I've been looking all over the Internet on this topic, only to find hearsay and repitition. Does anyone have experience or links to reliable research on the topic? From my understanding, the risk with an MAOI and anti-depressants in general is serotonin syndrome. However, bupropion is a norepinephrine/dopamine reuptake inhibitor - am I mistaken in saying that has absolutely nothing to do with serotonin syndrome? So, where is the risk, then, with this combonation? I don't want to hear more regurgitation, I would like a logical, scientific explanation. I want took ow why this has been labeled as dangerous when it logically doesn't add up and seems to have no experimentation to back the claims. I will be continuing my own research and will update this thread with new information on the topic. Thank you for your contributions.

The hazard from the combination of MAOI (particularly the RIMA moclobemide) and buproprion has very little to do with serotonin syndrome.As you rightly say, buproprion is an inhibitor of dopamine and norepinephrine reuptake, so if you imagine a synapse which has just pumped either of these neurotransmitters into the gap, the action of buproprion is to prevent their re-uptake thus facilitating their effect on the next neurone.Now if you throw a MAOI into the mix, the ability to limit the action of dopamine/norepinephrine is reduced further still as MAO is inhibited, preventing the breakdown of dopamine/norepinephrine thus making their effect even greater with toxic effects being seen (CNS excitation and hypertension).

The manufacturers advise avoiding concomitant use with moclobemide, the 'classic' pharmaceutical RIMA.

The risk of MAOIs and antidepressants really depends on the mechanism of action of the antidepressant, rather than the risk being serotonin syndrome across the whole range of antidepressants.

That does, of course, makes sense. What I am wondering is to what extent does this combonation affect the neurotransmitters in question? At what levels are they actually toxic? Can it lead to hypertensive crisis? Maybe it isn't this simple, but here is how I see it. Let's say Bupropian doubles the efficacy of said neurotransmitters. Let's also say a given RIMA does the same. This would amount to a 4x increase, no? That just does not sound dangerous. I'm a physicist, not a psychologist, but it seems I may be missing something here.

This sort of phrasing appears often in finding information:

"Antidepressants known as monoamine oxidase inhibitors (MAOIs) should not be taken together with Well- butrin, because the combination may potentially produce a toxic reaction that includes elevated temperature, high blood pressure, and extreme excitation and agitation."

"may potentially" sound like a scientific copout. Psychiatry is extremely agitating.

On one level, it is a cop-out, but one needs to bear in mind variations in individual physiology which are not fully elucidated.

I personally would be reluctant to mix the two.Ive seen people take a measly(!) 50-75mg of pure MDMA and get nystagmus, chattering jaw and retching.For me 160mg will do this.Again, this is variations in physiology between individuals at work.As a physicist, Im sure you know better than I the concept of non-linear kinetics.

And psychiatry ,in theory, should be the opposite of agitating, but I personally feel its one of the most nebulous of the medical disciplines due to the oft-times lack of physical signs which can be interpreted concretely.The signs which are used to reach a diagnosis can be interpreted in a variety of ways in psychiatry so give me chest pains or shortness of breath to suss out anytime!

Nothing good can come from combining these types of med´s with MAOI´s.

Agreed.