Any reason why tianeptine wouldn't play well with tramadol?

[《Plasticity》]

I know this thread is probably not NPD material but I feel this is the best place to get an accurate answer on interactions being that NPD is filled with people with a strong grasp of pharmacology. To my question, is there any reason tianeptine and tramadol would cause an adverse reaction when taken together?

I'm well aware of the new(ish) info about tianeptine being a mu full agonist but prior to this the running theory was that it's effects were a result of SSRE activity. Is tianeptine really an SSRE and if so will this SSRE activity cause problems with tramadol's serotonin release/SNRI activity? Any insight is greatly appreciated.

 

[sekio]

Tianeptine is not a serotonin releaser or MAOI, so there's no reason the two should interact. Even if tianeptine was primarily a SRE (Serotonin Reuptake Enhancer)... it would decrease postsynaptic serotonin concentrations, the opposite of what a SSRI does.

There's a case report of someone who dropped dead in the street with ~10x the normal therapeutic dose of tramadol and tianeptine in her blood. I'm not sure if it's really relevant but it goes to show that the combination is not as threatening as a MAOI+SSRI would be.

 

[endotropic]

They might have metabolic interactions that cause one or the other to build up more than you would expect so be careful with dose, same as when combining any two mu-agonists.

 

[《Plasticity》]

Thank you guys, solid answers as expected.