Posted by Cam W. on October 17, 2001, at 2:33:22
In reply to Re: zyprexa dose » Cam W., posted by JohnX on October 16, 2001, at 1:48:06
John - I have always found Serzone™ (nefazodone) to be a weird drug. It seems either really work well as an antidepressant, or not at all. I think that the serotonin-2 (5-HT2) blocking ability of the drug has a lot to do with it's ability to really screw-up some people. It's adverse actions in some people may have to do with the relative concentrations and locations of 5-HT2 receptors in these people.
Perhaps the "fogginess" that you experienced had something to do with Serzone's action in the reticular activating system (RAS); the part of the brain responsible for the sleep/wake mechanisms of the body. The RAS contains the raphe nuclei, which is the part of the brain with the densest concentration of serotonin receptors, so this might be the reason why Serzone works so well in improving "sleep architecture" (ie. Serzone supposedly "normalizes" the different stages of sleep). Perhaps the blocking of certain serotonin receptor subtypes in this area buggering up your sleep/wake cycle and the fogginess might be due to your brain being stuck in one of the stages of sleep, while you are awake (caveat - this is just me thinking out loud, and is a total guess on my part).
Serzone is a very potent inhibitor of CYP-3A3 and CYP-3A4 (which are closely linked), but it also inhibits, to a lesser extent, CYP-2D6 and CYP-1A2. Therefore it has the potential to increase plasma concentration of an incredibly wide range of medications, including caffeine. As for affecting herbs, the only one that I can think of affecting, off of the top of my head, is St.John's Wort.
The incidence of contracting tardive dyskinesia (TD) from Zyprexa™ (olanzapine) is very low, probably due to it's "tweaking" of the dopamine-2 (D2) receptor (rather than binding irreversibly to it, like the traditional antipsychotics do). Risperdal™ (risperidone), at higher doses ( >6mg/day) causes EPS, because it seems to bind tighter (although still less than most traditonals) to D2 receptors, and doses over 6mg/day seems to saturate D2 receptors in the basal ganglia more so than other atypicals
Also, I think that quite a few of the cases of TD reported to be caused by Zyprexa were, in actuality, the "unmasking" of TD caused by past traditional antipsychotic use. In some cases, traditional antipsychotics and anticholinergics (like Cogentin™ - benztropine) seem to hide the TD. Once these suseptible people switch to Zyprexa, the TD emerges. Again, I have no proof of this, other than what I have seen clinically. I was looking after one gentleman who had some mild signs of TD while taking Orap™ (pimozide) and Artane™ (trihexyphendyl). and when he was switched to Zyprexa, the TD came out with a vengence (ie. his tongue started flicking in and out of his mouth rapidly, all day, every day, while awake. In itself, Zyprexa seems not to cause TD very often at all.
Again, this post is full of guesses and musings, but no real, proven hard facts. - Cam
poster:Cam W.
thread:81232
URL: http://www.dr-bob.org/babble/20011015/msgs/81461.html