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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 17 of 17. This is the beginning of the thread.
Posted by bleauberry on December 26, 2009, at 16:34:35
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654524/
Everything you ever wanted to know about Milnacipran (Savella).
If the link is clickable try that. If not, just copy and paste. I tried the copy and paste just to be sure the web address worked. It does.
Very indepth look at this...my opinion...unsung hero.
I was going to cut and paste the article but it is just too long. Plan on spending about 10 minutes or more reading it. Very detailed and informative, with mechanism, graphs, comparison of trials from country to country, successful combinations, history of performance in Japan, treatment resistance potency, memory, sleep, anxiety, onset, dosing, side effects, and lots of stuff.
My own opinion...this drug is probably a potent workhorse in combinations with SSRIs or antipsychotics, though by itself it is plenty impressive.
Posted by SLS on December 26, 2009, at 17:20:45
In reply to Everything You Ever Wanted To Know About Savella, posted by bleauberry on December 26, 2009, at 16:34:35
> My own opinion...this drug is probably a potent workhorse in combinations with SSRIs or antipsychotics, though by itself it is plenty impressive.
To paraphrase something you said in an earlier post, if it were so impressive, you would hear more about it and see more people using it.
I have my doubts about milnacipran. However, I will not overlook it or exclude it from consideration. It might be that this drug has not been made visible enough to clinicians as an antidepressant.
- Scott
Posted by janejane on December 26, 2009, at 17:37:36
In reply to Everything You Ever Wanted To Know About Savella, posted by bleauberry on December 26, 2009, at 16:34:35
Very interesting, though a lot of the technical stuff was way over my head. I wonder why there are so few ADs there. Do pharmas just think it's not worthwhile because of the market size or does it have something to do with regulations? Why did it take so long for it to be approved here versus there? And why not for depression?
Posted by Sigismund on December 26, 2009, at 17:39:54
In reply to Re: Everything You Ever Wanted To Know About Savella, posted by SLS on December 26, 2009, at 17:20:45
I wonder how frequently it is used in Japan and the other countries in which it is available?
Posted by SLS on December 26, 2009, at 18:18:31
In reply to Re: Everything You Ever Wanted To Know About Savella » SLS, posted by Sigismund on December 26, 2009, at 17:39:54
> I wonder how frequently it is used in Japan and the other countries in which it is available?
I would also like to know how often Japanese doctors use adinazolam and rolipram, two antidepressant drugs that will never be seen in the US.
It is all so confusing and frustrating.
- Scott
Posted by janejane on December 26, 2009, at 18:42:37
In reply to Re: Everything You Ever Wanted To Know About Savella » SLS, posted by Sigismund on December 26, 2009, at 17:39:54
Article said paroxetine has largest market share at 50%, and milnacipran comes in second with 12.5% Next is fluvoxamine (unspecified).
Posted by bleauberry on December 26, 2009, at 19:52:14
In reply to Re: Everything You Ever Wanted To Know About Savella, posted by SLS on December 26, 2009, at 17:20:45
.
>
> To paraphrase something you said in an earlier post, if it were so impressive, you would hear more about it and see more people using it.True, but that was referring to a common well known antidepressant. Savella is not common or well known in the USA. Very popular outside the continent for quite some time.
>
> I have my doubts about milnacipran. However, I will not overlook it or exclude it from consideration. It might be that this drug has not been made visible enough to clinicians as an antidepressant.It hasn't been made visible at all! :-) I'm glad you won't exclude it. I honestly believe this drug is going to be a huge answer for so many people. Not just based on text, but based on what it did to me when all else including ECT failed.
All I can say is, it is "different". And I reiterate, I believe its strongest worth will be found as part of a combination with another SSRI, lithium, or antipsychotic.
Nothing is perfect. But as potential goes, I truly believe this drug has more than any other med we have at our disposal. I mean that.
There is so much in that article I think it will be likely to miss or forget a lot of key points. But hopefully someone will find it interesting or helpful in their pursuits.
>
>
> - Scott
Posted by Phillipa on December 26, 2009, at 23:14:59
In reply to Re: Everything You Ever Wanted To Know About Savella » SLS, posted by bleauberry on December 26, 2009, at 19:52:14
Just home remember people all respond differently Phillipa
Posted by bleauberry on December 27, 2009, at 6:28:49
In reply to Re: Everything You Ever Wanted To Know About Savella » bleauberry, posted by Phillipa on December 26, 2009, at 23:14:59
> Just home remember people all respond differently Phillipa
Good point Phillipa.
I think I am a good example of that. While urinary symptoms are listed as an uncommon side effect in men with Savella, my urinary stoppage was profound. The antidepressant effect however was also profound. The drug did what none of the others could do, and did what ECT could not do. That's pretty amazing.
I remember a guy here a few months ago who gave Savella a trial. He reported improved depression, but had to stop the med because of the unbearable agitation and rage he felt on the drug. I suspect one of several things in that case: His dose was too high; he needed more serotonin focus, either from tryptophan or an ssri in combination with Savella; or, as you pointed, he was one of the minority of people who the drug was just not suited for.
I think my overall point in this thread is that while we know there is not one single magic drug on the planet that will work for everyone, and that we all respond differently, I believe 5 to 10 years from now we are going to see that Savella has a much better track record in this regard than any of its current peers. I truly believe it is an undiscovered unsung hero, for a variety of reasons.
Posted by bulldog2 on December 27, 2009, at 11:25:34
In reply to Everything You Ever Wanted To Know About Savella, posted by bleauberry on December 26, 2009, at 16:34:35
> http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654524/
>
> Everything you ever wanted to know about Milnacipran (Savella).
>
> If the link is clickable try that. If not, just copy and paste. I tried the copy and paste just to be sure the web address worked. It does.
>
> Very indepth look at this...my opinion...unsung hero.
>
> I was going to cut and paste the article but it is just too long. Plan on spending about 10 minutes or more reading it. Very detailed and informative, with mechanism, graphs, comparison of trials from country to country, successful combinations, history of performance in Japan, treatment resistance potency, memory, sleep, anxiety, onset, dosing, side effects, and lots of stuff.
>
> My own opinion...this drug is probably a potent workhorse in combinations with SSRIs or antipsychotics, though by itself it is plenty impressive.I would think as monotherapy it would have a better track record than the ssris and snris in use in the USA. It has a more balanced ratio of serotonin and norepinephrine.
Posted by janejane on December 27, 2009, at 11:59:01
In reply to Re: Everything You Ever Wanted To Know About Savella, posted by bulldog2 on December 27, 2009, at 11:25:34
> I would think as monotherapy it would have a better track record than the ssris and snris in use in the USA. It has a more balanced ratio of serotonin and norepinephrine.
Yeah, seems like it might be good for people who develop apathy on SSRIs. Too bad about the urinary SEs, though. That's why I couldn't tolerate cymbalta.
Posted by Iansf on December 28, 2009, at 0:16:14
In reply to Re: Everything You Ever Wanted To Know About Savella » Phillipa, posted by bleauberry on December 27, 2009, at 6:28:49
> I think I am a good example of that. While urinary symptoms are listed as an uncommon side effect in men with Savella, my urinary stoppage was profound. The antidepressant effect however was also profound.<
I had a profound urinary stopppage problem with Reboxetine. Did you find anything to overcome that?
Posted by SLS on December 28, 2009, at 5:13:30
In reply to Re: Everything You Ever Wanted To Know About Savella, posted by Iansf on December 28, 2009, at 0:16:14
> > I think I am a good example of that. While urinary symptoms are listed as an uncommon side effect in men with Savella, my urinary stoppage was profound. The antidepressant effect however was also profound.<
>
> I had a profound urinary stopppage problem with Reboxetine. Did you find anything to overcome that?
Urecholine (bethanacol) often does the trick.
- Scott
Posted by highhatsize on December 28, 2009, at 12:01:40
In reply to Everything You Ever Wanted To Know About Savella, posted by bleauberry on December 26, 2009, at 16:34:35
I found out about Milnacipran about two years ago and was so anxious to try it that when the FDA postponed approval a year ago in October, I obtained it from Great Britain by mail. The brand name over there is "Ixel". It comes in 25 mg. and 50 mg. caps.
I took 25 mg. 2X daily as the patient instructions prescribed. When the second capsule took effect in the evening I couldn't urinate for twelve hours. It was scary.
Subsequently, I read on this forum that some posters thought that the prescribed dosage was enormously large. One poster had success by cutting it to 6 mg. from 25.
However, dividing a capsule in quarters is difficult, and the dysuria was frightful, AND I had terminated my Shrink so I would have had to admit to my g.p. that I was using a med unapproved by the FDA. Or, order more meds from GB. So I ended the trial. I had planned to resume the attempt at a lower dosage when the dysuria was not such a distinct memory, but never did. I was not so bad off that it was essential and I subsequently discovered that another drug, (read the diphenhydramine thread), made me feel, actually, pretty good.
One poster on this board stated about 18 months ago that he didn't know of anyone whose depression was NOT ameliorated by this drug. It was the side-effects that made people drop it.
My reaction was so immediate and severe that I never had the time to evaluate it.
Posted by bleauberry on December 28, 2009, at 18:21:17
In reply to Re: Everything You Ever Wanted To Know About Savella, posted by highhatsize on December 28, 2009, at 12:01:40
>
> One poster on this board stated about 18 months ago that he didn't know of anyone whose depression was NOT ameliorated by this drug. It was the side-effects that made people drop it.I would tend to agree with that. Obviously there will be someone who won't be helped by it, but I see that percentage being far lower than any other drugs. This is a good drug and unique in some unexplainable way.
>
> My reaction was so immediate and severe that I never had the time to evaluate it.Well, I am surprised this urinary side effect has turned up this often. I thought I was the only one! The studies indicated a small percentage. In the real world it would appear to be a higher percentage.
At pubmed, some hospital that did a clinical study, indicated that the remedy for the urinary symptoms is Flomax. Another poster here about a year ago said Flomax immediately cured the urinary problems he had from REboxetine.
I tried Flomax and yes it worked immediately. The problem was, my blood pressure is alredy very very low, and Flomax lowers blood pressure. So that perfect remedy for me turned out to not be so perfect. But it certainly does work as intended to get the urine flowing again.
I discovered by accident that a small dose of just 25mg every other day of Amisulpride improved the symptoms maybe about 50%. How or why I have not a clue. Amisulpride works on D2/D3 receptors and on 5ht7. Obviously the knowledge we have on Amisulpride is not complete.
My gut feeling is a little bit of Nortriptyline would help too, despite it actions of the supposedly guilty norepinephrine in this scenario. Nortriptyline has other functions that could offset it. I pee easier on Nortriptyline, so it is doing something. ???
SLS has a suggestion for an anticholinergic. The thing is though, savella doesn't really have any appreciable cholinergic effect. That said, I learned a long time ago to forget the theory crap...it doesn't work...an anticholinergic like SLS mentioned could indeed work very well. I would love to see someone try it and see. Maybe it will be me.
Posted by SLS on December 28, 2009, at 18:43:16
In reply to Re: Everything You Ever Wanted To Know About Savella, posted by bleauberry on December 28, 2009, at 18:21:17
> SLS has a suggestion for an anticholinergic. The thing is though, savella doesn't really have any appreciable cholinergic effect. That said, I learned a long time ago to forget the theory crap...it doesn't work...an anticholinergic like SLS mentioned could indeed work very well. I would love to see someone try it and see. Maybe it will be me.
I'm not sure how Flomax would help. Urinary retension and delayed micturition need not be the result of using a drug with anticholinergic properties. It can occur as the result of excess sympathetic activation. Either way, a parasympathetic pro-cholinergic like bethanechol may still make sense to try first. Flomax works on the alpha-1a/b receptors in the prostate. I don't think it affects smooth muscle tone in the bladder like bethanechol does. If Flomax works, that would be great. I imagine it would be pretty expensive, though.
- Scott
Posted by mtdewcmu on January 2, 2010, at 13:55:17
In reply to Re: Everything You Ever Wanted To Know About Savella, posted by SLS on December 26, 2009, at 17:20:45
> > My own opinion...this drug is probably a potent workhorse in combinations with SSRIs or antipsychotics, though by itself it is plenty impressive.
>
> To paraphrase something you said in an earlier post, if it were so impressive, you would hear more about it and see more people using it.
>
> I have my doubts about milnacipran. However, I will not overlook it or exclude it from consideration. It might be that this drug has not been made visible enough to clinicians as an antidepressant.
>
>
> - ScottGoing by that study by Cipriani, et al, it appears that the effectiveness of SNRIs is inversely related to their preference for norepinephrine over serotonin. So,
Effexor > Savella > Cymbalta > Reboxetine
It seems that serotonin has a far greater influence on depression.
The preferences for serotonin from high to low:
Effexor: 116
Savella: 9.15
Cymbalta: 7.23
Reboxetine: 0.121-from Goodman & Gilman.
Efficacy according to Cipriani, et al, from high to low:
Effexor: 1.28
Savella: 1.01
Cymbalta: 0.99
Reboxetine: 0.68The numbers are relative to Prozac.
This is the end of the thread.
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