# Anyone used moclobemide with SSRI?



## John Smith (Jul 14, 2009)

For those who SSRIs didn't work for? I know one needs to be extremely careful, I'm considering trying it and slowly increasing the dose.


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## arth67 (Aug 6, 2009)

I wouldnt, its a so called reversible MAOI which in australia is considered by most psychs as totally useless, its also not approved in the USA

I would try some other type of AD, with a wash out period between it and your old one


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## Medline (Sep 23, 2008)

John Smith said:


> For those who SSRIs didn't work for? I know one needs to be extremely careful, I'm considering trying it and slowly increasing the dose.


http://www.australianprescriber.com/magazine/18/4/100/1/


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## IllusionalFate (Sep 10, 2008)

Although SSRIs could probably be safely combined with moclobemide if you got the doses right, adding mirtazapine to the SSRI instead would likely be the more efficacious combination and serotonin syndrome wouldn't be a risk.


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## jim_morrison (Aug 17, 2008)

yeah, SSRI/SNRI + mirtazapine combos probly a more efficacious way to go.


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## Vini Vidi Vici (Jul 4, 2009)

id be really careful, u dont wanna end up throwing up in the toilet for 3 hours like me. i took a reversible MAO-A inhibitor (curcumin) with Effexor and got really really bad serotonin syndrome. SS stinks. dude take the smallest possible piece of the mocolobemide. dude if yer already on an SSRI, youve gotta raise dopamine and norepinephrine, and possible raise GABA. look for things that would raised DA and NA, but generally you should avoid other serotinergic agents. Mirtazapine is alot better option than mocolobemide, or u could try bupropion, Ritalin, Adderal, or something like that.


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## Medline (Sep 23, 2008)

Vini Vidi Vici said:


> SS stinks.


Well said Lieutenant Aldo Raine! (http://www.imdb.com/character/ch0106963/)


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## Medline (Sep 23, 2008)

remerongm said:


> Moclobemide is very effective...


I wouldn't call Moclobemide "very effective". Psychiatrists consider it weak in general.



> Many clinicians are finding that the new MAOI (or 'RIMA'), moclobemide, is not an effective antidepressant; this view is substantiated by some clinical trials which constitute evidence that moclobemide is no more effective than placebo. In my opinion it is totally ineffective, I gave up using it years, no decades, ago. The minimal effect it has on neurotransmitters is detailed in my recent review (5).


 http://www.psychotropical.com/maois_full.shtml

It has no dietary restrictions and a good side effect profile, if it was a "very effective" drug it would have had success on the market, but it didn't.

It has never been approved by the FDA, is seldom prescribed in Europe and considered a flop by Roche.


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## Medline (Sep 23, 2008)

irma said:


> what would happen if you just took a load of moclobemide at once? I have a few boxes of it, but I can't be bothered wasting a month to see if it works, and then have to take it every day to maintain some sort of effect. if you took about 5-10 300mg pills at once, would it have an anti anxiety/depression effect, or would you just get sick, or just do nothing?


You would likely just get agitated, anxious and develop sleep problems.


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## robotaffliction (Jul 24, 2009)

yeah the problem is you need at least 600mg/day of moclobemide to get a decent effect (my old doc used to go up to 900mg/day), and the risk of serotonin syndrome when combined with an SSRI is pretty damn significant at those doses... but it actually is fairly effective for some at the proper dose, and i believe it's still the #1 prescribed antidepressant in finland..

as far as better tolerability, maybe at low doses, but since most people who respond need 600-900mg a day, it's probably not much more tolerable than an SSRI at those doses..


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## jim_morrison (Aug 17, 2008)

Moclobemide gave me jaw clenching and insomnia like no other med, not sure why. It seemed to be free of sexual side effects though, not sure if that would apply to the higher dosages though.


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## John Smith (Jul 14, 2009)

I wouldn't say moclobemide is ineffective. I had possibly the worst headache I've ever had when I took 15mg of dexamphetamine with 600mg of moclobemide (pharmacist and the _manufacturer_ of the drug told me there wouldn't be an interaction, I later realised that MAO-A inhibits noradrenaline and not MAO-B) and noticed insomnia while on it, so it is certainly doing _something_.

When I used it for about a week while on selegiline I felt much more laid back and less sensitive, not sure if it was the combination of selegiline but the selegiline on its own had absolutely no effect.

Either way I'm stopping the SSRIs, I know that they're useless for me.


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## Vini Vidi Vici (Jul 4, 2009)

Medline said:


> Well said Lieutenant Aldo Raine! (http://www.imdb.com/character/ch0106963/)


totally


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## jim_morrison (Aug 17, 2008)

http://www.psychotropical.com/5_st_moc.shtml

According to this, yes moclobemide + an SSRI will most likely result in serotonin syndrome.


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## Vini Vidi Vici (Jul 4, 2009)

jim_morrison said:


> http://www.psychotropical.com/5_st_moc.shtml
> 
> According to this, yes moclobemide + an SSRI will most likely result in serotonin syndrome.


that article is surely true. but not only did i take a TON of Curcumin (MAO-A inhibitor), i took it with piperine which potentiates Curcumin greatly, and also has weak MAO inhibiting properties. And i took that stuff with Effexor...but then i also took 3 capsules of Bacopa Monniera Extract...after doing alot of research, it seems Bacopa might be an unselective serotonin agonist. no wonder i got SS.


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## jim_morrison (Aug 17, 2008)

That sucks, were you hospitalised?


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## Vini Vidi Vici (Jul 4, 2009)

nope. i was seriously considering asking my Mom to take me to the hospital....but ive gotten SS more than 4 times before that experience. none of my SS experiences were life -threatening....mostly just minor to moderate interactions. So i was completely familiar with the effects...i just sat in the bathroom like i usually do when i get SS. rocking back and forth seems to help relieve some of the muscle tension. getting SS makes me greatful for the life i have, however anxiety-ridden it may be. because when i get SS, i suddenly realize how good things were before i got it.


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## jim_morrison (Aug 17, 2008)

Damn, what gave you SS the other 4 times? If you read that psychotropical site, he seems to suggest that for serotonin syndrome to be likely, in most cases 2 or more serotonergic drugs need to be present, and one of those drugs usually must be an MAOI (including RIMAs.)


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## Vini Vidi Vici (Jul 4, 2009)

well one of the times, i took Lexapro with EMSAM, the selegiline patch. obviously, i didn't expect any interaction. but i had forgotten that some days i would put on 2 or 3 of the 9 mg patches. so apparently i got some MAO inhibition. and another time, i took some Lexapro with DXM and more Curcumin. And other times i have taken 1-2 grams of 5-htp with various SSRIs. i think all of my SS experiences are wimpy ones, if u know what i mean. they were painful, but not as bad a some people have gotten. and i only took the Lexapro on transient occaisions, (after discontinuing it after 3 months) so maybe some of what i thought was SS was merely amplified side-effects. ive always been very sensitive to even minute increases in serotonin levels.


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## jim_morrison (Aug 17, 2008)

It's odd that the combo of venlafaxine and mirtazapine are used so often together without causing any symptoms of SS if they truly were both pro serotonergic agents, it can be explained away somewhat by the fact that mirtazapine is also a 5ht2a antagonist, but as most long term mirtazapine users are aware, and as it's suggested on the psychotropical site, mirtazapine is probly not pro serotonergic at normal doses, and it's antidepressant properties are more likely due to it's potent 5ht2c antagonism and hence it causes noradrenaline and dopamine increase, so probably a more accurate functional description, would be to call it a noradrenaline and dopamine disinhibitor, rather than as an NaSSA.


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## Vini Vidi Vici (Jul 4, 2009)

maybe the drug companies wanted to put Mirtazapine into the Limelight...as a "Serotonergic/Noradrenergic antidepressant" without any of the typical SSRI side effects. i mean when i think about it, the most common hypothesis of depression is the low serotonin hypothesis, so therefore mirtazapine would get prescribed more if doctors thought it was like SSRIs, but simply without side effects. if Mirtazapine was labelled as something else, well, doctors might be more wary to prescribe it, if the mechanism is confusing and harder to understand.


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## jim_morrison (Aug 17, 2008)

yeah thats a good point, serotonin and noradrenaline have definitely stolen the limelight over the years. Its' sad how drug companies play into all of this.


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## IllusionalFate (Sep 10, 2008)

jim_morrison said:


> It's odd that the combo of venlafaxine and mirtazapine are used so often together without causing any symptoms of SS if they truly were both pro serotonergic agents, it can be explained away somewhat by the fact that mirtazapine is also a 5ht2a antagonist, but as most long term mirtazapine users are aware, and as it's suggested on the psychotropical site, mirtazapine is probly not pro serotonergic at normal doses, and it's antidepressant properties are more likely due to it's potent 5ht2c antagonism and hence it causes noradrenaline and dopamine increase, so probably a more accurate functional description, would be to call it a noradrenaline and dopamine disinhibitor, rather than as an NaSSA.


I don't see how mirtazapine is pro-serotonergic at all? Unless by binding to 5-HT2A/C it forces serotonin to bind to other postsynaptic subtype receptors (which would be a very mild increase). Since 2A facilitates dopaminergic transmission and 2C inhibits it, I doubt there is much effect on overall extracellular dopamine levels.

So NaSSa seems very accurate to me. Noradrenergic due to alpha-2 antagonism and selective serotonin subtype binding are both the main mechanisms of action.


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## jim_morrison (Aug 17, 2008)

I guess so but it's antihistamine potency is over 100 times as potent as it's alpha 2 properties, so it seems like it would be hard to achieve a very good antidepressant response from that mechanism without being really sedated all day long.

The odd thing is, that large meta analysis of 12 new generation antidepressants that they did recently showed mirtazapine to be number 1, I can only speak from my own personal experience with it, but for me it's not really that effective as an antidepressant, it's better for insomnia. *shrugs*.

As for it being pro-serotonergic, i asked my pdoc and he told me that binding to 5-HT2A/C receptors somehow upregulates them and acts stimulatory to them. Not sure if I believe that though.


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## IllusionalFate (Sep 10, 2008)

jim_morrison said:


> As for it being pro-serotonergic, i asked my pdoc and he told me that binding to 5-HT2A/C receptors somehow upregulates them and acts stimulatory to them. Not sure if I believe that though.


Your pdoc is smarter than most. Not saying he's correct on this, but my pdoc originally thought mirtazapine was an SNRI before I educated him. Apparently a good number of pdocs think mirtazapine is an SNRI because I've heard the same thing mentioned before.

As for this particular claim, I don't buy it. Sure, 2A/2C will upregulate due to antagonism at these sites, but only to a certain extent. Even when this happens, mirtazapine will be binding to and antagonizing these receptors. Homeostasis shouldn't be able to restore anywhere near baseline neurotransmission at these subtype receptors, let alone upregulating them to the point where neurotransmission is enhanced. If what he's saying is true then 5-HT2A antagonists wouldn't act as antipsychotics.


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## jim_morrison (Aug 17, 2008)

What exactly does upregulation specifically mean, and why does antagonism cause upregulation? I'm a little confused.


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## Vini Vidi Vici (Jul 4, 2009)

jim_morrison said:


> What exactly does upregulation specifically mean, and why does antagonism cause upregulation? I'm a little confused.


? i thought antagonism of 5ht2a/c receptors lead to downregulation (paradoxically) .....however, Mirtazapine isn't definetly a 5ht2c antagonist. Isn't it more likely a 5ht2c inverse agonist? it won't downregulate 5ht2c, because its not an antagonist. chronic treatment supposedly leads to an increased activity at 5ht2c, but not through receptor upregulation. Both Mianserin and Mirtazapine might be inverse agonists. antipsychotics have been shown to sometimes lead to a downregulation of 5ht2a receptors, even though they anatagonize the receptor.


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## IllusionalFate (Sep 10, 2008)

jim_morrison said:


> What exactly does upregulation specifically mean, and why does antagonism cause upregulation? I'm a little confused.


I really hope I'm right on this one, anyone correct me if I'm wrong.

Upregulation/downregulation is when a receptor protein is repeatedly biosynthesized in attempt to achieve homeostasis, however the body's ability to achieve homeostasis is limited. Say an antagonist like mirtazapine binds to 5-HT2A as an exogenous ligand - the body will try to regain activity by producing more receptors to compensate.

Most of the time, agonists and antagonists preferentially bind to the presynaptic autoreceptors, so an antagonist in very low doses will "trick" the neuron into thinking there isn't enough neurotransmitters in the synapse, which subsequently causes an increase in firing rate and postsynaptic neurotransmission.


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## jim_morrison (Aug 17, 2008)

IllusionalFate said:


> I really hope I'm right on this one, anyone correct me if I'm wrong.
> 
> Upregulation/downregulation is when a receptor protein is repeatedly biosynthesized in attempt to achieve homeostasis, however the body's ability to achieve homeostasis is limited. Say an antagonist like mirtazapine binds to 5-HT2A as an exogenous ligand - the body will try to regain activity by producing more receptors to compensate.
> 
> Most of the time, agonists and antagonists preferentially bind to the presynaptic autoreceptors, so an antagonist in very low doses will "trick" the neuron into thinking there isn't enough neurotransmitters in the synapse, which subsequently causes an increase in firing rate and postsynaptic neurotransmission.


Oh ok, so I guess in a way my pdoc was correct?


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## IllusionalFate (Sep 10, 2008)

jim_morrison said:


> Oh ok, so I guess in a way my pdoc was correct?


With the upregulation part yeah, but as for being pro-serotonergic via "stimulating" those receptor subtypes it sounds as if he was saying chronic dosing results in agonism or increased neurotransmission there, which I doubt is the case.


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## Vini Vidi Vici (Jul 4, 2009)

oh i c, the doc was talking about all receptors in general.


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## jim_morrison (Aug 17, 2008)

IllusionalFate said:


> With the upregulation part yeah, but as for being pro-serotonergic via "stimulating" those receptor subtypes it sounds as if he was saying chronic dosing results in agonism or increased neurotransmission there, which I doubt is the case.


Oh ok, the whole upregulation thing confuses me a little, but I agree, it certainly doesn't feel like a pro-serotonergic drug. No matter what the purported mechanism may be.


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