Posted by Cindy W on September 1, 2000, at 22:55:57
In reply to Re: Is Serzone evil?, posted by Adam on September 1, 2000, at 14:03:28
> Hey, Cindi,
>
> (Again, amateur alert, amateur alert...red flashing lights,etc.)From everything I have read in the literature, Serzone is not an effective
> treatment for OCD. It does no better than placebo, essentially, and it's mechanism of action may be part of the problem. It could even,
> theoretically, interfere with other drugs that are effective for OCD. I think for the average person, mCPP is not a problem, at any rate. It is
> produced in very small amounts compared to the concentration of the parent compound, like 2% of that at low doses, and, interestingly, even less at higher doses. I think this ratio, due to "non-linear pharmacokinetics" for nef. and "linear pharmacokinetics" for mCPP, may somehow be significant,especially if, as was shown to be the case in preclinical and clinical trials of nefazodone, the specific pharmacokinetic profiles of parent and mCPP vary significantly from the norm in certain individuals as far as these ratios go.
>
> Nefazodone has the weird effect of decreasing its own metabolism (via its potent inhibition of CYP4503A, hence the strange nonlinear increase
> in plasma levels with linear dose increase), so you've got all this stuff going on with relative concentration of parent and metabolites, relative
> binding kinetics at the relevant receptors, weird nonlinear ratios of parent and metabolites depending on dose, and so on. It seems to be a fairly complicated drug, though for most people worrying about any of this is completely unnecessary.
>
> With my luck I'm one of those poor slobs who probably somehow makes gobs of mCPP or possibly can't metabolize it well,such as may be the case of those with the "CYP4502D6 phenotype", though, as usual, the significance of that depends on who you ask.
>
> As for augmentation strategies for Effexor, the addition of an SSRI might be worth trying, or perhaps clomipramine, as you have said. some ideas that are untested by rigorous trials but have anecdotal evidence for efficacy are
> gabapentin and low-dose risperadol. Perhaps Zyprexa. I sometimes wonder if a high dose of sertraline might not be an interesting augmentor because of its effects on DA reuptake at high doses (though probably not significant). I
> think your doctor may be worried about upping the dose of Effexor higher than the one you are on because its effects on NE start to become pretty
> significant (speculation from an amateur, of course), and it would seem that good OCD drugs, if anything, only stimulate the serotonin system directly, and probably even down-regulate NE, with, of course, no concommitant NE-reputake inhibition. Perhaps the dream OCD drug would be something that acts as an SSRI and somehow also blocks NE production or signalling directly, maybe an alpha-adrenergic receptor antagonist. Serzone is a pretty weak SRI, a pretty weak NARI, complicated but mostly antagonistic at 5-HT2,
> and a little antagonistic at alpha1-ADR. A little of what you want, a bit more of what you don't. Nice for depression alone, perhaps, but, alas...
>
> I'm in the conundrum of taking an MAOI that seems to have its most potent effects on DA and NE, though at the doses I'm at it also effects serotonin. Such a combo might be good for some people, since treating OCD seems all about bringing serotonin, NE and DA into "balance", and for some people that can mean a direct noradrenergic and dopaminergic mechanism of actiom (though this seems to be the exception, not the rule). Depression, at this point, is my biggest concern. For me, frankly, the best
> treatment for OCD was and continues to be bahavioral therapy (though I haven't been for a CBT session in quite a while, due to concerns about insurance). I would give that a serious look. If you find something good for depression, and can augment well for OCD, great, but the best augmentation may be psychotherapeutic instead of pscychopharmacologic for some.
>
> > Adam, I found your post interesting, because I too have OCD and major depression. Effexor-XR has been pretty good about controlling the OCD symptoms (although I had a relapse recently, due to increased anxiety). Serzone alone did not improve my OCD, although it was a great antidepressant. Have you tried other anti-OCD drugs (e.g., Luvox, Prozac, Zoloft, Celexa, Paxil, Anafranil)? I'm thinking about asking my pdoc for something to augment the Effexor-XR to further combat the OCD because he isn't willing to let me increase the Effexor-XR above 375 mg/day (maybe Anafranil?). Your comments about Serzone's decreasing anxiety after a while were interesting, too. --Cindy W
Adam, thank you for the information about Serzone and Effexor-XR! Am not sure yet what to try. Have read all the behavior therapy stuff and have tried doing it; haven't found locally a behavior therapist who is familiar with OCD. My pdoc has some familiarity with OCD and is a good psychiatrist and good with meds, I think. But the Effexor-XR is definitely starting to not work for me (the more my anxiety increases, the more I start relapsing, counting, checking, hoarding, etc.). Just found out today that my Mom has lung cancer that metastasized to her spinal cord; so my anxiety is pretty well at maximum. Sounds like an OCD three day weekend to me!--Cindy W
poster:Cindy W
thread:44037
URL: http://www.dr-bob.org/babble/20000822/msgs/44264.html