What's the deal with "Auvelity"? (new NMDA receptor antagonist)

[Monocles]

Got a notification that some biotech stock shot up about 35% today. Turns out that company just got FDA approval for "auvelity" and is marketing it as the greatest thing to come out for depression treatment since SSRIs. Looking into it the chemical formulation seems to be "dextromethorphan HBr -bupropion HCl", and it has been challenging finding peer reviewed articles about how well it really works.

Perhaps I'm just too dumb to understand the pharmacology behind it, but isn't this basically just using cough syrup and adding bupropion to reduce the enzymatic breakdown?

Has anyone heard of this?

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[SubzDoc]

I knew an inpatient doc who would literally order cough syrup with the bupropion.

 

[theduderino]

Got a notification that some biotech stock shot up about 35% today. Turns out that company just got FDA approval for "auvelity" and is marketing it as the greatest thing to come out for depression treatment since SSRIs. Looking into it the chemical formulation seems to be "dextromethorphan HBr -bupropion HCl", and it has been challenging finding peer reviewed articles about how well it really works.

Perhaps I'm just too dumb to understand the pharmacology behind it, but isn't this basically just using cough syrup and adding bupropion to reduce the enzymatic breakdown?

Has anyone heard of this?

I wonder if this is similar to nudexta (dextromethorphan and quinidine, the latter also serving a role to reduce enzymatic breakdown). from what I remember nudexta had positive phase I/II trials around reducing agitation associated with neurocognitive issues and a sub-stellar phase III trial that never seemed to get published anywhere.

 

[Candidate2017]

Perhaps I'm just too dumb to understand the pharmacology behind it, but isn't this basically just using cough syrup and adding bupropion to reduce the enzymatic breakdown?

Has anyone heard of this?

Yes. This is a dream come true for some. Why crush and snort buproprion when you can crush and snort buproprion and dex in the same convenient pill?

 

[eternelle]

There was an article on this in the green journal a few months back:

Psychiatry Online

ajp.psychiatryonline.org

 

[whopper]

Seems to me this is one of those Contrave like situations. Why presecribe a medication costing hundreds of dollars a month when it's simply two meds put into one pill and those 2 meds are about $20 each?

 

[Stagg737]

From a molecular standpoint, I really don't understand how this is a "novel" mechanism like some are claiming it is. NMDA antagonism is involved with atomoxetine, fluoxetine, gabapentin, memantine, and amantadine. Why not just add some ketamine in there to really hit NMDA receptors, I bet patients would love it...

Seems to me this is one of those Contrave like situations. Why presecribe a medication costing hundreds of dollars a month when it's simply two meds put into one pill and those 2 meds are about $20 each?

You mean like Lybalvi? Or Symbyax? Why come up with entirely new molecules when we can just put 2 generics in one pill and jack up the price 10-fold?

 

[calvnandhobbs68]

From a molecular standpoint, I really don't understand how this is a "novel" mechanism like some are claiming it is. NMDA antagonism is involved with atomoxetine, fluoxetine, gabapentin, memantine, and amantadine. Why not just add some ketamine in there to really hit NMDA receptors, I bet patients would love it...



You mean like Lybalvi? Or Symbyax? Why come up with entirely new molecules when we can just put 2 generics in one pill and jack up the price 10-fold?

My recent fave? Aplenzin.

"Why take TWO tablets of Wellbutrin XL when you could take only ONE tablet for a mere 2K a month? What a steal!"

 

[allantois]

Why is my patient abusing cough syrup so depressed?? They should focus on making an amphetamine Jornay or Daytrana

 

[whopper]

You mean like Lybalvi? Or Symbyax?

At least for Lyalvi the mediction, Samidorphan, being added to Olanzapine isn't otherwise available. The bad thing, however, is people still can gain mad weight on Lybalvi. It doesn't prevent weight gain, it just makes the weight gain not as bad.

Symbyax? I don't see any reason to prescribe it at all.
"But but but what if your patient needs Olanzapine and Fluoxetine and you can only prescribe them one medication because the New World Order starts making it so we can only send one and only one medication? What do we do then Dr. Smartypants?"

 

[nexus73]

Do you know how much Lotrisone I prescribe on inpatient psych? Not much actually. But the hospitalists order for pretty much any rash that pops up as initial therapy.

 

[whopper]

I've prescribed Auvelity now in a few patients with amazing results. Of course it might not work, but it's efficacy is higher than that of SSRIs and SNRIs with a quick response rate.

The problem is will insurance pay for it, and if not why not just do Bupropion mixed with Dextromethorphan? I can see why one would want it all in 1 pill if the person has a history of abuse because the mixture prevents them being taken separately and Bupropion reduces Dextromethorphan abuse.

 

[clausewitz2]

I've prescribed Auvelity now in a few patients with amazing results. Of course it might not work, but it's efficacy is higher than that of SSRIs and SNRIs with a quick response rate.

The problem is will insurance pay for it, and if not why not just do Bupropion mixed with Dextromethorphan? I can see why one would want it all in 1 pill if the person has a history of abuse because the mixture prevents them being taken separately and Bupropion reduces Dextromethorphan abuse.

But it's vastly cheaper to have someone get DXM tablets off Amazon and combine with with plain old wellbutrin. auvelity is a racket, even if it happens to work.

 

[calvnandhobbs68]

Yeah the "prevents abuse" argument doesn't make a ton of sense when I can just go buy 100 tabs off amazon for 25 bucks right now.

 

[littlefred]

Yeah the "prevents abuse" argument doesn't make a ton of sense when I can just go buy 100 tabs off amazon for 25 bucks right now.

You guys seeing adult patients robotripping?

 

[clausewitz2]

You guys seeing adult patients robotripping?

No, they can usually get their hands on much better drugs.

 

[whopper]

But it's vastly cheaper to have someone get DXM tablets off Amazon and combine with with plain old wellbutrin. auvelity is a racket, even if it happens to work.

Agree. I've seen Auvelity work extraordinarily well, but a major problem is the price. If the patient is trustworthy you could consider educating them on taking 45 mg with Bupropion 100 mg daily. The advantage of Auvelity is the medication is all in the same pill so if you fear abuse they cannot abuse it (or so it seems, med is very new, we need time to observe). The Bupropion allegedly prevents the Dextromethorphan from being metabolized into the abusable metabolite.

 

[allantois]

Agree. I've seen Auvelity work extraordinarily well, but a major problem is the price. If the patient is trustworthy you could consider educating them on taking 45 mg with Bupropion 100 mg daily. The advantage of Auvelity is the medication is all in the same pill so if you fear abuse they cannot abuse it (or so it seems, med is very new, we need time to observe). The Bupropion allegedly prevents the Dextromethorphan from being metabolized into the abusable metabolite.

I have a patient abusing cough syrup, maybe I should put her on Wellbutrin hmm

 

[whopper]

Make sure it's Wellbutrin XL, and don't tell them that it blocks the abusive effects of Dextromethorphan 😎

 

[ObsequiousAplomb]

Doesn't the Wellbutrin make the dextromethorphan more abusable? Why are people saying it blocks the abuse potential while also saying it raises the level of the dxm? To me that just means you can get away with a lower dose of dxm.

That being said, I would also write a prescription for it as split pills. Even if the insurance would cover it, I would rather keep costs low.

 

[splik]

Doesn't the Wellbutrin make the dextromethorphan more abusable? Why are people saying it blocks the abuse potential while also saying it raises the level of the dxm? To me that just means you can get away with a lower dose of dxm.

Wellbutrin reliably causes seizures in overdose, that's how its addition makes it less abusable.

 

[whopper]

Allegedly Dextromethorphan's metabolite Dextrophan is what's more the factor in abuse of this substance vs the Dextromethorphan itself. Bupropion slows the metabolism of Dextromethorphan thus reducing production of Dextrophran. The problem with my statement is there aren't solid studies yet strongly backing up this theory although there is data supporting it.

This is why I'd be a bit hesitant to prescribe separate Bupropion and Dextromethorphan in a new patient where I didn't know them well. If it's Auvelity they got no choice. The med is already mixed together, but it's damned expensive.

 

[ObsequiousAplomb]

Wellbutrin reliably causes seizures in overdose, that's how its addition makes it less abusable.

I'm aware. Take two (or even four, since that's still not an OD of bupropion) Auvelity and 10 tablets of pure DXM. That's what I'm talking about.

It's like saying that the added Tylenol reliably limits the abuse potential of Percocet. It just makes it more dangerous to abuse.

Allegedly Dextromethorphan's metabolite Dextrophan is what's more the factor in abuse of this substance vs the Dextromethorphan itself. Bupropion slows the metabolism of Dextromethorphan thus reducing production of Dextrophran. The problem with my statement is there aren't solid studies yet strongly backing up this theory although there is data supporting it.

This is why I'd be a bit hesitant to prescribe separate Bupropion and Dextromethorphan in a new patient where I didn't know them well. If it's Auvelity they got no choice. The med is already mixed together, but it's damned expensive.

Well, there is that. Time will tell whether the pharmacokinetic manipulation really prevents euphoric reactions.

 

[nexus73]

Was this med approved without blinded RCTs?

 

[whopper]

This is the main study I've seen and published in the Green Journal.

Psychiatry Online

ajp.psychiatryonline.org

I've tried Auvelity on my patients who are treatment resistant based on this logic-1) new mechanism and already tried on several meds, 2) patients that stuck it out this long with me (usually by this time at least 3 antidepressants and an augmentation agent) I've had enough time to see if they are "trustworthy" of being placed on Dextromethorphan and Bupropion separately. Besides most insurance companies won't pay for it anyway unless you've tried at least 2 antidepressants.

I've had a number of patients significantly improve and this same batch are again, ahem, treatment-resistant. One of them was getting ECT and didn't need the ECT anymore. Another was getting IV Ketamine and feels the Auvelity works better than Ketamine.

I will try to get tradename Auvelity for the reasons I mentioned above but if "trustworthy" and the insurance won't pay for it I'll tell the patient to take Dextromethorphan and Bupropion 100 mg daily together at the same time.