipe for disaster, Shammy!
Click to expand...

Tramadol is the SNRI in my case, Effie. Only mentioned it as it's in the same class as venlafaxine and is related to tramadol so likely has some common effects. Venlafaxine does seem to be slightly less dodgy with sertonergics based on what I've seen in PD (not exactly extensive statistical analysis, admittedly) as it's widely used and those on it have always been shocked when I mention the issue(s) I've had with tram/sert combos. Never heard of venlafaxine causing any similar issues until this thread but tramadol is notorious for not playing nicely with other stuff.

It's a shame as it has been the most effective antidepressant I've used so far but I just don't trust it anymore. Far too difficult to totally avoid sert's unless you adopt near enough a total abstinence policy or have access to guaranteed uncut drugs. SS is way too serious (not to mention deeply unpleasant at the time) to take any chances with. I was matter-of-factly pottering about arranging to sacrifice myself in gory fashion outside me flat at dawn at one point in the delirium. That's scary stuff cos I wasn't even that far gone compared to the first brush with SS. Automatonism, delirium and high risk of multiple organ failure is not worth the anti-depressant effects for me and I am not prepared to totally give up other drugs just so I can take fuckin' tramadol. Will be looking to switch to something else... fuck knows what though :\

Also, the idea about it being the antihistamine causing the problem sounds very feasible to me. It's not just serotonergics that SNRI's have very dodgy reactions with - there's over 600 "severe" intreractions for tramadol listed and would imagine that's similar with other related drugs. Way too messy to be safe or practical for many, in my opinion.
 
Aha yeah I see, was thinking SNRI plus tramadol's similar sounding dodgy effects sounded bad, but I did know it had SNRI properties. Dopey effie!

Venlafaxine is a v effective antidep for me but I am going to be uber careful with combos in the future...

Sorry for short reply, chemical consumption awaiting :D
 
Treacle said:
How does this sound? Loratadine and SNRIs both have anticholingeric properties. This could result in anticholinergic toxicity syndrome:

Remember common signs and symptoms with the mnemonic, "red as a beet, dry as a bone, blind as a bat, mad as a hatter, and hot as a hare." The mnemonic refers to the symptoms of flushing, dry skin and mucous membranes, mydriasis with loss of accommodation, altered mental status (AMS), and fever, respectively.
Additional manifestations include sinus tachycardia, decreased bowel sounds, functional ileus, urinary retention, hypertension, tremulousness, and myoclonic jerking.
Patients with central anticholinergic syndrome may present with ataxia, disorientation, short-term memory loss, confusion, hallucinations (visual, auditory), psychosis, agitated delirium, seizures (rare), coma, respiratory failure, and cardiovascular collapse.

http://emedicine.medscape.com/article/812644-overview
Click to expand...
That definitely sounds similar doesn't it! Well done Treacle :)
 
That sounds spot on Treacle. Thank you :)

Good to know I don't need to worry about SS with opiates and venlafaxine, will stay the fuck away from laradatine and other anticholinerics though..
 
Makes sense to me too. If I'd taken an antihistamine (who knows - they might have bunged some of that in too :\) it would account for my symptoms too almost. Reads virtually identical to SS symptoms other than the gut/bowel and urine retention stuff (SS is the other way round - more like double incontinence, pissing like a racehorse and constant gut grumbling the whole time - first and last symptom to come and go just about).
 
I had urine retention, thought it was residual from the codeine (i get it terribly on opiates). Case closed I reckon, good fucking job Treac! :)
 
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