Making the addition of a third drug to mirtazapine and bupropion combination?

[JohnBoy2000]

So - three weeks in on Bupropion, 300 mg.

Some days, it's decent, but I expected to see a good impact after about two weeks.
Haven't full seen that yet.

So, I like to plan ahead.
I figure, another two weeks at 300 mg, then bump it to 450mg - give it another 4 weeks.

If that doesn't yield the desired outcome, I wish to waste no time implementing the appropriate augmentation strategies.

The options I am next considering are:

- Brintellix - or vortioxetine.

- Agomelatine - valdoxan.

- Reboxetine


The latter two have questionable efficacy but, they work on noradrenaline.
I'd have non-response to serotonergics in the passed, so it would be favorable for me to try something different.

I'm aware brintellix is a-typical, in that it does work on serotonin, but not in the reuptake inhibition sense, and has demonstrated efficacy where SSRI/SNRI's have not.


That being said, bupropion has had somewhat of a positive effect thus far.
It's quite activating - and I'm probably stronger on it that I was on any other med, so, I wouldn't wish to cut it out completely.

Therefore, the addition of a third drug to these two??

Would that be feasible?

Put aside the reduction in seizure threshold.
I'm not epileptic, nor have I ever had a seizure.

Hypertensive crises??
Though in Stahls book, he speculates about the potentiating effect reboxetine would have on bupropion, suggesting them as a possible combination...

Agomelatine?
Acting on melatonin?
An effect on noradrenaline and dopamine, though to what degree, I don't know...


I think the only one of these three that was approved by the FDA in the US was Brintellix.

Any insights?

 

[JohnBoy2000]

Oh - and the 4th consideration is

- moclobimide.

Clinical trials show comparable efficacy to other popular AD's at 600mg, so, why not....

 

[Solipsis]

Seems vital that you add details about your condition / the indication, because a lot of these meds do several things and their effectivity may vary on the indication. It's major / unipolar depression?
Still, if you're having most trouble getting activated or with anhedonia etc, the specifics might be meaningful. Also in the opposite way: things you are sensitive to may mean that some meds are better avoided so that side-effects and their impact don't overshadow effectivity.

 

[JohnBoy2000]

Seems vital that you add details about your condition / the indication, because a lot of these meds do several things and their effectivity may vary on the indication. It's major / unipolar depression?
Still, if you're having most trouble getting activated or with anhedonia etc, the specifics might be meaningful. Also in the opposite way: things you are sensitive to may mean that some meds are better avoided so that side-effects and their impact don't overshadow effectivity.

Correct.
Energy, combating fatigue, is my main concern.
When I have extreme debilitating fatigue, alright, there's distress there.
But, even on meds that aren't super effective, my condition does not really comprise of "sadness", or being, "down on myself".
It's energy, functionality, appetite, things like that, that are the main issues.
Extremely poor concentration.
My experience with serotonergics is that, that induce in me fatigue, and did little in terms of restoring cognitive function.
SSRI's, that it.

 

[Solipsis]

Moclobemide isn't safe to combine with many of these AD's if you were considering that. Mirtazapine I assume is to help with appetite and sleep, but it is unclear whether you are already taking this and how much - often it works best if you take a low dose of that only. Something like Brintellix could negate the effects on appetite and I have to wonder whether many of these triple combinations won't make your fatigue worse instead of making it better. If you are not getting good efficacy from a drug why would you stack instead of switching, unless you are very specifically aiming for a reported benefit from a combination.

Aren't you doing this under supervision of a psychiatrist? Shopping for an anti-depressant yourself is already questionable although perhaps you have no real choice, but when combining there aren't only the immediately dangerous interactions to be concerned with but also the influence they have on each other's metabolite from CYP2D6 here for example.

It's difficult that energy and appetite can be mutually exclusive to concentration when you look at it from an ADD paradigm, but if they are secondary effects of depression they don't have to be.

The bupropion certainly makes a lot of sense all things considered. Maybe if that isn't as effective as you hope it to be, switch it for another NDRI but other options don't nearly seem as good. I wish I could suggest Effexor but I've heard very bad things about coming off it.
It's delicate to choose another NDRI type drug that doesn't affect your appetite negatively and isn't too stimulating but I just doubt that complicating things is a better way to go. Maybe you can learn to manage your appetite if your energy, functionality and concentration improve from a catechol elevating pharm?

Agomelatine doesn't sound bad but if you want to combine it instead of taking it on its own, chances of getting e.g. more fatigue go way up.

 

[JohnBoy2000]

Moclobemide isn't safe to combine with many of these AD's if you were considering that. Mirtazapine I assume is to help with appetite and sleep, but it is unclear whether you are already taking this and how much - often it works best if you take a low dose of that only. Something like Brintellix could negate the effects on appetite and I have to wonder whether many of these triple combinations won't make your fatigue worse instead of making it better. If you are not getting good efficacy from a drug why would you stack instead of switching, unless you are very specifically aiming for a reported benefit from a combination.

Aren't you doing this under supervision of a psychiatrist? Shopping for an anti-depressant yourself is already questionable although perhaps you have no real choice, but when combining there aren't only the immediately dangerous interactions to be concerned with but also the influence they have on each other's metabolite from CYP2D6 here for example.

It's difficult that energy and appetite can be mutually exclusive to concentration when you look at it from an ADD paradigm, but if they are secondary effects of depression they don't have to be.

The bupropion certainly makes a lot of sense all things considered. Maybe if that isn't as effective as you hope it to be, switch it for another NDRI but other options don't nearly seem as good. I wish I could suggest Effexor but I've heard very bad things about coming off it.
It's delicate to choose another NDRI type drug that doesn't affect your appetite negatively and isn't too stimulating but I just doubt that complicating things is a better way to go. Maybe you can learn to manage your appetite if your energy, functionality and concentration improve from a catechol elevating pharm?

Agomelatine doesn't sound bad but if you want to combine it instead of taking it on its own, chances of getting e.g. more fatigue go way up.

Another NDRI?

Example?

I'm just tapering off effexor now, being replaced by bupropion.
And you're right.
It's a fucking nightmare.

Down to 37.5, I tried staggering the dose to every 48 hours, but the last 5 to 6 hours of that is hellish.
So, I plan to empty out a capsule, and ingest half the granules every 24 hours.
Give it a week on that and see how that goes.

Effexor was better than all the SSRI's, but the fatigue induced by the serotonin was not good, but some other side effects also a nightmare.

I figured, I benefited from mirtazapine and effexor, but not serotonergics - it must be their effects on noradrenaline that was doing something for me.

Therefore, the logical next step would be to try a pure noradrenergic.
3.5 weeks in, and it does give me some good days for sure - but it's just not consistent.
By example, yesterday and today, I crashed hard.

That being said, it has also positively affected my sleep for sure.

Some clinical trials indicate that bupropion at 150 mg is an effective theraputic dose, and question going beyond this.

I know it was administered at far higher doses when it was released initially, but simply cannot find information on that initial dosing regiment.
600 mg - as high as that?

 

[JohnBoy2000]

And yes I take mirtazapine now, as it is effective in restoration of functionality, sleep and appetite.

Honestly it's like a freakin' miracle drug for me.

I'm on 45mg.

I tried 60 mg, but the effect was reversed.

And no, I didn't find 15 mg worked better for sleep.
The opposite.
45 gives me better sleep - I would assume as a result of the improvement in mood at the higher dose.

 

[jaiho]

Moclobemide is safe with Mirtazapine & bupropion. You only need to worry about strong SRIs in combination with Moclobemide. Mirtazapine is a Serotonin antagonist so you don't need to worry there.

If you want maximum synergy, look at putting an SNRI with Mirtazapine. Moclobemide isn't that efficient when it comes to serious depression.

 

[Coolwhip]

Pramipexole, or a low dose of cariprazine, or deprenyl. Or something anti-glutamatergic like memantine or agomelatine.

 

[JohnBoy2000]

Pramipexole, or a low dose of cariprazine, or deprenyl. Or something anti-glutamatergic like memantine or agomelatine.

Agomelatine?

Melatonin - would that really affect executive function?

I'm also unaware of the effect of glutamatergics would have on executive function - euphoria state etc.

 

[Coolwhip]

I'm sorry but I'm not sure what you mean by an affect on executive function, or what your goals are exactly, but the brain is extremely complicated and many times it doesn't work as straight forward as we wish it did...do you currently feel blunted or overactive/distracted?

Or are you just talking energy/motivation in general...sometimes with depression you just need something to make you less depressed to give you energy back rather than something that gives you energy through NE or the like.

Don't confuse melatonin and agomelatine just because they hit the same receptors, very different drugs(pharmacokinetics, efficacy, etc) . Agomelatine has an anti-glutamatergic effect and resets the circadian rythm, getting better quality sleep can go a long ways for improving your state of mind.

But like I said, given what you are already on, pramipexole(or ropinirole) or deprenyl(big fan of this one, but would suggest you try pramipexole first) would be my first choices, you could also try abilify(works similiar to cariprazine)...don't know how you are sourcing these meds, sometimes it can be difficult to get psychs to prescribe things off-label(bring some literature in with you, with an emphasis on it being safe as much as effective for pramipexole/ropinirole)

Heck in the past I've even had good anti-depressant/anti-anxiety effects from a lower dose of lamictal(started at 25, moved to 50mg eventually)...helped with sleep, improved mood, made me more balanced in general, and at this low of a dose I didn't notice any cognitive blunting. And at this point I was feeling very anhedonic and dysthmic(on top of bouts of crippling morning depression and night time anxiety and insomnia). Sometimes meds can have an indirect snowballing effect by relieving the stress of other symptoms allows your mind to do more to help itself.

 

[adder]

Agomelatine has an anti-glutamatergic effect and resets the circadian rythm, getting better quality sleep can go a long ways for improving your state of mind.

Do you have any source for that? I find it doubtful that even if it somehow does affect glutamatergic system, the effect is minuscule compared to its effect at MT1 receptors, same as with 5-HT2C antagonism which is basically insignificant.

I'm aware brintellix is a-typical, in that it does work on serotonin, but not in the reuptake inhibition sense, and has demonstrated efficacy where SSRI/SNRI's have not.

Vortioxetine is a serotonin reuptake inhibitor and have agonistic, partial agonistic or antagonistic on a few 5-HT receptor subtypes, including 5-HT1A which is drug's secondary target, with affinity around one order of magnitude lower than that for serotonin transporter, so it does matter pharmacologically. 5-HT1A autoreceptor desentization is also implicated in delayed antidepressant efficacy of older SSRIs. I'm skeptical of antidepressants in general though and those new ones marketed as SMS's (SSRI+5-HT1A agonist/partial agonist) don't surpass older antidepressants in antidepressant effectiveness.