Posted by Adam on May 3, 2000, at 0:28:23
In reply to Parnate+Selegeline Temptation, posted by Judy on May 2, 2000, at 15:12:22
Hey, Judy,
The conventional wisdom is that such a strategy is HIGHLY contraindicated. In rare cases, people have had extremely bad reactions to combinations of MAOIs.
There have also been reports, in rare cases, of people having adverse reactions to combinations of low-dose selegiline and SSRIs. A review of these reports I read concluded that few if any of these were actual cases of serotonin syndrome, but that caution was still warranted.
Still further have been reports of hypertensive episodes on the normal 5mg b.i.d. regimen of selegiline plus either tyramine-rich foods or sympathomimetic drugs. Again, though rare, Somerset Pharmaceuticals have revised their literature to advise avoiding such combinations while on selegiline.
My personal, very non-MD oppinion is that low dose selegiline, in the 10mg/day range is already high enough to cause some inhibition of MAO-A, and in some individuals, this inhibition may be significant. Some papers have been published showing that complete inhibition of MAO-B can be achieved with doses as small as 2.5 mg b.i.d., and that 10mg/day is more than necessary to achieve therapeutic levels for Parkinson's disease.
Again, in my very, very unprofessional oppinion, doses of selegiline that are truly MAO-B specific (below 10mg/day, in all likelihood) should be relatively safe in combination with antidepressants, including non-selective MAOIs. However, I doubt very much any physician will feel comfortable risking such a combo., and to be good patients, we should listen to them, as frustrating as it is. I think your doctor may be right about at least one thing, though: It's not the combination that made you feel well. Selegiline, taken orally, has a half life of something like 6-8 hours. If you waited two weeks before starting Parnate, there would be negligible amounts of selegiline left in your system. Also, MAO levels would have returned to nearly baseline in the mean time. Even the amphetamine and methamphetamine metabolites,which have longer half-lives, would be essentially gone. In my experience, I have also had periods of uncanny euthymia during and immediately following a taper from an antidepressant I found not worth the side-effects. This was especially true of Remeron (mirtazapine). Here's my theory: The drug is having an effect on your mood, though not a robust one. However, it's hard to focus on that when side effects are making you feel so badly. As the side effects disappear, upon tapering off of a medication, you feel some of the mood elevating effects without feeling the adverse ones, not to mention a sense of relief at being drug-free for a change. Unfortunately, it doesn't last; relapse inevitably occurs. That may, in a loose sense, be what's up with you and Nardil/Marplan.
Now, you didn't have bad side-effects with selegiline, but you did feel euphoric shortly after taking Parnate. I have another theory: Parnate and selegiline have many similarities in chemical structure. The former is essentially amphetamine with a modified side chain, and the latter is metabolized into amphetamines. Both thus have some stimulant properties, as well as some other effects on the sympathetic nervous system. Parnate is actually one of the few antidepressants with abuse potential, in all likelihood because it's a stimulant. People who stop taking stimulants after prolonged use can and usually do get depressed, and, as expected, they perk right up again with the next fix, as long as that vicious cycle can last. You may have experienced something roughtly similar, and as soon as you were tolerized to the stimulant effects, Parnate's deficits as an antidepressant were soon recognized.
There might be some solutions to this problem. One would be to augment Parnate with lithium. Lithium, as well as Nardil and Marplan, have the ability (among other things) to potentiate the action of GABA (through a variety of complex, not always well-understood mechanisms), a property selegiline and Parnate certainly do not have. I think whatever "GABAnergic" effects the hydrazine MAOIs and lithium have, it defenitely benefits some people with depression, as well as some other problems related to anxiety. In a very crude sense, lithium might both augment and mitigate beneficially Parnate's action. There are, however, side effects with lithium augmentation to be reckoned with, too. It may still be worth a try, though.
You might also, since you seem to have responed so well mood-wise to initial treatment with Parnate, benefit from augmentation with a stimulant like dextroamphetamine or methylphenidate. This seems paradoxical to me, somehow, given your good response to Nardil and Marplan, though. I call this impression an "intuition", which, having no clinical expertise whatsoever, probably isn't worth much, though.
At any rate, given your good response to some MAOIs in the past, there's hope for Parnate still, either at higher doses, or augmented with something. It appears lithium is particularly good for some at giving Parnate the kick in the pants it needs to be effective. I seem to remember Elizabeth mentioning that she did well for a while on Nardil, but it pooped out, and then, after a lackluster initial response to Parnate, had a very robust response to the addition of lithium (perhaps she might comment, and/or correct me on things I have said above). You fit the first part of this picture. Perhaps you will fit the second.
Hope this is helpful.
> This is my second attempt at this message. The first disappeared in the registration process.
>
> First some background: I'm MAOI responder – specifically Nardil. It completely banishes my depression/anxiety/anhedonia. Unfortunately the side effects (severe edema, for one) make it impossible for me to take it anymore. I also responded relatively well to Marplan but the side effects were even more pronounced.
>
> I was switched to oral Selegeline, which had no side effects whatsoever; but it was only slightly beneficial in the beginning. By the time I had titrated up to 60 mg per day, I was as depressed as ever. My doctor wouldn’t increase the dosage further or augment because he was uncomfortable with Selegeline’s lack of track record as an AD at high doses.
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> I washed out Selegeline for two weeks and started Parnate at 10 mg a day. By the second day, I was in hypomanic heaven! That lasted for two weeks and pooped out, and I began titrating up by 10 mg every couple of weeks, with relative few side effects, until I got to 60 mg/day, where I am now. Never, since that first two-week period, has Parnate touched my anhedonia again.
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> My point (finally!). I’ve taken MAOI’s at least a half dozen times in the past, and each time I quit, I experience almost exactly four-weeks of lingering benefits afterwards. It just seems too coincidental to me that I felt so great for the first two weeks on Parnate. Is it possible that I was reacting to the combination of Parnate and the small amount of Selegeline remaining in my system? I meekly posed this question to my doctor and he pooh-poohed it, saying my brain had been robbed of Selegeline and it pounced on Parnate as soon as it was introduced. (Excuse the layman’s language – he was a bit more technical than that.) That seems too much of a coincidence to me – two weeks of goodness, then nothing?
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> Now I’m obsessed by the fact that I might have a side-effect-free cure for my depression sitting right in my medicine cabinet. My question is: What would be the risks of my trying a small amount (5 – 10 mg) of Selegeline with Parnate? (Besides my doctor throwing me out on my keester for self-medicating and never seeing me again?). It even seems to me I might be able to get away with a much lower daily dose of Parnate if my theory is correct.
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> I realize I’m asking a 'taboo' question here but I’m a bit desperate. In the past 16 years, I’ve run the gamut of AD’s and nothing works for me but MAOI’s. I'd appreciate any comments except "What are you, crazy?!?"
>
> Judy
poster:Adam
thread:31946
URL: http://www.dr-bob.org/babble/20000429/msgs/32001.html