Posted by Cindy W on August 30, 2000, at 21:57:10
In reply to Re: Is Serzone evil?, posted by Adam on August 30, 2000, at 11:59:46
> Disclaimer: I'm no doctor. Having said that...
>
> "Evil" is not a word I usually use to describe a drug, but I might have used it for Serzone in the past.
>
> JohnL's "low and slow" discussion is interesting. The method his doctor describes differs considerably with the dosing regimine my doctor used, which was a long period on a relatively low dose followed by a relatively rapid increase. This was then followed by (what I feel to be, anyway) a particularly misguided augmentation strategy with clozapine. After two months of this, I wound up in the hostpital. Not to say my depression or anxiety was never severe, but during this period, especially toward the end, I was in some deep pit of hell. It was simply awful, and despite a relapse of depression following my hospital stay and prior to my treatment with Selegiline, I never was that bad before or afterward. I believe strongly that this period of intense pain, anxiety, and, frankly, suicidality, having no other precipitating event that I could discern, was connected to the medication.
>
> Here's my take on it: For starters, I have been diagnosed with major depressive disorder, and an OCD-spectrum disorder, with some smatterings of more "classic" OCD symptoms. I was started on Serzone to help with depression, and it was thought (because Serzone is a weak SRI), that it might help with OCD also (not likely, in retrospect, given some of Serzone's properties). Since I had had sexual difficulties with Zoloft and Effexor, this seemed like an attractive option.
>
> One of the active metabolites of Serzone (nefazodone) is m-chlorophenylpiperazine (mCPP, also a metabolite of Serzone's close cousin, Trazodone). mCPP is a potent agonist of the 5-HT2 (serotonin-2) receptor, most relevantly in this case the 5-HT2C receptor subtype. mCPP is known to have potent anxiogenic properties. When administered to patients with OCD, it transiently exacerbates OCD symptoms. It may eventually cause relief of OCD symptoms, and more general forms of anxiety, with chronic exposure, as it is believed the receptor's activity is altered due to persistant hyperstimulation.
>
> I do not know the precise binding kinetics of nefazodone and its metabolites, but it appears that mCPP is a more potent 5-HT2 agonist than the parent compound is a 5-HT2 antagonist. I think the initial anxiety some may experience, particularly at low doses of Serzone, may have something to do with these and other rather complicated pharmacokinetics and dynamics. As the dose is increased, a combination of regulatory inhibition and antagonistic blockade of 5-HT2 may contribute to Serzone's anxiolytic properties. For OCD, however, it seems a therapeutically appropriate stimulation of 5-HT2C is a good thing, and eventually leads to relieffor some. A drug that at one phase inappropriately stimulates this receptor, and at the next blocks it, might be a poor candidate as a therapy.
>
> Additionally, clozapine, which for some reason was offered to me as a possibly efficatious augmentation for OCD symptoms and anxiety, has been more widely characterized as an exacerbator of OCD symptoms, again because it blocks serotonin receptors (as an interesting aside, I am doing particularly well on a drug thought to have fairly potent effects on the dopaminergic system, and clozapine blocks a number of dopamine receptors as well...the relationships between serotonin, dopamine, and NE are very complex in OCD, and might be connected to abnormalities in the COMT gene and/or serotonin signaling). In a nutshell, I think I got an early dose of a drug that initially caused me considerable discomfort because of my particular biology, which was then increased and augmented in such a way that could only make things worse by blocking any inhibatory signaling afterward. A mess. Do I have proof of this? Besides my remarkably unpleasant experience during that period, and its progression, absolutely none.
>
> I would say Serzone is at worst ineffective for most people, but a few should use it with caution or avoid it like the plague. I would say, additionally, maybe JohnL's doctor is onto something, vis-a-vis the ramping rate. I also find the observations of Serzone's narrow therapeutic dose range quite interesting, and would be grateful if some mechanistic explanation for this could be offered. It would appear that initial unpleasantness experienced by many on Serzone may be due to mCPP, and, ironically, this unpleasantness is specifically circmvented by the drug in the end. Most people don't seem to experience distress of this kind on Serzone, though, so it ought not to be expected. Just keep in mind that there can be complications.
>
> > Has anyone ever had any positive results with Serzone? It seems that either no one has, or only the people who hate it post here.
> > I have a bottle of Serzone sitting on my desk, but the more I read about it, the less comfortable I feel about taking it.
> > Please, any input will be appreciated.
> > J
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
poster:Cindy W
thread:44037
URL: http://www.dr-bob.org/babble/20000822/msgs/44109.html