Posted by Brainbeard on September 14, 2008, at 4:07:42
Serotonin Reuptake Inhibitors (SRI's) like the SSRIs, venlafaxine (Effexor) or clomipramine (Anafranil) increase the risk of gastrointestinal bleeding about threefold on their own, but about twelvefold when combined with NSAID painkillers such as Ibuprofen[1].
The theoretical reason why SRIs would increase the risk of bleeding is stated as follows:
"Serotonin is released from platelets in response to vascular injury and promotes vasoconstriction and a change in the shape of the platelets that leads to aggregation. Platelets cannot themselves synthesise serotonin. SSRIs inhibit the serotonin transporter, which is responsible for the uptake of serotonin into platelets. It could thus be predicted that SSRIs would deplete platelet serotonin, leading to a reduced ability to form clots and a subsequent increase in the risk of bleeding."[2]
Now, I pretty much freak out about this risk of secret inner bleeding that may lead to death at worst. So when I had to start SSRI-therapy some eight months ago and my P-doc suggested fLUVOXamine, I was happy to find that in De Abajo's authorative study[3] fluvoxamine was listed as having caused ZERO bleedings in more than 1500 cases[4](!). This may be some quirky kind of coincidence - it may also be caused by fluvoxamine being a weak-as-piss SSRI..
Anyway, to cut a long story short, I have to have a teeth pulled shortly, and with dental operations like this I tend to have a lot of post-operative pain. So I'm gonna need an NSAID - good ol' Ibuprofen, those 600mg powder sachets where they have added tons of sugar to hide the kilo's of salt that're in it. I got my doctor to prescribe me some stomach-protectors (proton pump inhibitors) and that should pretty much have my *ss covered[5].
Anyway, to cut a long story short, I'm tapering down the fluvoxamine not in the least because I'll be happy when I can take my Ibuprofen again more freely. The thing is, I'm moving over to tianeptine, a unique French antidepressant that is actually a Serotonin Reuptake ENHANCER. Using some simple thinking, one would expect that tianeptine wouldn't for the life of it increase the risk of gastrointestinal bleeding. But it doesn't seem to be as simple as that. First of all, tianeptine doesn't have a direct effect on the serotonin transporter, it doesn't speed the SERT-transporter up or anything[see 6]. The mechanism by which it enhances the reuptake of serotonin is unclear. Second, in an excellent article on tianeptine by Sheldon H. Preskorn[6], he states that:
"While tianeptine shares with the classical antidepressants the ability to reduce the expression of the SE transporter mRNA and the number of SE transporter binding sites, it does not modify the efficacy of SE synaptic transmission in the rat hippocampus even after sustained treatment."
Wait a minute.. Tianeptine reduces the number of serotonin transporter binding sites? Reduces the expression of the serotonin transporter mRNA? What does this mean man?! Would this have an effect on platelet function after all? Does reducing the number of serotonin transporter binding sites also mean that the serotonin transporters would have difficulty getting serotonin to platelets - thereby increasing the risk of bleeding?
ANYONE?!
[1] Aaron Levin, Physicians Urged to Warn Of SSRIs' Bleeding Risk, in: Psychiatr News September 1, 2006
Volume 41, Number 17, page 28; (No authors listed), Do SSRIs cause gastrointestinal bleeding?, in: Drug Ther Bull. 2004 Mar;42(3):17-8
[2] Carol Paton, Nicol Ferrier, SSRIs and gastrointestinal bleeding, in: BMJ 2005; 331:529-530
[3] Francisco José de Abajo, Luis Alberto García Rodríguez, Dolores Montero, Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study, in: BMJ. 1999 October 23; 319(7217): 11061109.
[4] Ibidem,table 2
[5] John Gever, Venlafaxine Joins SSRIs in Risk for Upper GI Bleeding, in: MedPage Today (website), Published: July 07, 2008
[6] Sheldon H. Preskorn, Tianeptine: A Facilitator of the Reuptake of Serotonin and Norepinephrine as an Antidepressant?, in: Journal of Psychiatric Practice, Volume 10(5) September 2004, 323-330
poster:Brainbeard
thread:851905
URL: http://www.dr-bob.org/babble/neuro/20080706/msgs/851905.html