Mirtazapine+Moclobemide?

[JohnBoy2000]

MAOI would only be an issue in a hypertensive crisis if someone had consumed tyramine. in the case of moclobemide not even an issue. MAOIs if taken with amphetamine at a really high dose maybe you could have serotonin toxicity. And a possible hypertensive crisis can be addressed by giving the patient some nifedipine to keep on hand. Also people on MAOIs generally have failed everything else and as such the risk to benefit ratio is weighed a little differently from someone without treatment resistant depression.

So, apart from amphetamines/methyphenidate, there aren't really contraindications for moclobimide?
Correct?

Also - isn't moclobimide considered particularly potent?
I had read in grazing that, some consider it less so than effexor.
Can that be true?

 

[WSH]

Also - isn't moclobimide considered particularly potent?

The normal dose for moclobemide is 300-600mg, which means that's it's extremely unpotent.

For example LSD, the benchmark for potency, is 3000-6000 times more potent.

That's the difference between making 1000 dollars per month and making a couple million dollars each and every month

 

[aced126]

The normal dose for moclobemide is 300-600mg, which means that's it's extremely unpotent.

For example LSD, the benchmark for potency, is 3000-6000 times more potent.

That's the difference between making 1000 dollars per month and making a couple million dollars each and every month

Not necessarily true. LSD needs to be made by clandestine chemistry which is why it is so lucrative. A molecule that is unpotent but easily made means tonnes of the stuff are still extremely easy to make.

 

[cr33py]

So, apart from amphetamines/methyphenidate, there aren't really contraindications for moclobimide? Correct? Also - isn't moclobimide considered particularly potent? I had read in grazing that, some consider it less so than effexor. Can that be true?

You shouldnt take SSRIs, tramadol, etc. with it just like any other MAOI. Its safe with tyramine. I meant that amphetamine was commonly used and still can be, if the person taking it knows the symptoms of ST and has nifedipine just in case. moclobemide isnt very effective compared to the irreversible MAOIs.

 

[JohnBoy2000]

You shouldnt take SSRIs, tramadol, etc. with it just like any other MAOI. Its safe with tyramine. I meant that amphetamine was commonly used and still can be, if the person taking it knows the symptoms of ST and has nifedipine just in case. moclobemide isnt very effective compared to the irreversible MAOIs.

Really?

Wiki tells me otherwise.

Apparently with non-reversible MAOI's, one can't eat chocolate, correct?
That's something that I can probably never do, that being the case.

Also - apparently, tyramine can be an issue with moclobimide, onset of headaches etc; the effects just dissipate quicker and aren't life threatening, but still somewhat important to watch ones diet to avoid these nasty by products.

 

[MeDieViL]

Mirtazepine will prevent ss, theres a report of ss in the literature but there was no mention of elevated body temp and the symptions pointed to overactivation of NE.

MAOIS with therapeutic dose sof dexamphetamine has been used in the old days for treatment resistant cases and was proven to be absolutely safe in controlled doses.

Stims with moclobemide could cause more anxiety as the ne would be prevented from being broken down.

 

[MeDieViL]

%HT2a can have potent anxiolytic and antidepressive effects, also potentially extremely effective for ocd and explains alot of the therapetic effects of treshold psychedelic doses.

Only in melancholic depression theres overactivation and this receptor is more likely to make someones depression worse.

 

[MeDieViL]

If I was the doctor, I sure as hell wouldn't risk it combining those two medications in my pati.

So youd let the patient suffer from ill mental health instead of discussing the potential risks for the benefit of the patient? because of alot of docters with that mentally many patients never achieve remission

Also, ebola extremely complex combinations? this is a extremely simple combo, and often are deseases or mental health issues caused by a combination of alot of factors like inflammation, oxidative stress, monoamine dysregulation combined leading to the issues, so a complex combination of selective meds each carefully selected to target issues in someone problems and the individual response definatly justifies complex combinations.

Some meds are so complex they do the same as several differened meds togheter, a tricyclic for exaple does simular things as a combo of prozac, mirtazepine and reboxetine, so the number of meds never means anything with reards to the conclusion wheter its excessive, depending on the individual and wheter some meds are stressfull for the liver or other side effects

 

[JohnBoy2000]

And, regarding your opinion on the potential efficacy of moclobimide?

In the 300 to 600mg range?

 

[MeDieViL]

I seem to recall a discussiong where a study showed its not better then placebo, also anecdotes seem to indicate its weak shit which doenst mean it cant be a very effective augmentation strategy, but again as with most drug a select sungroup would show a benefical response to it.

Its combined with amitryptiline for treatment resistant cases with some succes, so thats worth a try.

but really based on all your symptions its the best the make the best recommedation and response to past meds and recreational drugs

 

[cr33py]

If youre interested in psychopharm Id recommend some books by Dr. steven stahl.
Depression sucks. It steals your life little by little until theres nothing left. Personally Id investigate TMS treatment before irreversible MAOIs, maybe even ECT. There are other treatments out there as well, but when you get into stuff like DBS and implanting electrodes theres a lot more risk involved. Some people get that desperate.

 

[Cotcha Yankinov]

Not mirtazapine. Blocking the 5-HT2C receptor can elicit an antidepressant can begin to precipitate itself within only a few days. Alpha 2 and 5-HT2 2A antagonism augments this.

I think what you are thinking of is serotonin transporter blockage which then indirectly waits on serotonin to naturally downregulate 5-HT 2A 5-HT2C and 5-HT 1A presynaptic 1A receptors.

This therapeutic delay isn't needed with direct antagonistis.

You would think that we would see 2A/2C inverse agonists used for depression - as I recall 2A inverse agonists were tested for depression but don't do well, I don't know about 2Cc inverse agonists. Autoreceptor antagonists would probably be the most effective but serotonin syndrome risk would be high.

Also I'm under the impression a lot of the benefit of SSRIs has more to do with neurogenesis etc, so even if blocking 2C leads to a temporary mood lift via DA and NE release, I don't know if it would be sustainable.

 

[JohnBoy2000]

If youre interested in psychopharm Id recommend some books by Dr. steven stahl.
.

Currently researching.

Thanks for the tip.
Has a book called, "Prescribers guide that I'm reviewing ATM".

 

[theGirlWithBlueHair]

You would think that we would see 2A/2C inverse agonists used for depression - as I recall 2A inverse agonists were tested for depression but don't do well, I don't know about 2Cc inverse agonists. Autoreceptor antagonists would probably be the most effective but serotonin syndrome risk would be high.

Also I'm under the impression a lot of the benefit of SSRIs has more to do with neurogenesis etc, so even if blocking 2C leads to a temporary mood lift via DA and NE release, I don't know if it would be sustainable.

I believe mirtazapine is an inverse agonist, isn't it?

You are correct, they do induce neurogenesis:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121947/

But their effect on downregulating the 2A receptor is what's important, not on immediately blocking the 2C receptor. I would think that would be outweighed by their immediate activation of 2A?

 

[serotonin2A]

You would think that we would see 2A/2C inverse agonists used for depression - as I recall 2A inverse agonists were tested for depression but don't do well, I don't know about 2Cc inverse agonists. Autoreceptor antagonists would probably be the most effective but serotonin syndrome risk would be high.

Pindolol (an autoreceptor antagonist) has been trialed as an an adjunct for SSRIs but it wasn't effective.

Also I'm under the impression a lot of the benefit of SSRIs has more to do with neurogenesis etc, so even if blocking 2C leads to a temporary mood lift via DA and NE release, I don't know if it would be sustainable.

There certainly is a lot of correlational evidence indicating that neurogenesis in involved. But spine formation and other forms of synaptic reorganization have also been observed and could play an equally important role. Activation of neurotrophins such as BDNF may be the common target of antidepressants, with a range of downstream effects (reorganization if dendrites and synapses, neurogenesis, etc) that work in concert to reduce symptoms on depressed patients.

 

[theGirlWithBlueHair]

Increases in BDNF is one of the main mechanisms of antidepressants drugs:

http://www.sciencedirect.com/science/article/pii/S002839081530157X

I'm curious to know if you guys have heard of the melatonin/buspirone combination that promotes neurogenesis and results in antidepressant activity?

http://www.ncbi.nlm.nih.gov/pubmed/22998742


Autoreceptor antagonists really don't make sense as antidepressants. Why would you want more serotonin release in the first place? And then you are going to be antagonizing the 1A postsynaptic receptors...

What you would want would be a 1A full agonist, not an antagonist. Buspirone is a partial agonists, and it is a successful adjunct to SSRIs - when used appropriately of course.

 

[Cotcha Yankinov]

Pindolol (an autoreceptor antagonist) has been trialed as an an adjunct for SSRIs but it wasn't effective.

I was specifically thinking a somewhat selective 5-HT1B/1D antagonist - do you think that a 5HT1A antagonist is worth making inferences off of? It seems like 5HT1A activation is important for things like oxytocin, and pindolol isn't too selective it seems. Also, if you have seen this study and have glanced over it I will definitely take your word for it, but this study seems to imply that Pindolol worked okay for the first two weeks? (Maybe 5HT1A upregulation started to kick in after two weeks, or 5HT1A was responsible for trophic signaling/neural activity patterns and its not good to block it long term? Could 5HT1B/1D be responsible for trophic signaling as well?) http://ebmh.bmj.com/content/7/4/107.long

There certainly is a lot of correlational evidence indicating that neurogenesis in involved. But spine formation and other forms of synaptic reorganization have also been observed and could play an equally important role. Activation of neurotrophins such as BDNF may be the common target of antidepressants, with a range of downstream effects (reorganization if dendrites and synapses, neurogenesis, etc) that work in concert to reduce symptoms on depressed patients.

Is mTOR responsible for mediating much of the beneficial effects of BDNF on depression? And if new spine formation might be a way by which anti-depressants mediate their efficacy, might we see some benefits off using spine formation promoters/anti-depressants in those with diseases like schizophrenia/ASD/Alzheimer's that have a spine pruning component? I understand if the spine formation promotion occurs somewhat selectively with serotonin receptor stimulation then that might not be quite as effective as increasing spine formation with something more global (like with AMPA PAMs?)

 

[JohnBoy2000]

The other area to consider is:

Tricyclics with Mirtazipine??

Are they contraindicated in any respect??

My pharmacist seemed to think that due to the sedation factor, it might cause concern...

 

[theGirlWithBlueHair]

No, not really. I wouldn't think. Serotonin syndrome shouldn't either as mirtazapine antagonizes both major subtypes of excitatory 5-HT receptors.