A question for Deb r.e. Desipramine

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A question for Deb r.e. Desipramine

Postby raven » Wed Mar 16, 2005 3:43 am

This question was actually sparked by the previous question on what happened to Cari Loder. The Cari Loder regime used the tricyclic antidepressant lofepramine. As lofepramine metabolises to desipramine, would not the trials done some years ago on lofepramine be directly equivalent to desipramine?

There is a trial results full text here:

http://jnnp.bmjjournals.com/cgi/content/full/73/3/246

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Postby OddDuck » Wed Mar 16, 2005 5:02 am

Robin,

Maybe a little. I looked at this before. http://www.thisisms.com/modules.php?nam ... cari+loder This is some sort of "triple" drug therapy thing, plus, even though the drugs are similar, there are differences.

Plus, dosage is crucial. And the length of time taking it. It acts slowly and consistently. From what I've researched, etc., AND found personally, it takes 3 to 6 months to really start to see a difference, and I'd say takes at least one full year to realize major benefits.

They also did a study for ALS with desipramine, too. They saw what I saw when they looked into desipramine. The "proven" effects that it has. But remember, ALS is a totally different disease, except for the similarities for some axonal damage (from my information anyway). The main and basic thing that is completely disregarded with desipramine are two things. It keeps the immune system to a more Th2 balance (which is said is drastically needed in MS) WITHOUT totally compromising Th1 (Th1 will kick in when needed - desipramine simply keeps a better "balance" going) and increases IL10 (another main thing needed for MS) (not to mention the many other things I've shown evidence that it does, as we've all seen me post time and time again). As the NMSS has said, the biological support is definitely there. Remember, I never have said that desipramine would cure anything nor would it necessarily be anything miraculous on its own or work for ALL "patterns" of MS, but like some MS sufferers have said themselves, slowing this down (especially progressive MS, which is what I think desipramine may show the best benefit for) and providing any relief from MS degeneration would be greatly appreciated.

If you notice, ALS research is testing many of the same drugs that MS is and has been. The initial ALS study in MICE on desipramine, which was a very short one, though, found:

Animal Studies

Desipramine I

General Info:
Treatment: Desipramine
Model: G93A High Copy
Study start date: 12/2/2002
Study completed date: 3/14/2003
Institution: ALSTDF
Formulation point person: Mukur Gupta
In Vivo point person: Erin Williams

Rationale: Desipramine is FDA approved as a tricyclic anti-depressant. It’s used in the treatment of eating disorders like bulimia and in treating symptoms of diabetic neuropathy. It increases the level of IL-10 in a dose dependent manner. Inflammation is known to be a major culprit in ALS and IL-10, in Phase II clinical development , is a potent inhibitor of inflammation. Treatment with IL-10 prevented CNS inflammation in several models of neurodegeneration such as EAE, SCI, TBI and global ischemia via marked reduction of TNF-alpha, functional recovery and neuroprotection. As an anti-inflammatory cytokine, IL-10 may prevent glial activation and neuronal death and may be a possible treatment for ALS. IL-10 is known as the master anti-inflammatory cytokine or cell signaling protein. It’s an off switch for inflammation.

Study data
Notes: Desipramine is an IP study - 1x/d; 7d/wk - Day 50 start ....

Conclusions: Endpoints scored include mortality, neurological score and body weight. Results: Desipramine treatment resulted in a possible but weak positive trend in survival in litter matched treated males. Treated females show a positive trend in neurological score. No differences were observed in all other endpoints for either sex group. Desipramine has excellent CNS penetration. "


I seriously don't believe you can or should compare any two drugs together, no matter how "similar" they appear.

In any event, where is the harm in studying the darn drug (but by itself first, not in combination with ANYTHING until they know exactly what it does and does not do for MS, and THEN add a combination with it, such as an AED) for MS specifically?

But, I've given up on that route. Vanderbilt has it all (and was looking at it), not to mention the NMSS, who has not completely given up on it either. They are still just waiting for someone to apply to them to study it.

Plus, the thing is that I don't understand, they say "we need to keep the immune system at a more Th2 balance, but we don't have a drug that will do that".......Uh, yes we do. "We need to keep IL10 raised in MS, but we don't have any effective way to do that".......uh, yes we do. "We need to find something that will reduce Ca2 influx AND several other things, but we can't find anything that does that"...........uh, I found one. So, let's look at it another way, then. From deductive reasoning. We KNOW from YEARS of research what desipramine does and does not do. We KNOW it. So, if desipramine does NOT produce effects on the very things they "believe" is going wrong in MS and needs to be corrected, then maybe, just maybe, they are WRONG in what they think it is that IS going haywire in MS! See what I mean? Why ARE they afraid to treat MS with something that has been PROVEN to produce the very effects they "think" they need for MS treatment? Either way, we'll either find something that truly helps in MS, or we'll find that several theories regarding MS are incorrect and therefore, move on to other theories that may prove more "on point", if they do studies involving desipramine. Even bench studies.

Deb

EDIT: Oh, and Robin. Remember what the Auckland researchers found? Note my comments at http://www.thisisms.com/modules.php?nam ... t=auckland
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Postby raven » Wed Mar 16, 2005 7:43 am

Hi Deb

I wasn't trying to discredit your research, just making the point that there have been trials of lofepramine for MS. Lofepramine metabolises very quickly to Desipramine. Therefore in your efforts to get Desipramine more widely researched / accepted these previous trials may be of use.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11435905

The above extract appears to support your theories rather well.

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Postby OddDuck » Wed Mar 16, 2005 7:49 am

Robin, How ARE you? Doing much better, I hope??!!

Oh, yes..........I know you were being supportive. And I thank you SO much. I sincerely do apologize if my post appeared to have an underlying "frustration" or defensiveness to it (?) If so, it certainly wasn't intended at all. And certainly not directed at YOU in any manner. :)

It seems that we all find in so many ways and avenues (not just my "theory") things that could be studied more and/or better, but just aren't.

Deb

EDIT: Well, maybe they'll eventually (and hopefully soon) find some of the same things we have found and will question and research many of the things we do.
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Postby Arron » Wed Mar 16, 2005 9:36 am

This is really interesting...

"Methods: A placebo controlled, double blind, randomised study carried out in five United Kingdom centres on outpatients with clinically definite multiple sclerosis, measurable disability on Guy's neurological disability scale (GNDS), no relapse in the preceding six months, and not on antidepressant drugs. Over 24 weeks all patients received vitamin B-12, 1 mg intramuscularly weekly, and either lofepramine 70 mg and L-phenylalanine 500 mg twice daily, or matching placebo tablets. Outcome was assessed using the GNDS, the Kurtzke expanded disability status scale; the Beck depression inventory, the Chalder fatigue scale, and the Gulick MS specific symptom scale.

Conclusions: Patients with multiple sclerosis improved by 2 GNDS points after starting vitamin B-12 injections. The addition of lofepramine and L-phenylalanine added a further 0.6 points benefit. More research is needed to confirm and explore the significance of this clinically small difference. "


Looks intriguing... which makes me think, what is preventing the adoption of desipramine as a legitimate alternative therapy for MS? If you look at LDN, the reason people started playing with it is that it seemed relatively safe (the low dose part helps there) and furthermore, a Dr. (Bihari) was behind it with lots of anecdotal evidence.

Deb, maybe this is a far too simplistic point, but if you could get a "simple" M.D./GP/Neuro to evaluate and support desipramine rather than a researcher (Basically, skip the "clinical trial" portion until anecdotes justify it), it might get more traction?

just thinking out loud...
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Postby OddDuck » Wed Mar 16, 2005 11:27 am

Yeah, I hear ya, Arron. I have tried that route also. I have even had MS friends in other States talk to their physicians about looking into it and/or trying it, but they seem to get nowhere, also. (So far anyway.) I have even challenged them. I said "Don't believe me. I don't care. Just read up on it yourself and decide!" I can't even get them to do the "paper research" that I've done.

And I haven't been pushing for actual clinical trials for a while now. My proposal has been for bench research. (You know, though, for all we know, they ARE doing something with it and/or looking at it, but just aren't telling me. I know the one thing none of them are telling me is that I'm full of crap! That tells me they believe me allright.)

Remember, my doggone first neuro himself started (and witnessed) the whole thing in the first place. He knows what the possibilities may be. My (now former) PCP has it, and the neuros at Vandy have it.

But most neuros deal with the pharmas (and probably have to). I hate to sound conspiratorial (truly, I don't), but I'm telling ya. IF this were found to help at all, it is incredibly cheap. Plus, the "unspoken" tension behind many doctors is the threat from pharmas regarding "anti-trust" actions against physicians.

I also wrote to Aventis about it (who makes Norpramin - I won't take the generic desipramine. It's slightly different than the original. You know me, I researched that, too. :wink: ) Shoot, I'm not sure that even they want to pursue it, because it's not a big enough money maker for them, either. At least not as far as compared to all the "injectable" treatments which cost thousands.

Try to find an MS neuro who is NOT somewhat "tied up" with the pharmaceutical companies who will take the risk of prescribing it off label or something. Ya know? No pharma is going to want this to proceed nor to hear any neuro "back it". (Some of this information of mine comes from the "horse's mouth", too.)

That's why you'll see me get so frustrated. And why I finally gave up. I swear it's all "money motivated".

There is one other avenue to pursue yet, but I need to re-write all these months worth of "tidbits" I've been posting in some type of formal report, and man..............that's hard to do, and get everything all together, and rewrite it all with footnotes (yuck), etc.

Plus, the NMSS still has promised me that they are yet going to talk about it with Dr. John Richert when he gets on board there in April. But after he sided with pharmaceutical companies recently, I personally wonder whether he'll support that it be pursued.

Can you tell I'm discouraged? But, on the other hand, I am also enlightened that others are beginning to find some of the same evidence that supports some of my claims.

Surely, they can't ignore it forever. :? I mean, what the heck else do they have to offer MS sufferers? At least this is a chemical agent that has been on the market since the 60s and has MOUNDS of research done on it. And all we are talking about is a much lower dose than is required for full treatment of depression, even.

Doesn't it make you wonder, though, why none of these doctors (especially MS specialists) are reading what all of us are regarding ALL of these other options, not just this one?

I literally had to almost "scream" at my neuro, "What's the harm in just trying it?! You see that it is a pretty safe drug. I'm sensitive to medications, and that's one of the few I can take with no side effects, so come on. Let's just TRY IT!" He finally just said "Ok..........fine. I'll call it in."

(Literally having to argue and fight with your physician. What's wrong with that picture? :? :( :) )

Deb

EDIT: What I'd really love to do, except he would probably kill me, is to have a million letters go to my first neuro (because you don't even have to explain a thing to him - he has ALL my research since day one) and try to persuade HIM to get something going on this. He could get it done. He's high profile.
Last edited by OddDuck on Wed Mar 16, 2005 11:31 am, edited 1 time in total.
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Good thought!

Postby treez » Wed Mar 16, 2005 11:31 am

Good thinking Aaron,

One thing I noticed.....OddDuck pointed out the slow time to benefit from the Desipramine. A 24 week study group might just start to show benefits and then that would be the end of the study!

Also, B12 as been shown to improve many MS aspects. Study was even done that showed B12 in conjunction with interferons inproved effectiveness of that therapy,..........hummm? So one would ask - was / is it the B12 combination or just the B12, since these two have so little in common other than the B12 and the MS?

Don't ask for a link to the study RE: B12, I don't have a clue. I just remember the study and the results caught my attention. To the point I started taking B complex along with my ABC. We all know that can't hurt. B's all have a good rep. with MS in moderation.

Just thinking with the keyboard again.

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Postby Arron » Wed Mar 16, 2005 11:32 am

hmm... let's see how we can increase the dragnet somehow. Surely there MUST be some MS'ers who are taking desipramine "simply" as an antidepressant? Would it be valid to start with their experiences and try and build a knowledge/experience base? I know the dosages are off, but maybe it's worth a try?

You've put an awful lot of work into this and I truly hope it sees the light of day-- whether it ultimately proves to be useful or not it deserves its fair shake.
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Postby OddDuck » Wed Mar 16, 2005 11:35 am

Yes, you're correct, treez. (In my humble opinion.)

The thing is, I have always (for many years) taken extra B vitamins. Nothing showed real improvement, though, until taking desipramine. The first time I took desipramine, I was NOT on high B vitamins.

Plus, the biological research and substantiation I've done shows and supports what desipramine ALONE should do (remember, desipramine has genetic mechanisms of action, also, which something like B-12 would have nothing to do with)

You start trying too many things at one time, and then you won't know which thing produced which benefit.

Deb
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Postby OddDuck » Wed Mar 16, 2005 11:41 am

Thanks, Arron.

You'd have thought, though, with the thousands of people who read this site (especially the ones who don't post, too), someone would have posted that they had taken this.

The problem is, that TCAs just aren't prescribed that much anymore. And to prescribe desipramine with any of the injectable drugs would be............well, not advisable. You can't just haphazardly throw just any drug in combination with a TCA.

So, most MSers would likely not have been prescribed desipramine because of possible drug interactions, because as we know, most MSers are prescribed quite a few drugs to take in addition to one of the CRABS.

You'll find where if someone with MS is taking an anti-depressant for depression associated with MS, it won't be a TCA. It will be one of the serotonin anti-depressants.

That's my guess.

Deb
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paper-based argument

Postby Arcee » Wed Mar 16, 2005 11:45 am

Odd Duck -

I was so glad to read your last post as it mirrored something I have been mulling for a few days. I've read your posts and can follow your technical argument as best I can, but I have been wondering how I could potentially share this information with my doctors in a substantive way. Which led me to wonder if you have produced a document that ties all the arguments together and has the sourcing. No doubt it would be a lot of work, but I was thinking that you probably had given the researchers you have dealt with something in writing. So I guess I am wondering whether there is a full blown or even an executive summary kind of document to be shared (or to be created to be shared?).

I suspect that I would be rebuffed by my doctors (and it may not even be an appropriate fit for me since I am early RRMS), but I see a couple of angles that I could potentially pursue. 1) My neuro has nothing to offer me since I have "flunked" all the CRABs, but he's a big advocate of getting on treatment early and 2) my integrative physician is way more open minded.

So, just thought I would toss the comment/query out there...

- Arcee
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Postby OddDuck » Wed Mar 16, 2005 12:05 pm

Arcee,

Personally, I'd say if you are early MS AND you can't take any of the CRABS, then all the better to try this, if you can get your doctor to agree. (Oh, and that's not medical "advice" at all. I'm just saying that I certainly can see your point, ya know?)

The only thing really that is sort of "cut down", but doesn't refer to my sources, is the original narrative I put together last year. It is posted in the Story Archives under "June, 2004".

See, I started redoing it to add all the additional things I found, and then got overwhelmed. I need to get back to it, I suppose.

I just talked so doggoned much, and researched and posted so much there for so long, that I got ahead of myself!! :wink: Especially organizational-wise.

Deb

EDIT: Hey, push the point how effective desipramine has also shown itself to be in fibromyalgia, which is VERY similar to MS (at the very least symptomatically). Remember, though, I think there may be some types of MS that even this won't prove to be helpful, but like I told my neuro, if it doesn't appear to be terribly harmful, you have no other options, and you are trying a small dose anyway, what's the harm in TRYING it? Especially under your doctor's supervision?
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