Psycho-Babble Medication Thread 87093

Shown: posts 1 to 25 of 30. This is the beginning of the thread.

 

Serzone: Does it even work?

Posted by dhldn on December 16, 2001, at 11:14:55

Nefazodone is a recent different 'non SSRI' drug closely related to trazodone. It claims to be an antidepressant. It blocks the post synaptic 5-HT2A receptors (see 'receptor affinities') and may have some weak (probably clinically insignificant) serotonin reuptake inhibitor activity. It is thought to increase serotonergic activity. Whether that is to a useful extent remains questionable and from my analysis of the evidence unlikely.

The problems and difficulties caused by this drug mean that careful consideration will frequently relegate it to a priority insufficiently high to warrant its use in primary care.

So far experience suggests that it is not a satisfactory antidepressant.

It is a relatively troublesome drug. Indeed it serves as a good illustration of the pharmacological points to assess when considering a new drug.

1 Its half-life of 1.5 - 4 hours is inconveniently short. Multiple daily dosing is required; at least twice daily, maybe three or even four times. The preferred range for half-life is 12-36 hours. That allows once daily dosing without to long a time to steady state, which would create a longer time lag before optimum improvement.

2 It has not one, but several, active metabolites about which little is known (but two of them are potent 3A4 inhibitors). This is an undesirable characteristic.

3 Plasma levels of both nefazodone and it's metabolites show very great inter-individual variation making dosage adjustment difficult and therapeutic drug monitoring desirable (but it is unavailable).

4 Nefazodone has another undesirable property-- that of 'non-linear' pharmacokinetics. Nefazodone and its two main metabolites are potent inhibitors of cytochrome P450 3A4; so it blocks its own metabolism (via cytochrome P450 3A4) and thus the blood level goes up out of proportion to the dose increase. This makes dose adjustment more tricky and may increase the chance withdrawal effects.

5 It retains significant alpha 1 blocking activity (like the tricyclic antidepressants) and thus has the side effect of postural hypotension.

6 Interactions with drugs metabolised by 3A4 do occur and are clinically significant, eg benzodiazepines, anti-histamines, TCAs and ergotamine (risk of serious toxicity).

7 It requires titration over a period of time.

Like some other new drugs, my view is that there is insufficient evidence of its effectiveness for the long term treatment of major depression compared to the best of the old TCAs (and sertraline).

It is too early to claim it is safer, either in over-dose or for rare serious side effects. Indeed there have recently been three cases of severe liver damage reported in association with nefazodone (see 'new').

In my opinion there is no more reason why this drug should act as an antidepressant than, say, cyproheptadine which also blocks the post synaptic 2A receptors. My experience and interpretation of the evidence leads me to the view that this drug (like its progenitor, trazodone) is not a useful antidepressant.

Trazodone, which is very similar indeed to nefazodone, has been around for over twenty years. It has never gained much of a reputation as an antidepressant; it is perhaps best thought of as an interesting non-benzodiazepine hypnotic with the advantage of having a low fatal toxicity index. There seems little reason to suppose that nefazodone will be much different; indeed since whatever place there may be for such a drug is already taken up by trazodone (in most countries) there may not be an 'ecological niche' for nefazodone and I would not be surprised if it were taken off the market.

Nefazodone is metabolised (inter alia) into an anxio-genic metabolite called 'm-CPP' and this may cause problems in a rather curious way (see cytochrome P450 enzymes interactions; 'curiouser and curiouser')

Note-- it is unlikely that nefazodone works as a clinically effective serotonin reuptake inhibitor at all.

As an inevitable consequence of their mode of action all serotonin reuptake inhibitors reduce platelet serotonin content. This is because platelets themselves do not produce serotonin, they take it up from the plasma. To do this they use the same uptake mechanism as do pre-synaptic neurons. If serotonin reuptake is blocked then platelets become greatly depleted of serotonin.

Neither trazodone nor nefazodone significantly reduce platelet serotonin in humans, ergo, they probably do not act as serotonin reuptake inhibitors. Further evidence that neither trazodone nor nefazodone are capable of significantly increasing brain 5-HT is that they do not cause serotonin syndrome if mixed with monoamine oxidase inhibitors. All other SRIs used in humans are likely to cause life-threatening serotonin syndrome if mixed with monoamine oxidase inhibitors.

***** Click 'view references' to go to the references screen where you can also see the associated notes / abstract summary.


Dr Ken Gillman MRC Psych

PsychoTropical Research


 

Re: Serzone: Does it even work? - Sometimes » dhldn

Posted by Cam W. on December 16, 2001, at 12:15:52

In reply to Serzone: Does it even work?, posted by dhldn on December 16, 2001, at 11:14:55

dhldn - Careful with making blanket statements about approved drugs. I use to do it all the time (eg. BuSpar, Seroquel), but it seems that there is always a person or two who have been greatly help by these medications, when seemingly all else has failed. It is a case of throwing the baby away with the bath water.

As for the antidepressant ability of trazodone, when it was first released, I found that a number of my elderly patients with depression became functional again, after starting Desyrel™ (trazodone). Yes, the drowsiness is a problem, especially at first, but many do overcome it at doses of 450mg to 600mg a day.

The most troublesome side effect I noticed with trazodone being used as an antidepressant, was an enormous increase in libido, in those tolerating higher doses. It literally turned little old ladies into sex machines (or so said their, sometimes desparate, husbands). Also, I did notice, but am not sure it was caused by trazodone, that several of those who were taking trazodone got that "cow tongue"; a rolling and flicking of the tongue, usually seen with TD.

Anyway, I have seen Serzone™ (nefazodone) also successfully treat both old and young people for depression. I have seen it work in lower (100mg) doses at bedtime, as an adjunctive antidepressant for those taking SSRIs, but having in bed, runminating thoughts. Serzone seems to give a more restful sleep than the currently available hypnotic agents (including trazodone).

At lower doses, I have not found m-CPP to be a problem. You do not see many people get anxious after taking Serzone, especially as an add-on.

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.

As with those who want to take Effexor™ (venlafaxine) off of the market, I do not think that Serzone should be removed. It would just be one less tool in our armamentum.

IMO - Cam

 

Re: Serzone: Does it even work?

Posted by Darwin on December 16, 2001, at 15:15:01

In reply to Serzone: Does it even work?, posted by dhldn on December 16, 2001, at 11:14:55

Nefazadone worked for me, but only for about a month. During that month, it relieved my dysthymia better than any other antidepressant I had tried. After that month, I started developing severe mental fatigue and backache which eventually caused me to quit Nefazadone. I wonder if those metabolites you mentioned had anything to do with the negative side effects.

From anecdotal reports, I get the impression that Nefazadone does tend to "Poop Out" earlier and more often than most antidepressants. One rarely reads of long term success stories with Nefazadone.

Nefazadone does have an advantage over Trazadone in that it is a much weaker alpha-1 antagonist. Thus, related side effects such as priapism and orthostatic hypotension are less of a problem.

I would like to point out that re-uptake inhibition of serotonin or norepinephrene or dopamine is probably not a requirement for antidepressant efficacy. For example, the mysterious tricyclic antidepressant Trimipramine is not a re-uptake inhibitor yet is recognized as an effective antidepressant.

Darwin

 

Re: Serzone: Does it even work?

Posted by Noa on December 19, 2001, at 18:48:46

In reply to Re: Serzone: Does it even work?, posted by Darwin on December 16, 2001, at 15:15:01

Works for me. Two and a half years and counting.

 

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

Posted by Rick on December 24, 2001, at 20:12:31

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

> 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?

If #1 or #2 apply, do you have any ideas on what kinds of dosages and dosing schedules are used? E.g., assuming Serzone potently inhibits modafinil (which has a half-life of about 15 hours after repeated dosing) could a small, sub-theraputic dose such as 75/day of Serzone taken morning-only with modafinil (also taken morning-only) raise modafinil blood levels? Would this essentially be extending modafinil's half life?

And a more-general question, implicit above, is: To what extent is the dosage required to elicit "useful" enzyme inhibition from the inhibitor tied to its own effective half-life (and/or theraputic range)? This question is especially applicable to Serzone given its highly non-linear pharmacokinetics (sp?)).

Any thoughts would be *greatly* appreciated!

Rick


 

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


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