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Re: Moclobemide dosage and pill frequency Berty McNotBerty

Posted by Tomatheus on November 18, 2005, at 22:41:50

In reply to Moclobemide dosage and pill frequency, posted by Berty McNotBerty on November 17, 2005, at 9:24:19

Berty,

Welcome to Psycho-Babble.

Where did you hear that 300mg of moclobemide inhibits MAO-A by 80 percent? It's an interesting figure, but I question its validity. According to a research article reviewing moclobemide and other RIMAs (Nair et al., 1993), ex vivo animal experiments have found that moclobemide inhibits MAO-A by up to 80 percent in the brain and liver 30 minutes after drug treatment. The article did not state the dosage of moclobemide that was used is these animal experiments.

In the research studies that I've read concerning the effects of moclobemide on humans, I have not found any data stating that certain dosages (e.g., 300mg) of moclobemide are capable of inhibiting MAO-A by a certain percentage (e.g., 80 percent). I suspect that the reason for this is that there is strong evidence in the scientific literature indicating that MAO-A levels vary considerably among humans. Studies measuring MAO-A levels in cultured skin fibroblasts and placenta have found that MAO-A activity varies "over 50-fold among control individuals" (Hotamisligil et al, 1991). More recently, genetic association studies have found statistically significant correlations between genetic variants that encode for abnormally high levels of MAO-A and certain psychiatric conditions (major depression, sleep disturbance, depressed suicide, panic disorder, phobic spectrum anxiety disorders, and ADHD). So, given the evidence that MAO-A activity varies from one individual to the next, the level of MAO-A inhibition from moclobemide would also vary from person to person.

Based on the research studies I've read on moclobemide, there also seems to be a consensus that moclobemide's inhibition of MAO-A is inconsistent over time because of the drug's short-acting nature. So, even if 300mg of moclobemide is capable of inhibiting MAO-A by 80 percent in a given individual (but not necessarily other individuals because MAO-A levels naturally vary) after 30 minutes, the level of MAO-inhibition would likely drop over a 12-hour period. As one meta-analysis of moclobemide and brofaromine (Lotufo-Neto et al., 1999) put it, it has been found that 92 percent of moclobemide is excreted from humans within 12 hours of ingestion. It is for this reason and because of moclobemide's reversibility that I think moclobemide tends to be less effective than irreversible MAOIs, such as Nardil and Parnate.

So, to answer your question about moclobemide doses exceeding 300mg/day, I think that higher doses do have the potential to be more beneficial than doses of 300mg/day or lower because moclobemide's inhibition of MAO-A (at 300mg/day) is likely a lot lower than 80 percent in many individuals, and because taking the medication three to four times a day would probably produce a more consistent effect (but still likely less consistent than the longer-acting irreversible MAOIs). If the primary effect you're looking for is MAO-A inhibition, I think it would be a good idea to try raising your dose, but I would suggest Nardil for a stronger and more consistent effect. If you're looking primarily to increase dopamine (which would be better achieved by a medication that is more selective to MAO-B), it might be best to wean off of the moclobemide and just go with deprenly. Moclobemide, being relatively selective to MAO-A, tends to raise serotonin and norepinephrine more than it does dopamine.

As far as taking deprenyl (or other meds) on alternate days, I really can't say if there would be any downsides to this, as I've never tried it.

Thanks for your question. Let me know if I could be of more help.

Tomatheus

==

REFERENCES

Hotamisligil, G. S., & Breakfield, X. O. (1991). Human monoamine oxidase A gene determines level of enzyme activity. American Journal of Human Genetics, 49, 383-92.

Lotufo-Neto, F, Trivedi, M., & Thase, M. E. (1999). Meta-analysis of the reversible inhibitors of monoamine oxidase type A moclobemide and brofaromine for the treatment of depression. Neuropsychopharmacology, 20, 226-47.

Nair, N. P. V., Ahmed, S. K., & Ng Ying Kin, N. M. K. (1993). Biochemistry and pharmacology of reversible inhibitors of MAO-A agents: Focus on moclobemide. Journal of Psychiatric Neuroscience, 18, 214-25.

==

> Hello everyone, This is my fist post on Dr Bob but I've been a visitor for ages, it's cool so many people arte helpful and supportive.
> But anyway, I've just started Moclobemide at 300mg per day & was wandering about dosage. I've heard that 300mg per day inhibits MAO-A by 80% so was wondering why peoples dosage can go up to 1200mg, all of the MAO-A would presumably be inhibited at dosages below that (I'm guessing). Also I've heard less dopamine is synthesised when MAO-A is inhibited by 80% or more. I was wandering if anyone knew therefore what benefits there would be of a dose of more than 300/450mg per day?
>
> Another thing, Ive been considering adding low dose deprenyl to the 300mg moclobemide (after a couple of weeks depending on how the moclobemide goes) and I'm thinking of taking 5mg every other day (I've tried deprenyl on its own before but it increased anxiety). Are there any downsides to taking deprenyl on alternate days (or any sort of pills for that matter).
> Thanks.


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poster:Tomatheus thread:579587
URL: http://www.dr-bob.org/babble/20051112/msgs/580289.html