![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 25 of 28. This is the beginning of the thread.
Posted by Lynne on October 24, 1999, at 10:15:38
I would like to find more information about Selegiline use for depression and ADD. I have read everything on these boards. Does anyone know where I could find more info?
Posted by andrewb on October 24, 1999, at 12:05:13
In reply to Selegiline Info??, posted by Lynne on October 24, 1999, at 10:15:38
> I would like to find more information about Selegiline use for depression and ADD. I have read everything on these boards. Does anyone know where I could find more info?
Where to search:
1) go to the top of this page and connectot the tips page and do a keyword search for seligiline.
2) search medline, again doing a keyword search, for relevant medical abstracts
3) search Alta Vista or a similar search engine under the keyword 'seligiline' or 'deprenyl' (a brand name for seligiline)
Posted by dj on October 24, 1999, at 12:09:18
In reply to Re: Selegiline Info??, posted by andrewb on October 24, 1999, at 12:05:13
And if you discover anything really interesting about it, please report back to this babelogue pharmacopeia
> > I would like to find more information about Selegiline use for depression and ADD. I have read everything on these boards. Does anyone know where I could find more info?
>
> Where to search:
> 1) go to the top of this page and connectot the tips page and do a keyword search for seligiline.
> 2) search medline, again doing a keyword search, for relevant medical abstracts
> 3) search Alta Vista or a similar search engine under the keyword 'seligiline' or 'deprenyl' (a brand name for seligiline)
Posted by Adam on October 24, 1999, at 20:07:42
In reply to Selegiline Info??, posted by Lynne on October 24, 1999, at 10:15:38
Hey, Lynn,
The truth is, there isn't that much out there about the use of selegiline in depression. It's kind of an
odd choice for that indication, actually, since it was developed as an adjunct therapy for Parkinsons. Medline
seaches won't turn up very muc: there are only three papers that I have been able to find that even deal with
the idea of using selegiline in humans for depression. There was one using the forced-swim model in rats where
selegiline, both orally and transdermally, has an antidepressant-like effect. A search on the writings of Dr.
Ivan at Depression Central (Dr. Bob has links to this page, I think in the Tips section of his page) comes up
with only one reference to selegiline, with the remarkable statement that it isn't a very good antidepressant.That fact is, I may be involved in what is the only large study of selegiline in depression that has been done
(ongoing at McLean Hospital and other places). Just about everything out there on selegiline in the literature
and on the web refers to its use in Parkinson's, though some stuff also deals with its possible uses in delaying
the onset of Alzheimer's Disease. There are other rather flakey references to selegiline's life-extending
properties and its use as a "smart" drug. All of this is relevant, probably, only if you are taking selegiline
in low doses (5-10mg/day) where its effects on monoamine oxidase A are negligible. If you look in the PDR or
similar drug-info databases, what you'll find is explicit instructions NOT to use selegiline above 10mg/day
because of the potential for dietary issues. That's excactly what you'll have to do if you use it as a treatment
for depression. You might even have to take it in doses five to ten times as large as the "normal" dose to treat
depression, and there's virtually nothing out there describing such a scenerio.What there is to know is this:
It has a much higher specificity for MAO-B than MAO-A, but at doses in the 50-60 mg/day range, it starts to have
significant effects on MAO-A, irreversibly inhibiting it.In addition to blocking the breakdown of dopamine, it also can inhibit the reuptake of dopamine, boosting it
independantly of its effects on MAO.Among its major metabolites are L-amphetamine and L-methamphetamine. These L enantiomers are not nearly as potent
as the D forms, though they do have some effects, perhaps even some differential effects on the noradrenergic system
(though I have only seen one paper from way long ago that referred to such differences btw. amphetamine isomers).At the doses needed to treat depression, you have to worry about the food and drug interactions you would with
any MAOI.It appears that those who have responded well in the past to selegiline as an AD had fewer issues with anxiety
than those who had anxiety problems. One reference, using a limited sample size, but something to think about.That's all I can think of that might be relevant. I'm sorry I don't have the specific references in front of me.
It's all in Medline, though it took me a while to dig up some of these things, and I had to use some creative
keyword combinations. I hope more info. becomes available in the future. As my doctor said, it's considered
by many to be a "whacky" treatment for depression.It has worked for me, and, it would appear, a bunch of other people too, typically with few side-effects, and
I guess that's what's most important. Try it, and see what happens. Unfortunately, the literature doesn't
seem to be much of a guide.> I would like to find more information about Selegiline use for depression and ADD. I have read everything on these boards. Does anyone know where I could find more info?
Posted by john on October 27, 1999, at 9:41:15
In reply to Selegiline Info??, posted by Lynne on October 24, 1999, at 10:15:38
hi, you might want to try a medline search. I can't remember the address, but just type in MEDLINE on a search engine, such as www.google.com and you'll see the website. the search is free and includes abstracts from much clinical research.
good luck.
Posted by Adam on November 2, 1999, at 18:08:27
In reply to Selegiline Info??, posted by Lynne on October 24, 1999, at 10:15:38
> I would like to find more information about Selegiline use for depression and ADD. I have read everything on these boards. Does anyone know where I could find more info?
Well, don't I feel silly. Right here on Dr. Bob's site is a little
thread in the tips section on selegiline for depression.Try this link:
http://www.dr-bob.org/tips/split/Selegiline-for-depression.html
And, for convenience, here is a list of papers discussing the use of selegiline
as an antidepressant. Some of these I found, some I missed, apparently. So,
anyway, here they are...
Steur EN, Ballering LA: Moclobemide and selegeline in the treatment of depression in Parkinson's
disease (letter). J Neurologhy, Neurosurgery & Psychiatry 1997; 63: 547.Sunderland T, et. al.: High-dose selegiline in treatment-resistant older depressive patients. Arch
Gen Psychiatry 1994; 51: 607-15.Mcgrath PJ et. al.: A placebo-controlled trial of L-deprenyl in atypical depression. Psychopharm
Bull 1989; 25: 63-7.Mann JJ, et. al.: A controlled study of the antidepressant efficacy and side effects of (-)-deprenyl,
a selective monoamine oxidase inhibitor. Arch Gen Psychiatry 1989; 46: 45-50.Quitkin FM, et. al.: l-deprenyl in atypical depressives. Arch Gen Psychiatry 1984; 41: 777-81.
Birkmayer W, et. al.: L-deprenyl plus L-phenylalanine in the treatment of depression. J Neural
Transmission 1984; 59: 81-7.Mendlewicz J, Youdim MBH: L-deprenil, a selective monoamine oxidase type B inhibitor, in the
treatment of depression: a double blind evaluation. Br J Psychiatry 1983; 142: 508-511.Mann JJ, et. al.: Differential efficacy of L-deprenyl, a selective MAO type-B inhibitor, in
endogenous and nonendogenous depression. Psychopharm Bull 1982; 18: 182-4.
Posted by Judy on November 2, 1999, at 19:39:38
In reply to Re: Selegiline Info??, posted by Adam on October 24, 1999, at 20:07:42
Adam,
There is possibly more information in your October 24th post about the use of Selegeline as an AD than there is on the entire web! I had read your post before my Pdoc appointment last Friday, but unfortunately I didn't commit it to memory. If I'd had your phone number, I swear I would have called you from his office!
I took Selegeline about three years ago after my Pdoc spotted a small blurb on it's possibility as an AD (probably in the What's New & Whacky column) of one of his Psych Journals. Since I thrive on Nardil but can't endure the side effects (severe edema and almost total bladder and bowel shut-down), he was grasping at the straw that Selegeline might prove beneficial as well, with less side effects. As a matter of fact, it did help with the depression (at only 15 mg per day) but, as you read somewhere, it was less effective for anxiety and I needed to add Xanax to keep that at bay.
Three years later, I have exhausted just about all the AD's in all the classes, and asked my Pdoc on Friday if I could revisit Selegeline, at higher doses this time. After looking through every book in his office, he could find no information regarding dosage except for use in treating Parkinson's. I was telling him about your transdermal patch study and the other things I had learned from the web, and as he started to write the prescription, he halted, looked up at me and said, "Did anyone mention what oral dose they were taking?" It was funny, but sad too because there's NO information out there!
SO, my question to you or anyone else who might know, is have you seen a 'guestimate' anywhere hinting at what oral dose Selegeline becomes relatively effective as an AD. My suspicion is that if I take a high dose, I will be right back in the full-MAOI realm of side effects. I'm starting at 10 mg per day, as of today, increasing to 20 mg per day, and then I'll give that some time before increasing again. Also, any clue at what oral dose one would have to begin monitoring the diet for tyramines? (Not that it's a problem for me - I've taken MAOI's so many times that I almost follow the diet/OTC drug restrictions out of habit whether I'm taking an MAOI or not!)
Thanks,
Judy
Posted by Adam on November 3, 1999, at 17:24:31
In reply to Selegiline Oral Dosage - Adam?, posted by Judy on November 2, 1999, at 19:39:38
Hey, Judy,
Well, I'm not a doctor, but I've seen and heard of doses as high
as 60mg/day of selegiline. The low end seems to be around 40mg/day.
But, as you pointed out, there isn't much info out there. Check
out the Dr. Bob Tips section that I referenced in my last post.I would imagine a good approach would be to get up to 40mg/day
as quick as you can and then titrate more carefully based on how
your mood responds after that point. This post in the Tips looks
like it contains useful information on dosing:>From: [email protected] (David Reiser, M.D.)
>Date: Wed, 8 Jan 1997 20:12:43 -0800
>Subject: Selegiline for depression>Selegiline is a good antidepressant. Doses use to treat depression, unlike those for
>Parkinsons's disease, are in the 40 to 60 mg per day range. I give selegiline to my depressed
>patients all the time, usually in the 15 to 30 mg bid range. I start at no more than 5 mg bid and
>work up slowly. What you must be sure to tell your patient is that at these higher doses
>selegiline becomes non-selective and can produce a full blown MAOI food reaction, just as
>any MAOI can. Hence, your patient will need to be educated about food restrictions, drug
>restrictions, and the use of sublingual nifedipine in an emergency. MAOI rises at these higher
>doses of selegiline can and do occur.Now as far as how long it will take to ramp up, I really don't know. That
may really depend on your level of comfort. Interestingly, a potential
scenerio for me is that I went for eight weeks on no selegiline at all and
was suddenly switched to a 20mg/day patch immediately. Perhaps this could
be done so easily because of the different metabolite profile in transdermal
vs. oral delivery of selegiline. From what I've read, you will get more
L-amphetamine and L-methamphetamine production taking it orally, which could
be a bit of a nuisance. My guess is you could get up to a therapeutic dose
pretty quickly, given the mildness of the side effects. I imagine it is a
very individual thing. One famous poster to psychobabble couldn't tolerate
selegiline at 40mg/day doses, and got no antidepressant effect anyway. Others
find it easlily tolerated and very efficacious.Good luck to you!
> Adam,
>
> There is possibly more information in your October 24th post about the use of Selegeline as an AD than there is on the entire web! I had read your post before my Pdoc appointment last Friday, but unfortunately I didn't commit it to memory. If I'd had your phone number, I swear I would have called you from his office!
>
> I took Selegeline about three years ago after my Pdoc spotted a small blurb on it's possibility as an AD (probably in the What's New & Whacky column) of one of his Psych Journals. Since I thrive on Nardil but can't endure the side effects (severe edema and almost total bladder and bowel shut-down), he was grasping at the straw that Selegeline might prove beneficial as well, with less side effects. As a matter of fact, it did help with the depression (at only 15 mg per day) but, as you read somewhere, it was less effective for anxiety and I needed to add Xanax to keep that at bay.
>
> Three years later, I have exhausted just about all the AD's in all the classes, and asked my Pdoc on Friday if I could revisit Selegeline, at higher doses this time. After looking through every book in his office, he could find no information regarding dosage except for use in treating Parkinson's. I was telling him about your transdermal patch study and the other things I had learned from the web, and as he started to write the prescription, he halted, looked up at me and said, "Did anyone mention what oral dose they were taking?" It was funny, but sad too because there's NO information out there!
>
> SO, my question to you or anyone else who might know, is have you seen a 'guestimate' anywhere hinting at what oral dose Selegeline becomes relatively effective as an AD. My suspicion is that if I take a high dose, I will be right back in the full-MAOI realm of side effects. I'm starting at 10 mg per day, as of today, increasing to 20 mg per day, and then I'll give that some time before increasing again. Also, any clue at what oral dose one would have to begin monitoring the diet for tyramines? (Not that it's a problem for me - I've taken MAOI's so many times that I almost follow the diet/OTC drug restrictions out of habit whether I'm taking an MAOI or not!)
>
> Thanks,
>
> Judy
Posted by JohnB on November 5, 1999, at 19:45:49
In reply to Re: Selegiline Oral Dosage - Adam?, posted by Adam on November 3, 1999, at 17:24:31
Hi, Judy. I don't have depression, but I took Selegiline (Deprenyl) in the hopes that it would treat my social phobia. I started initially at 15 mg/day, which is supposed to keep it irreversible and selective for MAO-B. This means the effect is mostly dopaminergic. I didn't get any anxiety relief at this dosage, so i spoke with the psychdoc and we titrated up to 60 mg/day, in increments of +10mg every 4 days. At 60 mg/day, i felt wonderful and very sexual. Almost too sexual. However, it did nothing for my social phobia. I'd say the effect was nothing like with either Nardil (an irreversible, non-selective, Hydrazine MAOI) or Parnate (an irreversible, non-selective, NON-hydrazine MAOI)or Marplan (an irrerversile, non-selective, Hydrazine MAOI). Hope this helps at least a little.
Good luck, Judy. JohnB
Posted by Judy on November 5, 1999, at 21:07:46
In reply to My Experience with Selegiline 60mg/day, posted by JohnB on November 5, 1999, at 19:45:49
Thanks, JohnB, I can use all the info I can get!
When I took Selegiline (Eldepryl) several years ago (15 mg/day which was all my Pdoc would allow at the time because nobody knew anything about its use as an AD), it showed some AD potential even at that low dose. But the anxiety you mentioned was a problem so I had to augment with Xanax all the time and it eventually chased me away.
Did Nardil work really well for you (as it does for me except for the side effects)? How would you rate Nardil regarding sexuality (drive/ability) as compared to Selegiline? I was totally dead from the waist down while taking Nardil and wonder if I can expect the same from Selegiline at higher doses. Marplan caused the same side effects as Nardil for me and Parnate was way too ennervating for me to stay on it long enough to find out. After all these "sexual duds" I can't imagine finding something that made me feel "too sexual."
Have you since found a solution for your social phobia? I've been reading good things about Reboxitine for social phobia (and that it may be one of the few drugs that can be combined with an MAOI, which might be interesting).
Thanks again ~ Judy
Judy
Posted by dj on November 6, 1999, at 13:28:29
In reply to My Experience with Selegiline 60mg/day, posted by JohnB on November 5, 1999, at 19:45:49
Perhaps, JB, you or someone else might be kind and thoughtful enough to translate the MAOI distinctions you made below into English with an explanation of why they are labeled as irreversible?
> I'd say the effect was nothing like with either Nardil (an irreversible, non-selective, Hydrazine MAOI) or Parnate (an irreversible, non-selective, NON-hydrazine MAOI)or Marplan (an irrerversile, non-selective, Hydrazine MAOI). Hope this helps at least a little.
>
> Good luck, Judy. JohnB
Posted by JohnB on November 6, 1999, at 13:39:50
In reply to Re: My Experience with Selegiline 60mg/day, posted by Judy on November 5, 1999, at 21:07:46
Hi, Judy! Responses after each of your questions-
Thanks, JohnB, I can use all the info I can get!
>
> When I took Selegiline (Eldepryl) several years ago (15 mg/day which was all my Pdoc would allow at the time because nobody knew anything about its use as an AD), it showed some AD potential even at that low dose. But the anxiety you mentioned was a problem so I had to augment with Xanax all the time and it eventually chased me away.
>
> Did Nardil work really well for you (as it does for me except for the side effects)?
YES, NARDIL WAS VERY EFFECTIVE FOR MY SOCIAL PHOBIA, BUT ONLY AT 60MG/DAY. I STILL SUPPLEMENTED WITH KLONOPIN (1-2MG/DAY) WITH AN EXTRA 1-2MG BEFORE A MAJOR PRESENTATION.
-------------------
How would you rate Nardil regarding sexuality (drive/ability) as compared to Selegiline? I was totally dead from the waist down while taking Nardil and wonder if I can expect the same from Selegiline at higher doses.NARDIL WAS 100% SEXUAL ANESTHESIA. THEY SHOULD MANDATE IT FOR PERVERTS! SELEGILINE WAS VERY INVIGORATING, SEXUALLY - ESPECIALLY AT THE HIGHER DOSAGE OF 40-60 MG/DAY. ALMOST TOO MUCH - BEYOND WAS I COULD ACHIEVE IN TERMS OF SEXUAL RELIEF. IT WAS ALSO DEVOID OF ANY OTHER SIDE EFFECTS. NO WEIGHT GAIN, NO DRY MOUTH, NO SWEATING, NO SLOWED SPEECH, ETC. IT JUST DIDN'T HELP MY ANXIETY.
----------------------
Marplan caused the same side effects as Nardil for me and Parnate was way too ennervating for me to stay on it long enough to find out. After all these "sexual duds" I can't imagine finding something that made me feel "too sexual."
>
> Have you since found a solution for your social phobia? I've been reading good things about Reboxitine for social phobia (and that it may be one of the few drugs that can be combined with an MAOI, which might be interesting).I'M LOOKING FORWARD TO TRYING REBOXETINE WHEN IT COMES OUT. I'M CURRENTLY ON MARPLAN 60MG/DAY, AND IT PROVIDES SOME RELIEF, BUT HAS MORE SEXUAL DYSFUNCTION THAN I'D LIKE - ERECTILE/ANORGASMIA, ETC. CONTINUING ON KLONOPIN HAS BEEN A REAL SAVIOR - SORT OF THE CONSTANT WHEN I'VE CHANGED MEDS. NEVERTHELESS, I DON'T LIKE ITS NEGATIVE EFFECT ON MY SHORT-TERM MEMORY, THE DROWSINESS, AND IMPAIRED COGNITION.
NEXT WEEK, I'M GOING TO TALK WITH MY DOC ABOUT SEVERAL ALTERNATIVES - HE'S A GOOD PSCYHOPHARMACOLOGIST, AND WILLING TO TRY ANYTHING, WITHIN REASON. THE ALTERNATIVES ARE -
(1) HIGH DOSE BUSPAR (SOMEWHERE IN THE NEIGHBORHOOD OF 60 MG/DAY). PUBMED HAS A GOOD ARTICLE BY FRANKLIN SCHNEIER, SUGGESTING EFFICACY APPROACHING 70% AT 60MG/DAY. THEIR DEFINITION -WAS 70% OF SOCIAL PHOBICS REPORTEDLY MUCH/VERY IMPROVED.
(2) HIGH DOSE GABAPENTIN (3600MG/DAY). AGAIN, ANOTHER RECENT ARTICLE IN PUBMED, BY PARKE-DAVIS PHARMACEUTICALS. I HAD TRIED THIS BEFORE, BUT AT 1800 MG/DAY. AT THAT SUB-THERAPEUTIC DOSE, I NOTICED NO EFFECT, WHATSOEVER. NO SIDE EFFECTS, AS WELL.
(3) BUSPAR/ZOLOFT COMBINATION. MORE PUBMED RESEARCH, AGAIN. BUSPAR APPARENTLY ACTS IN A WAY TO INCREASE THE EFFECT OF SSRI'S AND THEIR ME-TOO COUSINS. THIS COMBINATION IS SUPPOSED TO BE VERY INVIGORATING - ZOLOFT (UP TO 200MG/DAY), AND BUSPAR (40MG/DAY)
(4) NARDIL, WITH SOME ADJUNCTIVE MED TO COUNTER THE CARBOHYDRATE CRAVING AND SEXUAL DYSFUNCTION. MAYBE SEE IF SELEGILINE COULD BE ADDED,OR SOMETHING ELSE. I KNOW HE HAS EXPERIENCE PRESCRIBING BUPROPION AND MAOI'S, EVEN THOUGH THIS IS CONTRAINDICATED IN THE CONSERVATIVE DRUG LITERATURE.> Thanks again ~ Judy. YOU'RE VERY WELCOME, JUDY. JOHNB :)
Posted by Adam on November 7, 1999, at 22:08:02
In reply to Re: reversible chemical distinctions?, posted by dj on November 6, 1999, at 13:28:29
Irreversible monoamine oxidase inhibitors (sometimes referred to as suicide monoamine oxidase inhibitors) bind to monoamine oxidase
and react with it chemically. This reaction leads to the formation of an unbreakable covalent bond between the enzyme and the drug
metabolite/enzyme adduct. By unbreakable I mean it cannot be dissociated by the enzyme itself or under conditions that would preserve
the enzyme. Because of where this bond is formed, MAO cannot react with its normal substrates. This effectively destroys the enzyme.Reversible MAOIs do not form unbreakle bonds with monamine oxidase. They can be dissociated from MAO without destroying it under
normal physioligical conditions, leaving the enzyme unaltered by the interaction. Because of the placement, strength, and duration
of this interaction, the reversible MAOI can still interfere with the enzymes ability to catalyse reactions with its normal substrates.In either case, the result is increased levels of some neurotransmitters.
"Specific" MAOIs have greater affinities for one or the other of the two MAO species, MAO-A or MAO-B. MAO-A preferentially breaks down
(oxidatively deaminates) serotonin and norepinepherne, though it does degrade dopamine to a lesser extent. MAO-B breaks down only
dopamine and phenylethylamine. Both forms of the enzyme can break down tyramine. So, an MAOI that inhibits one but not both of the MAOs
will lessen the danger of the "cheese effect", the adverse reactions one can experience from elavated levels of the amino acid tyramine
in the brain.Tranylcypromine, phenelzine, and isocarboxazid are examples of irreversible, non-specific MAOIs. They bind both MAO-A and B and destroy them.
Clorgyline and pargyline are examples of irreversible inhibitors of MAO-A.Moclobemide, befloxatone, and brofaromine are examples of reversible inhibitors of MAO-A (RIMAs) They transiently bind with MAO-A and leave
the enzyme unchanged by the interaction.Selegiline and rasagiline are expamples of irreversible inhibitors of MAO-B (selegiline has a much higher affinity for MAO-B, but starts to
have significant effects on MAO-A at high doses).I have seen references to reversible inhibitors of MAO-B (RIMBs?) but I do not know what these drugs are.
> Perhaps, JB, you or someone else might be kind and thoughtful enough to translate the MAOI distinctions you made below into English with an explanation of why they are labeled as irreversible?
>
> > I'd say the effect was nothing like with either Nardil (an irreversible, non-selective, Hydrazine MAOI) or Parnate (an irreversible, non-selective, NON-hydrazine MAOI)or Marplan (an irrerversile, non-selective, Hydrazine MAOI). Hope this helps at least a little.
> >
> > Good luck, Judy. JohnB
Posted by Elizabeth on November 8, 1999, at 0:22:43
In reply to Re: reversible chemical distinctions?, posted by Adam on November 7, 1999, at 22:08:02
> Irreversible monoamine oxidase inhibitors (sometimes referred to as suicide monoamine oxidase inhibitors)
I understand where this nickname comes from, but don't you think it's just a *little* bit tasteless?
> Tranylcypromine, phenelzine, and isocarboxazid are examples of irreversible, non-specific MAOIs. They bind both MAO-A and B and destroy them.
I've occasionally heard tranylcypromine referred to as "semi-reversible" (or something like that). Any idea what that's supposed to mean?
Posted by dj on November 8, 1999, at 2:29:42
In reply to Re: reversible chemical distinctions?, posted by Adam on November 7, 1999, at 22:08:02
Adam,
Thanks for the learned dissertation. After reading it twice I believe I have the gist of it, though some of the scientific jargon still leaves me a bit puzzled. I take it then that monamine oxidase is what MAO refers to and that MAOs have a negative impact on one's neurotransmitters that is treated in different ways by different MAOI's (what would the I stand for, then?) which because of their configuration have differing impacts on one's bio-chemistry and those that most negatively effect either but not both MAO's A & B most positively inhibit negative side effects from forbidden foods. Is that an apt summarization?
> By unbreakable I mean it cannot be dissociated by the enzyme itself or under conditions that would preserve
> the enzyme. Because of where this bond is formed, MAO cannot react with its normal substrates. This effectively destroys the enzyme.
>
> Reversible MAOIs do not form unbreakle bonds with monamine oxidase. They can be dissociated from MAO without destroying it under normal physioligical conditions, leaving the enzyme unaltered by the interaction.
Because of the placement, strength, and duration of this interaction, the reversible MAOI can still interfere with the enzymes ability to catalyse reactions with its normal substrates.
>
> In either case, the result is increased levels of some neurotransmitters.
>
> "Specific" MAOIs have greater affinities for one or the other of the two MAO species, MAO-A or MAO-B. MAO-A preferentially breaks down (oxidatively deaminates) serotonin and norepinepherne, though it does degrade dopamine to a lesser extent. MAO-B breaks down only dopamine and phenylethylamine. Both forms of the enzyme can break down tyramine.So, an MAOI that inhibits one but not both of the MAOs will lessen the danger of the "cheese effect", the adverse reactions one can experience from elavated levels of the amino > acid tyramine in the brain.
Posted by Adam on November 8, 1999, at 16:49:56
In reply to Re: reversible chemical distinctions? -- Adam?, posted by dj on November 8, 1999, at 2:29:42
> Adam,
>
> Thanks for the learned dissertation. After reading it twice I believe I have the gist of it, though some of the scientific jargon still leaves me a bit puzzled.Sorry, I hope I wasn't overly discursive.
>I take it then that monamine oxidase is what MAO refers to and that
Yes, MAO=monoamine oxidase. MAOI=monoamine oxidase inhibitor.
>MAOs have a negative impact on one's neurotransmitters that is treated in different ways by different MAOI's (what would the I stand for, then?)
I'm not sure MAOs have a "negative impact" per se. They chemically alter neurotransmitters in a way that inactivates them. This is a normal process, and messing
with it can cause problems. Since depression can be treated by boosting neurotransmitter levels in the synapse, MAOIs can be used to treat it. The cost is side
effects.>which because of their configuration have differing impacts on one's bio-chemistry and those that most negatively effect either but not both MAO's A & B most positively inhibit negative side effects from forbidden foods. Is that an apt summarization?
I'm not certain I understand this sentence correctly, but here's what I can say: The two enzymes are quite close in structure but are not exactly alike. They have some
overlap in function, and also have some distinctive functions. One overlapping function is the deamination of tyramine. To put it simply, if tyramine gets into your brain,
it somewhat mimics the action of another neurotransmitter and causes a cascade of events that can culminate in what is known as "hypertensive crisis," a sickening and
potentially dangerous elevation in blood pressure. By targetting one but not both of the MAOs, you do not so much "positively inhibit" this adverse response as simply allow
some portion of the body's normal biochemistry to do its job.
> So, an MAOI that inhibits one but not both of the MAOs will lessen the danger of the "cheese effect", the adverse reactions one can experience from elavated levels of the amino > acid tyramine in the brain.That's exactly it.
Posted by Adam on November 8, 1999, at 17:10:31
In reply to Re: reversible chemical distinctions?, posted by Elizabeth on November 8, 1999, at 0:22:43
> > Irreversible monoamine oxidase inhibitors (sometimes referred to as suicide monoamine oxidase inhibitors)
>
> I understand where this nickname comes from, but don't you think it's just a *little* bit tasteless?Yes, it is more than a little tasteless. Sorry! I didn't mean to bring up the "S" word in a cavalier fashion.
I guess non-depressed biochemists think it's just fine.
>
> I've occasionally heard tranylcypromine referred to as "semi-reversible" (or something like that). Any idea what that's supposed to mean?I saw that too, and no, I don't know what it means. Most of what I know about the chemical interactions of these
irreversibles with MAOI I found in an old extract on the metabolism of phenelzine by MAO-A, and assumed the situation
was analogous for the others. I couldn't find really specific references to tranylcypromine's interaction, which
stinks since it is the one I'm most interested (heck, I'll probably be on it in a few months). I can only assume,
as you surely have, that binding to MAO doesn't always lead to an unbreakable bond being formed, and that it can
sometimes pop off. How that might happen I haven't a clue.
Posted by Scott L. Schofield on November 9, 1999, at 17:17:58
In reply to Re: Selegiline Info??, posted by Adam on October 24, 1999, at 20:07:42
> That fact is, I may be involved in what is the only large study of selegiline in depression that has been done (ongoing at McLean Hospital and other places). The truth is, there isn't that much out there about the use of selegiline in depression. It's kind of an odd choice for that indication, actually, since it was developed as an adjunct therapy for Parkinsons. <Actually, I believe the drug was originally investigated as an antidepressant. It was dropped for that indication for lack of efficacy. I guess some really smart person decided to try it for Parkinson's. I think the threshold of selectivity is about 30 mg/day.
There is actually quite a bit in the literature regarding the use of selegiline as an antidepressant. To find it, you have to start from about 1980. John Mann, whose work was noted in another post, has probably had the most experience with it.
By the way, I once tried to get into a venlafaxine study at McLean Hospital. They do good things there.
Good Luck.- Scott
Posted by Scott L. Schofield on November 9, 1999, at 17:29:19
In reply to Re: Selegiline Info??, posted by Adam on October 24, 1999, at 20:07:42
> That fact is, I may be involved in what is the only large study of selegiline in depression that has been done (ongoing at McLean Hospital and other places). <
I would be very interested to know how you do on selegiline. I tried it years ago, but I don't think I made it any higher than 40 mg/day. It really sucks being treatment-resistant. I wish I would see more posts from people for whom selegiline has worked well. I was under the impression that it wasn't very good as an antidepressant. I would consider putting it on my short-list if I were to hear more good things about it. First-hand experiences would be compelling, regardless of what the researchers have to say about it.- Scott
Posted by Adam on November 9, 1999, at 18:01:27
In reply to Re: Selegiline Info??, posted by Scott L. Schofield on November 9, 1999, at 17:29:19
It seems there is more than I was able to find on the use of selegiline and depression, and
I'm still trying to figure out how I missed it. I typically do Advanced PubMed Searches and
use search words like "selegiline", "L-deprenyl", "(-)-deprenyl" "Eldepryl" , "depression" ,
"antidepressant" and so on and came up with very little that seemed relevant. Obviously I
need some way to refine my searches. Thanks for the tip on the author.I'm doing pretty well on selegiline. It has been a good choice in some respects, and less than
optimal in others. My mood has definitely improved, and I'm often now in this rather strange
state of feeling happier but still anxious. I don't sleep a whole lot, but that hasn't been too
much of a problem. I seem to be getting enough. When I first started responding, I felt super-
wound-up and a little euphoric. It was nice, but I think if I had kept going that way I would
have eventually collapsed. What I guess was hypomania went away after a couple weeks, I felt a bit
down (I rather liked the hypomanic me), but I seemed to have settled into a good place. I'm not
perfect, but no drug has done the job for me like this one has.I just need to figure out what I'll be doing in the future. When the study ends, I have the choice
of trying to take selegiline orally, or trying something else and hoping the patch makes it to
market soon/at all. I'm not sure I want to mess around with generic selegiline. At the same time,
to buy Eldepryl in the amounts I am likely to need as an antidpressant therapy could be a problem:
it's tres expensive and I'm not sure how my insurance company is going to feel about offlabel
treatments taken at such volumes (60mg/day = 12 Eldepryl/day). I might wind up on tranylcypromine.
This has me a bit scared. The best thing about selegiline (taken transdermally, at least) has
been its tolerability. If I don't react well to tranylcypromine? Such is the path I've chosen.
> > That fact is, I may be involved in what is the only large study of selegiline in depression that has been done (ongoing at McLean Hospital and other places).
> I would be very interested to know how you do on selegiline. I tried it years ago, but I don't think I made it any higher than 40 mg/day. It really sucks being treatment-resistant. I wish I would see more posts from people for whom selegiline has worked well. I was under the impression that it wasn't very good as an antidepressant. I would consider putting it on my short-list if I were to hear more good things about it. First-hand experiences would be compelling, regardless of what the researchers have to say about it.
>
> - Scott
Posted by Cindy on November 10, 1999, at 9:10:53
In reply to Selegiline Info??, posted by Lynne on October 24, 1999, at 10:15:38
> I would like to find more information about Selegiline use for depression and ADD. I have read everything on these boards. Does anyone know where I could find more info?
Waiting at the doctor's yesterday, I was reading old issues of womens magazines...and one had an ad for this drug as an aid for senile doggies! I couldn't believe it! (it was all about how to improve your pet's memory in its old age!!!)--Cindy
Posted by Lynne on November 10, 1999, at 9:26:49
In reply to Selegiline Info??, posted by Lynne on October 24, 1999, at 10:15:38
> I would like to find more information about Selegiline use for depression and ADD. I have read everything on these boards. Does anyone know where I could find more info?
I have been using Selegiline oral form and after 5 weeks I am noticing its affect. It does help with depression, but it causes insomnia. There was a BIG difference between name brand and generic. I hated the name brand and the price, the generic was alot cheaper and alot better.I am taking 25mgs a day. It did take a long time before I noticed it was working.
Posted by Scott L. Schofield on November 10, 1999, at 14:14:46
In reply to Re: Selegiline Info??-Scott, posted by Adam on November 9, 1999, at 18:01:27
> I typically do Advanced PubMed Searches and use search words
like "selegiline", "L-deprenyl", "(-)-deprenyl" "Eldepryl" ,
"depression" , "antidepressant" and so on and came up with very
little that seemed relevant. I might wind up on tranylcypromine. This has me a bit scared.
The best thing about selegiline (taken transdermally, at least)
has been its tolerability. If I don't react well to
tranylcypromine? Such is the path I've chosen. What I guess was hypomania went away after a couple weeks, I
felt a bit down (I rather liked the hypomanic me). <Oh yeah - keep an eye out for the precipitation of mania. If you
did indeed experience hypomania with selegiline, a "full-blown"
mania might occur with *any* drug. If you do get manic, you
probably won't recognize it as such. You might not even believe
the people around you when they tell you that you are manic. I
didn't. I thought it was a good idea for me to let my family know
to be on the alert. Chances are, you don't have this potential at
all. (I don't mean to scare you any more than you are already.
It's just a reasonable caveat).I think MAO-inhibitors are making a come-back. It was criminal for
psychiatrists to avoid prescribing them. I couldn't believe it
when I read posts in which even tricyclics were avoided. I should
think that after trying five different SSRIs in succession without
results, one might at least entertain the idea of using one of
them. Imipramine (Tofranil) IS the "gold-standard" by which other
antidepressants are compared.* Requisite disclaimer.
Posted by Adam on November 10, 1999, at 18:43:47
In reply to Re: Selegiline Info??-Scott, posted by Scott L. Schofield on November 10, 1999, at 14:14:46
>
I should make clear that no one who saw me was prepared to say I
was in a manic state, but it was suggested. I certainly had some
interactions with friends that I guess left them scratching their
heads. I have to admit, the idea of experiencing mania just
once intrigues me, as I know it shoudn't. I'm definitely on the
lookout, though. If tranylcypromine is my next choice, that may
be a real concern. A big dose of Parnate is an awful lot like
taking a small dose of amphetamine, and if my response to Parnate
is even _better_ than selegiline moodwise, yeah, it could be
interesting. No way to know for sure.I agree MAOIs are under-utilized, not that I'm particularly psyched
about having to take one. I'll miss certain things, I'm sure, once
I can't eat or drink them anymore. I'm scared sometimes I'll get
in a accident and somebody will shoot me up with something
sympathomimetic (still gotta get that bracelet). I can see why no
one would want to prescribe an MAOI anymore than one would be jumping
for joy to have to take one, but the fact remains they work well for
some, including me, and may be the only thing that works.C'est la vie.
Posted by jamie on November 12, 1999, at 3:50:19
In reply to Re: Selegiline Info??, posted by Lynne on November 10, 1999, at 9:26:49
>
>
> I have been using Selegiline oral form and after 5 weeks I am noticing its affect. It does help with depression, but it causes insomnia. There was a BIG difference between name brand and generic. I hated the name brand and the price, the generic was alot cheaper and alot better.I am taking 25mgs a day. It did take a long time before I noticed it was working.Lynne could you elaborate on the difference between brand and generic? Why so much difference? Aren't they the same thing? I don't get it. Help me out here. When you say brand name, what was it called? What is the generic called? How were they different?
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