MAOI: Parnate

[Foreigner]

I hate anti-depressants but I need to take them. I have not however found much success with SSRIs in the past. The sexual side effects are terrible. I also don't trust other kinds of anti-depressants like Wellbutrin.

What was offered to me last time was mirtazapine but I didn't take it.

A friend who has taken many anti-depressants over the years recommended the MAOI parnate to me. I got my MD to prescribe it despite her hesitations, but now I'm looking at the dietary restrictions and I don't think I can handle it. I already have a digestive disease that restricts my diet. Now I can't even make a pot of soup and leave it in the fridge to eat over the course of a few days because spoilage could increase tyramine? Also, no ferments allowed? I kind of rely on those for gut health.

Parnate looks attractive because in theory it could increase the concentrations of all the neurotransmitters.

On the other hand, maybe mirtazapine would better?

I need something because I'm going to kill myself any day now.

Does anyone here have experience with parnate?

 

[sekio]

As I understand it, MAOIs are pretty much the gold standard for antidepressant effects, possibly crossing into mania.

I would recommend you try something that was more selective for MAO-B like transdermal selegeline, or possibly a reversible MAO-A inhibitor like moclobemide, neither of which require the same restriction of dietary tyramine.
Harmaline is a natural product reversible MAO-A inhibitor if that is more your speed.
Generally the reversible MAO-A inhibitors have equal antidepressant effects but without the need to be paranoid around tyrosine decarboxylation. Likewise, if you block only one of the isoforms, there is at least some capacity to process tyramine, but blockade of both enzymes leads to tyramine buildup and hypertensive nasties.

If you find neither of those work, maybe you can try an irreversible, non-selective MAOI like tranylcypromine or phenelzine.

Mirtazepine is not comparable... wiki: Mirtazapine has antihistamine, α2-blocker, and antiserotonergic activity. It is specifically a potent antagonist or inverse agonist of the α2A-, α2B-, and α2C-adrenergic receptors, the serotonin 5-HT2A, 5-HT2C, and the histamine H1 receptor. Unlike many other antidepressants, it does not inhibit the reuptake of serotonin, norepinephrine, or dopamine, nor does it inhibit monoamine oxidase.

strong or aged cheeses: cheddar, Swiss, Parmesan; Stilton, Gorgonzola or blue cheeses; Camembert, feta, Muenster. Cheeses made from pasteurized milk are lower in tyramine: American, ricotta, cottage, farmer's, and cream cheese. Other dairy products are also lower in tyramine: yogurt, fresh milk, sour cream, soy cheese, soy milk, Havarti cheese, Brie.
meats that are cured, smoked, or processed, such as salami, pepperoni, dry sausages, hot dogs, bologna, bacon, corned beef, pickled or smoked fish, caviar, aged chicken livers, soups or gravies made from meat extract. Some meat products are lower in tyramine: fresh or frozen meat, poultry, and fish; eggs; canned meats or fish freshly opened; luncheon meats except salami.
pickled or fermented foods: sauerkraut, kimchi, tofu (especially stinky tofu), pickles, miso soup, bean curd, tempeh
condiments: soy, shrimp, fish, miso, teriyaki, and bouillon-based sauces. Lower in tyramine: ketchup, mustard, Worcestershire sauce, salad dressing; vegemite, Pro-mite, marmite[8]
drinks: beer (especially tap or home-brewed), vermouth, red wine, sherry, liqueurs. Lower in tyramine: decaffeinated coffee, tea or soda; club soda; fresh or soy milk; bourbon; gin; rum; vodka
beans, vegetables, and fruits: soybeans and soybean products, snow peas, broad (fava) beans and their pods; raw onions; oranges, grapefruit, lemons, limes, tangerines, pineapple. Lower in tyramine: most fresh, canned or frozen vegetables; raisins. raspberries and avocados have moderate levels.
chocolate and mistletoe

That's an awful lot of stuff to not eat... I like my pepperoni, snausage, hot dogs, beans, aged cheddar etc!

 

[Foreigner]

I've thought about selegiline. I used to take it as part of my nootropic stack but I didn't find it very antidepressant for some reason.

What I like about parnate is that it seems to cover all the neurotransmitters. But moclobemide seems to do that as well. My concern with that drug, as mentioned in the wiki is, "with long-term use of moclobemide, there is a significant down-regulation of B-adrenoceptors" -- I don't like this, it means that the body gets less responsive to adrenaline, which would really suck in my day to day life! I do a lot of exercise and what not. I also don't like that it apparently increases prolactin initially... my prolactin is already elevated.

My doctor knows nothing about MAOIs but is willing to go on my say so. I don't trust taking parnate because I'm going to make a food mistake.

As I understand it, MAOIs are pretty much the gold standard for antidepressant effects, possibly crossing into mania.

I would recommend you try something that was more selective for MAO-B like transdermal selegeline, or possibly a reversible MAO-A inhibitor like moclobemide, neither of which require the same restriction of dietary tyramine.
Harmaline is a natural product reversible MAO-A inhibitor if that is more your speed.
Generally the reversible MAO-A inhibitors have equal antidepressant effects but without the need to be paranoid around tyrosine decarboxylation. Likewise, if you block only one of the isoforms, there is at least some capacity to process tyramine, but blockade of both enzymes leads to tyramine buildup and hypertensive nasties.

If you find neither of those work, maybe you can try an irreversible, non-selective MAOI like tranylcypromine or phenelzine.

Mirtazepine is not comparable... wiki: Mirtazapine has antihistamine, α2-blocker, and antiserotonergic activity. It is specifically a potent antagonist or inverse agonist of the α2A-, α2B-, and α2C-adrenergic receptors, the serotonin 5-HT2A, 5-HT2C, and the histamine H1 receptor. Unlike many other antidepressants, it does not inhibit the reuptake of serotonin, norepinephrine, or dopamine, nor does it inhibit monoamine oxidase.


That's an awful lot of stuff to not eat... I like my pepperoni, snausage, hot dogs, beans, aged cheddar etc!

 

[Nagelfar]

As I understand it, MAOIs are pretty much the gold standard for antidepressant effects, possibly crossing into mania.

One of my closest friend's mother was an M.D., she herself had depression and underwent ECT. I talked to my friend to get her number not too long ago to discuss going about that. I broke down my medication history, and she basically said the next step for treatment resistant depression would be to get off everything and go to an MAOI — which in her words "actually work" but are not a first line go-to because of all the dietary restrictions and complications with taking anything else.

 

[Foreigner]

One of my closest friend's mother was an M.D., she herself had depression and underwent ECT. I talked to my friend to get her number not too long ago to discuss going about that. I broke down my medication history, and she basically said the next step for treatment resistant depression would be to get off everything and go to an MAOI — which in her words "actually work" but are not a first line go-to because of all the dietary restrictions and complications with taking anything else.

It seems like moclobemide has enough selectivity to allow for tyramine to be processed. According to the wiki, it's heavily MAO-B and only starts to heavily affect MAO-A at higher doses (or was it the other way around?).

Either way, everything I'm reading indicates that the MAOI class are superior for depression and anxiety treatments, and even enhance sexuality rather than suppressing it. These are all pluses for me.

I just don't like what I'm reading about adrenergic down-regulation. It would mean that when adrenaline response is needed, the body would be less responsive. On the one hand, that could help chill a person out, on the other hand it could mean that the body is less adaptive to physical activity... and I live a very physically active life. It does say that this is a long-term effect... but define "long-term".

Unless I'm reading this wrong.

 

[sekio]

. According to the wiki, it's heavily MAO-B and only starts to heavily affect MAO-A at higher doses (or was it the other way around?).

it's a reversible inhibitor of MAO-A, no acitivity on MAO-B

"with long-term use of moclobemide, there is a significant down-regulation of B-adrenoceptors" -- I don't like this, it means that the body gets less responsive to adrenaline,

so, to phrase this another way, moclobemide has activity as a beta blocker as well
note that the alpha-adrenoreceptors are the more important ones in controlling adrenaline secretion, esp. alpha-2a adrenoreceptors (which are autoreceptors controlling adrenaline release, antagonist: yohimbine, agonist: clonidine)
plus if it develops gradually you will have time to accommodate to it
if you are suicidal I would not be so concerned about future possibilities, you probably need to focus on immediately getting on a working maoi

also, wiki:

The reversible binding to MAO-A by moclobemide allows amines such as tyramine to displace moclobemide from MAO-A allowing its metabolism and removing the risk of a hypertensive crisis that occurs with irreversible MAO inhibition. Of 2300 people in multiple clinical trials who were treated with moclobemide in doses up to 600 mg with no dietary restrictions, none experienced a tyramine-mediated hypertensive reaction. As the pressor effect of moclobemide is so low, dietary restrictions are not necessary in people eating a normal diet, in contrast to irreversible MAOIs. However, some rare cheeses that have a high tyramine level may possibly cause a pressor effect and require caution. The potentiation of the pressor effect of tyramine by moclobemide is only one seventh to one tenth of that of irreversible MAOIs. In order to minimize this potentiation, postprandial administration (taken after meals) of moclobemide is recommended

 

[emkee_reinvented]

Any reason you didn't give Mirtazepine a try?

My only experience with an AD and I am very positive about it. Appetite and restful sleep as well as lowering stress related shit.

 

[Foreigner]

Any reason you didn't give Mirtazepine a try?

My only experience with an AD and I am very positive about it. Appetite and restful sleep as well as lowering stress related shit.

I just want to try something that is guaranteed to work and MAOIs have a really good track record for efficacy.

If for some reason I couldn't do an MAOI, mirt would be my backup choice... even though it has a totally different mechanism.

 

[AlphaMethylPhenyl]

As much as I'm against playing neurologist to self-advocate for a medication, this may help: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067815/

I don't think MAOIs are a guarantee. I've known several people who found better ad effects from SSRIs than MAOIs. But in terms of all-around efficacy for mental illness, they are hard to beat.

The diet thing is very important to stick to. When you learn more about how your body reacts to these dietary limitations, you may not have to watch things as readily.

Yeah I mean knowing the mechanism doesn't really translate to knowing if its good for you or not. Maybe roughly. But not so much.

 

[Foreigner]

Yeah I mean knowing the mechanism doesn't really translate to knowing if its good for you or not. Maybe roughly. But not so much.

That's a very good point.

With the MAOI I'm considering, I won't have to worry about diet. Jury's still out on whether or not it'll work for me though.

 

[AlphaMethylPhenyl]

Thanks. It's a lesson I had to learn.

Curious to know what one you're looking at, but can understand if you don't want to say.

From what I've learned, yes nonselective MAOIs will increase levels of dopamine, nor/ep., serotonin, trace amines, and maybe even GABA, but MAO exists in the presynaptic cell, and thus only affects a portion of all monoamine/catecholamine neurotransmitters. Otherwise, they are repackaged by VMAT, metabolized by COMT, in the synapse, or otherwise disposed of. I think. Not entirely sure to be honest.

 

[sekio]

Jury's still out on whether or not it'll work for me though.

The sad thing with human pharmacology is that the only way to know for sure what effect a drug will have is to try it and see.

I would give moclobemide a shot and see what happens.

 

[Foreigner]

Is

The sad thing with human pharmacology is that the only way to know for sure what effect a drug will have is to try it and see.

I would give moclobemide a shot and see what happens.

Is it possible for the beta blocker effect to be permanent even if I stop taking it? The wiki says there is significant downregulation. I wouldn't want that to be permanent? That type of thing is why people get pacemakers.

What's the point of taking an antidepressant if it lowers your blood pressure do much you can't exercise?

I have moclobemide 150mg but I'm afraid to start taking it. I don't want to replace one ill with another.

 

[AlphaMethylPhenyl]

I don't think there's sufficient evidence for that.

People get depressed in different ways. Lots of meds out there for depression. Side effects vary. Bottom line is that there's never a medication without some sort of side effect. It's not a bad thing, though. It's good to not like your meds too much, as I'm sure you've read of on this site.

Is that why you're not trying it? You seemed quite chipper to try an MAOI before.

 

[Bravoncius Roxford]

The sad thing with human pharmacology is that the only way to know for sure what effect a drug will have is to try it and see.

I would give moclobemide a shot and see what happens.

Moclobemide is a really weak MAOI with an IC50 of 6.5 uMol. The reason why it is work at all is because it has extremely high oral BV, extremely low plasma protein binding and, above all, because it inhibit the cytochrome450 enzymes that metabolizes it, so it produces extremely high plasma levels of the molecule. But there is a consensus now among psychiatrists and pharmacologists that the recommended daily dose of 300 mg is not very effective for most except for some people. Now it is agreed that the effective range is 600-1,200 mg for most adults, and that some people might need up to 2,400 mg, which is micromolar levels of the drug. But most people respond at least with some improvement with doses of 1,200 mg. But we know that moclobemide does inhibit MAO-A at clinical doses because it produces acute serotonin syndrome when combined wiith clinical doses of an SSRI.

Now tranylcypromine is a serious and very potent MAOI that irreversibly destroys both MAO-A and MAO-B by binding covalently to the N5 nitrogen of the flavin residue of MAO. It is one of the most effective antidepressants know, especially for severe melancholic(endegenous) depression that does not respond to selective monoamine reuptake inhibitors like S-citalopram and reboxetine. But it is a potentially dangerous drug. TCP is more associated with hypertensive cisris than any other MAOI. Back in 1964, the FDA remporarilly removed TCP from the market due to a series of deaths associated with it being used in combination with either tyramine-rich foods or sympathomimetic relesing amines. Most of the deaths came via hemorragic strokes to the blood vessels of the brain from increases in systolic pressure to over 250 mmm. It is a serious medicine that should ohly be used as a last resort for severely depressed patients that did not respond to more selective antidepressants. And even then, it's use should be only done under the care of an expert physician that has experience dealing with non-selective, irreverislbe MAOIs.

 

[FnX]

Moclobemide has really helped me. More than any other anti-depressant. Dosage? Usually 2x 300mg a day. I have to keep it it on the low side tho since I also take d-amph. Clonidine and alprazolam are the mediators here.

 

[plumbus-nine]

@FnX Interesting. To me, moclobemide had no positive effects at all, at same dosage. But had the impression that 600mg/d is what they recommend as max dosage? I had to try d-amph as well to check the interactions and whether it is active at all. Took maybe 2mg (had 5mg capsules and eyeballed) which gave me tachycardia and an increase in BP of maybe 20-30mmhg but no positive feelings either. How much amph do you take? Yeah, clonidine works well here, I took 75 or 150mcg and after 15min the adverse effects were gone.

I've read that the dietary restrictions vary greatly between individuals. Believe it was even here on BL (was a long time lurker) where somebody said besides things like soy sauce etc. he didn't need to watch diet but of course worked up very slow and carefully.

I am very interested in these irreversible MAOIs as well but up to now both feared them and couldn't get a prescription for one. Some research chemical which turned out to be a MAOI-A inhibitor and SNRI gave me the best mood lift ever and being usually depressed all the time it would be such a gift to have this effect again, even when it'd be only half of it.

Cause of that I thought about combining a sub-threshold dose of a MAOI, low enough for not to require diet, and a low dose of a SSRI. When you can combine MAOI+amphetamine, then why not with a SSRI? What do you folks think about?

 

[FnX]

@FnX . But had the impression that 600mg/d is what they recommend as max dosage?

Actually, there is some new research that suggests dosages up to 1200mg provide yet additional benefits, let me see if I can find you a source... google is fidgety today. I give you my word though, they did a study for dosage ranges of 900mg - 1200mg daily and found additional efficacy when compared to 600mg/d. Turns out it has some other, less known mechanism of action than just the inhibition of MAO-A.

 

[Foreigner]

Just an update. I went with moclobemide in the end. I felt immediate relief within a couple of days of taking it, but after several weeks I stopped noticing it. It also did something funky to my bowels, but I can't say what. IBD (not to be confused with IBS) patients often have excess gut serotonin and I wonder if the drug somehow amped it up locally.

During the time when it was working, it felt great and I would endorse this drug. My sex drive went up, I had more wakeful energy, and my spiraling suicidal thoughts were gone. I was taking 150mg twice daily, btw.

The twice daily dosing was a pain because I could never get the timing just right along with my other medications, plus taking it with food. It still worked better than an SSRI ever did though.

 

[Xorkoth]

Sorry it didn't keep working, that's unfortunate, but I'm glad to hear you at least got a period of relief. Sometimes just lifting out of depression for a short time can be so incredibly heartening. Just to remember that it is, in fact, possible. Depression is so hard to see out from even when you intellectually know that it is a temporary subjective state.