Bupropion inhibiting metabolism of other drugs?

[JohnBoy2000]

CYP2D6 - significantly inhibited by bupropion.

Where other drugs are metabolised by this enzyme.

By example; venlafaxines metabolism to pristiq (o-desmethyl-venlafaxine), significantly reduced - raised blood concentrations of the original drug.

My concern is with Lofepramine, the tricyclic extensively metabolized to desipramine.
That metabolism would, theoretically, be vastly reduced.

As it is speculated that lofepramines efficacy stems significantly due to being a pro-drug to desipramine - thus inhibiting the efficacy of the drug itself.

This is what happens on paper.

Any insights as to whether this translates in practice also?
Would the degree of metabolic inhibition be significant?


The other option I may have would be to progress to Mianserin - the mirtazapine analogue - in favor of lofepramine but what.
Mianserin is hella expensive in comparison.

Speculation as to the efficacy of Mianserin?

Does it induce somnolance and appetite stimulation - similar to mirtazapine?

Some people complain of significant slowing in motor function with mianserin but, the same is said of mirtazapine - and personally, it increased my motor function.

 

[JohnBoy2000]

I could also substitute the bupropion for atomoxetine - or reboxetine.

But there doesn't seem to be a whole lot of data surrounding their efficacy as AD's.

Only Stald keeps saying is his books that they could both be potentially efficacious - you know - theoretically.

 

[JohnBoy2000]

I suppose to answer my own question a little - mianserin also metabolised by CYP2D6.
Same deal with that.
Same deal wtih maprolaline.

And actually - same deal with mirtazapine - but only a percentage of it, I think 30, metabsolized by that enzyme.

There have been reports of tricycllic toxicity in elderly from concurrent use of bupropion.

Not exactly ideal.

Isn't bupropion one of the most popular augmenting agents?
Surely there's a way around this somehow.

 

[JohnBoy2000]

I'm getting this curious tension in my head that I haven't experienced previously.

That's with 300mg bupropion, plus 70 mg lofepramine - per day.
With 45 mg remeron at night.

Lofepramine has cleared up my IBS entirely - but I'm apprehensive about reducing the bupropion on account of possible less energy.

CYP2D6 is inhibitied by bupropion, blocking the metabolism of lofepramine - to desipramine.
Raise in blood plasma levels.

Could the tension headache pertain to that?

 

[cr33py]

I have seen people with gut issues improve on desipramine before. Im not sure why that is. Anti-inflammatory effect? vasoconstriction? driving fluid out of the colon (tendency towards constipation).
that combo might be driving up your blood pressure a bit, wouldnt hurt to check it.

 

[JohnBoy2000]

My pharmacist seemed to think the IBS relief was not related to the drug properties, as much as just the drug itself working for me.

I was feeling horrible the last few days taking bupropion with the lofepramine.
I woke up last night after about 2 hours sleep, feeling like I wanted to fucking kill a motherfucker.
Serous agitation.

Didn't take my dose this morning (bupropion), and feeling better already.

 

[Cotcha Yankinov]

Relief of IBS with serotonergics has been reported, this could be due to an anti-cytokine effect of serotonin. You could see something similar with NRI, especially considering that NRI increases serotonin.

I think amitriptyline in particular might be antagonizing Toll Like Receptors but I could be wrong.

It could also be due to direct influences on gut neurotransmission and then downstream effects on peristalsis, see the enteric nervous system (wiki should have something).

 

[JohnBoy2000]

I ceased the bupropion - and am now taking just lofepramine.

IBS - back like a crazy ex-girlfriend.

Horrible.
I was totally free of it - what a relief.

Apparently one case study had been done where a lady taking bupropion, the plasma levels of the tricyclic she was concurrently taking, elevated by 4 or 5 times - due to the inhibition of its metabolism by bupropions effect on the metabolic enzyme.

Well - whatever the case, it's back for me in the worst possible way, and I'm up to 140 mgs, two thirds of the full dose - though just started that last night.

 

[cr33py]

bupropion is a cyp2d6 inhibitor and desipramine uses 2d6. too lazy to track down exactly what lofepramine itself is metabolized by, but Im pretty sure about desipramine. Id try either raising lofepramine alone, or add small amounts of bupropion to raise the desipramine metabolite. Interesting that you also had an IBS response to this where SSRIs havent done anything. You may want to take this a step further and see if you can meet with a gastroenterologist and find out if they know exactly what this med is accomplishing and what else you can use thats available in the UK.