Interaction between buspiron and tramadol

[Edu-85]

I have been on buspirone for some time now for anxiety. I recently had surgery and have been taking hydrocodone, I ran out and couldn't make it to the doc this week. I have some tramadol from a while back. My question is, is tramadol OK to take while on buspar? I can't find a lot of info on it online.

It's listed as a major drug interaction due to possible serotonin syndrome. But i can't find a single case of those two meds causing SS.

It seems like a pretty slim possibility. But, I'm still hesitant.

I also know you allnarent doctors and I should take your suggestions with a grain of salt. But are there any of you who have taken these together?

Is the SS possibility overblown?

Thanks

 

[kleinerkiffer]

The problem with this combination is three-fold:
1. Metabolism
Both Buspirone and Tramadol are metabolized by CYP450 isozymes. Tramadol is metabolized via CYP2D6 (into M1, this metabolite is far more active as opioid-receptor agonist, so you want a lot of it) and CYP3A4 and CYP2B6 (those aren't as important for analgesia). Buspirone is primarily metabolized via CYP3A4 so there will be competetive inhibition. I'm not sure wether buspirone or tramadol has higher affinity. This can either lead to more M1 or a higher buspirone concentration, which can be dangerous.

2. Seizure treshold
Tramadol is known to induce seizures over 400 mg (and iirc there's at least one report of a woman having a seizure after 300 mg I think) due to the SNRI activity. While buspirone isn't a reuptake inhibitor it seems to increase norepinephrine (at least in the endothelium of blood vessels) and I found this

It does not appear to interact with anticonvulsants. In animal models, however, buspirone has been shown to be proconvulsant. The drug is contraindicated in Britain for use in patients with epilepsy because of these findings. In addition, one case report cites a patient who sustained a seizure after an overdose of buspirone. Some authors do recommend buspirone for anxiety in patients with epilepsy. Careful observation is recommended for the use of buspirone in this patient population until more information is available.

https://www.epilepsy.com/learn/prof...c-drugs-developmental-disabilities/comorbid-4
While a single case report isn't much I personally wouldn't risk it

Now to the main problem:
3. Serotonin syndrome (or better serotonin toxicity)

SS is presumed to result from high levels of centralnervous system 5-HT. The syndrome is thought to be mediatedthrough the specific postsynaptic receptor subtype, 5-HT1A, the receptor responsible for antidepressant and anxiolyticeffects. Stimulation of postsynaptic 5-HT2Areceptors may alsobe involved in producing SS

https://www.researchgate.net/public...void_the_Use_of_Tramadol_With_Antidepressants

Serotonin syndrome is a potentially life-threatening syndrome that is precipitated by the use of serotonergic drugs and overactivation of both the peripheral and central postsynaptic 5HT-1A and, most notably, 5HT-2A receptors.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/

Buspirone acts as an agonist of the serotonin 5-HT1A receptor with high affinity. It is a preferential full agonist of presynaptic 5-HT1A receptors, which are inhibitory autoreceptors, and a partial agonist of postsynaptic 5-HT1A receptors.

Wikipedia
Now I think in most cases of SS it's due to the combo of drugs that increase serotonin, be it via reuptake-inhibition, increase in synthesis or increased release, leading to high activation of 5-HT receptors.
With buspirone you take an serotonin receptor agonist and with tramadol a SNRI.
This is only a guess and like you said, I'm not a doctor. With buspirone being a partial agonist of postsynaptic 5-HT1A receptors and only with some affinity for 5-HT2A I see it like this. At the 5-HT1A serotonin and buspirone compete for the binding site and buspirone is only a partial agonist, meaning the intrinsic activity is less than with serotonin, so less activation of the receptor. With 5-HT2A we have competition as well, so imo (as you said take it with a grain of salt) the potential of SS shouldn't be too high as they'll compete and not add up.

With this all being said I still see some problems with the combination and imo better be safe than sorry and not take it.

 

[kleinerkiffer]

And welcome to Bluelight, glad to have you here


If you want to I can move the thread to Neuroscience and Pharmacology as your question is too complexe for BDD


(Can't edit right now, so sorry for the double post)

 

[Edu-85]

The problem with this combination is three-fold:
1. Metabolism
Both Buspirone and Tramadol are metabolized by CYP450 isozymes. Tramadol is metabolized via CYP2D6 (into M1, this metabolite is far more active as opioid-receptor agonist, so you want a lot of it) and CYP3A4 and CYP2B6 (those aren't as important for analgesia). Buspirone is primarily metabolized via CYP3A4 so there will be competetive inhibition. I'm not sure wether buspirone or tramadol has higher affinity. This can either lead to more M1 or a higher buspirone concentration, which can be dangerous.

2. Seizure treshold
Tramadol is known to induce seizures over 400 mg (and iirc there's at least one report of a woman having a seizure after 300 mg I think) due to the SNRI activity. While buspirone isn't a reuptake inhibitor it seems to increase norepinephrine (at least in the endothelium of blood vessels) and I found this https://www.epilepsy.com/learn/prof...c-drugs-developmental-disabilities/comorbid-4
While a single case report isn't much I personally wouldn't risk it

Now to the main problem:
3. Serotonin syndrome (or better serotonin toxicity)
https://www.researchgate.net/public...void_the_Use_of_Tramadol_With_Antidepressants
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/
Wikipedia
Now I think in most cases of SS it's due to the combo of drugs that increase serotonin, be it via reuptake-inhibition, increase in synthesis or increased release, leading to high activation of 5-HT receptors.
With buspirone you take an serotonin receptor agonist and with tramadol a SNRI.
This is only a guess and like you said, I'm not a doctor. With buspirone being a partial agonist of postsynaptic 5-HT1A receptors and only with some affinity for 5-HT2A I see it like this. At the 5-HT1A serotonin and buspirone compete for the binding site and buspirone is only a partial agonist, meaning the intrinsic activity is less than with serotonin, so less activation of the receptor. With 5-HT2A we have competition as well, so imo (as you said take it with a grain of salt) the potential of SS shouldn't be too high as they'll compete and not add up.

With this all being said I still see some problems with the combination and imo better be safe than sorry and not take it.

Thank you.

So you're thinking the potential for seizures is a bigger threat than ss with this combo?

 

[Edu-85]

Maybe I should be specific also. I'm taking 30mg buspirone, 15mg twice a day.

I was thinking of taking 100mg of tramadol

 

[Edu-85]

And welcome to Bluelight, glad to have you here


If you want to I can move the thread to Neuroscience and Pharmacology as your question is too complexe for BDD


(Can't edit right now, so sorry for the double post)

And yes, that is fine.

 

[kleinerkiffer]

Od -> n&pd