![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 18 of 18. This is the beginning of the thread.
Posted by Luke Jarett on August 29, 2000, at 23:48:34
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
Posted by stjames on August 30, 2000, at 1:52:14
In reply to Is Serzone evil?, posted by Luke Jarett on August 29, 2000, at 23:48:34
> 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
james here....Drugs and meds are not good or bad. It depends on the person
and with some drugs what some people do with them. You are correct, people come here alot
if they don't do well on a med. Serzone is an effectibe AD in many people but some hate it. I am sure someone on this list
has taken Serzone and done well. It is safe to say that with every AD some love one and others hate the same one.
Here we say, Your Milage May Vary.Perhaps it would help if you tell us how you came to feel you need this drug. Are you depressed ? How can we help you ?
James
Posted by JohnL on August 30, 2000, at 5:18:14
In reply to Is Serzone evil?, posted by Luke Jarett on August 29, 2000, at 23:48:34
> 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.
> JLuke,
It does seem hard to find anyone doing well with Serzone, doesn't it!? But in reality, there are actually people doing very well with it. They pop up from time to time here at this board. I've seen various success stories with Serzone. They do exist!I once talked with a doctor who was experiencing an unusual degree of success with Serzone among his patients. He shared with me his secret. Very simply, it involves 'slow and low'.
Specifically, this is how he achieves success with Serzone...
1)He starts patients at 25mg a day. If that goes well, then 50mg a day is fine as soon as the next day. Dosing time is late afternoon or at dinner. (Bedtime is too late.)
2)The patient is to remain at that 25mg or 50mg for 4 to 7 days.
3)Then increase by another 25mg. Stay there for another 4 to 7 days.
4)Continue the same way in 25mg steps. Remain at a certain dose a little longer if needed...do not increase dose until the patient is comfortable with the current dose.
5)When the patient reaches 300mg and more increase seems needed, then begin split dosing...300mg in late afternoon/dinner, and an additional 25mg at lunch. Continue the same 25mg step increase at 4 to 7 day intervals, adding the new dose at lunchtime.Advantages: The patient adjusts much smoother to the medication.
Disadvantage: It takes more time. If someone is very depressed, they may need additional counseling, coaching, and support to help them persevere and stay committed until higher dose levels are achieved.For some kwirky reason, Serzone can be finnicky. If dose is increased too much or too fast, or started at the normal 100mg level, all kinds of weird reactions (like the ones you've read about at this board...anxiety, anger, tension, oversedation, increased depression, etc) can happen. Not sure why. But it can mostly be avoided with the above mentioned low-n-slow method.
Another thing about Serzone is that it can have a very narrow therapeutic window. Too little won't work, and too much won't either. A difference of 25mg in one direction or the other can make all the difference in the world. This is another advantage of increasing in 25mg steps...so we don't accidentally blow right past our magic but narrow therapuetic window. We don't know ahead of time what dose will be our magic dose, but it will be pleasantly obvious when it occurs. Don't want to accidentally miss it.
The long trial could be worth it, because Serzone is known for providing good sleep and good sex.
One clue I've noticed over time that can predict whether Serzone is right for you or not is this...If it gives you tinnitus (loud ringing in the ears), then it isn't the med for you. Don't even bother continuing. Tell the doc it gives you bad tinnitus and try something else instead. If there's no loud ringing in the ears, that's a good sign. These are not documented predictors, but rather observations I've noticed over the years.
So regardless of the instructions your doctor gave you, try the above method instead. It is another doctor's method, one who is experiencing good success rates with Serzone.
John
Posted by Cindy W on August 30, 2000, at 9:04:50
In reply to Re: Is Serzone evil?, posted by JohnL on August 30, 2000, at 5:18:14
> > 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
>
> Luke,
> It does seem hard to find anyone doing well with Serzone, doesn't it!? But in reality, there are actually people doing very well with it. They pop up from time to time here at this board. I've seen various success stories with Serzone. They do exist!
>
> I once talked with a doctor who was experiencing an unusual degree of success with Serzone among his patients. He shared with me his secret. Very simply, it involves 'slow and low'.
>
> Specifically, this is how he achieves success with Serzone...
> 1)He starts patients at 25mg a day. If that goes well, then 50mg a day is fine as soon as the next day. Dosing time is late afternoon or at dinner. (Bedtime is too late.)
> 2)The patient is to remain at that 25mg or 50mg for 4 to 7 days.
> 3)Then increase by another 25mg. Stay there for another 4 to 7 days.
> 4)Continue the same way in 25mg steps. Remain at a certain dose a little longer if needed...do not increase dose until the patient is comfortable with the current dose.
> 5)When the patient reaches 300mg and more increase seems needed, then begin split dosing...300mg in late afternoon/dinner, and an additional 25mg at lunch. Continue the same 25mg step increase at 4 to 7 day intervals, adding the new dose at lunchtime.
>
> Advantages: The patient adjusts much smoother to the medication.
> Disadvantage: It takes more time. If someone is very depressed, they may need additional counseling, coaching, and support to help them persevere and stay committed until higher dose levels are achieved.
>
> For some kwirky reason, Serzone can be finnicky. If dose is increased too much or too fast, or started at the normal 100mg level, all kinds of weird reactions (like the ones you've read about at this board...anxiety, anger, tension, oversedation, increased depression, etc) can happen. Not sure why. But it can mostly be avoided with the above mentioned low-n-slow method.
>
> Another thing about Serzone is that it can have a very narrow therapeutic window. Too little won't work, and too much won't either. A difference of 25mg in one direction or the other can make all the difference in the world. This is another advantage of increasing in 25mg steps...so we don't accidentally blow right past our magic but narrow therapuetic window. We don't know ahead of time what dose will be our magic dose, but it will be pleasantly obvious when it occurs. Don't want to accidentally miss it.
>
> The long trial could be worth it, because Serzone is known for providing good sleep and good sex.
>
> One clue I've noticed over time that can predict whether Serzone is right for you or not is this...If it gives you tinnitus (loud ringing in the ears), then it isn't the med for you. Don't even bother continuing. Tell the doc it gives you bad tinnitus and try something else instead. If there's no loud ringing in the ears, that's a good sign. These are not documented predictors, but rather observations I've noticed over the years.
>
> So regardless of the instructions your doctor gave you, try the above method instead. It is another doctor's method, one who is experiencing good success rates with Serzone.
> John
Luke, I took Serzone for several months, and really felt it helped and liked the way it made me feel. The first couple of weeks were hard (I had a lot of mood swings and felt kind of weird) but after that, I felt really great. My social anxiety was down, I slept great, it didn't interfere with sexual feelings, and my depression dissipated. I'd still be taking it if it also helped with OCD. Now I'm on Effexor-XR but don't have the sense of well-being I had on Serzone.--Cindy W
P.S. Noa posted some great information about Serzone in the past and how it worked for her.
Posted by Adam on August 30, 2000, at 11:59:46
In reply to Is Serzone evil?, posted by Luke Jarett on August 29, 2000, at 23:48:34
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
Posted by noa on August 30, 2000, at 17:09:28
In reply to Re: Is Serzone evil?, posted by JohnL on August 30, 2000, at 5:18:14
> >Very simply, it involves 'slow and low'.
I agree. This is generally a good way to go with a lot of meds.I have had success with serzone. It was rough to start--initial adverse effects were challenging, but they went away.
Serzone is one of two ADs in my cocktail, so I cannot speak to how it is as a solo. But for me it is very helpful, especially since in counteracts the negative effects of the effexor. They seem, for me and my nervous system, to be a good complementary combo. Where the effexor is activating, causing good and bad activation, the Serzone seems to calm the system down. They seem to work together well.
Each person has a unique set of reactions to different meds. The same med can cause opposite reactions in different people.
So, low and slow to start is a good idea, and if you have adverse effects, consider that it MIGHT be worth sticking with it for a month, at least that was my experience.
There are lots of posts in the archives about initial adjustment to Serzone, both from people who got through it and found the serzone helpful, and from people for whom the negative effects were intolerable. You might want to do a search and read some of them.
Hope this helps.
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
Posted by Cindy W on August 30, 2000, at 21:59:38
In reply to Re: Is Serzone evil?, posted by noa on August 30, 2000, at 17:09:28
> > >Very simply, it involves 'slow and low'.
> I agree. This is generally a good way to go with a lot of meds.
>
> I have had success with serzone. It was rough to start--initial adverse effects were challenging, but they went away.
>
> Serzone is one of two ADs in my cocktail, so I cannot speak to how it is as a solo. But for me it is very helpful, especially since in counteracts the negative effects of the effexor. They seem, for me and my nervous system, to be a good complementary combo. Where the effexor is activating, causing good and bad activation, the Serzone seems to calm the system down. They seem to work together well.
>
> Each person has a unique set of reactions to different meds. The same med can cause opposite reactions in different people.
>
> So, low and slow to start is a good idea, and if you have adverse effects, consider that it MIGHT be worth sticking with it for a month, at least that was my experience.
>
> There are lots of posts in the archives about initial adjustment to Serzone, both from people who got through it and found the serzone helpful, and from people for whom the negative effects were intolerable. You might want to do a search and read some of them.
>
> Hope this helps.
Noa, what dosages are you taking now, of Effexor-XR and Serzone? My pdoc doesn't want me to go above Effexor-XR and I'm taking only 50 mg/day of Serzone. Lately, I feel so tired I can't function and don't know if this is depression or something else (Effexor-XR pooping out? burnout?). I had a blood test a week ago and am going back to the nurse practitioner this Friday. Don't think my thyroid is messed up (have had it tested before) but don't know why it's so hard to get out of bed in the morning, and why I'm so clumsy once I do get up. Hope things are going well for you!--Cindy W
Posted by noa on August 31, 2000, at 17:40:13
In reply to Re: Is Serzone evil? » noa, posted by Cindy W on August 30, 2000, at 21:59:38
I currently take 300 mg of effexor xr, in the ams, and 300 mg. of serzone, at around 6 pm. It seems to be a good recipe for me.
I had taken 375 effexor/225 serzone for a long while, but still felt my nervous system was overstimulated. So, I suggested trying the current balance, and my pdoc approved. It has really been an improvement.
Initially, the increase in serzone made me sleepy, but I have adjusted. Now, about 30 minutes after dosing, I do feel very tired, but I perk up again about 30-45 minutes after that. Then, I am not feeling sedated (as I had with trazodone), but I can get a good night's sleep. I take it at 6 pm because any later and it hasn't kicked in sufficiently for sleep, and doesn't wear off sufficiently by morning. This dosing time seems to work well for me.
Posted by Cindy W on August 31, 2000, at 21:52:25
In reply to Re: Is Serzone evil? » Cindy W, posted by noa on August 31, 2000, at 17:40:13
> I currently take 300 mg of effexor xr, in the ams, and 300 mg. of serzone, at around 6 pm. It seems to be a good recipe for me.
>
> I had taken 375 effexor/225 serzone for a long while, but still felt my nervous system was overstimulated. So, I suggested trying the current balance, and my pdoc approved. It has really been an improvement.
>
> Initially, the increase in serzone made me sleepy, but I have adjusted. Now, about 30 minutes after dosing, I do feel very tired, but I perk up again about 30-45 minutes after that. Then, I am not feeling sedated (as I had with trazodone), but I can get a good night's sleep. I take it at 6 pm because any later and it hasn't kicked in sufficiently for sleep, and doesn't wear off sufficiently by morning. This dosing time seems to work well for me.Noa, how did you get your pdoc to prescribe both? My seems reluctant to prescribe more than one thing at a time.--Cindy W
Posted by noa on September 1, 2000, at 9:18:42
In reply to Re: Is Serzone evil?, posted by Cindy W on August 31, 2000, at 21:52:25
I didn't have to do anything. My pdoc uses polypharmacy all the time. Maybe you need to consult with someone else, because it seems to me that a pdoc unwilling to combine meds is behind the times.
Posted by Adam on September 1, 2000, at 14:03:28
In reply to Re: Is Serzone evil? » Adam, posted by Cindy W on August 30, 2000, at 21:57:10
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
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
Posted by paul on September 2, 2000, at 1:37:08
In reply to Re: Is Serzone evil?, posted by stjames on August 30, 2000, at 1:52:14
first off-a med has no personality, no volition, no desires, no emotions nor any possible way to develop any of the above. evil or lack thereof rests solely in the hands of the prescriber and in how they respond to your responses to a particular drug. i have had VERY good luck on serzone-i've been on it for more than a couple of years and take it in conjunction with clonopin and seroquel. in other words,
YES THERE IS SOMEONE HERE WHO HAS BEEN HELPED BY IT!!
all you can do is try it and you might want to keep a journal of your reactions to look over should you decide to drop it, adjust the dosage or whatever. other people's experiences belong to other people-i too have had HORRID reactions to prescribed drugs. this is a hard road we walk and sometimes the cure may feel worse than the disease-seroquel was this way in the beginning. some meds have an adjustment period and only you can decide if the adjustment is more than you can deal with. good luck and keep us posted.
p(c(l))
Posted by Adam on September 2, 2000, at 14:47:04
In reply to Re: Is Serzone evil? » Adam, posted by Cindy W on September 1, 2000, at 22:55:57
Hey, Cindy,
No problem. I'm terribly sorry to hear about your mother, and hope her recovery is swift. Take care of yourself, and try really hard to keep busy with brainless activities like exercise, things that keep you focused on something emotionally neutral and burn a lot of energy, which will help you relax. I've always found strenuous exercise helps me cope with lots of emotional stress and general anxiety. Stay away from caffeine and don't be afraid to sip at a glass of wine occasionally to smooth out the edges, being very conscious of course to do this in great moderation (you don't want alcohol to become your drug of choice) and keeping all drug restrictions in mind.
I should qualify my statements about drugs and their effects on NE to say that, at least in some parts of the brain, NE is actually secreted more with chronic SSRI use. However, there seems to be some modified signalling that can down-regulate the effects of NE. Again, I guess the key concept is "balance" or "normalization" of NE and DA systems via enhanced serotonin signaling, with stimulation at the 5-HT2C receptor an important component, though almost certainly not the only component. Whatever is going on, NE reuptake inhibition isn't part of the equation, it would seem. There are complicated reasons for the modified sensitivity to NE, from receptor-mediated effects to ion channels and effects on circulation that I am just starting to get a handle on. In fact, desipramine, which is almost exclusively a NE reuptake inhibitor (ignoring the anti-histaminergic, cholinergic-muscarinic stuff) makes a great active placebo in a clomipramine trial for OCD. Though a metabolite of clomipramine is an NE reuptake inhibitor, the parent compound is almost exclusively (and very potently) acting at the serotonin transporter.
At any rate, again, it seems the best drugs for OCD, after a good ten-or-so years now, are still the SSRIs. Some people say SSRIs are superior to clomipramine, some say just the opposite. The SSRIs are certainly easier to take. In general the SSRIs are thought to be superior to venlafaxine for OCD, though for comorbid depression, there's more to consider, obviously. Augmentation strategies, again, are many. I seem to be seeing lots of good things about low dose (the dose is very important) risperidone, to repeat that one option. Though in general addition of a neuroleptic is thought to be most helpful for those with tics, a recent small, placebo controlled trial of risp.+SSRI showed promise for some refractory to SSRI alone, and there was no obvious cluster of symptoms that responded best. That's good news for some, since I think low-dose risp. is relatively easy to take.
Others I forgot to mention are pindolol and buspar augmentation, which seem to help some, depending on who you ask.It's all very complicated. You can find, in the literature, examples of even nefazodone or mirtazapine helping people with OCD (though, mechanistically, this doesn't make sense - beware the mechanism - but don't forget it), as well as imipramine and amitryptiline (so-called tertiary amine TCAs, which include clomipramine, all having a fair amount of serotonergic activity). Those other TCAs have only about half the life-span or less of clomipramine, though.
An uncommon monotherapy is an MAOI, usually phenelzine or tranylcypromine (the former being great for social phobia), though those seem to have limited efficacy for OCD in general. For those who are helped, comorbid depression is usually a big factor, which complicates interpretation considerably.
Well, I hope I got all of this right. Again, trust your doctor over all. Where do you live? I might be able to find out about CBT specialists in your area if I can tap the vine properly. CBT for OCD is my personal favorite as an addition to drug therapy. It's potent, it lasts longer, it has applications outside of the disorder, and it has NO side effects.
Best of luck to you, and again, best wishes to your mother.
Adam
> 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
Posted by Cindy W on September 2, 2000, at 21:59:15
In reply to Re: Is Serzone evil? » Cindy W, posted by Adam on September 2, 2000, at 14:47:04
> Hey, Cindy,
>
> No problem. I'm terribly sorry to hear about your mother, and hope her recovery is swift. Take care of yourself, and try really hard to keep busy with brainless activities like exercise, things that keep you focused on something emotionally neutral and burn a lot of energy, which will help you relax. I've always found strenuous exercise helps me cope with lots of emotional stress and general anxiety. Stay away from caffeine and don't be afraid to sip at a glass of wine occasionally to smooth out the edges, being very conscious of course to do this in great moderation (you don't want alcohol to become your drug of choice) and keeping all drug restrictions in mind.
>
> I should qualify my statements about drugs and their effects on NE to say that, at least in some parts of the brain, NE is actually secreted more with chronic SSRI use. However, there seems to be some modified signalling that can down-regulate the effects of NE. Again, I guess the key concept is "balance" or "normalization" of NE and DA systems via enhanced serotonin signaling, with stimulation at the 5-HT2C receptor an important component, though almost certainly not the only component. Whatever is going on, NE reuptake inhibition isn't part of the equation, it would seem. There are complicated reasons for the modified sensitivity to NE, from receptor-mediated effects to ion channels and effects on circulation that I am just starting to get a handle on. In fact, desipramine, which is almost exclusively a NE reuptake inhibitor (ignoring the anti-histaminergic, cholinergic-muscarinic stuff) makes a great active placebo in a clomipramine trial for OCD. Though a metabolite of clomipramine is an NE reuptake inhibitor, the parent compound is almost exclusively (and very potently) acting at the serotonin transporter.
>
> At any rate, again, it seems the best drugs for OCD, after a good ten-or-so years now, are still the SSRIs. Some people say SSRIs are superior to clomipramine, some say just the opposite. The SSRIs are certainly easier to take. In general the SSRIs are thought to be superior to venlafaxine for OCD, though for comorbid depression, there's more to consider, obviously. Augmentation strategies, again, are many. I seem to be seeing lots of good things about low dose (the dose is very important) risperidone, to repeat that one option. Though in general addition of a neuroleptic is thought to be most helpful for those with tics, a recent small, placebo controlled trial of risp.+SSRI showed promise for some refractory to SSRI alone, and there was no obvious cluster of symptoms that responded best. That's good news for some, since I think low-dose risp. is relatively easy to take.
> Others I forgot to mention are pindolol and buspar augmentation, which seem to help some, depending on who you ask.
>
> It's all very complicated. You can find, in the literature, examples of even nefazodone or mirtazapine helping people with OCD (though, mechanistically, this doesn't make sense - beware the mechanism - but don't forget it), as well as imipramine and amitryptiline (so-called tertiary amine TCAs, which include clomipramine, all having a fair amount of serotonergic activity). Those other TCAs have only about half the life-span or less of clomipramine, though.
>
> An uncommon monotherapy is an MAOI, usually phenelzine or tranylcypromine (the former being great for social phobia), though those seem to have limited efficacy for OCD in general. For those who are helped, comorbid depression is usually a big factor, which complicates interpretation considerably.
>
> Well, I hope I got all of this right. Again, trust your doctor over all. Where do you live? I might be able to find out about CBT specialists in your area if I can tap the vine properly. CBT for OCD is my personal favorite as an addition to drug therapy. It's potent, it lasts longer, it has applications outside of the disorder, and it has NO side effects.
>
> Best of luck to you, and again, best wishes to your mother.
>
> Adam
>
>
> > 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 WAdam, thank you for your kind post and your concern! Am waiting to see what they decide about my Mom. My family suggested I wait a few days before I come visit (5-6 hour drive each way). Will ask my pdoc about the meds you suggest, when I see him on the l8th. I do know the Effexor-XR isn't helping recently, since my home, car, and office look like landfills. Haven't found a CBT therapist locally (I live in San Luis Obispo, California); the closest I could find were in Los Angeles and San Francisco, although some pdocs (psychiatrists) as close as Santa Barbara treat OCD (with meds of course). Am trying not to go crazy, and am trying to sleep, eat, drink water, and not go crazy. (I don't drink wine; it doesn't mix with AD's and I have never cared for alcohol even before I took AD's). Again, thank you!--Cindy W
Posted by Ronnie on November 10, 2000, at 10:33:18
In reply to Re: Is Serzone evil?, posted by Adam on August 30, 2000, at 11:59:46
I am finishing up my third week of being on Serzone. I had suffered from
chronic depression, intense anxiety, obssesive thoughts and felt like I had
not had a good night of sleep in forever.My doctor started me on 100 mg a day,
at bed time for four days, and then upped it to 200 mg for another four. The
target was to get to 300 mg and see how I reacted. For the first week and a half I
was OK, I felt a little better emotionally, was thinking and seeing things more clearly but
suffered from fatigue, dry mouth and horrible headaches that made me very irritable! Once
I reached the target dosage I crashed emotionallly! I hit the lowest I had been and my obssesive
thoughts became more powerful. I Called my doctor and requested to up my dosage to 400 mg.
This has been the turning point for me. I upped my meds on about four or five days ago and have been
feeling great ever since. I wouldnt say I am euphoric but my outlook is brighter and I feel like I
am in a good place. So "knock on wood" that I stay here for a long, long, while. As far as the obssesive thoughts go I feel better prepared to handle them.Good luck to everyone in finding peace of mind, I mean
that from the bottom of my heart.
Posted by kazoo on November 12, 2000, at 23:57:20
In reply to Re: Is Serzone evil?, posted by Ronnie on November 10, 2000, at 10:33:18
Lewd did I live, evil I did dwel.
kazoo
This is the end of the thread.
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