Posted by Pitviper on October 16, 2007, at 3:05:27
In reply to Re: Please help w new ? about selegiline prozac combo » Larry Hoover, posted by Meagan on October 12, 2007, at 14:24:00
Hi Meagan. I'm assuming you're using the pill form of selegiline, and not the patch (since the patch is in 6 mg increments).
> Thank you Lar, I did indeed mean that selegiline at higher doses would inhibit serotonin breakdown, similar to prozac.
Selegiline and Prozac don't have the same mechanism of action at any dose.
Monoamine oxidase (MAO) is an enzyme that catalyzes the breakdown, as you say, of serotonin and other monoamines (norepinephrine, dopamine). So MAO inhibitors will prevent these monoamines from being broken down, increasing the concentration of extracellular monoamines.
*Reuptake* inhibition is entirely different. A serotonin reuptake inhibitor, like Prozac, prevents stray serotonin molecules from being sucked back into cells, again increasing the amount available extracellularly.
It's the combination of the two different mechanisms that leads to the serotonin syndrome when MAOIs are combined with SRIs (not just the SSRIs, but drugs like Effexor and Cymbalta, certain tricyclics (clomipramine, imipramine, amitriptyline, and doxepin are contraindicated with MAOIs, while desipramine, nortriptyline, and amoxapine present minimal risk, if any). You are right that selegiline is a selective inhibitor of MAO-B at low doses but loses its selectivity at higher doses. 20 mg (orally) is a bit on the low side for depression, actually. For Parkinson's the recommended dose
I tried selegiline a while ago, at 40 mg/day, without success (had better luck with Parnate). However, even this dose may actually have been too low.
Fenfluramine is neither a MAOI nor an SRI. The way it works is analogous to amphetamine, only fenfluramine causes serotonin to be released rather than dopamine. This leads to subsequent depletion of serotonin (also not an issue with Prozac). Another drug that works this way is MDMA, the street drug Ecstasy.
(Phentermine, incidentally, is a mild stimulant, akin to amphetamine, but considered to have less abuse potential. "Fen/phen" (or should it be "phen/fen?") was a protocol using phentermine and fenfluramine in combination for weight loss, usually with phentermine taken in the morning and fenfluramine at bedtime. Fenfluramine, not phentermine, was the cause of the heart valve defects and PPH, which caused it to be taken off the market. Phentermine is still available in the U.S.)
I do not think that heart valve damage is a realistic concern with your combination. Prozac does not cause the type of problems that you get with fenfluramine, and neither do MAOIs.
The serotonin syndrome is what you have to watch out for. You should familiarize yourself with the symptoms so you can be on the lookout for them. There have been at least a couple of reports of serotonin syndrome when nonselective MAOIs were combined with L-tryptophan.
But actually, I think your doctor's idea of taking you off the Prozac makes sense. It seems to me, from what you've said, that the Prozac isn't making much of a contribution. Eliminating the Prozac would make it safer to try higher, nonselective doses of selegiline. I doubt that you will have a problem with 20 mg but of course you should keep your eyes open, of course.
If selegiline by itself should prove inadequate, there are antidepressants that you can take safely in combination with MAOIs.
However, I think your doc's claim about chronically depressed people having "too much MAO" is mistaken. I'm not sure where he would get this idea. He may be oversimplifying, as many doctors do, believing they are doing their patients a favor; you did mention he hasn't been very informative. There are no known consistent lab findings in depressed individuals, and while some may have elevated MAO, it's certainly not universal.
> is it too simplistic to equate what happened to patients on Phen-Fen with the combo I am presently taking?
Exactly right.
Good luck to you.
Pitviper
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URL: http://www.dr-bob.org/babble/20071009/msgs/789528.html