Posted by Brainbeard on September 8, 2009, at 13:56:43
In reply to Re: Increasing SSRI/SNRI above the 'regular' doses., posted by bleauberry on September 8, 2009, at 12:50:39
> For example, at 50mg Zoloft has already reached nearly 98% occupancy of serotonin reuptake sites.
I don't think that is correct. In Preskorn's online book about the SSRIs, you see the percentages of serotonin reuptake inhibition (SRI) for the usual therapeutic doses of most SSRIs. You can see the table here: http://www.preskorn.com/books/ssri_s3.html#tab3-7. 50mg of sertraline leads to 80% inhibition of the reuptake pump. That is still far removed from oversaturation.
When you look at figure 5.3 from the same book -
http://www.preskorn.com/books/ssri_s5.html#fig5-3 - you see that there is a huge difference in serotonin reuptake inhibition between a 25 and a 50mg dose of sertraline (about 55 vs. 80%). After that, the curve for SRI is slowly but steadily rising, reaching about 90% of serotonin uptake reduction at 200mg. So even after 200mg, a further decrease of serotonin reuptake would be theoretically possible.Here: http://www.springerlink.com/content/c37438727t74156l/ is an interesting study that measured serotonin receptor occupancy at high doses of venlafaxine, sertraline and citalopram. Unfortunately, the doses aren't menioned in this abstract. In accordance with Preskorn, the abstract mentions that the minimum therapeutic dose (50mg for sertraline) of any SSRI yields about 80% serotonin receptor (5HT) occupancy. The higher doses in this study yielded a 5HT occupancy of 85%, which was considered significant. The abstract concludes thus: 'It is likely that 15% unoccupied 5-HTT remains, which should be addressed in future drug development.'
So there you go: an incentive to experiment with ultra-high doses of SSRIs.Oversaturation of serotonin receptors comes at a price though: serotonergic side-effects will peak (diarrhea, emotional numbness, sexual dysfunction), while the risk of abnormal bleeding increases dramatically since SRI also inhibits blood platelets, responsible for clotting.
poster:Brainbeard
thread:916056
URL: http://www.dr-bob.org/babble/20090902/msgs/916100.html