Nuedexta

[Doc Samson]

Has anyone else tried this stuff yet? I have an N of 2, but so far it's like a magic potion for the brain injured. My 2 cases were:

Middle aged man with large PICA CVA, diagnosed with cerebellar cognitive affective syndrome, persistent episodic agitation/agression when frustrated. Failed trials of Zyprexa, Depakote, and Haldol. 3 days into a trial of Nuedexta was like a new man, cracking jokes and working with PT.

Middle aged woman s/p very, very bad unhelmeted motorcycle MVA with diffuse brain injury. In a veil bed, yelling all day long, swinging at nurses. Failed Zyprexa, Depakote, Haldol, and Neurontin. One day into a trial of Nuedexta, nursing was able to give her her first shower in weeks, was laying peacefully in bed when I saw her this p.m.

Sigma-1s are officially my new favorite receptors.

---

Members don't see this ad.

 

[Majesty]

What was your other N?

I come across a few of these patients every once in a while and I have one right now whose psychosis is relatively controlled with depot invega but i have tried everything from depakote to topamax etc etc.

I know nothing about this medication. Is there a good CME or article?

 

[heyjack70]

Has anyone else tried this stuff yet? I have an N of 2, but so far it's like a magic potion for the brain injured. My 2 cases were:

Middle aged man with large PICA CVA, diagnosed with cerebellar cognitive affective syndrome, persistent episodic agitation/agression when frustrated. Failed trials of Zyprexa, Depakote, and Haldol. 3 days into a trial of Nuedexta was like a new man, cracking jokes and working with PT.

Middle aged woman s/p very, very bad unhelmeted motorcycle MVA with diffuse brain injury. In a veil bed, yelling all day long, swinging at nurses. Failed Zyprexa, Depakote, Haldol, and Neurontin. One day into a trial of Nuedexta, nursing was able to give her her first shower in weeks, was laying peacefully in bed when I saw her this p.m.

Sigma-1s are officially my new favorite receptors.

Do you have any disclosures you'd like us to know about?

 

[Majesty]

A lot of times these patients are on a lot of meds and have a lot of comorbidities. How does this thing interact?

 

[Doc Samson]

Do you have any disclosures you'd like us to know about?

No - But I'm seriously thinking of getting one.

 

[Doc Samson]

A lot of times these patients are on a lot of meds and have a lot of comorbidities. How does this thing interact?

It's dextromethorphan and quinidine, so QTc and serotonin syndrome are a concern. Otherwise seems fairly benign.

 

[Chrismander]

It's dextromethorphan and quinidine, so QTc and serotonin syndrome are a concern. Otherwise seems fairly benign.

Isn't that what the kids call "robo-tripping"? Do recreational users just use way more dextromethorphan, or are we just blissing these patients out? Not that that's a bad thing--your patients seem to have improved a lot.

Also, have you heard of anyone using it for end-stage dementia related behavioral outbursts?

 

[OldPsychDoc]

Isn't that what the kids call "robo-tripping"? Do recreational users just use way more dextromethorphan, or are we just blissing these patients out? Not that that's a bad thing--your patients seem to have improved a lot.

Also, have you heard of anyone using it for end-stage dementia related behavioral outbursts?

So I'm actually just hearing about this here from the esteemed Doc Samson--apparently the DM is acting as an NMDA receptor antagonist and sigma1 agonist, with the quinidine slowing its metabolism by P450 2D6.

And yep, it's what the cool kids are doing these days... (or is robotripping already passe?).

 

[Manicsleep]

Hypotehtically, what if you already have something fairly common like prozac, wellbutrin onboard and an unaware physician throws on cimetidine later. On top of that they take extra dextromethorphan at home.

What could happen beyond the 'robo-trip'?

 

[Doc Samson]

OPD - is that William Hartnell in your new avatar?

 

[whopper]

I was never a big fan of Dr. Who despite being a huge sci-fi fan, but man did I find the old Dr. Who pinball game cool.

 

[OldPsychDoc]

OPD - is that William Hartnell in your new avatar?

Sufficiently Old?

(I'm counting down to the new season next month...)

I was never a big fan of Dr. Who despite being a huge sci-fi fan, but man did I find the old Dr. Who pinball game cool.

Have you seen the new go-round, Whopper? Vastly superior writing and production values vs. the older ones, while maintaining the humor and attitude.

 

[Doc Samson]

Sufficiently Old?

(I'm counting down to the new season next month...)




Have you seen the new go-round, Whopper? Vastly superior writing and production values vs. the older ones, while maintaining the humor and attitude.

I was an avid fan through the Tom Baker and Peter Davidson years of my youth, hung around for some Colin Baker, but then just found subsequent iterations too slick for my liking. I much prefer the clunky intimidation of the Daleks, the Cybermen (the stars of many a childhood nightmare), and the Master to any CGI nonsense.

 

[Ibid]

Rule of thumb, if its in colour its rubbish.

With respect to the original Dr. v the rest, the original was far more gritty, never in touch with his female side, intellectually curious and didn’t give a four x for his side kicks.
[YOUTUBE]http://www.youtube.com/watch?v=bKg9tuSbXmk&NR=1[/YOUTUBE]

 

[synaptonemal]

Wow, $5200 for some magic cough syrup? I want one of those disclosures too!

Seriously, plenty of established SSRIs, tricyclics, and mood stabilizers have shown efficacy for labile affect from neuro Dxs such as stroke, TBI, etc and been used for years; but no one's gonna fund an NDA and marketing blitz for these until you can slap some quinidine and a patent on em and call it a breakthrough. I don't know whether to laugh or cry..

Bottom line, labile affect from TBI etc is generally best not approached as a psychosis. I've had the best luck with Lamictal but also seen SSRIs / TCAs work great for many.

eg:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1963355/

 

[Doc Samson]

Wow, $5200 for some magic cough syrup? I want one of those disclosures too!

Seriously, plenty of established SSRIs, tricyclics, and mood stabilizers have shown efficacy for labile affect from neuro Dxs such as stroke, TBI, etc and been used for years; but no one's gonna fund an NDA and marketing blitz for these until you can slap some quinidine and a patent on em and call it a breakthrough. I don't know whether to laugh or cry..

Bottom line, labile affect from TBI etc is generally best not approached as a psychosis. I've had the best luck with Lamictal but also seen SSRIs / TCAs work great for many.

eg:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1963355/

From a CL perspective, Lamictal and SSRIs are all well and good, but we don't have the weeks-months to wait for efficacy. SNFs/rehabs won't take a patient that's too agitated to participate in therapy. They won't take a pt requiring IV Haldol. Benzos are a bad idea. Atypicals snow the patient. This stuff seems to work in days, keep the patient awake enough to actually begin to mobilize, and stabilize them enough that they can be transferred to a lower level of care where you and other learned colleagues can begin the process of cross-tapering them onto Lamictal. Or we can just spend the thousands of dollars per day to keep them on a 1:1 in a general hospital bed while we save money on the meds.

 

[Majesty]

Wow, $5200 for some magic cough syrup? I want one of those disclosures too!

Seriously, plenty of established SSRIs, tricyclics, and mood stabilizers have shown efficacy for labile affect from neuro Dxs such as stroke, TBI, etc and been used for years; but no one's gonna fund an NDA and marketing blitz for these until you can slap some quinidine and a patent on em and call it a breakthrough. I don't know whether to laugh or cry..

Bottom line, labile affect from TBI etc is generally best not approached as a psychosis. I've had the best luck with Lamictal but also seen SSRIs / TCAs work great for many.

Its never approached as a psychosis but using 'antipsychotics' doesn't mean you are treating psychosis. Sometimes, there is just no other choice. I am just curious as to the effect of dextromethorphan and treatment of labile affect because the possibilities are exciting.
Supposedly, this is not for dementia related issues.
What about dual diagnosis patients who are multiple drug heavy users and have histories that go back to pre-teen years.

I wonder if you can just give dextromethorphan and quinidine. Or DM and some other 2D6 blocker such as an SSRI. The trick is to find a psych patient on a 2D6 blocker.

I agree though, the price is way too high. Reminds me of Makena and a little bit of Rozerem.

 

[Doc Samson]

Drugstore.com is quoting $500 per month BTW

 

[Fermata]

Wow, $5200 for some magic cough syrup? I want one of those disclosures too!

Toss in the gin and tonic for the quinine.

I don't see the harm in having something else in the armamentarium. DS's point seems valid in regard to bridging the gap.

 

[synaptonemal]

I wonder if you can just give dextromethorphan and quinidine. Or DM and some other 2D6 blocker such as an SSRI. The trick is to find a psych patient on a 2D6 blocker.

Exactly. Actually, I wonder if at this point you could just give dextromethorphan alone. We looked over their approval study in journal club, and compared to their previous rejected study they were forced to cut the quinidine dose sharply because of FDA concern re causing arrythmias and drug interactions. At the dose now being used efficacy at 12 wks seemed pretty marginal (4 fewer episodes vs 3 for placebo?) and they didn't run any comparisons vs DM alone, one wonders why. I was surprised that it was approved. Anyway, I think it should be fine to try if SSRIs/TCAs don't work, but I'm pretty skeptical that its superior to any of the existing options. You might be surprised at how quickly they can work in unstable affect compared to the weeks required for a primary mood disorder, eg from the 2007 review above

Antidepressants have been shown to reduce the frequency and severity of crying or laughing episodes after a stroke, often within days, rather than the weeks typically expected before antidepressant effects are seen. SSRIs should be regarded as the first-line choice when treating poststroke PLC, given the greater tolerability of SSRIs and their lower propensity to have effects on the cardiovascular system, compared with tricyclic antidepressant drugs. The doses of the SSRI medications that were effective in treating PLC in the studies described above (fluoxetine 20 mg, sertraline 50 mg and citalopram 10–20 mg) are at the low end of the therapeutic range used for treating depression. Case reports suggest that bupropion, mirtazapine, venlafaxine and lamotrigine may be effective for PLC in people who cannot tolerate, or do not respond to, SSRIs.

It can be pretty difficult to tease out problems with control of affective expression from a primary mood disorder (or an agitated delirium, etc etc); a lot of times neuro docs can fail to ask if the patient is really feeling depressed or just having crying jags with less mood component. If there's any doubt, no harm in trying an SSRI as purely affective sx can sometimes respond within days.

Anyway, I think one of the crappiest recent trends in pharma research is so many attempts to relabel existing generics or repackage them as an on-patent combo. For instance can you believe the reapproval of doxepin as a branded med (Silenor) for sleep. What a breakthrough!

 

[Doc Samson]

Again - I'm not particularly excited about this for PBA. I am impressed with the rapid and consistent improvement in agitation and aggression in my brain injured patients. I am a very big proponent of using the least costly med available, but frankly I often don't have good options for these folks that work with any speed and they end up stuck in the general hospital while we futz around with SSRI and mood stabilizer titrations.

 

[Trebor]

Exactly. Actually, I wonder if at this point you could just give dextromethorphan alone. We looked over their approval study in journal club, and compared to their previous rejected study they were forced to cut the quinidine dose sharply because of FDA concern re causing arrythmias and drug interactions. At the dose now being used efficacy at 12 wks seemed pretty marginal (4 fewer episodes vs 3 for placebo?) and they didn't run any comparisons vs DM alone, one wonders why. I was surprised that it was approved. Anyway, I think it should be fine to try if SSRIs/TCAs don't work, but I'm pretty skeptical that its superior to any of the existing options. You might be surprised at how quickly they can work in unstable affect compared to the weeks required for a primary mood disorder, eg from the 2007 review above

Your journal club could have dug a bit deeper:
It didn't pull out the earlier Phase III study that did test DM alone...it was equivalent to placebo.

The patients averaged about 5-7 outbursts/day at study onset so the 12-week reduction from 5 to 4 on average is about right but less for placebo than you note. Overall there was an an average 80% decrease in emotional outbursts relative to baseline and a 48% decrease relative to placebo. At the end of the study remission rates (no outbursts for prior 2 weeks) was ~50%.

I agree the direct comparisons to SSRI's/TCA's still need to be done.

 

[RedPakotaSea]

So I'm actually just hearing about this here from the esteemed Doc Samson--apparently the DM is acting as an NMDA receptor antagonist and sigma1 agonist, with the quinidine slowing its metabolism by P450 2D6.

And yep, it's what the cool kids are doing these days... (or is robotripping already passe?).

Very interesting...dextromethorphan is actually a very poor NMDA antagonist. Its affinity is probably not relevant at doses mentioned. The metabolite, dextrorphan (DXO), is responsible for NMDA antagonism, hence the dissociative effects, but conversion to DXO would be inhibited by quinidine.

DM does, however, have very strong affinity for SERT (Ki: 23 nM), as well as 10x lower, but relevant affinity for NET and sigma-1 (~200 nM). I don't know how they got through FDA approval without mentioning this.

 

[Doogie P Howser]

Has anyone else tried this stuff yet? I have an N of 2, but so far it's like a magic potion for the brain injured.

I've been following the development and testing of this drug for quite a while now and it seems to be generating several stories and comments like your own.

As the poster above indicates, Dex alone doesn't work any better than placebo but Nuedexta seems to have quite a remarkable effect on a variety of these emotional types of issues.

The company has a couple of presentations here for anyone that is interested.
http://www.b2i.us/profiles/investor/fullpage.asp?f=1&BzID=958&to=cp&Nav=0&LangID=1&s=0&ID=1537

Even more interesting is 3 different organizations have done large scale studies recently on PBA and have come up with some very surprising results.

The MS association recently did a well controlled survey of their members and out of about 5200 MS patients..48% have indicated they have PBA symptoms ranging from mild to severe.
And current treatments are doing very little for them (only 10% being treated with other drugs are getting any satisfactory results)

The survey is here.

http://www.msassociation.org/news_center/article.asp?a=_msaa_survey_pba

The Brain injury association did a survey recently as well and came back with even higher numbers..80%.
http://www.biausa.org/AnnouncementRetrieve.aspx?ID=63586

And, the stroke organization did as well and came back with 53%.
http://www.stroke.org/site/News2?JS...1d&page=NewsArticle&id=9577&news_iv_ctrl=1202

Read the MS report and you'll see that it's so widespread they're considering that even depression itself in many cases may even really be PBA.

As for the cost, when considering just the two basic ingredients it is costly but that's not where the cost is. It's in what I think was 10 years of development and testing and hundreds of millions of dollars getting it approved. Thank the FDA and current system I guess for that.

In any event, the drug is seemingly having some incredible results for not only PBA but other conditions outside of "laughing and crying" and as Doc Samson indicates, aggression and agitation and yelling. Quite remarkable I think when you consider that we're talking about something this seemingly basic and overall, very safe compared to many other drugs out there.

For disclosure purposes I'm not connected with the company in any way.
I have recently bought some common shares in Avanir because of my research and have been following your thread as part of my due diligence.
And thought i'd bring these things to your attention because mainly this drug really seems to be helping a lot of people and could be a breakthrough for other uses as well.

The company also recently announced they're going into testing with it for MS pain. The PBA testing showed that it had a very positive impact on both MS pain And diabetic pain as well.

Aspirin for the brain might very well describe this drug it appears.

Best of luck to all. And thanks for the interesting read and allowing me to join in the discussion.

 

[Majesty]

Your journal club could have dug a bit deeper:
It didn't pull out the earlier Phase III study that did test DM alone...it was equivalent to placebo.

The patients averaged about 5-7 outbursts/day at study onset so the 12-week reduction from 5 to 4 on average is about right but less for placebo than you note. Overall there was an an average 80% decrease in emotional outbursts relative to baseline and a 48% decrease relative to placebo. At the end of the study remission rates (no outbursts for prior 2 weeks) was ~50%.

I agree the direct comparisons to SSRI's/TCA's still need to be done.

Ok. But do you need quinidine? Can any 2D6 blocker do the job? If so, what is the justification for the cost.

 

[Trebor]

Ok. But do you need quinidine? Can any 2D6 blocker do the job? If so, what is the justification for the cost.

A critically important question that I don't have an answer for and I hope others explore further.

My understanding is that quinidine is the most potent 2D6 inhibitor and that SSRIs have varying 2D6 inhibition potencies. Obviously there is a large interindividual variation in 2D6 activity also. Whether that becomes clinically relevant I can't say.

 

[Doogie P Howser]

Some may find this interesting. Public Broadcasting has been airing a documentary the last few months in various markets regarding PBA.

http://www.pbainfo.org/patient/understanding_pba/understanding-pba

 

[Doogie P Howser]

Has anyone else tried this stuff yet? I have an N of 2, but so far it's like a magic potion for the brain injured. .

Doc, your magic potion comment might have been right on.

They just announced today an IND Filing for MS Pain...AND announced within the year they'll also be filing an IND for "other forms of emotional lability – specifically anger, irritability, and other behavioral symptoms of dementia."

http://finance.yahoo.com/news/Avanir-Pharmaceuticals-prnews-3255707009.html?x=0&.v=1

 

[Manicsleep]

I've been following the development and testing of this drug for quite a while now and it seems to be generating several stories and comments like your own.

As the poster above indicates, Dex alone doesn't work any better than placebo but Nuedexta seems to have quite a remarkable effect on a variety of these emotional types of issues.

The company has a couple of presentations here for anyone that is interested.
http://www.b2i.us/profiles/investor/fullpage.asp?f=1&BzID=958&to=cp&Nav=0&LangID=1&s=0&ID=1537

Even more interesting is 3 different organizations have done large scale studies recently on PBA and have come up with some very surprising results.

The MS association recently did a well controlled survey of their members and out of about 5200 MS patients..48% have indicated they have PBA symptoms ranging from mild to severe.
And current treatments are doing very little for them (only 10% being treated with other drugs are getting any satisfactory results)

The survey is here.

http://www.msassociation.org/news_center/article.asp?a=_msaa_survey_pba

The Brain injury association did a survey recently as well and came back with even higher numbers..80%.
http://www.biausa.org/AnnouncementRetrieve.aspx?ID=63586

And, the stroke organization did as well and came back with 53%.
http://www.stroke.org/site/News2?JS...1d&page=NewsArticle&id=9577&news_iv_ctrl=1202

Read the MS report and you'll see that it's so widespread they're considering that even depression itself in many cases may even really be PBA.

As for the cost, when considering just the two basic ingredients it is costly but that's not where the cost is. It's in what I think was 10 years of development and testing and hundreds of millions of dollars getting it approved. Thank the FDA and current system I guess for that.

In any event, the drug is seemingly having some incredible results for not only PBA but other conditions outside of "laughing and crying" and as Doc Samson indicates, aggression and agitation and yelling. Quite remarkable I think when you consider that we're talking about something this seemingly basic and overall, very safe compared to many other drugs out there.

For disclosure purposes I'm not connected with the company in any way.
I have recently bought some common shares in Avanir because of my research and have been following your thread as part of my due diligence.
And thought i'd bring these things to your attention because mainly this drug really seems to be helping a lot of people and could be a breakthrough for other uses as well.

The company also recently announced they're going into testing with it for MS pain. The PBA testing showed that it had a very positive impact on both MS pain And diabetic pain as well.

Aspirin for the brain might very well describe this drug it appears.

ASA for the brain huh? Why not say its better than the Polio vaccine and PCN combined?
Something doesn't smell right about your post. Looks like a pharma post to me.

 

[Doogie P Howser]

ASA for the brain huh? Why not say its better than the Polio vaccine and PCN combined?
Something doesn't smell right about your post. Looks like a pharma post to me.

I understand it may look that way but as I stated above in my disclosure, i'm not connected with the company in any way. Nor do I work in the industry. I do own common shares in Avanir however and that's what initially peaked my overall interest in this. But that's not the source of my statements nor enthusiasm noted in my posts above. That stems from my research into this drug and its effectiveness. I would point out to you and others that I didn't write what Doc Samson did. He did. And he called this a magic potion and saw what really can only be described as amazing results in his two patients. 1 and 3 days respectively to see results like that? In what certainly appears to be hard to treat patients no less where nothing else was working.

And along comes cough medicine and Q...and seemingly safe and harmless and benign as that..it works wonders? That's worthy of discussion my friend...and that's what i'm here for.

Admittedly that's a small number for him but in my subsequent links i've been demonstrating what I've been seeing out there. And it's not small in terms of the market of people for whom this can help.

In fact, for PBA alone, that appears to be about 7 Million or more people in the U.S. alone. And about 2.6 to 4 Million of them in surveys have been identifying this as a burden to them with some having 40 to 50 episodes per week. That can ruin someones life for sure.

But here's the thing. This drug is really helping these people and literally..in these short amount of days its just turning their lives around so much so that for 70 to 90% of them..they're having 80% fewer episodes..and for 50%..complete remission.

But here's even more the thing..as I dug into this and the individual patient stories it just became clear that this drug was about more than that. And those same stories were out there about many of these other indications for agitation and aggression..and yelling. And then the whole pain issue and how it was helping that. And then apparently dementia as well now judging by the companies news release today.

Aspirin for the brain? You decide. I think I have..and it is quickly becoming that.

I want to also point out some other things to you folks. I've recently heard in a company presentation that about 70 independant doctors now have joined the company and are out there giving presentations ...apparently so impressed with the kind of results they've been seeing. They're hearing patients come up to them saying this changed their entire life..in days..from things that have plagued them for years. Personally, I think that's great and the fact this is starting to help a lot of people is really the goal of any drug.

I'll close again by saying I have no connection at all to the company..nor the pharmacutical industry. My purpose here is to get information and to share it. And my excitement really comes from the drug itself and it's potential and the stories i'm hearing.

Cough medicine and Quinidine. Who woulda thunk that?

 

[Doogie P Howser]

Wondering what any Docs or Medical students might think about this.

The article I link to below from back in 2005 notes a University of Florida study that was done on Fibromyalgia patients whos pain appears to have been reduced by taking Dextromethorphan alone. Both 60 and 90mg doses were administered with the 90mg dose being effective in both kinds of tests ran and the 60mg, in just one compared with placebo.

And for both doses, the resulting benefits were temporary.

I'm curious as to what any of you might think about Nuedexta for this? It would seem to address many of the drawbacks noted in that study namely
how fast the Dex is breaking down thereby also eliminating the need for the higher doses of Dex alone which seem to be a concern as to overmedicating the patients with that alone.

According to the Wiki article I link to below an estimated 2 to 4% of Americans are affected by Fibromyalgia which would be an enormous market if this were proven to be effective for something like that.

In any event, I thought you'd be interested to have this brought to your attention and to hear any comments and discussion about this.
This could be an interesting breakthrough and perhaps help a lot of people
if it were to be effective for this.

Thank you all.

http://www.sciencedaily.com/releases/2005/05/050519141247.htm

http://en.wikipedia.org/wiki/Fibromyalgia

 

[RedPakotaSea]

Is there any evidence that Nuedexta is superior to SSRIs?

As I pointed out in my post above, it appears likely that dextromethorphan is simply a serotonin reuptake inhibitor and possibly also a weak inhibitor of the norepinephrine transporter at relevant doses. It may sound sexier to say that the mechanism of action is sigma agonism, but many drugs are sigma agonists, including most SSRIs.

Interesting study:

Zawertailo LA, Tyndale RF, Busto U, Sellers EM. Effect of metabolic blockade on the psychoactive effects of dextromethorphan. Hum Psychopharmacol. 2010 25(1):71-9.

It appears that "robo-tripping" is unlikely to be potential side effect, as 2D6 inhibition leads to accumumlation of DM (decreased conversion to DXO), which is associated with increased measures of dysphoria and decreased measures of drug liking and euphoria. A similar phenomenon occurs in poor metabolizers who experience dysphoric effects from higher doses of DM.

 

[Doogie P Howser]

Is there any evidence that Nuedexta is superior to SSRIs?

Good Morning RedpakotaSea,

Good question and to answer that, I don't know personally about any direct comparisons.

What I would point out though is this survey done by the MS Association recently of 5200 patients.

I link below to the summary data of that survey and they state the following on page 8 of 34.

"Of those who are treated for their PBA episodes (25%) only 10% are satisfied with their treatment."

Which would seem to suggest that 90% of those being treated with other drugs aren't achieving any or very good results.

That's about as close as I can come in my individual research to addressing whatever else is out there on the market.

I would then point out however the results that were seen with the Nuedexta testing which was noted above. With 80% seeing a great deal of improvement and with 50% seeing complete remission even. That's also what attracted me to Doc Samson's original post where he tried this on patients he had tried several other things on with no result.and then in 1 and 3 days..saw the results he did with this.

From my lay persons point of view I just think it's very exciting. And not only for the PBA but what it might mean for pain patients as well.

Anyways..just trying to throw all this out there to you folks for some critical analysis. I know you won't hold anything back so I think that's good to examine it from that kind of critical perspective.

Here's the MS survey details..
http://www.msassociation.org/PDFs/PBA MSAA Survey Summary Report FINAL.pdf

Have a great day.

 

[Trebor]

Is there any evidence that Nuedexta is superior to SSRIs?

As I pointed out in my post above, it appears likely that dextromethorphan is simply a serotonin reuptake inhibitor and possibly also a weak inhibitor of the norepinephrine transporter at relevant doses. It may sound sexier to say that the mechanism of action is sigma agonism, but many drugs are sigma agonists, including most SSRIs.

RedPakotaSea,
Have you had a chance to review this study?: http://www.ncbi.nlm.nih.gov/pubmed/17689532 It echoes many of the points you have made. However it also notes that dextromethorphan is concentrated in brain tissue 7-68x that of plasma levels so the concentration is sufficient to have significant NMDA antagonism.
http://www.ncbi.nlm.nih.gov/pubmed/8103583
http://www.ncbi.nlm.nih.gov/pubmed/8622162

In addition, dextromethorphan seems to have higher sigma 1 affinity and is more selective for sites that are most likely to mediate PBA. What is your view on the clinical implication of those findings?

As for evidence that Nuedexta may be better than SSRI's, I agree it is limited but there is some. Subgroup analysis of the patients in their phase III study that were on SSRIs upon entry suggests a similar degree of treatment effect (measured by the CNS lability scale) between those on SSRI at study entry and those not with actually a somewhat greater (NS) effect in the SSRI group. Unfortunately, this analysis is only available as an abstract (attached) and was generated by Avanir (company making Nuedexta) employees/consultants. That abstract also suggests that the mechanisms of action are likely to differ.

Given the tenor of some promotional-type posts in this thread I think it best that I provide disclosure that I am not in any way affiliated with Avanir but I do own stock in Avanir. I think I have in the past and if I continue to post to this thread I will attempt to limit all comments to factual/verifiable information.

 

[RedPakotaSea]

I'm more impressed by the anecdotes than the roundabout reasoning from the limited existing data. You'd think that a head-to-head trial with an SSRI would be worthwhile for Avanir judging by confidence in the drug's superiority. Though, of course, there's another more proven route for the pharmaceutical industry...hype in lieu of data. Pardon my skepticism.

I agree that DM likely displays NMDA activity at the doses mentioned in the third study (up to 10 mg/kg!), but at the doses present in Nuedexta (20 mg), I think it's unlikely to play a significant role. DM's affinity for SERT is >300x that of NMDA.

DM does have higher sigma-1 affinity than SSRIs...I'm not ruling out that sigma-1 is involved in the therapeutic effect. I'm not sure what you mean by more selective for sites that are most likely to mediate PBA.

Interestingly, chloroquine also has high sigma-1 affinity. Maybe this is responsible for the mood changes reported? Another DM metabolite, dimemorphan, also has higher sigma-1 selectivity than DM and displays anticonvulsant activity. I'm certainly interested to see if anything therapeutic comes out of sigma receptor ligand research...

 

[masterofmonkeys]

Wondering what any Docs or Medical students might think about this.

The article I link to below from back in 2005 notes a University of Florida study that was done on Fibromyalgia patients whos pain appears to have been reduced by taking Dextromethorphan alone. Both 60 and 90mg doses were administered with the 90mg dose being effective in both kinds of tests ran and the 60mg, in just one compared with placebo.

And for both doses, the resulting benefits were temporary.

I'm curious as to what any of you might think about Nuedexta for this? It would seem to address many of the drawbacks noted in that study namely
how fast the Dex is breaking down thereby also eliminating the need for the higher doses of Dex alone which seem to be a concern as to overmedicating the patients with that alone.

According to the Wiki article I link to below an estimated 2 to 4% of Americans are affected by Fibromyalgia which would be an enormous market if this were proven to be effective for something like that.

In any event, I thought you'd be interested to have this brought to your attention and to hear any comments and discussion about this.
This could be an interesting breakthrough and perhaps help a lot of people
if it were to be effective for this.

Thank you all.

http://www.sciencedaily.com/releases/2005/05/050519141247.htm

http://en.wikipedia.org/wiki/Fibromyalgia

I'd avoid opiates period in someone with fibromyalgia unless there was a clear medical inciting event. And even then I'd be stingy.

 

[IAmAUser]

.

 

[Doogie P Howser]

seriously this makes me uncomfortable. my hospital does not allow reps in the door and this is why... can anyone kick this person?

I made full and complete disclosure in my first post. Without prompting I might add and did disclose that I am a shareholder in Avanir, hence my interest and research into this and how I found this thread in the first place.

I am not a pharma rep. I am not connected in any way, shape or form or compensated by Avanir or any drug company.

I am not a Doctor, certainly never played one on Tv despite my name I selected here ....but I believe I've contributed a great deal to this thread by providing others here information that apparently many if not most were unaware of that has been developing about this issue. And, I would point out, these are several thousand person surveys conducted by the MS. Association, Brain Injury Association, and Stroke organiztion.


My posts have been completely on topic..respectfull...and I think educational. At least as much as they can be from a laypersons point of view.


All in all, I don't think that's cause to be booted.

My information questioned? Debated by you? Completely refuted if you want to? Please. By all means. Go ahead. That is why I'm here asking the questions. Because honestly, this does seem almost "too good to be true".

But at the same time...I ask why can't there be something that comes along every once in a while that is as good as those things you mention?

After all, someone DID come up with the polio and other vaccines that changed the shape and course of medicine.

And I'm NOT saying that this IS it. I'm digging and digging and digging some more. But I DO have to tell you that every rock i'm turning over is coming up with more and more positives about this.

I again want to point out to you that I didn't start this thread. Doc Samson did by quoting his experience with his two patients.
I would also point out to you that when asked if he had any disclosures..he said No "but I'm seriously thinking of getting one".
And far be it from me to suggest what he or anyone else should do in this thread but what I am saying is if I was in his shoes..I would be too.

Because he's far from being alone in what he's seen and in fact the company now in their presentations are coming up with several people taking this that after just DAYS on this are saying this turned their entire life around from these issues that have been so damaging to them for years.

Please..before forming an opinion go to the links i provided and read what they have to say about this. Read the companies presentation regarding their trials and how effective this is.

That is what i'm trying to bring to the table here for discussion and debate. If you see something WRONG in the data itself..that's what I'd like to hear. I fully respect your and others opinions here and as far as I'm concerned..you and your patients are going to be the ultimate determiners here. Not these studies and links I've provided.

But none of what I've brought to the table is reason to be booted.

I would also like to say this. I have read a LOT of forums and posts in the time i've been researching this. And I have been EXTREMELY touched by the burden that some of these people are facing. And if one word I can say or one post I can make can help people like that, then THAT is what I'm all about and this is worth it.

I'm hopeful that given that, you'll reconsider your comments.

I will also say that it's my intention to now sit back and read your comments and discussion and analysis about this issue. It's not my intention to burden this thread with my posts. What I would like to do however is if i see or find anything else of the kind of significance I feel is in my above links..to post those. And again..to let you doctors and/or students debate them.

Other than that, i'm just on the sidelines.

Best of luck to all.

Respectfully,

Doogie Howser...Not an MD.

 

[billypilgrim37]

I don't think he wanted you removed from the forum. I think he wanted someone to literally kick you.

 

[Doogie P Howser]

I don't think he wanted you removed from the forum. I think he wanted someone to literally kick you.

lol

Trust me..that wouldn't be the first time.

But how about we do this just as a little side wager.
Like I said I'm not connected with the company in any way.
Nor am I a Pharma rep.

I did disclose however that I have bought shares in the drug company that makes nuedexta.

That company is Avanir Pharmacutical and this is the information on them.

http://finance.yahoo.com/q?s=AVNR

Right now the stock is trading at 3.95 a share.

Let's just see in time how well or how poorly it does in time because of this. My moneys on this doing at least reasonably well.

I mention this just for fun however and am by no means suggesting anyone buy this stock. Just to throw something out there that you can all follow along with me if you'd like to maybe add another dimension to this thread. And, you'll get to kick me real hard if it flops. But I get to say i told you so if it does well. Deal?

In any event. I don't want to make this thread be about me so unless and until I have some news or something else I think is significant to share, i'll just now stay on the sidelines and be quiet.

Please though..feel free to debate this away as to the merits of this drug or to bash it if you see fit. Debate is good and I think we all learn from it in the end.

Thanks.

 

[Doogie P Howser]

Exactly. Actually, I wonder if at this point you could just give dextromethorphan alone. !

There's an interesting article here on the whole PBA issue.

It indicates a study was done comparing DM + Q versus just DM.

Here's what it said on that issue..

"More recently, the combination of DM 30 mg plus quinidine sulphate (Q) 30 mg given twice daily (DM/Q) was investigated as a treatment for PBA among persons with ALS. Brooks and colleagues48 compared 65 ALS patients treated with combination DM/Q, versus 30 patients with DM alone, and 34 patients with Q alone. They found significant differences (P=.001) in score on the CNS-LS, a measure of PBA severity, among groups, with the group receiving the combination showing significantly greater improvement than either the DM- or Q-alone groups. "

Interesting article overall...
http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=378

 

[wmro1280]

Doogie,

You say you're not associated with Avanir, you're not a doctor, and it doesn't sound like you're a med student either. So do you mind my asking what exactly what brings you to SDN? You clearly know a lot about Nuedexta (and all of it good), which makes me wonder whether you're tradestoxx11.

BTW to the "real" docs & students on SDN, watch out for posers like Doogie who come to boards like this and talk about new drugs. They may sound intelligent (like Doogie) but they're simply trying to pump up the value of their stock.

They're having great fun at our expense over on the Avanir message board on Yahoo finance:

http://bit.ly/h2XVgu

And they're even looking for new forums/blogs to pump Nuedexta:

http://bit.ly/ftOvCd

 

[Doogie P Howser]

Doogie,

You say you're not associated with Avanir, you're not a doctor, and it doesn't sound like you're a med student either. So do you mind my asking what exactly what brings you to SDN?

My posts above fully disclosed both my interest in this drug for its medical purposes and disclosed that I own stock in Avanir and have brought forth what I feel is a great deal of good information.

I am not here to pump anything. I'm here for research and to contribute whatever I can as a layperson.
And frankly, to even suggest that my discussing this with the 3 or 4 docs above would somehow help my investment is really quite absurd.

Avanir trades about 20 million dollars worth of shares per day. I doubt we'll be moving the stock anytime soon.

I would also add that on a personal level, my investment is even secondary to what I strongly feel is that this drug can help a lot of people
with some very serious medical issues they're having.

Here is a thread that i found in fact where it is doing just that with the person named "sassy" who has made 3 posts there about what this drug has done for her.

http://neurotalk.psychcentral.com/showthread.php?t=148191&highlight=Nuedexta

I think that's great and with there being many more out there like her
I feel that the docs here should know about it and I also VERY much welcome their feedback..positive or negative about what they see for this drug overall.

In closing, I would also point out that you just joined this site..and I don't see any disclosure from YOU. You however are bringing links to a yahoo message stock board where this thread is being discussed. Perhaps you are SHORT this stock and looking to derail this discussion because you're afraid that an honest assessment of it will hurt your bet that the stock will fall in price?

One would hope not because as far as I'm concerned..what's most important to ME is that patients are helped in the best way possible. Whether it's with this drug or not.

And no, I am not "tradestox" on that site.
Apparently reading a few posts though, he's someone that is also very bullish on this potential as well.

 

[Doogie P Howser]

And By the way..as for the poster WMRO1280...the poster who just joined this thread and site even.and the poster with no disclosures and who's bringing a yahoo stock thread here I would also point out that there is a MASSIVE amount of shares short this stock and what appears to be a very concerted effort out there to undermine both the stock and this drugs rollout. WMRO might very well be a part of that effort.

Here is the latest report showing a massive 30 million shares SHORT this companies stock..meaning 30 millions shares hoping the drug fails completely.

They are afraid of honest discussion.

http://www.bloomberg.com/news/2011-...-vs-free-float-as-of-march-31.html?cmpid=yhoo

As for me, I will again say I made my disclosure..without prompting..in my very first post and I welcome..good or BAD..any legitimate opinions about this drug.

What I am finding out there however is several stories now like the one i linked to above. That poor woman has sufferered for YEARS from PBA..being told by doc after doc it was just her being emotional.
FIVE DAYS on this drug and she found the same results that Doc Samson did with his patients.

I think that's pretty exciting, and very worthwhile really digging into here and letting people know about it so it can be discussed and debated on both sides.

If I was short this stock though, I'd probably be pretty concerned about that and it sounds like WMRO just might be one of them.

In any event...this is my last discussion about the stock. It's not what i'm here for.

Thank you for not distracting the real purpose of the thread any further WMRO1280.

 

[Doogie P Howser]

curious what docs think about the poster in this thread named "Dejibo" (post # 5 in the thread).


He's discussing that along with his crying episodes he has Irritability and is quick to be emotional in that regard.

I mention that because of Docs samsons patient where he said the person had "agitation and aggression" which Nuedexta proved to be effective at resolving.

Is "laughing and crying" too narrow a description when describing what PBA is and should it more encompass these other various emotional states as well? Curious what any doc or student might think about this.

Thanks

http://neurotalk.psychcentral.com/showthread.php?t=148191&highlight=Nuedexta

 

[Manicsleep]

Not sure how many others are getting personal messages but I got a PM from wmro regarding what doggie is saying on another post.

Both of these are bad actors. I would suggest this thread be locked. I have alerted my own message to the mods.

If the mods need, I can forward the PM to them. This is unhealthy and destructive to a reasonable discussion. These 2 clearly have motivation that is financial in nature. I would suggest that fellow SDN'ers make up your mind regarding this medication based on scientific data and clinical experience, not on two buffoons who only care for the bottom line and who have no respect for who may be helped or hurt by their actions.

 

[BioLife23]

I know this thread is super old now, not sure if anyone is still interested in this topic..but do you think a combination of the DM and propranolol could have similar effects to DM and quinidine?