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Pseudobulbar Affect, Hypersensibility, Chronic Stress & The Big Picture

dopamimetic

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We have that exotic disorder called 'Pseudobulbar Affect' (PBA) - emotional lability, labile affect (and now it becomes confusing) - emotional incontinence, a condition that seems to mainly occur secondarily to brain injury or a destructive neurologic disease like ALS, MS, Huntington's, etc.

PBA may often be misdiagnosed as clinical depression; however, many clear distinctions exist.

In some cases, depressed mood and PBA may co-exist. In fact, depression is one of the most common emotional changes in patients with neurodegenerative disease or post-stroke sequelae. As a result, it is often comorbid with PBA. Comorbidity implies that depression is distinct from PBA and is not necessary for, nor does it exclude, a diagnosis of PBA.

So they are beating around the bush somewhat, as it is not that uncommon when it comes to mental / mood disorders - to differentiate things that can be different but also the same, or the other way round (if you don't understand what I'm trying to say, don't worry, that's intended ;)).

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Mechanistically, PBA is a disinhibition syndrome in which pathways involving serotonin and glutamate are disrupted. (source)

I feel there is a major problem in our society that we think of illnesses as isolated cases. Person A is depressed. B has OCD. D has ADHD. E has physical pain. F has Parkinson's. Dependent on what the first diagnosis was, one will get on the one or other route of treatment - 'mentally ill' or 'neurologically / physically ill'. This is hyper-abstracted, but it's a hard reality that influences and sometimes destroys numerous lives.

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Theory: Genetic predispositions cause some people to become more 'sensible' than others. Depending on the environment, childhood, family, peers etc. one may grow up in peace, or somewhen emotions become overwhelming, initiating a one-way road of latent chronic stress, mental as well as physical (inflammation, oxidative stress, etc) --> leading to a fragile personality.

Why do we treat the ones as healthy individuals who just have a coincidence of some weird genetics & need help, while others are 'mentally ill' and deserve their living hell ... !?

(A bit exacerbated, I know. :))
 
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The pharmacological treatment is weird too. Nuedexta, low dose dextromethorphan and quinidine sulfate.
 
That Nuedexta indeed is why I´m coming up with all this Pseudobulbar Affect ;) it´s really weird at the first sight, but they really are into something relevant - I´d love to read about the background, who and why thought of giving DXM together with an CYP enzyme inhibitor to people with this exotic disorder. It might be completely coincidentally, but I´d bet they made the same connections in mind as I do currently ... it´s hard to explain because I´m not a professional at all but it amazes me to see that this is actually FDA approved.

It truly looks like just some strange pharmaceutical intervention, but they are hitting a hidden - yet - important button. It´s about NADPH oxidase, genetics, stress-related mood disorders, glutamate excitotoxicity and up to some neurodegenerative illnesses.. maybe!
 
I think your thinking is pretty spot on, especially the glutamate excitotoxicity. I am not well read on the genetic or stress components of this unusual disorder but now am curious. Lets see what we can find. Yet another reason why pharmacology is fascinating. Who ever would have thought DXM would have an application like this.
 
The mean area-under-the-curve (AUC) concentration of dextromethorphan is increased as the dose is increased from 20 mg to 30 mg. By contrast, a 20-fold increase occurs with dextromethorphan 30 mg/quinidine 10 mg. Dextromethorphan exposure is increased by about 20-fold, compared with dextromethorphan administered without quinidine. (Source)
So we're actually talking about 20x 20mg = 400mg daily dosage of DXM when calculated without the quinidine! Okay, that's not exactly low dosage any more.

But that's crazy:

Product Cost Based on Average Wholesale Price
Dextromethorphan hydrobromide 20-mg/quinidine sulfate 10-mg capsules (Nuedexta) $586
Dextromethorphan hydrobromide 15-mg capsules, 7.5–15-mg lozenges $10–$32
Quinidine sulfate 200 mg and 300 mg immediate-release tablets $6–$12
 
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