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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 22 of 22. This is the beginning of the thread.
Posted by bleauberry on July 14, 2009, at 14:52:19
My doctor says he sees a dramatic difference in his patients' responses to nortriptyline depending on which company manufactured it. He always gives each patient a sequential trial of several different manufacturers to find the right one. One may be anxiety provoking, one may be all dirty side effects and nothing else, one may be neutral, and one may be a huge winner. He has seen it so many times that it is now standard procedure with him whenever he prescribes nortriptyline to run through a series of them. He says prescribing nortriptyline is like opening a can of worms, but that the results of methodical detective work are usually quite rewarding with the right version of that drug.
I've called my pharmacy to see what brands they have available. They are:
Brand Pamelor
Generic Teva
Generic Taro
Generic Watson
Generic MallinckroctI'm just curious what versions of Nortriptyline some of you have used? Does anyone have any knowledge of which of the above or other manufacturers are known for superior quality?
I'll have to try them all, and we all respond differently, so in that respect my questions are kind of pointless. But still, I am curious. :-)
Posted by bulldog2 on July 14, 2009, at 16:01:28
In reply to Nortriptyline Generic or Brand Favorites?, posted by bleauberry on July 14, 2009, at 14:52:19
> My doctor says he sees a dramatic difference in his patients' responses to nortriptyline depending on which company manufactured it. He always gives each patient a sequential trial of several different manufacturers to find the right one. One may be anxiety provoking, one may be all dirty side effects and nothing else, one may be neutral, and one may be a huge winner. He has seen it so many times that it is now standard procedure with him whenever he prescribes nortriptyline to run through a series of them. He says prescribing nortriptyline is like opening a can of worms, but that the results of methodical detective work are usually quite rewarding with the right version of that drug.
>
> I've called my pharmacy to see what brands they have available. They are:
> Brand Pamelor
> Generic Teva
> Generic Taro
> Generic Watson
> Generic Mallinckroct
>
> I'm just curious what versions of Nortriptyline some of you have used? Does anyone have any knowledge of which of the above or other manufacturers are known for superior quality?
>
> I'll have to try them all, and we all respond differently, so in that respect my questions are kind of pointless. But still, I am curious. :-)You must try Teva from Israel. They know how to make a good generic. I used Pamelor years ago which was execellent and Teva is the bomb. For me had a robust ad effect at 50 mg. Smooth and no anxiety and took the whole thing at night to sleep like a baby.
Posted by linkadge on July 14, 2009, at 19:46:01
In reply to Nortriptyline Generic or Brand Favorites?, posted by bleauberry on July 14, 2009, at 14:52:19
I personally don't see how this is possible.
Nortriptyline is nortriptyline. The molecule is identical whoever manufactures it. With some generics I can see an argument that it is less bioequivilant than another. With nortriptyline there is a blood test to determine what level the drug is at. If a doctor uses a blood test, he can find a blood level that works, then it really shouldn't matter what brand is given as long as the drug level is the same.
My 2 cents.
Linkadge
Posted by Phillipa on July 14, 2009, at 19:52:05
In reply to Re: Nortriptyline Generic or Brand Favorites?, posted by linkadge on July 14, 2009, at 19:46:01
Only one I took was pamelor and only at l0mg plastered me to the bed couldn't get up finally managed at 2pm and was going to bed at a decent hour then. That was the end of it for me as needed to live. Phillipa
Posted by bleauberry on July 15, 2009, at 5:30:40
In reply to Re: Nortriptyline Generic or Brand Favorites?, posted by linkadge on July 14, 2009, at 19:46:01
> I personally don't see how this is possible.
Well. actually, neither do I. But you and I do not have 25 years worth of patient experience either. I guarantee you my doctor would not be doing this just for grins. And being generics, there certainly isn't any under-the-table motive involved. He has seen what he has seen. Different is different.
>
> Nortriptyline is nortriptyline.I was reading some chemistry stuff last night on this topic. Actually, nortriptyline is not nortriptyline. The end molecule looks the same, yes, but it has finite characteristics that are different depending on the actual manufacturing process, crystalization, and a bunch of stuff that is over my head I didn't understand.
>The molecule is identical whoever manufactures it. With some generics I can see an argument that it is less bioequivilant than another.
Even the generic companies themselves admit in writing that bioequivelance does not equal therapeutic equivelance. There is a 7% allowable error in the amount of the drug. There is a 20% allowable error in the bioequivelance of the drug. FDA rules. None of them have been tested for "clinical" effectiveness. In private studies where they were, differences were noted, but not found to be significant enough for the FDA to take action. Of course, that is on a large group average and in doing so waters down what happened on individual bases.
Something else that is important is that the supposed bioequivalance is measured with a single dose, a single blood sample, in HEALTHY volunteers. I'm sorry, none of those things are in any way realistic with the real world of doctor's offices and prescribing guidelines.
>With nortriptyline there is a blood test to determine what level the drug is at. If a doctor uses a blood test, he can find a blood level that works, then it really shouldn't matter what brand is given as long as the drug level is the same.
But it does. One either has to be blind or extremely arrogant to immediately dismiss the reported cases with a shrug of a shoulder.
>
> My 2 cents.
>
> Linkadge
>
>I will try to find the article I read last night the explained all this stuff very well and then post it here for you to read. There is actually a lot more involved here than what we see at a mere glance.
Posted by SLS on July 15, 2009, at 7:12:23
In reply to Re: Nortriptyline Generic or Brand Favorites?, posted by linkadge on July 14, 2009, at 19:46:01
> I personally don't see how this is possible.
>
> Nortriptyline is nortriptyline. The molecule is identical whoever manufactures it.I'm sure you read of my experience with two different generic preparations of lamotrigine. Both allowed me to relapse. I also found that there was quite a difference between generics.
GSK 200mg > Teva 300mg > Mylan 500mg
On the Mylan lamotrigine at 500mg, I still wasn't getting as much therapeutic effect as 200mg of the GSK Lamictal. I refused to go any higher.
I am also aware that for one person, Teva was much better than Dr. Reddy (nice name). I might have been able to get away with 250mg of the Teva.
The texture and consistency of the different pills were disparate enough that one could imagine that there might be differences in absorption. The formula for exipients is different among preparations of the same drug. The drug is the same in each preparation, it is everything else that is different.
I'll be interested to read what Bleauberry came up with about their actually being a difference in molecular composition of various preparations of the same drug. I read one thing that suggested that sometimes the drug interacts with the excipients to yield an ineffective compound.
Larry Hoover would be a good person to explain the difference in tolerances allowed by the FDA of drug content of generics. I think the variance in bioequivalence is 10% higher of lower than the original brand name, making a 20% spread.
I have taken several brands of nortriptyline without seeing any different in therapeutic effect.
I don't know what the answer is.The generic companies should probably be required to run clinical trials comparing their drug preparations using the original brand as a comparator. However, this might dissuade companies from investing the money to bring some drugs to market, especially the cheaper ones.
- Scott
Posted by SLS on July 15, 2009, at 7:31:56
In reply to Re: Nortriptyline Generic or Brand Favorites?, posted by SLS on July 15, 2009, at 7:12:23
> I don't know what the answer is.
>
> The generic companies should probably be required to run clinical trials comparing their drug preparations using the original brand as a comparator. However, this might dissuade companies from investing the money to bring some drugs to market, especially the cheaper ones.Maybe the generic drugs can be subject to a large battery of tests not yet conceived that would obviate the need for clinical trials. The generic drugs would have to be subject to the same environment as exists in the digestive tract to see if there are interactions that result in chemical reactions between drug and excipients. I'm sure we can think of a bunch of tests, including extended pharmacokinetic trials using healthy volunteers rather than single-dose assays. I'm sure the technology for any of these things already exists. It is just a matter of the experts brainstorming what types of testing would be ideal to establish the sort of bioequivalence that would guarantee therapeutic equivalence.
- Scott
Posted by linkadge on July 15, 2009, at 15:26:14
In reply to Re: Nortriptyline Generic or Brand Favorites?, posted by SLS on July 15, 2009, at 7:31:56
>Well. actually, neither do I. But you and I do >not have 25 years worth of patient experience >either. I guarantee you my doctor would not be >doing this just for grins. And being generics, >there certainly isn't any under-the-table motive >involved. He has seen what he has seen. >Different is different.
Not necessarily. Patients are unreliable. There are so many other factors that can be responsible for a patient relapsing. Patients want, however, to believe that their recovery is the result of just one factor (for example an antidepressant).Antidepressant trials too are not reliable. In one study, drug A will beat drug B and in another study drug B will beat A. That one generic does better than another in some study doesn't mean anything.
People relapse all the time but people want *something* to blame their relapse on. I have never seen a *blinded* A-B-A traial design which proves that a patient relapses when switching to generic and then gets better when returning to the original drug. All of the studies showing patients relapsing on generic drugs are unblinded.
I believe that aside from bioequivilancy, there is no difference between one generic to another. So long as the company knows how to synthesize the drug properly.
I mean take SLS. Ok so he relapsed when he switched to generic lamotrigine. No offense SLS, but you are relapsing all the time, drug change or no drug change.
Linkadge
Posted by linkadge on July 15, 2009, at 15:29:42
In reply to Re: Nortriptyline Generic or Brand Favorites?, posted by SLS on July 15, 2009, at 7:31:56
You never hear of patients doing better on a generic than they did on a brand name do you?
Drug companies producing brand name drugs take shortcuts too. Money is money.
Linkadge
Posted by SLS on July 15, 2009, at 16:02:14
In reply to Re: Nortriptyline Generic or Brand Favorites?, posted by linkadge on July 15, 2009, at 15:26:14
> I mean take SLS. Ok so he relapsed when he switched to generic lamotrigine. No offense SLS, but you are relapsing all the time, drug change or no drug change.
I am somewhat offended. It is insulting to summarily invalidate my observations simply because I am not in full remission. I do have a stable partial response right now that depends on the effectiveness of lamotrigine. This improvement was lost once I began taking generics; the worsening persisting for the entire two months that I took them. I recovered within days of returning to GSK Lamictal. My doctor has been collecting Teva lamotrigine pill bottles from his patients who have relapsed on it. It is quite a collection. I don't think Teva is necessarily a bad generic drug company, but this particular preparation is inferior to GSK Lamictal.
By the way, after doing some reading, I think 300mg of lithium is probably ideal for what I want to accomplish.
- Scott
Posted by linkadge on July 15, 2009, at 17:30:59
In reply to Re: Nortriptyline Generic or Brand Favorites? » linkadge, posted by SLS on July 15, 2009, at 16:02:14
>My doctor has been collecting Teva lamotrigine >pill bottles from his patients who have relapsed >on it. It is quite a collection. I don't think >Teva is necessarily a bad generic drug company, >but this particular preparation is inferior to >GSK Lamictal.
People have also relapsed on regular lamotrigine.
The only way I would believe that the relapse was infact the change of drug is if the patient had no idea there was a drug change.
Linkadge
Posted by bleauberry on July 15, 2009, at 17:45:07
In reply to Re: Nortriptyline Generic or Brand Favorites?, posted by linkadge on July 15, 2009, at 15:29:42
> You never hear of patients doing better on a generic than they did on a brand name do you?
>
> Linkadge
That is not true.The physician I mentioned has discovered through trial and error over 25 years a particular generic manufacturer of a popular pain medication that is BETTER than brand. He won't use brand with that prescription.
Just to put his reputation and expertise in perspective, I drive 3 hours oneway to see him. You know how picky I am and my general disdain of doctors. A voluntary 6 hour roundtrip drive speaks volumes of this particular physician. As I was leaving, a family in the waiting room spoke French. I asked where they were from. Canada. A 6 hour oneway drive. Surely there are closer doctors at home and in USA? A family flew in and lived in a motel for a couple months to be treated by him...from Alaska...about 2000 miles away. These examples put this doctor's experience and reputation in perspective for this particular topic.
I agree with you patients are not as a group reliable or stable. But 25 years does a lot to work out the biases and wrinkles of that variable. That kind of timeline and experience allows legitimate trends to show themselves. Observant humans notice trends. They are not facts, but they are enough evidence to take a closer look and issue some respect to that trend. When that is done, the trend is either proved or disproved. In this doctor's office, it has proved itself reliably enough over time often enough that it is mandatory procedure to respect the trend and guide one's behavior based on that trend. It was proven to not be fluke, random, disease fluctuation, or placebo. It is a real trend seen by observant eyes, but most definitely experienced by countless patients, SLS and myself and probably a hundred others in pbabble archives. I don't think they all imagined it and I don't think it was a wave in their illness. The timing and was too suspicious to rule it out.
25 years is enough time to challenge a trend through real live trials. That has been done. The results are predictable. Randomness and placebo would not be that predictable.
I can tell from your comments several things:
1. Everything I wrote was not read. Or, it was read by the eyes, but was instantly zapped from entering the thoughts.
2. The above comment from a poster concerning Pamelor and Teva was not read and absorbed or contemplated, nor were a hundred others on these pages of pbabble.
3. Some people take the stance of a neutral judge, that is, they gather evidence from defense and prosecution without any preconceived idea of where things are going, and then render a decision after putting oneself in the defense shoes, and then in the prosecution shoes, and then weighing the balance between the two to come up with a decision. This judge is fully capable of taking the stance of the defense, and is fully capable of taking the stance of the prosecution, seeing both sides of the fence completely. This judge hunts for ways to disprove both sides. This judge hunts for ways to prove both sides. Then there is enough evidence to render a personal decision.
4. Some people take the stance of making a preconceived decision based on emotion or linited presentation of evidence without considering any particular evidence or by quickly discarding any evidence that puts their own stance in question.
I do love your posts here and I click on every Link post that ever pops up. You've got some great stuff and awesome ideas. We can agree to disagree on this particular topic. I think in time, a couple or a few years, you'll see more of the "trend" to take a second look. For now, all is cool.
I just wish my thread would stay on topic. I'm looking for people's opinions or experiences on different manufacturers of Nortriptyline, not a debate on generic versus brand. We can do that on a new thread.
Nortriptyline. Bring it on.
Posted by SLS on July 15, 2009, at 18:16:21
In reply to Re: Nortriptyline Generic or Brand Favorites?, posted by linkadge on July 15, 2009, at 17:30:59
> The only way I would believe that the relapse was infact the change of drug is if the patient had no idea there was a drug change.
You are entitled.
- Scott
Posted by SLS on July 15, 2009, at 18:27:01
In reply to Re: Nortriptyline Generic or Brand Favorites?, posted by bleauberry on July 15, 2009, at 17:45:07
> Nortriptyline. Bring it on.
I can't offer you very much information. I have been using generic nortriptyline for 10 years or so. I have not had a problem. However, I can't guarantee that I have used different manufacturers. I have used different pharmacies, though.
- Scott
Posted by yxibow on July 16, 2009, at 10:13:51
In reply to Re: Nortriptyline Generic or Brand Favorites?, posted by SLS on July 15, 2009, at 18:16:21
> > The only way I would believe that the relapse was infact the change of drug is if the patient had no idea there was a drug change.
>
> You are entitled.
>
>
> - ScottI actually would agree here...
I didn't "relapse" when I went to generic, and Teva (which is a company that fairly often gets that position) had a 180 day exclusive on it.
A double blind study on any changes in effectiveness should be done on a number of brand -> generic switches.
I'm not one for "propaganda", but the entire FAQ on generics should really be read at the FDA -- sure maybe its their "propaganda", but its at least worth a look.
I know, I'm concerned too about medications that have a very fine line for me -- Seroquel would be one.... as for the other one, Valium, I've been taking one or another generic all along.
Hate to say it, but sometimes a trial on -not- knowing on one of one's more "low liability" prescriptions as to whether it is generic could prove or disprove the belief that generics are solely the contributor to one's problem, and not merely correlation and causation issues.
As for the TCA in mention.... practically all TCAs out there dosed would be generic by this point so I fail to see how it makes a difference ?
I've never received "brand" Anafranil. I have received two generic brands of clomipramine in the past.......I usually try to get medications a few days earlier anyhow, which usually runs through insurance about at the 25th day or so, so if I get a different one I just mix and match until its blended off to the next one.
But each to their own.-- Jay
Posted by SLS on July 16, 2009, at 11:14:56
In reply to Re: Nortriptyline Generic or Brand Favorites? » SLS, posted by yxibow on July 16, 2009, at 10:13:51
I didn't ask to be the subject of a double-blind investigation in order to prove anything to anyone. I am reporting my experience and how I interpret it.
Simple.
If you wish, you can use Medline to find studies dedicated to testing Lamictal to lamotrigine generics. Even though some of these studies demonstrate the inferiority of the generic product, they are not blinded studies. That's a shame, really. I should have allowed myself to deteriorate further until such a study was published, especially in light that there are studies with conflicting results. When it comes to cherry picking, I think I'll choose the investigation where n=1, me.
- Scott
Posted by SLS on July 16, 2009, at 13:00:46
In reply to Nortriptyline Generic or Brand Favorites?, posted by bleauberry on July 14, 2009, at 14:52:19
> I've called my pharmacy to see what brands they have available. They are:
>
> Brand Pamelor
> Generic Teva
> Generic Taro
> Generic Watson
> Generic Mallinckroct
>
>
> I'll have to try them all, and we all respond differently, so in that respect my questions are kind of pointless. But still, I am curious. :-)Perhaps it makes sense to go with Pamelor first, since it is the proven product. If you respond well, wait for the passage of time to establish a stable response and then experiment with the generics to see if you can save yourself some money. I understand that you might find one of the generics to be superior to the brand name, but doesn't it make sense to try the brand name first?
I don't think it makes sense to wait 2-4 weeks to establish the efficacy of each preparation of the series. How else would you know which drugs will work long term? If you don't respond to the first drug, what would compel you to continue with your selection process? I'm just trying to save you some time and frustration.
I hope you glean the improvement you are looking for in your condition with nortriptyline - regardless of which preparation you choose.
- Scott
Posted by bulldog2 on July 16, 2009, at 14:04:32
In reply to Re: Nortriptyline Generic or Brand Favorites? » bleauberry, posted by SLS on July 16, 2009, at 13:00:46
> > I've called my pharmacy to see what brands they have available. They are:
> >
> > Brand Pamelor
> > Generic Teva
> > Generic Taro
> > Generic Watson
> > Generic Mallinckroct
> >
> >
> > I'll have to try them all, and we all respond differently, so in that respect my questions are kind of pointless. But still, I am curious. :-)
>
> Perhaps it makes sense to go with Pamelor first, since it is the proven product. If you respond well, wait for the passage of time to establish a stable response and then experiment with the generics to see if you can save yourself some money. I understand that you might find one of the generics to be superior to the brand name, but doesn't it make sense to try the brand name first?
>
> I don't think it makes sense to wait 2-4 weeks to establish the efficacy of each preparation of the series. How else would you know which drugs will work long term? If you don't respond to the first drug, what would compel you to continue with your selection process? I'm just trying to save you some time and frustration.
>
> I hope you glean the improvement you are looking for in your condition with nortriptyline - regardless of which preparation you choose.
>
>
> - ScottThe ultimate test of how a specific generic works is my SUBJECTIVE experience. I don't care wether double blind tests back up my subjective experience.
Wether the generic is chemically equivalent within a certain tolerance is not the issue. Fillers are often different and who can say how they play into how a certain chem reacts withtin ones body.
Posted by atypical on July 19, 2009, at 1:02:25
In reply to Re: Nortriptyline Generic or Brand Favorites?, posted by linkadge on July 14, 2009, at 19:46:01
> I personally don't see how this is possible.
>
> Nortriptyline is nortriptyline. The molecule is identical whoever manufactures it. With some generics I can see an argument that it is less bioequivilant than another. With nortriptyline there is a blood test to determine what level the drug is at. If a doctor uses a blood test, he can find a blood level that works, then it really shouldn't matter what brand is given as long as the drug level is the same.
>
> My 2 cents.
>
> LinkadgeI agree with your point about blood levels. If the blood level of nortriptyline is at a certain therapeutic level, shouldn't it not matter if it's generic or not? I took Danbury Pharmaceutical's version and had blood levels done. I disagree with what you say later on about difference between generic and brand. For me, as just one example, the case was clear. When I switched to generic sertraline from Zoloft, relapse. Increasing the dose didn't do much. There was no other factor.
Posted by linkadge on July 19, 2009, at 14:38:43
In reply to Re: Nortriptyline Generic or Brand Favorites?, posted by atypical on July 19, 2009, at 1:02:25
>For me, as just one example, the case was clear. >When I switched to generic sertraline from >Zoloft, relapse. Increasing the dose didn't do >much. There was no other factor.
See thats what I don't necessarily believe (no offence). Even if a generic is 20% less bioequivalent, this is nothing that a doubling of dose won't more than correct.
It doesn't necessarily matter if there was another factor. People relaspe. People have placebo responces. Depression is known to have one of the highest placebo responces of any illness. If people think they are getting the good stuff, it will work, if they think they are getting something less than that, they may relapse.
Linkadge
Posted by bleauberry on July 19, 2009, at 17:40:29
In reply to Re: Nortriptyline Generic or Brand Favorites?, posted by linkadge on July 19, 2009, at 14:38:43
> >For me, as just one example, the case was clear. >When I switched to generic sertraline from >Zoloft, relapse. Increasing the dose didn't do >much. There was no other factor.
>
> See thats what I don't necessarily believe (no offence). Even if a generic is 20% less bioequivalent, this is nothing that a doubling of dose won't more than correct.Well, a whole lot of people didn't believe the earth was round either, despite some rather obvious hints that is was.
A whole lot of people didn't believe a bacteria was the primary cause of ulcers, despite seeing with their own eyes antibiotics worked. It takes time for the nonbelievers to admit, ok, something's up here, and then even more time to say, well yeah it's fairly well proven now but it wasn't back then.
I like controversy and debate because it keeps everyone on their toes and in the longrun brings out the best results that neither side might have predicted or been able to do solo.
I've seen some professional debates on the web the last few days amongst scientists and doctors about the generic versus brand thing. Honestly, the ones arguing in favor of this thing being real blow the nonbelievers in the weeds in terms of evidence presentation and explanation as to the variables involved. As I said previously, there are many things going on here. If you are looking simply at blood levels of a drug, you've touched maybe 10% of what is really happening that you haven't considered or seen yet.
>
> It doesn't necessarily matter if there was another factor. People relaspe. People have placebo responces. Depression is known to have one of the highest placebo responces of any illness. If people think they are getting the good stuff, it will work, if they think they are getting something less than that, they may relapse.
>
> Linkadge
>I think for the average garden variety depression patient who doesn't know a thing about psychiatry or what is happening to them, yeah, the above stuff is fairly true. For those who are seasoned in this illness and its treatment, they know the difference between relapse, placebo, waves, ebbs and flows, and such. You just know. The high placebo rates don't come with people like us...they come from the cherrypicked squeaky clean samples of clinical trials that are not remotedly the same as the sample at pbabble.
Posted by linkadge on July 22, 2009, at 7:34:50
In reply to Re: Nortriptyline Generic or Brand Favorites? » linkadge, posted by bleauberry on July 19, 2009, at 17:40:29
Of course *anything* is possible. What I am saying is that I personally don't think it is likely that generics are responsbile (in large) for what some patients propose.
I mean really, patients start to complain that they were fine on the brand name then all of a sudden they get symptoms which are (a) not their original symptoms (b) not symptoms of withdrawl (c) not symptoms of increased dose - you start to wonder. The claims are often just too outlandish.
I think the greatest cause of relapse is generalized medication poopout or loss of placebo effect.
Med poopout is remarkably common. It is very common for people to be taking the same dose of the same brand of the same AD and it just stops working as well.
Nobody likes to believe meds can poop out. It is easier just to try and blame it on the inferiority of a generic.
Its just like vitamins (my gosh). This therapist I was seeing (a health nut), tried to tell me (without any form of scientific justification) that my (generic synthetic) b vitamins were less bioavailable than his (brand name synthetic) b vitamins. They're synthetic water soluble b vitamins!! Its all the same!!
Linkadge
This is the end of the thread.
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