Psycho-Babble Medication Thread 87093

Shown: posts 6 to 30 of 30. Go back in thread:

 

Re: RE: Using Serzone to Raise Levels of Other Meds

Posted by stjames on December 25, 2001, at 11:50:47

In reply to RE: Using Serzone to Raise Levels of Other Meds » Cam W., posted by Rick on December 24, 2001, at 20:12:31

> > The enzyme inhibition by Serzone has been used to advantage, by some doctors in our area. It can artificially raise levels of certain drugs, without increasing their dose. This may be a good option for those who poorly absorb certain medications.
>
> Cam -
>
> Are you saying that the docs (1) sometimes add Serzone soley to raise levels of other drugs; or (2) choose it over other *treatment-augmentaton* candidates to take advantage of this property; or (3) select it as the primary AD to take advantage of potentially-beneficial interactions?


This is one of the keys to polypsycopharm, many of the psyco meds effect each other, raising level of the primary or secondary (or both) med(s). I can take less Effexor because I take a small amount of Remeron.

james

 

Re: RE: Using Serzone to Raise Levels of Other Meds

Posted by dove on December 26, 2001, at 14:40:27

In reply to Re: RE: Using Serzone to Raise Levels of Other Meds, posted by stjames on December 25, 2001, at 11:50:47

I take 400 mgs. of Serzone per day not only for its anti-anxiety effects but to augment a number of other meds. The meds it affects the most (I'm going by completely non-professional personal feelings here) are:

Amitriptyline: increases potency, less Ami needed to get the job done. My p-doc says that adding Serzone to older TCA's can really lower the TCA's required effective dosage, thus, resulting in less side-effects from the TCA if it needed to be taken alone.

Neurontin: works synergistically, both seem to add longer half-lives to other meds and do a better job taking the edge off of my anxiety and depression.

Prozac: induces a smoother "feel", less wound-up, *significantly* less libido problems.

Adderall: decreases ups-and-downs, allows a much smoother feeling (Neurontin also seems to work this way with the Adderall).

Klonopin: Currently, I'm honestly not sure how Serzone effects this med at all.

dove

 

Re: RE: Using Serzone to Raise Levels of Other Meds » Rick

Posted by Cam W. on December 26, 2001, at 19:04:43

In reply to RE: Using Serzone to Raise Levels of Other Meds » Cam W., posted by Rick on December 24, 2001, at 20:12:31

Rick - I think that the pdocs I know use it to primarily raise levels of other drugs (without having to take higher doses of those drugs), while at the same time hoping for a little extra antidepressant activity.

As for how to do it; I believe that is very individualized. Many factors have to be taken into consideration (past med use and response, what is hoped to be accomplished with the augmentation, disorder - and/or subtype - being treated, supposed status of one's cytochrome system, etc., etc., etc.).

I do not think that I could make a blanket statement for using this type of therapy, nor do I think that it is an option for everyone. I do find that this sort of augmentation is fairly much a "last gasp" strategy, when most others have failed.

I tend to think that this sort of therapy is from the "let-us-throw-a-bunch-of-treatments-against-the-wall-and-see-which-one-sticks" school of treatment. I am not a big fan of this, but sometimes one has to resort to whatever works.

- Cam

 

Re: RE: Using Serzone to Raise Levels of Other Meds » Cam W.

Posted by Rick on December 27, 2001, at 15:48:50

In reply to Re: RE: Using Serzone to Raise Levels of Other Meds » Rick, posted by Cam W. on December 26, 2001, at 19:04:43

Cam -

Thanks, that definitely helps clarify things.

But let me distill this to my primary question, to see if you have a feel for it or at least can make an educated guess (I'm certainly not looking for a "blanket statement"):

Assuming the patient has a "typical" cytochrome system with respect to the relevant enzymes, is it reasonable to think that a very small dose of Serzone, e.g. 75 mg, might lead to a significant metabolic inhibition? Or does this seem unlikely? All of the Serzone interaction studies I've seen are based on a typical monotherapy dosage of 400 mg, which says nothing about what the interaction effects (if any) from a lower dosage would be.

Thanks,
Rick


> Rick - I think that the pdocs I know use it to primarily raise levels of other drugs (without having to take higher doses of those drugs), while at the same time hoping for a little extra antidepressant activity.
>
> As for how to do it; I believe that is very individualized. Many factors have to be taken into consideration (past med use and response, what is hoped to be accomplished with the augmentation, disorder - and/or subtype - being treated, supposed status of one's cytochrome system, etc., etc., etc.).
>
> I do not think that I could make a blanket statement for using this type of therapy, nor do I think that it is an option for everyone. I do find that this sort of augmentation is fairly much a "last gasp" strategy, when most others have failed.
>
> I tend to think that this sort of therapy is from the "let-us-throw-a-bunch-of-treatments-against-the-wall-and-see-which-one-sticks" school of treatment. I am not a big fan of this, but sometimes one has to resort to whatever works.
>
> - Cam

 

Re: RE: Using Serzone to Raise Levels of Other Meds » Rick

Posted by Cam W. on December 27, 2001, at 20:30:43

In reply to Re: RE: Using Serzone to Raise Levels of Other Meds » Cam W., posted by Rick on December 27, 2001, at 15:48:50

Rick - I have seen doses of Serzone used from 75mg once daily to 150mg twice daily, in cases where I have "thought" that the doc was trying to manipulate blood levels of other medication. I was not always privy to what the docs were doing. I was also usually not told what the blood levels of concomittant meds were. Sometimes, I think, that poor absorbers of medications (eg. certain benzos, clozapine, clomipramine, come to mind) were given Serzone to increase the levels that they were absorbing. I feel that using this method to increase is not a primary, nor a secondary choice, but a last gasp.

I am definitely not saying that anyone should use this method to increase blood levels of other meds, as I know of no studies that show how much of an increase any particular dose of Serzone would produce.

I guess that I am saying that I would be extremely uncomfortable using this method without being under the close watch of a physician. There are just too many variables involved; and most of these variables are not realized until after the fact.

Sorry - Cam

 

Re: RE: Using Serzone to Raise Levels of Other Meds

Posted by Sunnely on December 27, 2001, at 22:52:56

In reply to RE: Using Serzone to Raise Levels of Other Meds » Cam W., posted by Rick on December 24, 2001, at 20:12:31

The idea of adding a (cheaper) drug to raise the blood levels and effects of another drug had been entertained in the past. The driving force is mainly costs (Pharmacoeconomics). For example, grapefruit juice, which markedly inhibits the enzyme CYP3A4, had been entertained to be added to cyclosporine, a costly anti-rejection drug. For now, this idea had been dropped due to lack of knowledge as to risks (cyclosporine toxicity) vs. benefits (savings) of the combination. FYI, a depressed patient on Serzone (Prozac and Luvox, to some extent) and cyclosporine may unknowlingly benefit dually from the use of these antidepressants: 1) antidepressant effect and 2) lesser dose of cyclosporine used, therefore, less cost.

 

Re: RE: Using Serzone to Raise Levels of Other Meds » Cam W.

Posted by Rick on December 28, 2001, at 14:59:08

In reply to Re: RE: Using Serzone to Raise Levels of Other Meds » Rick, posted by Cam W. on December 27, 2001, at 20:30:43

Cam -

Don't apologize -- this is very helpful!

I won't bore you with the whole story, but for several reasons I dropped Serzone from from my very-successful clonazepam/Serzone/modafinil combo for severe (but not debilitating) social phobia. This is an experiment related to some adverse effects that I thought might be related to the Serzone, and has been going on for four weeks. Since I'm not and never have been clinically depressed (as far as I know), this is a situation where I can afford to experiment without much risk (mentally at least -- see the "aside" below).

So far things seem OK as far as the social phobia goes. (Unfortunately, it may be a different story with regard to resolution of the adverse effects I thought might resolve by dropping Serzone, but I want to give it more time, and again that's a different story anyway.) The one downside theraputically-speaking is that my treatment now seems to become less-potent later in the day. So I tried taking just .25mg extra clonazepam in the afternoon (added to the 1 mg I take in the morning), but that small afternoon supplement makes me tired.
I'm guessing the reason for this might be that the Serzone was potentiating one or both of the other meds. So what I'm toying with is the idea of continuing the experiment in a slightly-less-pure fashion by dropping most of the Serzone but keeping a little of it as a CYP3A4 inhibitor so that the clonazepam might remain potent longer...OR so the modafinil anti-fatigue effect might stay potent longer to allow me to take .25mg clonazepam in the afternoon without getting kinda tired.

If I was depressed, I definitely wouldn't be chancing this. But I know I do great theraputically with 300-400 mg Serzone in the mix, and quite well theraputically with zero (other meds unchanged), so in my case I see no risk. But generally speaking, I can definitely appreciate your cautious stance and call for close supervision.

A detailed aside: The strangest effect of dropping the Serzone is that modafinil now has definite effects on my blood pressure and resting heart rate. While my morning blood pressure is good as alway, it is now averages systolic 20-25 points higher later in the day than when Serzone was in the combo, i.e. it went from low-normal to high-normal (which has recently been shown to be more of a cardiovascular risk than previously believed). But what's *really* surprising is that if I bump the modafilil from 100 mg to 200 mg, as I've always done once every few weeks, my later-in-the-day blood pressure shoots to as high as 160/110. Even after I go back to 100 mg, it still takes a few days for the BP to go back down. (The first-thing-in-the-morning readings, before I take any meds, stay OK throughout.) When I was on 300 mg Serzone, going to 200 mg modafinil would have *no* effect on my blood pressure! Similar story with resting heart rate. Since cutting out the Serzone, I get afternoon readings averaging 100 beats per minute, vs. about 80-85 before. And when I raise the modafinil to 200, it goes up a lot more. I've had a number of afternoon readings, while relaxing, of 120 beats per minute. (As with BP, dropping the Serzone hasn't had much effect on my first-thing-in-the-morning heart rate, regardless of modafinil dosage).

Rick

 

Re: RE: Using Serzone to Raise Levels of Other Meds » Sunnely

Posted by Rick on December 28, 2001, at 15:17:51

In reply to Re: RE: Using Serzone to Raise Levels of Other Meds, posted by Sunnely on December 27, 2001, at 22:52:56

I've actually entertained the idea of taking some supposedly-standardized grapefruit or grapefruit-seed supplements -- until I remembered (from one of your posts?) that grapefruit only affects drugs with substantial firt-pass metabolism. That would exclude both clonazepam and modafinil.

I've dug up some research, mostly (but not all) based on in-vitro studies, that several herbal preparations appear to be CY3A4 inhibitors. Besides grapefruit preparations, the only examples I can think of off the top of my head are Milk Thistle and Bitter Orange Peel (has some of the same constituents as grapefruit.

There have been some conflicting reports, and as you know in vitro results don't always match in vivo. St. John's Wort, for example, appeared to be a strong CYP3A4 inhibitor in vitro, but later in vivo studies suggest it is actually an inducer. And since drugs with substantial first-pass metabolism tend to be used for the studies (that includes cyclosporine, doesn't it?), I would imagine that inferring interactions with drugs like clonazepam or alprazolam would be even iffier. Maybe these (potential) CYP3A4 inhibitors tend to have their effects in the gut like grapefruit juice.

Rick

> The idea of adding a (cheaper) drug to raise the blood levels and effects of another drug had been entertained in the past. The driving force is mainly costs (Pharmacoeconomics). For example, grapefruit juice, which markedly inhibits the enzyme CYP3A4, had been entertained to be added to cyclosporine, a costly anti-rejection drug. For now, this idea had been dropped due to lack of knowledge as to risks (cyclosporine toxicity) vs. benefits (savings) of the combination. FYI, a depressed patient on Serzone (Prozac and Luvox, to some extent) and cyclosporine may unknowlingly benefit dually from the use of these antidepressants: 1) antidepressant effect and 2) lesser dose of cyclosporine used, therefore, less cost.

 

Re: RE: Using Serzone to Raise Levels of Other Meds

Posted by dove on December 29, 2001, at 7:27:48

In reply to Re: RE: Using Serzone to Raise Levels of Other Meds » Sunnely, posted by Rick on December 28, 2001, at 15:17:51

First, I want to say "wow!" to those blood pressure readings! That's some seriously interesting and kind of scary after-effects. Have you had blood pressure stability problems in the past? Those are major moves for systolic pressure numbers!

Second item, my pharmacist freaks whenever my p-doc adds another SSRI-like med to the already in place Serzone, as they're both CYP3A4 inhibitors. She told me people have actually died from taking Serzone with an SSRI and/or TCA.

Yet, many people, myself included, find that the Serzone can be very helpful when running out of options med-wise. Adding a very small amount of Serzone when you were previously taking a larger amount should not hold too many surprises for you. Especially if you are aware and knowledgeable of the meds and their possible risks and effects and have already used them in combination before. JMHO, I'm not encouraging med-experimentation w/o Dr. approval, it just seems like you know what you're doing.

dove

 

Re: RE: Using Serzone to Raise Levels of Other Meds » dove

Posted by Rick on December 30, 2001, at 14:14:59

In reply to Re: RE: Using Serzone to Raise Levels of Other Meds, posted by dove on December 29, 2001, at 7:27:48

Thanks for the helpful perspective.

I was first told I had moderate-to-mild high blood pressure two-and-a-half years ago, just about the same that time I learned that my longtime mental burden was something called "social phobia" and went to a pdoc seeking treatment. I used to have high blood pressure, until I started an earnest diet (lost 50 pounds gradually and have stayed there) and started taking anti-anxiety meds. I've always thought that the weight loss was the main reason for the BP drop, with both direct (physical side-effect) and anti-anxiety effects of my meds playing a secondary role. I think Serzone, and before that Celexa, was doing a lot to keep the BP down (Serzone is known for its potential BP-lowering effects.) And now I realize that modafinil by itself (or at least with concomitant clonazepam) may increase it...with Serzone attenuating that effect.

Two other notes: Before Serzone and Celexa, I *was* using pindolol -- a BP-med (beta blocker)with serotonergic effects -- as an augmentor, so that was certainly helping keep the BP down. Also, the first psychotropic I ever took, the MAOI Nardil, turned me from hypertensive to hypotensive within a week -- with no other meds!

Anyway, all the time I was on a Serzone/modafinil/clonazepam combo (which I'll likely return to if my experiment doesn't pan out), by BP was low normal all the time. Incidentally, if you look at BP variability charts for non-hypertensive people, there can be quite a lot of variation from hour to hour, but nothing like what I've had lately -- and of course it shouldn't veer much out of the "normal" range very often.

Rick

> First, I want to say "wow!" to those blood pressure readings! That's some seriously interesting and kind of scary after-effects. Have you had blood pressure stability problems in the past? Those are major moves for systolic pressure numbers!
>
> Second item, my pharmacist freaks whenever my p-doc adds another SSRI-like med to the already in place Serzone, as they're both CYP3A4 inhibitors. She told me people have actually died from taking Serzone with an SSRI and/or TCA.
>
> Yet, many people, myself included, find that the Serzone can be very helpful when running out of options med-wise. Adding a very small amount of Serzone when you were previously taking a larger amount should not hold too many surprises for you. Especially if you are aware and knowledgeable of the meds and their possible risks and effects and have already used them in combination before. JMHO, I'm not encouraging med-experimentation w/o Dr. approval, it just seems like you know what you're doing.
>
> dove

 

Serzone: Does it even work? - I think so

Posted by allisonm on December 30, 2001, at 14:56:17

In reply to Re: Serzone: Does it even work? - Sometimes » dhldn, posted by Cam W. on December 16, 2001, at 12:15:52

Thank you all for this thread. I've found it interesting, although occasionally over my head.

I've tried Zoloft, Effexor, Remeron, lithium, Wellbutrin, Celexa, Neurontin, and Serzone over 4 years in different combos, blah, blah, blah.

I have found that WB at 150mg/2x a day and Serzone 150mg/2x a day to be the most effective so far. I started Serzone in March (I think -- I have not been paying as much attention, which might be good). Good sleep, but not as sound as Remeron. Weight loss sted that uncontrollable gain. I don't feel I obsess as much as I used to. Sometimes when anxiety from special circumstances comes up, I take low dose Ativan.

My pdoc was looking to MAOIs as the next step, but I was very reluctant. The Serzone was one of those nearing-the-end, why-not-give-it-a-try types of prescriptions. My pdoc said he'd had very little luck with it, but then said that I never react to drugs in the way he expects. It's working.

Then again, some circumstances in my life have changed for the better in the last 10, 6 and 2 months. How to gauge? Can't.

I do hope they keep it on the market. I'm feeling a whole lot better.

Thanks again for the info.

alli

 

Re: RE: Using Serzone to Raise Levels of Other Meds » dove

Posted by Noa on December 31, 2001, at 15:03:56

In reply to Re: RE: Using Serzone to Raise Levels of Other Meds, posted by dove on December 29, 2001, at 7:27:48

>CYP3A4 inhibitors

Dove, could explain what this means? Thanks.

 

Re: RE: Using Serzone to Raise Levels of Other Meds » dove

Posted by Rick on January 1, 2002, at 12:44:58

In reply to Re: RE: Using Serzone to Raise Levels of Other Meds, posted by dove on December 29, 2001, at 7:27:48

> Second item, my pharmacist freaks whenever my p-doc adds another SSRI-like med to the already in place Serzone, as they're both CYP3A4 inhibitors. She told me people have actually died from taking Serzone with an SSRI and/or TCA.

The polypharmacy case I remember seeing cited had Serzone and at least three other psychotropic meds. So I'm guessing that your "and/or" is actually an "and." (I seem to recall the chemically-related trazodone was involved in one case.)

There are actually a few documented cases of women who had severe liver dysfunction after taking Serzone *alone*. I think they were poor metabolizers of liver enzyme CYP3A4, which Serzone uses for its own elimination in addition to inhibiting (restricting/delaying its availability to) other drugs that need it for eliminination (a la the examples you mentioned). One woman died, one had the damage reversed upon stopping Serzone, and one had a successful liver transplant. Even though this kind of reaction is said to occur in less than one out of every 200,000 users, the FDA has required that a warning be added to Serzone's monograph.

If you take Serzone, you should have liver function tests once a year (twice even better), and *definitely* have them if you're simultaneously taking other drugs that use or affect CYP3A4 enzymes, as I had been (Klonopin/clonazepam and Provigil/modafinil). In my case, as I would suspect for the majority of people without pre-existing liver impairment or hepatic risk factors such as excessive imbibing, everything has always checked out fine. Risks are probably somewhat higher in the elderly, although the three reports of Serzone-only severe toxicity were in women ranging from 14 (age alone engendered some controversy in that case) to 63.

Also, I've found shocking ignorance of the potential Serzone interactions among doctors, even pdocs. With any AD, and with Serzone in particular, look up possible interactions yourself if your doctor doesn't cite them, or if he says, "there aren't any." Serzone raises blood-levels of the cholesterol-lowering statins -- some dramatically -- which can have potentially dangerous results (muscle degeneration) in susceptible individuals...and the problem might not even be recognized as serious soon enough to avoid serious damage. I have a friend taking Lipitor/atorvastatin whose doctor gave her Serzone without any knowledge that the interaction could in essence quadruple (if memory serves) the Lipitor dosage. (Fortunately she was on a small dose of Lipitor to begin with.) It also greatly increases BuSpar/buspirone levels, and on average doubles Xanax/alprazolam levels (and presumably those of other benzos that are hepatically-cleared via CYP3A4, such as Klonopin/clonazepam).

Incidentally, while it depends on dosages, I get the impression serotonin syndrome has occured with Serzone + SSRI, but is rare. I think it's more likely to occur with SSRI+SSRI, and certainly more likely to occur with SSRI + MAOI.

Rick

 

Re: Serzone: Does it even work? - I think so » allisonm

Posted by Rick on January 1, 2002, at 12:50:15

In reply to Serzone: Does it even work? - I think so, posted by allisonm on December 30, 2001, at 14:56:17

> I have found that WB at 150mg/2x a day and Serzone 150mg/2x a day to be the most effective so far. I started Serzone in March (I think -- I have not been paying as much attention, which might be good). Good sleep, but not as sound as Remeron. Weight loss sted that uncontrollable gain. I don't feel I obsess as much as I used to. Sometimes when anxiety from special circumstances comes up, I take low dose Ativan.

Nice to hear Serzone is helping you. I've often wondered about the Serzone/Wellbutrin combo. Did you start with SZ and add WB, or vice versa? Or start both at once? I ask because I know that Wellbutrin, at least solo, can worsen anxiety for many.

Rick

 

Re: Serzone: Does it even work? - I think so - PS » allisonm

Posted by Rick on January 1, 2002, at 12:55:55

In reply to Serzone: Does it even work? - I think so, posted by allisonm on December 30, 2001, at 14:56:17

> I do hope they keep it on the market. I'm feeling a whole lot better.

Do you have specific reason to suspect Serzone's being discontinued? If not, I doubt you have anything to worry about. I do know it has a smaller market share than the SSRI's, but I still see it on many "most-prescribed drugs" lists.

However, I *do* notice that the the Bristol-Myers-Squibb website no longer says anything about having an extended-release version in the pipeline. Hmmm...

Rick

 

Re: Serzone: Does it even work? - I think so - » Rick

Posted by allisonm on January 1, 2002, at 15:00:51

In reply to Re: Serzone: Does it even work? - I think so - PS » allisonm, posted by Rick on January 1, 2002, at 12:55:55

Hi, Rick!

I have been taking Wellbutrin SR for 2.5 years -- first as an augment to Remeron, then as a primary with a Remeron augment, then with Remeron and Neurontin augments, then just with Neurontin augment, then with Celexa augment, now with Serzone. Of everything I've taken, WB has helped the most, but it needs help. Serzone has helped WB the most.

I've no real information re' continued marketing of Serzone, just have a feeling (maybe paranoia? or just garden-variety depressive cynicism? :-) ) that maybe it won't be around long because:

1. I read here that few people find it helps;
2. I've read elsewhere doctors' comments that they have few patients that respond;
3. my own doctor says he's had little luck with it; and last but not least:
4. because I'm taking it and it seems to be working.

As drug companies continue to come out with new products promising that they will be the solution for all of one's problems, maybe Serzone will be cast aside.

This info in recent posts on liver damage is scary.

That's all. Thanks and Happy New Year.

alli


 

Re: Serzone: Does it even work? - Rick, Allison

Posted by Mair on January 1, 2002, at 18:03:53

In reply to Re: Serzone: Does it even work? - I think so - » Rick, posted by allisonm on January 1, 2002, at 15:00:51

> allison - I'm glad to see that you're doing well and that the serzone continues to work for you. Since serzone was the drug from hell for me, i guess you and i are no longer on the same drug track. (-: After dropping serzone last summer, I managed to do okay on just WB Sr. for a few months and have only recently added lamictal. I've not really noticed any difference yet but I've only just reached 100 mgs and maybe it'll take a longer period of time to quantify.

Rick - I know of no reason why you can't mix serzone and wb since allison is doing it so successfully. Wb never really gave me a lot of anxiety although the wb-serzone mix made me feel variously over-drugged or anxious. For me, an occasional dose of xanax was helpful. My main longer term problem with serzone (aside from it's ineffectiveness) was a cognitive dulling. It affected my motor skills also - I was always dropping stuff. I attributed all of this (mostly forgetfulness) to perimenopause and stress until I went off serzone. All of these symptoms then disappeared.

I know it's worked well for lots of people - my experience is that we all react very idiosyncratically to these drugs so its hard to predict what might work for someone. I had high hopes for it, however, that just didn't pan out.

Mair

 

Re: RE: Using Serzone to Raise Levels of Other Meds

Posted by dove on January 2, 2002, at 15:02:24

In reply to Re: RE: Using Serzone to Raise Levels of Other Meds » dove, posted by Rick on January 1, 2002, at 12:44:58

>
>So I'm guessing that your "and/or" is actually an "and." (I seem to recall the chemically-related trazodone was involved in one case.)
>

Yes! It is indeed an "AND", and thank you!

>
>Incidentally, while it depends on dosages, I get the impression serotonin syndrome has occurred with Serzone + SSRI, but is rare. I think it's more likely to occur with SSRI+SSRI, and certainly more likely to occur with SSRI + MAOI.
>

I also agree with the above statements. The SSRI + SSRI interactions and potential for serotonin syndrome are significantly higher than any Serzone + SSRI combo. And the MAOI + SSRI is a high risk given.

>
>I think they were poor metabolizers of liver enzyme CYP3A4, which Serzone uses for its own elimination in addition to inhibiting (restricting/delaying its availability to) other drugs that need it for elimination (a la the examples you mentioned).
>
>If you take Serzone, you should have liver function tests once a year (twice even better), and *definitely* have them if you're simultaneously taking other drugs that use or affect CYP3A4 enzymes, as I had been (Klonopin/clonazepam and Provigil/modafinil).
>

Multiple meds that utilize and inhibit the CYP3A4 enzyme can lead to the highly talked about and infamous "serotonin syndrome". It seems almost bizarre to me--as a prescribed consumer--that Serzone inhibits the very enzymes it needs for processing and elimination. The whole spectrum of the Cytochrome P450 and its enzymes and their inhibitors, antagonizers, and inducers is so cross-wired and enmeshed (at least for me) that it is difficult to locate where, exactly, the benefits and the drawbacks of intermixing meds are or aren't.

However, they do seem to work together in a beneficial manner that suits my needs, and I'm willing to play short-term guinea pig for those results.

dove

 

Re: Serzone: Does it even work? - I think so - » allisonm

Posted by Rick on January 3, 2002, at 13:05:30

In reply to Re: Serzone: Does it even work? - I think so - » Rick, posted by allisonm on January 1, 2002, at 15:00:51

> I've no real information re' continued marketing of Serzone, just have a feeling (maybe paranoia? or just garden-variety depressive cynicism? :-) ) that maybe it won't be around long because:
>
> 1. I read here that few people find it helps;
> 2. I've read elsewhere doctors' comments that they have few patients that respond;
> 3. my own doctor says he's had little luck with it;

Internet groups, and especially P-B, seem more negative towards Serzone than what I've personally encountered, which is hardly a large sample size:

-- A friend whose been greatly satisfied, with no side effects, using it for GAD
-- A GP who said it's a great antidepressant (but was clueless about interactions)
-- A Pdoc who said, "Serzone's a strange med. It doesn't seem to help as often as many of the others, but there are a number of depressed or anxious people who do great with it." (Yourself included, of course!)
-- My own positive experience, although I'm concerned about possible adverse memory effects, and I'm beginning to think it's helped me more due to beneficial side effects and interactions than its own anxiolytic properties.

>and last but not least:
> 4. because I'm taking it and it seems to be working.

LOL! I know THAT feeling!!

The internet medical reviews and studies (NOT all manufacturer-funded!)seem more positive about Serzone than the groups, although there are more than a few very negative ones that complain especially of the interactions and non-linear dosing.

All told Serzone seems to get its highest marks when anxiety is a major component of the disorder being treated.

Rick

Rick

 

Re: Serzone: Does it even work? - Rick, Allison » Mair

Posted by Rick on January 3, 2002, at 13:15:20

In reply to Re: Serzone: Does it even work? - Rick, Allison, posted by Mair on January 1, 2002, at 18:03:53

>My main longer term problem with serzone (aside from it's ineffectiveness) was a cognitive dulling. It affected my motor skills also - I was always dropping stuff. I attributed all of this (mostly forgetfulness) to perimenopause and stress until I went off serzone. All of these symptoms then disappeared.

Memory impairment is one of the two main reasons I'm trying a Serzone-less period. (Again, a disclaimer, since I don't want to encourage anyone to suddenly dump their AD to "experiment": It's safe for me to be without an AD since I'm not clinically depressed.)

Oddly, this change seems to be helping my LONG-term memory more than anything. And yes, I think Serzone made me even a bit klutzier than usual. BTW, I'm by no means writing Serzone off...I'm still in the experimenting stage. As I've mentioned before, it seemed to provide me with a number of plusses, even if they were mostly beneficial side effects and interactions.

Rick

 

Re: RE: Using Serzone to Raise Levels of Other Meds » dove

Posted by Rick on January 3, 2002, at 13:29:30

In reply to Re: RE: Using Serzone to Raise Levels of Other Meds, posted by dove on January 2, 2002, at 15:02:24

>It seems almost bizarre to me--as a prescribed consumer--that Serzone inhibits the very enzymes it needs for processing and elimination.

It is strange, but it's not at all uncommon. For example, one of the other meds I take, Provigil, is both an inhibitor (though less so than Serzone) and substrate of CYP3A4. At higher doses, it can sometimes induce its own metabolization. In other words, once in awhile it will reduce its own effectiveness. I've sometimes wondered if this is what's going on on the occasional days that Provigil doesn't seem to work as well for me, although I'm on a pretty conservative dosage.

Rick

 

Re: Serzone: Does it even work? - Rick, Allison » Rick

Posted by allisonm on January 4, 2002, at 9:35:31

In reply to Re: Serzone: Does it even work? - Rick, Allison » Mair, posted by Rick on January 3, 2002, at 13:15:20

Now all of this cognitivve dulling talk makes me nervous. I have felt "stupider" on Serzone and on WB before that. With Serzone I'm forgetful and spacey (like walking into rooms ALL the time and forgetting why), and I find I get tongue-tied a LOT. It gets embarrassing. I can't remember the words I want to say and have to pause or let others finish my sentence, or trying to use many lesser words to say what I could once say in one word. EX: I had a horrible time one day trying to describe "sentimental value" to someone because I couldn't come up with the words. I don't seem to notice the WB problem so much, or maybe they've folded in together.

On the other hand, as my pdoc has pointed out, I have been under a lot of stress lately, and it's only going to get worse for awhile; I'm going back to college fulltime after 19 years at the end of this month. I hope my brain works.

Thanks.
Allison

> >My main longer term problem with serzone (aside from it's ineffectiveness) was a cognitive dulling. It affected my motor skills also - I was always dropping stuff. I attributed all of this (mostly forgetfulness) to perimenopause and stress until I went off serzone. All of these symptoms then disappeared.
>
> Memory impairment is one of the two main reasons I'm trying a Serzone-less period. (Again, a disclaimer, since I don't want to encourage anyone to suddenly dump their AD to "experiment": It's safe for me to be without an AD since I'm not clinically depressed.)
>
> Oddly, this change seems to be helping my LONG-term memory more than anything. And yes, I think Serzone made me even a bit klutzier than usual. BTW, I'm by no means writing Serzone off...I'm still in the experimenting stage. As I've mentioned before, it seemed to provide me with a number of plusses, even if they were mostly beneficial side effects and interactions.
>
> Rick

 

SERZONE - THE FACTS from Synopsis of Psychiatry

Posted by jimmygold70 on January 4, 2002, at 14:31:58

In reply to Re: Serzone: Does it even work? - Rick, Allison » Rick, posted by allisonm on January 4, 2002, at 9:35:31

This is taken from Kaplan and Sadock's Synopsis of psychiatry, 8th Edition

-------------------------------------------
NEFAZODONE
-------------------------------------------
Nefazodone (Serzone) is an antidepressant medication structurally related to trazodone (Desyrel) and unrelated to the classical tricyclic and tetracychc drugs, the monoamine oxidase inhibitors (MAOIs), serotonin-specific reuptake inhibitors (SSRIs), and other available antidepressant drugs. Although trazodone is distinctive in having more marked sedative effects than those found with most other antidepressants, ne-fazodone is relatively free of this adverse effect and generally well tolerated. Nefazodone is less likely than the SSRIs to adversely affect sexual functioning.

CHEMISTRY

Nefazodone is a phenylpiperazine analogue of trazodone. Its molecular structure is shown in Figure 35.3.24-1.

PHARMACOLOGICAL ACTIONS

Pharmacokinetics

Nefazodone is rapidly and completely absorbed, but it is then extensively and variably metabolized so that the bioa-vailability of active compounds is about 20 percent of the oral dose. Its half-life is 2 to 4 hours, and dosing must be twice daily. Steady-state concentrations of nefazodone and its principal active metabolite, hydroxynefazodone, are achieved within 4 to 5 days. Metabolism in older people, especially women, is about half that seen in younger patients; thus lower doses are recommended in elderly patients.

Pharmacodynamics

Nefazodone is an inhibitor of serotonin uptake and, more weakly, of norepinephrine reuptake. It also acts as an antagonist of the serotonin type 2 (5-HT2) receptor, antagonism of
which is thought to treat anxiety and depression. The net effect of serotonin reuptake inhibition and 5-HT2 receptor blockade is thought to be selective activation of serotonin type 1 (5-HT1) receptor, which has been suggested to improve both anxiety and depression. Nefazodone causes mild antagonism of the a1-adrenergic receptors and can predispose some patients to orthostatic hypotension. There is no significant activity at a2- and beta-3-adrenergic, serotonin type 1A(5-HT1A), cholinergic, dopaminergic, or benzodiazepine receptors.

EFFECTS ON SPECIFIC ORGANS AND SYSTEMS

The main effects of nefazodone are on the central nervous system (CNS). The main extra-CNS effects are related to a1-adrenergic antagonism, which may cause orthostatic hypotension. Unlike its structural relative trazodone, nefazodone has not been reported to cause priapism.

Cardiovascular Effects

In premarketing trials, 5.1 percent of patients taking nefazodone experienced a significant drop in blood pressure, compared with 2.5 percent of placebo patients. Although there was no increase in true syncopal events, symptoms of postural hypotension were experienced by 2.8 percent of patients treated with nefazodone. This rate compares with postural hypotension in 0.8 percent of placebo-treated, 1.1 percent of SSRI-treated, and 10.8 percent of tricyclic antidepressant-treated patients. Sinus bradycardia was seen in 1.5 percent of nefazodone-treated patients compared with 0.4 percent of placebo-treated patients. Nefazodone should therefore be used with caution in patients with underlying cardiac conditions, history of stroke or heart attack, dehydration, and hypovolemia and in patients under treatment with antihypertensive medications.

Activation of Mania

In patients with known bipolar illness, 1.6 percent of those treated with nefazodone experienced mania, compared with 5.1 percent of tricyclic-treated patients and 0 percent of placebo-treated patients. The activation of mania in unipolar patients was no higher with nefazodone than with placebo. Therefore, nefazodone may be a drug to try earlier in the treatment of patients with a history of manic episodes. Electroconvulsive therapy and the antidepressant lithium are least likely to activate mania.

THERAPEUTIC INDICATIONS

Nefazodone has been approved for the treatment of depression on the basis of data from at least two large clinical trials. Nefazodone has been shown to be equally as efficacious as imipramine, fluoxetine, and paroxetine for treatment of moderate, severe, melancholic, nonmelancholic, chronic, and recurrent depression. Preliminary clinical reports indicate that nefazodone may also be an effective treatment for depression accompanied by anxiety, such as for panic disorder and panic with comorbid depression or depressive symptoms, for obses-
sive-compulsive disorder, for premenstrual dysphoric disorder, and for the management of chronic pain of neuropathic or non-neuropathic origin. Although small studies report that nefazodone was associated with a trend toward a reduction in obsessive thoughts, a case report documents the initial appearance of obsessive thoughts during nefazodone treatment, which ceased when the drug was discontinued. More data are needed to establish whether nefazodone is as effective for obsessive-compulsive disorder as are the SSRIs and clomipramine.

PRECAUTIONS AND ADVERSE REACTIONS

In preclinical trials, 16 percent of patients discontinued nefazodone because of an adverse event. The most common reasons for discontinuance were nausea (3.5 percent), dizziness (1.9 percent), insomnia (1.5 percent), and agitation (1.2 percent). The adverse reactions reported with nefazodone are listed in Table 35.3.24-1. The adverse events were dose dependent and tended to appear at significant levels only in the dosing range of 300 to 600 mg a day. Nefazodone causes little sexual dysfunction, weight gain, or cardiotoxicity. Nefazodone and trazodone are unusual among antidepressants, in that they do not decrease but, rather, increase REM sleep and improve sleep continuity. However, nefazodone is much less likely than trazodone to produce daytime sedation.
Nefazodone was not shown to cause cancer in laboratory animals or to cause mutagenesis in several common assays. It caused mild loss of fertility at doses comparable to 3 times the highest recommended human dose. Although no teratogenic effects were noted, early neonatal mortality of laboratory animal offspring occurred with doses in the mothers comparable to 5 times the highest recommended human dose. There are no data on the effects of nefazodone on human mothers. Nefazodone should therefore be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus. It is not known whether nefazodone is excreted in human breast milk. Therefore, it should not be used by women who are breast-feeding.


Table 35.3.24-1
Adverse Reactions Reported with Nefazodone
(300-600 mg a day)
________________%
Headache 36
Dry mouth 25
Somnolence 25
Nausea 22
Dizziness 17
Constipation 14
Insomnia 11
Weakness 11
Lightheadedness 10
Blurred vision 9
Dyspepsia 9
Infection 8
Confusion 7
Scotomata 7


DRUG INTERACTIONS

As is true for all antidepressant medications, nefazodone should not be given concomitantly with MAOIs. In addition, nefazodone has particular drug-drug interactions with the tria-zolobenzodiazepines, triazolam (Halcion) and alprazolam (Xanax), with so-called third-generation antihistamines, terfen-adine (Seldane) and astemizole (Hismanal), and with cisapride (Propulsid) because of the inhibition of cytochrome P450 (CYP) isoenzyme CYP 3A4 by nefazodone. Potentially toxic levels of each of these drugs can develop after administration of nefazodone, whereas the levels of nefazodone are generally not affected. The manufacturer recommends that the dose of triazolam be lowered by 75 percent, the dose of alprazolam be lowered by 50 percent when given concomitantly with nefazodone, and terfenadine and astemizole not be used at all with nefazodone.
Nefazodone may modestly increase levels of concomitantly administered haloperidol (Haldol). Nefazodone may slow the metabolism of digoxin; therefore, digoxin levels should be followed carefully in patients taking both medications. Conversely, nefazodone appears to reduce the bioavailability of propranolol (Inderal), and concomitant use of these two drugs should prompt a reevaluation of the dose of propranolol on clinical grounds. Nefazodone should not be given within 14 days of beginning or stopping an MAOI.

LABORATORY INTERFERENCES

No laboratory interferences have been reported for nefazodone.

DOSAGE AND ADMINISTRATION

Like other antidepressant drugs, nefazodone begins to improve mood between 2 and 4 weeks of initiation of therapy. The recommended starting dose of nefazodone is 100 mg 2 times a day. To limit the development of adverse effects, the dosage should be slowly tapered up to increments of 100 to 200 mg a day at intervals of no less than 1 week per increase. Older patients should receive doses about two thirds of the usual nongeriatric doses, with a maximum of 400 mg a day. Dosages should be lowered in patients with hepatic impairment. In common with other antidepressants, clinical benefit of nefazodone usually appears after 2 to 4 weeks of treatment. Nefazodone is available in 100, 150, 200, and 250 mg tablets.

REFERENCES

Baldwin DS, Hawley CJ, Abed RT, Maragakis BP, et al: A multicenter double-blind comparison of nefazodone and paroxetine in the treatment of outpatients with moderate-to-severe depression. J Clin Psychiatry 57 (2, Suppl): 46, 1996.
Ellingrod VL, Perry PJ: Nefazodone: A new antidepressant. Am J Health System Pharm 52: 2799, 1995.
DeMartmis NA, Schweizer E, Rickels K: An open-label trial of nefazodone in high comorbidity panic disorder. J Clin Psychiatry 57: 245, 1996
Feiger A, Kiev A, Shnvastava RK, Wisselink PG, Wilcox CS: Nefazodone versus sertraline in outpatients with major depression. Focus on efficacy, toler-ability, and effects on sexual function and satisfaction. J Clin Psychiatry 57 (2, Suppl): 53, 1996.
Lader MH: Tolerability and safety: Essentials in antidepressant pharmacotherapy. J Clin Psychiatry 57 (2, Suppl): 39, 1996.
Marcus RN, Mendels J- Nefazodone in the treatment of severe, melancholic, and recurrent depression. J Clin Psychiatry 57 (2, Suppl): 19, 1996.
Nemeroff CB, DeVane CL, Pollock BG: Newer antidepressants and the cytochrome P450 system. Am J Psychiatry 153: 311, 1996.
Robinson DS, Marcus RN, Archibald DG, Hardy SA: Therapeutic dose range of nefazodone in the treatment of major depression J Clin Psychiatry 57 (2, Suppl): 6, 1996.

 

Re: Serzone: Does it even work? - Rick, Allison » allisonm

Posted by Rick on January 5, 2002, at 0:33:46

In reply to Re: Serzone: Does it even work? - Rick, Allison » Rick, posted by allisonm on January 4, 2002, at 9:35:31

I'm betting your brain will work just fine.

There are times when I've had sometimes-embarrassing word-finding dificulties on Serzone (can happen with SSRI's too, you know), but plenty of other times when the words -- and ideas -- have flowed better than they ever did pre-Serzone. In fact, at work, my best analyses in years -- which earned several awards and bonuses for creativity and impact -- were put together while I was taking Serzone (along with Klonopin and Provigil).

Now, if I could only remember what they were...
(*mostly* joking...)

Rick

>Now all of this cognitivve dulling talk makes me nervous. I have felt "stupider" on Serzone and on WB before that. With Serzone I'm forgetful and spacey (like walking into rooms ALL the time and forgetting why), and I find I get tongue-tied a LOT. It gets embarrassing. I can't remember the words I want to say and have to pause or let others finish my sentence, or trying to use many lesser words to say what I could once say in one word. EX: I had a horrible time one day trying to describe "sentimental value" to someone because I couldn't come up with the words. I don't seem to notice the WB problem so much, or maybe they've folded in together.
On the other hand, as my pdoc has pointed out, I have been under a lot of stress lately, and it's only going to get worse for awhile; I'm going back to college fulltime after 19 years at the end of this month. I hope my brain works.

Thanks.
Allison

 

Re: Serzone: Does it even work? - Rick, Allison » Rick

Posted by allisonm on January 6, 2002, at 21:03:57

In reply to Re: Serzone: Does it even work? - Rick, Allison » allisonm, posted by Rick on January 5, 2002, at 0:33:46

Rick,
Thanks for the encouragement. Maybe if things don't work, I can buy extra memory at the university bookstore... Or I might do well to take a vow of silence. Better to say nothing and be thought a fool than to speak and remove all doubt, right?

allisonm

> I'm betting your brain will work just fine.
>
> There are times when I've had sometimes-embarrassing word-finding dificulties on Serzone (can happen with SSRI's too, you know), but plenty of other times when the words -- and ideas -- have flowed better than they ever did pre-Serzone. In fact, at work, my best analyses in years -- which earned several awards and bonuses for creativity and impact -- were put together while I was taking Serzone (along with Klonopin and Provigil).
>
> Now, if I could only remember what they were...
> (*mostly* joking...)
>
> Rick
>



This is the end of the thread.


Show another thread

URL of post in thread:


Psycho-Babble Medication | Extras | FAQ


[dr. bob] Dr. Bob is Robert Hsiung, MD, bob@dr-bob.org

Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.