Bupropion Revisted (POTS + Fatigue / Cytokines / Anti-viral / Brain Mitochondria)

[Jesse2233]

Caveat: Obviously this is a common drug, and likely tried to little avail by many on here. But it seems to be effective for a subset as some patients (1) and doctors (2) (3) have reported.

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I've been doing research on Bupropion (Wellbutrin) and found some interesting things beyond its effects as a anti-depressant. This drug has been discussed before, but not with the following research and anecdotes as guides for discussion. I'd be interested to know if anyone has experienced any similar benefits while taking it.

To summarize it may:

1. Reduce pro-inflammatory cytokines in mice (IL-1beta, TNF-alpha and IFN-gamma) (4)
   
   
2. Act as an anti-viral against herpes family viruses in 8 human case studies (EBV, HHV, HSV) (5)
   
   
3. Increase brain metabolism in mice (Krebs cycle enzyme SDH in the prefrontal cortex and cerebellum, and the electron transport chain in the hippocampus, cerebellum and striatum) (6)

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Here are some interesting anecdotal accounts:

A woman experiencing of 6 months of extremely debilitating post-viral fatigue following EBV (7)

Two POTS patients (8)

Two patients with 8 and 10 year histories with ME/CFS (9)

 

[EtherSpin]

interesting! I started on it in mid to late 2014 because I'd had sporadic and severe bouts of (neuroinflammatory,says doc) depression and heard from a friend that it was a novel anti depressant that could help perhaps with energy levels and weight loss.
I noticed that the time release tab kept me up beyond any normal sleep issues so I tried cutting a notch in the tablet and taking full dose and its probably placebo but I felt mentally hyper active and got a ridiculous result on a video game i play (never matched again)

I decided to just try half the dose (ill check what that is and add to thread later) by literally cutting the tablet in half. Im still on that to this day and to be honest I don't notice any benefits but when I look at the span that I've been on the tablets my apparent reactivations of herpes family viruses is much lower - I don't get the swollen glands so much anymore twice a year now perhaps rather than being like that a few days of every month

I'll follow this thread and add anything that occurs to me!

 

[adreno]

Didn't work well for me. Something to do with also being an nicotinic receptor antagonist, I believe.

 

[silky]

Didn't work well for me. Something to do with also being an nicotinic receptor antagonist, I believe.

Can you explain more about that Adreno?

 

[adreno]

Can you explain more about that Adreno?

J Pharmacol Exp Ther. 2000 Oct;295(1):321-7.
Bupropion is a nicotinic antagonist.
Slemmer JE1, Martin BR, Damaj MI.
Author information

Abstract
Neuronal nicotinic receptors are ligand-gated ion channels of the central and peripheral central nervous system that regulate synaptic activity from both pre- and postsynaptic sites. The present study establishes the acute interaction of bupropion, an antidepressant agent that is also effective in nicotine dependence, with nicotine and nicotinic receptors using different in vivo and in vitro tests. Bupropion was found to block nicotine's antinociception (in two tests), motor effects, hypothermia, and convulsive effects with different potencies in the present investigation, suggesting that bupropion possesses some selectivity for neuronal nicotinic receptors underlying these various nicotinic effects. In addition, bupropion blocks nicotine activation of alpha(3)beta(2), alpha(4)beta(2), and alpha(7) neuronal acetylcholine nicotinic receptors (nAChRs) with some degree of selectivity. It was approximately 50 and 12 times more effective in blocking alpha(3)beta(2) and alpha(4)beta(2) than alpha(7.) This functional blockade was noncompetitive, because it was insurmountable by increasing concentration of ACh in the nAChRs subtypes tested. Furthermore, bupropion at high concentration failed to displace brain [(3)H]nicotine binding sites, a site largely composed of alpha(4)beta(2) subunit combination. Given the observation that bupropion inhibition of alpha(3)beta(2) and alpha(4)beta(2) receptors exhibits voltage-independence properties, bupropion may not be acting as an open channel blocker. These effects may explain in part bupropion's efficacy in nicotine dependence. Our present findings suggest that functional blockade of neuronal nAChRs are useful in nicotine dependence treatment.
PMID: 10991997

 

[silky]

Thank you @ Adreno

 

[cporro]

i was on bupropion for a year. my doctor seemed to pick it out of a hat. when i asked about it he said it had less side effects. he believed i was simply depressed. i believe depression is a medical problem.

bupropion helped more than any other thing i've tried. i've tried a lot. diet, supps, testosterone injections, meditation, yoga, running...on and on. i felt less depressed and had a steady reliable type of energy. i went back to school. had the most productive year of my life in maybe 20 years.

after about a year it started to poop out. my doctor said lets up the dosage. i was already on 300mg which is high. side effects like seizure start ramping up around 450. i decided to get off it. my doctor had told me that people on it for a year often stabilized and had a new higher baseline. he also told me it was easy to get off, not addictive.

getting off bupropion was terrible. i experienced a new low. completely joyless living. no pleasure from anything. did not want to be social. couldn't think well. it took me 3 tries to get off it. never in my life has something been so hard to get off of. not coffee, not alcohol, not tobacco, nothing.

since getting off bupropion i've had months of fatigue like never before. worse depression than before. i keep looking for something natural that might work by the same mechanism. i ask doctors if we can learn something from this limited success i've had. nothing.

i've been feeling bad for months now. i still have some bupropion. it's a difficult decision. i'm certain going back on it would help me. but i know if i do go on it i will have to stay on it for the rest of my life. the rest of my life even if it poops out. even if i get seizures. even if i have bad side effects. even if i need to use other drugs along with it. bummer man.

 

[Rvanson]

Was on Bupropion for a few years. Was OK as anti-depressant but insomnia was an issue. Started having Gastro
Esp. Reflux disease (GERD). The minute I stopped Bupropion, it went away and has not returned.

 

[Swim15]

i was on bupropion for a year. my doctor seemed to pick it out of a hat. when i asked about it he said it had less side effects. he believed i was simply depressed. i believe depression is a medical problem.

bupropion helped more than any other thing i've tried. i've tried a lot. diet, supps, testosterone injections, meditation, yoga, running...on and on. i felt less depressed and had a steady reliable type of energy. i went back to school. had the most productive year of my life in maybe 20 years.

after about a year it started to poop out. my doctor said lets up the dosage. i was already on 300mg which is high. side effects like seizure start ramping up around 450. i decided to get off it. my doctor had told me that people on it for a year often stabilized and had a new higher baseline. he also told me it was easy to get off, not addictive.

getting off bupropion was terrible. i experienced a new low. completely joyless living. no pleasure from anything. did not want to be social. couldn't think well. it took me 3 tries to get off it. never in my life has something been so hard to get off of. not coffee, not alcohol, not tobacco, nothing.

since getting off bupropion i've had months of fatigue like never before. worse depression than before. i keep looking for something natural that might work by the same mechanism. i ask doctors if we can learn something from this limited success i've had. nothing.

i've been feeling bad for months now. i still have some bupropion. it's a difficult decision. i'm certain going back on it would help me. but i know if i do go on it i will have to stay on it for the rest of my life. the rest of my life even if it poops out. even if i get seizures. even if i have bad side effects. even if i need to use other drugs along with it. bummer man.

300mg isn’t a high dose, that’s standard. 450mg isn’t going to cause seizures unless you are incredibly prone and/or combine with other medication. I’ve seen plenty of people go higher.

I’d be much more worried about the withdraws you experienced and potentially being reliant on it for life but seizures wouldn’t be the thing I worry about.

 

[mitoMAN]

I had 450mg for a year and we even went up to 1000mg with drug monitoring in serum levels

i am a fast metabolizer and didn't even reach recommended serum levels at 1000mg.

however I noticed some increasing effect at 450mg compared to 300mg

no benefit from higher dosages tho

 

[junkcrap50]

I had 450mg for a year and we even went up to 1000mg with drug monitoring in serum levels

i am a fast metabolizer and didn't even reach recommended serum levels at 1000mg.

however I noticed some increasing effect at 450mg compared to 300mg

no benefit from higher dosages tho

1000mg of Bupropion? Never heard someone go that high. How did you do drug monitoring in serum levels? What did you test for? Never heard of serum testing for psychiatric drugs.

Was your doctor worried about down regulation of your dopamine receptors at such a high dose? My doctor said that bupropion will downregulate dopamine receptors, so if one doesn't see benefits at an increased dose (like 300mg), higher doses won't work. Is he right?

getting off bupropion was terrible. i experienced a new low. completely joyless living. no pleasure from anything. did not want to be social. couldn't think well. it took me 3 tries to get off it. never in my life has something been so hard to get off of. not coffee, not alcohol, not tobacco, nothing.

since getting off bupropion i've had months of fatigue like never before. worse depression than before. i keep looking for something natural that might work by the same mechanism. i ask doctors if we can learn something from this limited success i've had. nothing.

You likely were having an effect from the dopamine withdrawal, since bupropion works like a dopamine reuptake inhibitor (SDRI). Take away Bupropion, less dopamine hitting your receptors before metabolizing. In addition, my psychiatrist said that bupropion can, due to its mechanism, downregulate dopamine receptors, which is, after a while it stops to be as effective.

To anyone else who may help:
In my experience using Bupropion, I had a huge immediate effect, but lost it all when switching to a different formulation. Within a couple days starting XR 150mg, I felt essentially "cured". Like, I felt so good, I was seriously committing to enroll back in school full time (theoretical physics) but missed the registration deadline by 2 days. However, I slowly lost all the bupropion benefits over 3-4 weeks when I switched from Bupropion XR to Buporior SR 100mg. Stupid me told the doctor that it takes a while to kick in effect in the morning and should I wake up at 4am to take my dose. Switching back, and staying on bupropion XR did nothing, even upping the dose to 300mg.

I thought that I overloaded and down regulated my dopamine receptors switching to SR 100mg from XR 300mg. Except, SR does not cause a higher plasma or receptor concentration works (and thus higher dopamine levels) than XR. See quote below. Some doctors even use SR to XR when recommending tapering bupropion. So I have no idea why switching would make me lose benefit.

"Once-daily bupropion XL is bioequivalent to both twice-daily bupropion SR and thrice-daily bupropion as evidenced by similar peak plasma concentrations (Cmax), area under the curve (AUC), and plasma concentration versus time profiles (data on file, GlaxoSmithKline, Research Triangle Park, N.C.). "
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1163271/
https://psychopharmacologyinstitute...f-bupropion-an-illustrated-overview-2051-4056

My psychiatrist did say that, when I suggested upping my dose to XR 300mg, that bupropion will down regulate your dopamine receptors since they will see more dopamine and naturally respond via feedback loop. And that higher doses won't help any more if you don't see an effect at 300mg from 150mg.

Except now that I've written it all out, I've gained some clarity. Was my switching from SR to XR not the cause of loss of effect? Seems like it was coincidentally timed when the "honeymoon period" was wearing off. Was it just natural receptor down regulation what would have happened if I stayed on XR dose? To me, it seems complete downregulation would be too fast to happen after 10 weeks. Sounds like this is similar to what happen to you @Hip, see your quotes below. But yours was very immediate, 2 weeks.

I had this experience myself with the drug Wellbutrin (bupropion), an antidepressant and stimulant, which gave me almost full remission from most of my ME/CFS, ADHD and anhedonia symptoms for exactly 2 weeks at a dose of just 60 mg per day, and then mysteriously just stopped working.

I thought I had found my own personal solution to ME/CFS; however, two weeks after I started taking Wellbutrin, it just mysteriously stopped working entirely. I've never found any good explanation for this; I thought it might be tolerance build-up, so stopped the drug for a few months; but when I resumed it again, no luck. My Wellbutrin experience detailed in this post.

Though if you search online for "Wellbutrin honeymoon", you see that there are a subset of people who take Wellbutrin for depression, and get two fantastic weeks initially, followed by a complete loss of efficacy of this drug. I'd love to know why this happens.

I too would like to know why this happens. Did you ever figure out an answer? I'll be digging back through pages of these old threads to see if I can learn more.

 

[Hip]

I too would like to know why this happens. Did you ever figure out an answer?

I looked into it quite a bit, but I never found a good explanation for the "Wellbutrin honeymoon".

I found it astonishing that this drug could create such potent improvements, and then stop working entirely after a few weeks. Definitely is not tolerance build-up, because I tried a 2 month washout period without taking it, and when I restarted I still did not get any of the original benefits.

I can only speculate it might be due to some adaptive epigenetic changes that permanently render Wellbutrin ineffective.

 

[xebex]

I tried wellbutrin, only managed 2 days, it worked instantly for my orthostatic intolerance, but within two hours of taking it gave me pretty bad tinnitus, it sounded like a car alarm going off in my head, stopped after two days, but the tinnitus took about two months to fade and is still there just not as bad. Frustrating cos it felt that it could have been very helpful, however as per sporros experience i wonder if i had a lucky escape, i use ritalin now and it gives a similar effect without the tinnitus, but only works for two days then i need a day off then start again, or it causes the symptoms i'm trying to fix. Over time it seems to be less effective but if i up the dose it makes me worse. So i stick to the dose and just pulse it. I think eventually it won't work any more and i'll give up on it.

 

[mitoMAN]

1000mg of Bupropion? Never heard someone go that high. How did you do drug monitoring in serum levels? What did you test for? Never heard of serum testing for psychiatric drugs.

Was your doctor worried about down regulation of your dopamine receptors at such a high dose? My doctor said that bupropion will downregulate dopamine receptors, so if one doesn't see benefits at an increased dose (like 300mg), higher doses won't work. Is he right?

I had been misdiagnosed as major depression so I went through lots of shit including Psychiatry.
No regular Psychiatrist had ever done TDM (Therapeutic Drug Monitoring).

The Psychiatry was the first place where they controlled serum levels of all medications I was getting.
Afterwards I educated myself about TDM and only consulted doctors that are familiar with therapeutic drug monitoring or part of a TDM science community.

Did you have your metabolizing pathways checked?
CYP2B6 is the main metabolizer of Bupropion.

Especially as a CFS patient, we have VERY VERY different metabolism from regular people (even if we dont have genetic markups for it)
So I would highly suggest that if the maximum dosage of a certain drug is not working, it has to be looked into IF there is a metabolic reason for this.

LEAKY gut can also be a problem for malabsorption btw. Or GUT issues in any way.


my serum levels of 1000mg bupropion where these of reference level of 300mg bupropion on a healthy control.
According to German TDM Guidelines at least.

So my dosage was safe for me, but maybe dangerous for another person!

Also: I was taking XL Wellbutrin.
IR is very dangerous dont take that one. SR might not be as beneficial as well. Bupropion is a very weird drug to be honest.
I noticed a signficiant improvement from increasing 300mg to 450mg BUT no improvement after that. 800mg, 1000mg etc all no extra benefit.


TDM:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687654/

 

[junkcrap50]

I had been misdiagnosed as major depression so I went through lots of shit including Psychiatry.
No regular Psychiatrist had ever done TDM (Therapeutic Drug Monitoring).

The Psychiatry was the first place where they controlled serum levels of all medications I was getting.
Afterwards I educated myself about TDM and only consulted doctors that are familiar with therapeutic drug monitoring or part of a TDM science community.

Wow. I have never heard of this! Thank you so very, very much. I've briefly looked into it just now.

Wow. I had no idea you could test actual psychiatric drugs like bupropion levels in the blood. And at very common labs like Quest & Labcorp. This may be huge for me and a family member. Now, if only the neurotransmitter saliva & blood tests could be improved to be more accurate and useful!

And this idea is not even new or cutting edge. This "idea" or method has been done in other diseases and other drugs. I've heard of it used there, (eg: kidney disease). And even the literature for applying it to psychiatry is 10 years old. Perhaps Europe is farther along than the US.

Did you have your metabolizing pathways checked?

Yes. I have. So I can easily look up my SNPs and various drugs.

Checking your metabolic pathways is JUST now beginning to enter psychiatry clinics in the US. Just saw a brochure for a testing lab in my doctor's office. But the tests only check a handful of genes. And most doctors ignore or never heard of it.

 

[Judee]

I'm starting to wonder if this disease did not mess up something with our dopamine receptors. Last week I had the best day in a long while after trying dopa mucuna (just a pinch) to raise my dopamine levels. It helped but then gave me headaches and facial tightness for several days afterward. The same thing that happened with tyrosine a few years back when I tried that.

Even so, I still want to see if I can find something to help me with this.

Now whenever someone says something helps them, I've been going to the internet and typing in that substance and dopamine. For instance, someone here said Chinese Skullcap was helping them and others with ME and I found this posted on a blog: Chinese Skullcap (Scutellaria baicalensis) - Another dopamine reuptake inhibitor. Has also been shown to prevent iron-induced neurodegredation of the dopaminergic system. https://www.longecity.org/forum/topic/67585-17-random-dopaminergic-supplements/

Thyme tea has been helping me and another site on raising dopamine levels lists it under Carvacol: Carvacrol is another chemical that helps produce dopamine when taken in low doses. https://helloendless.com/10-ways-to-increase-dopamine-to-boost-your-productivity/

That site also lists chocolate and butyrate.

Anyway, try it and see. If something seems to make you feel better, do a search online and see if there is a link.