![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 10 to 34 of 34. Go back in thread:
Posted by Adam on December 20, 1999, at 2:53:09
In reply to Re: Selegiline Expertise Needed Again(Long/Boring), posted by Judy on December 19, 1999, at 12:48:02
Just as an aside, I experienced a severe worsening of my illness while on Serzone, and read
with interest and distrubance that you found it difficult to deal with. I got so bad I
wound up in the hospital. I was a mess, a "death please take me now" kind of violently
relentless despair. I have so often wondered if Serzone precipitated this episode, or if
it was just a coincidence.Having said that, I tried Remeron, and did not experience anything as troubling. Nearly
irresistalbe somnolence was the primary side effect, and yes, strange as it seems, this
did get a bit better as I raised the dose (up to 45mg/day). I never got too much of an
antidepressant response out of it, and it always left me feeling very tired. But compared
to the first couple of weeks in the end it was relatively tolerable. The first day I
took it I wanted to crawl on the floor from my bed to the bathroom rather than walk. It
was unreal.> Jeez you guys! Look at the times you're posting! And I'm moaning about MY sleep problems!!!
>
> >Can you share with us your history? I bet some good ideas will come up.
>
> Let me start by telling you that I AM an MAOI responder. I could be the 'poster child' for Nardil. I've taken it five times over the past 15 years and I am the best possible person I could ever be when taking it. Unfortunately, the side effects (severe edema, almost complete shutdown of my entire excretory system) have eliminated it from my list of possibilities. I've lost my 'safety net'! It's also probably unfortunate that Nardil is the yardstick by which I measure all other AD's because I don't think I will ever find another that provides the robust, wonderful hypomanic benefits that Nardil does.
>
> >I think I remember reading that 80mg was the maximum dose of selegiline used in depression
>
> I've never seen 80 mentioned before - but I wonder what 80 would do to my nightmarish sleep if it's bad at 60 mg.
>
> >Only the experts or the brave would augment the maoi.
>
> You're right! My Pdoc is self-admittedly not one of the brave. He would augment with lithium, however. He also admits that he's not sophisticated enough to recommend drug cocktails and would prefer that I see a big-time psychopharm in Boston for that.
>
> >If you are going from black to blue, that could be a good sign. You are, at least, maybe,
> a partial responder, which could mean that a) you will contiune to improve, or b) you have a good chance of responding to an augmentation strategy such as the addition of low-dose lithium. Non-responders to MAOI treatment are less likely to achieve a full response from lithium augmentation.
> >If you can, you might want to stay with the 60mg for another full 2 or 3 weeks
>
> This is the unknown that bothers me...am I a responder to Selegiline, obviously a completely different drug than Nardil? Nardil showed benefit within the first two weeks - is it possible that Selegiline could possibly kick-in after so much longer? Or is from 'black' to 'blue' as good as it's ever going to get? With or without augmentation? Tough questions to answer when a drug has little or no track record.
>
> >I seem to be barely dreaming at all. A this point, the insomnia is more than an equitable trade for the despair that preceeded it
>
> Not dreaming, for me, is a sign that an MAOI is working. I too missed dreaming when I took Nardil; but like you, I felt the insomnia and lack of dreams were well worth it for the relief it provided. My hellish nights right now are making me very concerned about Selegiline's effectiveness.
>
> >Maybe if you give us a history of your diagnosis, treatment, doses, reasons for discontinuing, etc.
>
> My Dx is, and I quote, "Major Depression at worst; Severe Dysthymia my best"
>
> TCA's tried: Imiprimine, Desiprimine - very little AD benefit, big weight gain, severe sweating.
>
> SSRI's: Tried all but Celexa. No AD benefit. Every one made me too fatigued to function. No amount of time made them tolerable.
>
> Effexor: Little AD benefit, too enervating
>
> Effexor SR: A disaster (for 6 weeks at 150 mg). No AD benefit. Tremors, muscle weakness. Flu-like symptoms.
>
> Klonapin: Fatigue. No benefit.
>
> Welbutrin: Way too enervating! Felt like a 'nervous breakdown' Couldn't give it a decent trial.
>
> Lithium (alone): Fatigue bordering on Coma
>
> Serzone: Worse fatigue than Lithium (if possible), with aggression and hostility from out of the blue. If I'd had the physical strength, I would have thrown myself in front of a bus to put an end to the way it made me feel!
>
> Marplan: AD benefit (nothing like Nardil though). Slower kick-in than Nardil. Worse edema.
>
> Parnate: Too enervating. Very short trial.
>
> ECT & Rememon: Both have been offered. I feel as if ECT is only a temporary measure with no medicinal backup. Remeron - after my debacle with Serzone, the thought of taking it scares the heck out of me (Can I believe that it becomes enervating at high doses?)
>
> There are more that don't come to mind right now - I wish I'd written them all down over the years. Combining any of the above really makes me skittish - like trying to make a 'right' with two 'wrong's' I do wonder if Parnate might be worth another shot if I augmented it with something (what?) to counteract the aggitation it causes.
>
> One other question. I am scheduled to have a thyroid function test done right after the holidays. I'm also wondering whether diminishing Estrogen (I'm guessing menopause isn't too far away) might be the cause of drugs that I've taken before acting differently now (i.e. Effexor was a relatively benign drug several years ago - SR almost did me in a few months ago. And the increased edema with Nardil recently? - it was never that bad before).
>
> Thanks for your responses and anything else you might be able to add. Judy
>
>
>
>
>
>
Posted by David Mitrtzer on December 20, 1999, at 9:44:19
In reply to Re: Selegiline Expertise Needed Again(Long/Boring), posted by Adam on December 20, 1999, at 2:53:09
How about Pindolol as a potentiator for Selegiline? Anyone tried it, or have any thoughts?
Posted by Judy on December 20, 1999, at 18:44:41
In reply to Re: Selegiline Expertise Needed Again(Long/Boring), posted by Adam on December 20, 1999, at 2:53:09
Adam - I would bet the farm that Serzone played a part in what led up to your hospitalization. I have dubbed it "the most dangerous drug I've ever taken." Every morning I would sleep through the alarm clock radio set at full volume. My husband then started to call home when it was time for me to get up, get my daughter on the phone and tell her to wake me. A couple of frightening times, my brain was awake enough to know that she was at my bedside, but I was, for a minue or so, unable to respond or even move my body. It was just like coming out of anesthesia! In little better than that condition, I would then drive 40 miles to work - over the Sagamore Bridge and down the Cape.
Besides the near fugue state I was in, I started to become overly-angry and hostile (at the time I thought it was just my fatigue). I actually told the boss's wife where to go one morning! (Believe me, I'd thought it many times, but *never* would have verbalized it!) It wasn't until after I stopped taking Serzone that I read somewhere that it can cause feelings of agression and hostility.
For some, Serzone may be a blessing; but I couldn't possibly recommend it to anyone! I'm wondering if our particular brain chemical makeup responds favorably to MAOI's, but strikes back at Serzone. (BTW, I have the same urge to push Nardil on treatment-resistant people that you do with Selegiline.)
As for Remeron - I am plain scared to death of any drug that makes me feel sedated. Too much like depression (or Serzone!). Besides, most of us don't have the luxury of being able to sleep out the early stages of a sedating drug. Do I sound like I'm making excuses for not trying everything in my power to get well? I hope not. I'm just truly afraid I can't deal with one more trial and nasty failure.
I guess an appointment with the big-time psychopharm is in order. Thanks so much for all your suggestions. Judy
> Just as an aside, I experienced a severe worsening of my illness while on Serzone, and read
> with interest and distrubance that you found it difficult to deal with. I got so bad I
> wound up in the hospital. I was a mess, a "death please take me now" kind of violently
> relentless despair. I have so often wondered if Serzone precipitated this episode, or if
> it was just a coincidence.
>
> Having said that, I tried Remeron, and did not experience anything as troubling. Nearly
> irresistalbe somnolence was the primary side effect, and yes, strange as it seems, this
> did get a bit better as I raised the dose (up to 45mg/day). I never got too much of an
> antidepressant response out of it, and it always left me feeling very tired. But compared
> to the first couple of weeks in the end it was relatively tolerable. The first day I
> took it I wanted to crawl on the floor from my bed to the bathroom rather than walk. It
> was unreal.
Posted by JohnL on December 21, 1999, at 2:18:35
In reply to Re: Selegiline Expertise Needed Again(Long/Boring), posted by Adam on December 20, 1999, at 2:41:45
Adam, couple questions for you. Your experiences on serzone and remeron mirror mine almost exactly, which makes me wonder if I might have a high likelihood of responding to selegiline as you have. First, didn't you say selegiline boosts libido and desire? Is it still that way? Second, at any point did you have any male difficulties in sex? I was reading about selegiline side effects and one of them listed is 'sexual dysfunction'. I thought, huh? Better ask Adam bout that...Thanks. JohnL
Posted by Adam on December 21, 1999, at 8:30:45
In reply to Re: Selegiline Expertise Needed Again-Adam, posted by Judy on December 20, 1999, at 18:44:41
Judy,
Thanks for your response. It sure is strange how one person's cure is another person's curse.
I wish you the best of luck with this. I wish everybody the best of luck with this. Nothing would make me happier if we all could find something that can be tolerated and helpful at the same time. Take care of yourself.
> Adam - I would bet the farm that Serzone played a part in what led up to your hospitalization. I have dubbed it "the most dangerous drug I've ever taken." Every morning I would sleep through the alarm clock radio set at full volume. My husband then started to call home when it was time for me to get up, get my daughter on the phone and tell her to wake me. A couple of frightening times, my brain was awake enough to know that she was at my bedside, but I was, for a minue or so, unable to respond or even move my body. It was just like coming out of anesthesia! In little better than that condition, I would then drive 40 miles to work - over the Sagamore Bridge and down the Cape.
>
> Besides the near fugue state I was in, I started to become overly-angry and hostile (at the time I thought it was just my fatigue). I actually told the boss's wife where to go one morning! (Believe me, I'd thought it many times, but *never* would have verbalized it!) It wasn't until after I stopped taking Serzone that I read somewhere that it can cause feelings of agression and hostility.
>
> For some, Serzone may be a blessing; but I couldn't possibly recommend it to anyone! I'm wondering if our particular brain chemical makeup responds favorably to MAOI's, but strikes back at Serzone. (BTW, I have the same urge to push Nardil on treatment-resistant people that you do with Selegiline.)
>
> As for Remeron - I am plain scared to death of any drug that makes me feel sedated. Too much like depression (or Serzone!). Besides, most of us don't have the luxury of being able to sleep out the early stages of a sedating drug. Do I sound like I'm making excuses for not trying everything in my power to get well? I hope not. I'm just truly afraid I can't deal with one more trial and nasty failure.
>
>
Posted by Adam on December 21, 1999, at 8:51:38
In reply to Re: Selegiline Expertise Needed Again - -Adam, posted by JohnL on December 21, 1999, at 2:18:35
JohnL
It doesn't suprise me at all that sexual dysfunction is a side effect of selegiline. Different people respond differently, that's perhaps the only axiom I could trust, in regards to meds, and based on the stories I have read here. Perhaps the similarities in our responses to other drugs might be predictive, but I wouldn't count on that. Also, I'm currently taking selegiline in such a different manner (transdermally vs. orally) than most people here will be able too. Transdermal delivery changes the pharmicokinetics of selegiline quite a bit. I am, myself, scared sh#tless about what will happen in three months when the study I am in is over and I have to give up the patch. But this much I can say it true about me now: Sex is NOT a problem. I, um, just got more evidence of that last night (I am, as they say, a little giddy at the moment). Does it _enhance_? It sure doesn't hurt. I have spent so many previous years trying to deal with sexual dysfunction that it's hard to know anymore what my "normal" level of functioning is. I pretty much have to look back to my early twenties for that (I'm about 2.5 months shy of 30). I would say I am at that level now, but...(oh, what the hell), I have not experienced an almost ravenous sexual hunger like this in a LONG time. Actually, there's no "almost" about it. I would say performance is as good as ever (and I'm older now), and desire is, hooahh...words can hardly describe. If there is a problem, it might be that my stamina is a bit adversely affected. I'm hoping with a little concentration to deal with that. It's not a big concern, I don't think. We'll see.
>
> Adam, couple questions for you. Your experiences on serzone and remeron mirror mine almost exactly, which makes me wonder if I might have a high likelihood of responding to selegiline as you have. First, didn't you say selegiline boosts libido and desire? Is it still that way? Second, at any point did you have any male difficulties in sex? I was reading about selegiline side effects and one of them listed is 'sexual dysfunction'. I thought, huh? Better ask Adam bout that...Thanks. JohnL
Posted by Adam on December 21, 1999, at 11:33:43
In reply to Re: Selegiline Augmentation, posted by David Mitrtzer on December 20, 1999, at 9:44:19
That definitely seems like a good idea, for depression at least. I've read that pindolol (like other beta-blockers) can cause sleep disturbances. I've had such a hard time with insomnia lately with selegiline alone I find the thought of such a combination a bit scary, but it seems worth trying, at least. What I'm not altogether clear on, based on what I've read in abstracts, is if pindolol really has an additive benefit as an augmentation, or if it just hastens response. Any thoughts on this?
Posted by Rick on December 21, 1999, at 15:06:11
In reply to Re: Selegiline Expertise Needed Again - -JohnL, posted by Adam on December 21, 1999, at 8:51:38
JohnL-
I'm back to taking a small amount (10 mg -- no food restrictions!) of Selegiline orally with my 2.0 mg Klonopin and 5 mg. Pindolol. And, my sexual reaction sounds just like what Adam is seeing with the patch. Unbelievable sexual desire and "sensations", but maybe actually a tad less stamina (but that could very well be from one of the other meds, or the combo, rather than the Selegiline itself).
Once again, everyone's prone to different side effects. For example, look at how many meds list BOTH hypertension and hypotension as possible side effects.
Rick
----
> JohnL
>
> It doesn't suprise me at all that sexual dysfunction is a side effect of selegiline. Different people respond differently, that's perhaps the only axiom I could trust, in regards to meds, and based on the stories I have read here. Perhaps the similarities in our responses to other drugs might be predictive, but I wouldn't count on that. Also, I'm currently taking selegiline in such a different manner (transdermally vs. orally) than most people here will be able too. Transdermal delivery changes the pharmicokinetics of selegiline quite a bit. I am, myself, scared sh#tless about what will happen in three months when the study I am in is over and I have to give up the patch. But this much I can say it true about me now: Sex is NOT a problem. I, um, just got more evidence of that last night (I am, as they say, a little giddy at the moment). Does it _enhance_? It sure doesn't hurt. I have spent so many previous years trying to deal with sexual dysfunction that it's hard to know anymore what my "normal" level of functioning is. I pretty much have to look back to my early twenties for that (I'm about 2.5 months shy of 30). I would say I am at that level now, but...(oh, what the hell), I have not experienced an almost ravenous sexual hunger like this in a LONG time. Actually, there's no "almost" about it. I would say performance is as good as ever (and I'm older now), and desire is, hooahh...words can hardly describe. If there is a problem, it might be that my stamina is a bit adversely affected. I'm hoping with a little concentration to deal with that. It's not a big concern, I don't think. We'll see.
> >
> > Adam, couple questions for you. Your experiences on serzone and remeron mirror mine almost exactly, which makes me wonder if I might have a high likelihood of responding to selegiline as you have. First, didn't you say selegiline boosts libido and desire? Is it still that way? Second, at any point did you have any male difficulties in sex? I was reading about selegiline side effects and one of them listed is 'sexual dysfunction'. I thought, huh? Better ask Adam bout that...Thanks. JohnL
Posted by Davis Mirtzer on December 21, 1999, at 15:16:39
In reply to Re: Selegiline Augmentation, posted by Adam on December 21, 1999, at 11:33:43
Adam, I can't answer the latter question, but the only sleep disturbance Pindolol (prescribed for high blood pressure) seems to give me is relentlessly weird dreams. I've heard the sleep-disturbance warnings too, but at 5 mg/day I actually get to sleep quicker and wake up much less during the night since starting Pindolol.
I haven't taken Selegiline; I'm just doing research and weighing options.
DM
> That definitely seems like a good idea, for depression at least. I've read that pindolol (like other beta-blockers) can cause sleep disturbances. I've had such a hard time with insomnia lately with selegiline alone I find the thought of such a combination a bit scary, but it seems worth trying, at least. What I'm not altogether clear on, based on what I've read in abstracts, is if pindolol really has an additive benefit as an augmentation, or if it just hastens response. Any thoughts on this?
Posted by Adam on December 21, 1999, at 16:47:23
In reply to Re: Selegiline Augmentation, posted by Davis Mirtzer on December 21, 1999, at 15:16:39
Yeah, the biggest things I see are nightmares and insomnia. Is 5mg/day considered a low dose? 10mg/day seems to be the norm.
> Adam, I can't answer the latter question, but the only sleep disturbance Pindolol (prescribed for high blood pressure) seems to give me is relentlessly weird dreams. I've heard the sleep-disturbance warnings too, but at 5 mg/day I actually get to sleep quicker and wake up much less during the night since starting Pindolol.
>
> I haven't taken Selegiline; I'm just doing research and weighing options.
>
> DM
>
> > That definitely seems like a good idea, for depression at least. I've read that pindolol (like other beta-blockers) can cause sleep disturbances. I've had such a hard time with insomnia lately with selegiline alone I find the thought of such a combination a bit scary, but it seems worth trying, at least. What I'm not altogether clear on, based on what I've read in abstracts, is if pindolol really has an additive benefit as an augmentation, or if it just hastens response. Any thoughts on this?
Posted by David Mirtzer on December 21, 1999, at 23:40:26
In reply to Re: Selegiline Augmentation, posted by Adam on December 21, 1999, at 16:47:23
Well, as I said I'm actually taking it for hypertension, and the recommended STARTING dose is 10 mg. But oddly enough 5 mg seem to do the trick for me, all taken in the morning (and Pindolol's not even extended-release like many other beta blockers).
In research I've done on Pindolol used as an augmenting agent for antidepressants, I usually see things like, "2.5 mg tid, although some patients may require 5.0 mg tid for adequate response". My pdoc says Selegiline itself lowers blood pressure in many people, so you'd have to be careful to monitor BP when taking Pindolol aong with it.
BTW, my "weird dreams" with Pindolol aren't so much "nightmares" as they are incomprehensible and/or "uncomfortale", although I've heard about people having nightmares when on beta blokers.
-----
> Yeah, the biggest things I see are nightmares and insomnia. Is 5mg/day considered a low dose? 10mg/day seems to be the norm.
>
> > Adam, I can't answer the latter question, but the only sleep disturbance Pindolol (prescribed for high blood pressure) seems to give me is relentlessly weird dreams. I've heard the sleep-disturbance warnings too, but at 5 mg/day I actually get to sleep quicker and wake up much less during the night since starting Pindolol.
> >
> > I haven't taken Selegiline; I'm just doing research and weighing options.
> >
> > DM
> >
> > > That definitely seems like a good idea, for depression at least. I've read that pindolol (like other beta-blockers) can cause sleep disturbances. I've had such a hard time with insomnia lately with selegiline alone I find the thought of such a combination a bit scary, but it seems worth trying, at least. What I'm not altogether clear on, based on what I've read in abstracts, is if pindolol really has an additive benefit as an augmentation, or if it just hastens response. Any thoughts on this?
Posted by Zeke on December 25, 1999, at 23:53:27
In reply to Selegiline Expertise Needed Again, posted by Judy on December 18, 1999, at 14:19:35
I would think if you are in the Boston area that seeing a psychpharm there is a fantastic idea.
As for sleep, Xanax definetly interferes with REM sleep, and I believe Selegiline may also. What about trying a little Melatonin (0.3mg) at bedtime in place of the Xanax (so long as seasonal affective disorder isn't part of your depression). Melatonin should help with the sleep without blocking REM. (Not sure though of any interactions with Selegiline -- anyone have any ideas?)
Re Pindolol: it blocks serotonin autoreceptors and theoretically only AUGMENTS other meds that effect serotonin. Supposedly when SSRIs (for example) increase synaptic serotonin, the autoreceptors sense this and consequently cause a reduction in serotonin production (and probably other effects) and this comprimises the antidepressant effect. But the pindolol blocks this and the SSRI doesn't cause negative feedback. I keep saying 'theoretically' because this doesn't explain the delayed response to ADs or the effect ADs have on neurogenesis. So Pindolol (and the SSRIs etc) may likely not be completely described by these explanations. Its curious to me that Pindolol is being tried with Selegiline, as it does not directly effect serotonin but dopamine and phenethylamine which are 'downstream' from serotonin.
Lastly, you mentioned estrogen and that is worth considering. I recently was reading an Australian webpage where it referred to estrogen as an adjucnt in depression. I guess they consider estrogen like docs in the states consider lithium and pindolol etc. Also estrogen does have antidepressant effects in itself and this is receiving more and more documentation in the medical literature. (Interestingly, both Selegiline and estrogen have been shown beneficial in Alzheimer's and in terms of both memory and mood. And like Selegiline, estrogen has a neuroprotective effect, and receptors for estrogen definitely exist in the brain.) The only relative concern is edema which may occur from the estrogen. But then again, the edema produced in you from Nardil may not occur with estrogen (or occur to any significant degree). I think estrogen is certainly worth considering. (BTW do a medline search on estrogen and affective disorder if you want to know more. There is more.)
Posted by Judy on December 26, 1999, at 10:59:00
In reply to Judy -- Selegiline, Pindolol, Melatonin & Estrogen, posted by Zeke on December 25, 1999, at 23:53:27
Thanks, Zeke! I will do a medline search on estrogen. I have a 'gut' feeling that estrogen, or lessening amounts of it, may be playing a significant part in the changing personna of my depression and the reason why previously used AD's affect me differently now. (Or perhaps my aging synapses and receptors are just rolling over and dying at a faster rate!)
Melatonin? Is that indicated with MAOI's? Not sure if anyone knows what is/isn't indicated with Selegiline at high doses. Another medline search maybe. Besides the sleep problems, I DO need Xanax (or something) for the anxiety that Selegiline isn't touching - or may even be exascerbating.
Great explanation of Pindolol's mechanism. I too wondered why it would be of benefit with Selegiline. In general, I've always wondered why it is that SSRI's just DO NOT work for me. They make me so fatigued that I wouldn't notice any benefit if it were there. Is it possible that Seratonin just isn't my problem brain chemical, or is there another mechanism of SSRI's that pushes my 'coma' button? Is it possible that Pindolol might lessen my SSRI- induced fatigue?
I'll do those web searches when I have a quiet moment today. If I find anything promising (or confusing), I hope you'll be here to run them by. Thanks again. Judy
Posted by Rick on December 26, 1999, at 18:31:55
In reply to Re: Judy -- Selegiline, Pindolol, Melatonin & Estrogen, posted by Judy on December 26, 1999, at 10:59:00
While Selegiline was designed as a dopamine-enhancing agent, the attached monograph section suggests that Selegiline's long-lasting metabolites *may* help discourage serotonin re-uptake. Thus, it is not necessarily illogical to think that the serotonergic beta blocker Pindolol could potentiate Selegiline, as it purportedly does for SSRI's and other AD's.
While I also feel that Selegiline is neutral-to-negative for anxiety (that's why I keep my dose very low -- all I use it for now is a little mental activation and alertness, which 5 mg does seem to provide), low-dose Pindolol itself sure seems to supply a mildly calming effect that nicely builds on my Klonopin's benefits. For all I know, I could get that same effect from various other beta blockers; but since Pindolol is the only one with serotonergic effects, I'm not so sure.
One thing I am fairly sure about is that Pindolol is not a good candidate to help with the fatigue. Indeed, just like other beta blockers, it causes fatigue in many people. This side-effect is especially prevalent for the cardio non-selective BB's, which include Pidolol and Propronolol (Inderal) among others. For me, anything above 5 mg starts to cause a little sleepiness, especially when taken at night. I haven't needed anything for sleep since taking Klonopin (even though I rarely take it after 6 p.m.). Back when I was taking an occasional Xanax at bedtime, I really felt groggy the next day. In fact, if you don't mind weird dreams and your blood pressure isn't too low, bedtime Pindolol might be a gentler sleep-inducer with fewer downside effects and some possible anti-anxiety benefits.
ATTACHMENT (from Selegiline monograph):
It is important to be aware that selegiline may have pharmacological effects unrelated to MAO B inhibition. As noted above, there is some evidence that it may increase dopaminergic activity by other mechanisms, including interfering with dopamine re-uptake at the synapse. Effects resulting from selegiline administration may also be mediated through its metabolites. Two of its three principal metabolites, amphetamine and methamphetamine, have pharmacological actions of their own; they interfere with neuronal uptake and enhance release of several neurotransmitters (e.g., norepinephrine, dopamine, serotonin). However, the extent to which these metabolites contribute to the effects of selegiline are unknown.
**********************************************
> Thanks, Zeke! I will do a medline search on
estrogen. I have a 'gut' feeling that estrogen,
or lessening amounts of it, may be playing a
significant part in the changing personna of my
depression and the reason why previously used AD's affect me differently now. (Or perhaps my aging
synapses and receptors are just rolling over and
dying at a faster rate!)
>
> Melatonin? Is that indicated with MAOI's? Not
sure if anyone knows what is/isn't indicated with
Selegiline at high doses. Another medline search maybe. Besides the sleep problems, I DO need
Xanax (or something) for the anxiety that
Selegiline isn't touching - or may even be
exascerbating.
>
> Great explanation of Pindolol's mechanism. I
too wondered why it would be of benefit with
Selegiline. In general, I've always wondered why
it is that SSRI's just DO NOT work for me. They
make me so fatigued that I wouldn't notice any
benefit if it were there. Is it possible that
Seratonin just isn't my problem brain chemical, or
is there another mechanism of SSRI's that pushes
my 'coma' button? Is it possible that Pindolol
might lessen my SSRI- induced fatigue?
>
> I'll do those web searches when I have a quiet
moment today. If I find anything promising (or
confusing), I hope you'll be here to run them by.
Thanks again. Judy
Posted by Zeke on December 27, 1999, at 11:46:31
In reply to To Judy and Zeke re: Selegiline and Pindolol, posted by Rick on December 26, 1999, at 18:31:55
> One thing I am fairly sure about is that Pindolol is not a good candidate to help with the fatigue.
That's a good point (the anti-anxiety effect of pindolol and the other beta-blockers). However, the doses of pindolol used with antidepressants are typically lower than those used for hypertension and the anergia is logically much less also.
> ATTACHMENT (from Selegiline monograph):
> It is important to be aware that selegiline may have pharmacological effects unrelated to MAO B inhibition. As noted above, there is some evidence that it may increase dopaminergic activity by other mechanisms, including interfering with dopamine re-uptake at the synapse. Effects resulting from selegiline administration may also be mediated through its metabolites. Two of its three principal metabolites, amphetamine and methamphetamine, have pharmacological actions of their own; they interfere with neuronal uptake and enhance release of several neurotransmitters (e.g., norepinephrine, dopamine, serotonin). However, the extent to which these metabolites contribute to the effects of selegiline are unknown.A fraction of selegiline is metabolized to to amphetamines and these are levo-methamphetamine and levo-amphetamine, which effect norepinephrine but not dopamine (at least not to any significant degree). Theoretically, this is why the dextroamphetamines are 4 to 6 times stronger than levoamphetamines. Also note that the government allows levo-methamphetamine (aka l-desoxyephedrine) to be sold over the counter in Vicks Inhalers. (Look at the active ingredient listed the nest time you visit your local drug store.) Re serotonin, methamphetamine but not amphetamine has some effect in itself. I'm not sure of how the levo isomer effects serotonin compared to the dextro.
Still, enhancing dopamine processes might reasonably effect serotonin even without imediate interaction of the two drugs.
An additional note about estrogen is that it reportedly increases serotonin by virtue of decreasing production of MAO (MAO-A?). Affective disorders and anxiety in persons with estrogen (and/or testosterone) deficiency is thought to be due to excess MAO which 'mops up' too much serotonin. Estrogen also seems related to Nerve Growth Factor and depressed persons tend to exhibit shrunken hippocampal structures.
Re melatonin, I though you (Judy) might try it at bedtime in place of Xanax -- to allow more REM. I'd think you could continue Xanax at other times. (Just a thought...)
Posted by anita on January 1, 2000, at 16:50:38
In reply to Re: Judy -- Selegiline, Pindolol, Melatonin & Estrogen, posted by Judy on December 26, 1999, at 10:59:00
Hi Judy,
I've always had low estrogen and have suspected it may be a factor in depression. All I've read about estrogen seems to indicate that this could be the case. However, when I was on nardil, the only AD that actually seemed to have a significant effect, my estrogen levels got a little lower and my testosterone level was sky-high.
I'm only in my early 30s, so I think for me I've just had low estrogen all my life (late puberty, painful and irregular and usu. 30+ day periods). I think I felt better when I was taking birth control pills years ago, but then again that was a better time of my life.
Anybody know of any studies on estrogen and the sleep cycle?
anita
Posted by Scott L. Schofield on January 2, 2000, at 14:15:56
In reply to Re: Judy -- Selegiline, Pindolol, Melatonin & Estrogen, posted by anita on January 1, 2000, at 16:50:38
> Hi Judy,
>
> I've always had low estrogen and have suspected it may be a factor in depression. All I've read about estrogen seems to indicate that this could be the case. However, when I was on nardil, the only AD that actually seemed to have a significant effect, my estrogen levels got a little lower and my testosterone level was sky-high.
>
> I'm only in my early 30s, so I think for me I've just had low estrogen all my life (late puberty, painful and irregular and usu. 30+ day periods). I think I felt better when I was taking birth control pills years ago, but then again that was a better time of my life.
>
> Anybody know of any studies on estrogen and the sleep cycle?
Just a quick contribution…
The use of estrogen for treatment-resistant depression in women is another one of those hormonal treatment strategies that are sometimes employed, regardless of baseline levels. As another point of interest is the fact that many clinically depressed women - even those who are treatment-resistant - feel better while they are pregnant. Afterwards, depression usually returns. I imagine that this phenomenon is directly related to the changes in estrogen and progesterone levels, but I don't recall the sequence of these changes and how they may correlate to the observed changes in mood. The football game is on and I'm too lazy to look into it right now.
I don’t know anything about a relationship between estrogen levels and sleep. The effect that Nardil had on your testosterone levels is interesting. I don’t know anything about that either. Sorry.
- Scott
Posted by Zeke on January 2, 2000, at 21:58:33
In reply to Re: Judy -- Selegiline, Pindolol, Melatonin & Estrogen, posted by anita on January 1, 2000, at 16:50:38
> Anybody know of any studies on estrogen and the sleep cycle?Look at the last several parargraphs on this page:
http://www.nami-nyc-metro.org/diagnosi/depress.html
Posted by Judy on January 3, 2000, at 12:47:50
In reply to Re: Judy -- Selegiline, Pindolol, Melatonin & Estrogen, posted by Zeke on January 2, 2000, at 21:58:33
Thanks to your all for your advice/suggestions/theories. My doctor has finally returned from vacation and I'm awaiting a return call from him today.
Selegiline didn't see me through the holidays very well on its own. I'm not sure if augmenting it will do the trick, but I'd sure like to give it a try before trashing it. I've also made an appointment for a full physical and will ask for thorough thyroid and estrogen levels and anything else they want to check.
Rick - does Melatonin need to build up in one's system or is it a quick-in/quick-out drug like a sleeping pill would be?
Thanks again, all. Judy
Posted by Adam on January 4, 2000, at 11:10:32
In reply to Re: Judy -- Selegiline, Pindolol, Melatonin & Estrogen, posted by Judy on January 3, 2000, at 12:47:50
A couple of salient points (perhaps):
Melatonin: I have considered using melatonin to help with what appears to be selegiline-induced insomnia and sleep-cycle disturbance. I had some concern about this combination because melatonin is a seratonin derivative, concerns that seem to be legitimate based on a bad experience Elizabeth had combining mel. with an MAOI. However, I have been able to find no mechanistic basis for melatonin-induced seratonin syndrome. Recently I spoke with my doctor about such a combo, and he also felt this was a bad idea, though he admitted he could provide no rationale beyond what I stated above. Just FYI.
On selegiline and exogenous sex hormones: Before you combine selegiline and estrogen treatment, please consider the following (I came across it a while ago when searching for info. on selegiline metabolism):
Br J Clin Pharmacol 1999 Mar;47(3):249-54
Dose linearity study of selegiline pharmacokinetics after oral administration: evidence for strong drug interaction with female sex steroids.
Laine K, Anttila M, Helminen A, Karnani H, Huupponen R
Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.AIMS: The purpose of this study was to characterize the dose relationship of selegline and desmethylselegiline pharmacokinetics within the selegiline dose range from 5 to 40 mg. METHODS: Eight female subjects, of whom four were using oral contraceptives, ingested a single dose of 5 mg, 10 mg, 20 mg or 40 mg of selegiline HCl in an open four-period randomized study. Concentrations of selegiline and desmethlylselegiline in serum were measured by gas chromatography for 5 h. As it became evident that the use of oral steroids had a drastic effect on selegiline concentrations, the pharmacokinetic analyses were performed separately for oral contraceptive users and those not receiving any concomitant medication. RESULTS: The total AUC and Cmax of selegiline were 10-to 20-fold higher in those subjects taking oral steroids compared with subjects with no concomitant medication; this finding was consistent and statistically significant at all the four dose levels. The dose linearity of selegiline pharmacokinetics failed to be demonstrated in both groups. The AUC and Cmax of desmethylselegiline were only moderately higher (about 1.5-fold; P=NS at each dose level) in the subjects taking oral steroids than in those not receiving concomitant medication. The AUC values of desmethylselegiline increased in a dose linear manner in subjects with no concomitant medication, but not in the oral steroid group. The metabolic ratio (AUC(desmethylselegiline)/AUC(selegiline)) was several-fold lower in the group receiving oral steroids compared with the no-concomitant-medication group (P Thanks to your all for your advice/suggestions/theories. My doctor has finally returned from vacation and I'm awaiting a return call from him today.
>
> Selegiline didn't see me through the holidays very well on its own. I'm not sure if augmenting it will do the trick, but I'd sure like to give it a try before trashing it. I've also made an appointment for a full physical and will ask for thorough thyroid and estrogen levels and anything else they want to check.
>
> Rick - does Melatonin need to build up in one's system or is it a quick-in/quick-out drug like a sleeping pill would be?
>
> Thanks again, all. Judy
Posted by Judy on January 4, 2000, at 19:24:58
In reply to Re: Judy -- Selegiline, Pindolol, Melatonin & Estrogen, posted by Adam on January 4, 2000, at 11:10:32
Adam - I appreciate your definitely salient points. Interesting, and scary, about Selegiline and oral contraceptives. Just out of curiosity, the article mentioned several times "female sex/oral steroids" - would the reaction be the same to pure Estrogen do you think?
Anyway, your salient points are unfortunately moot points. I finally talked to my doctor and he felt my response to Selegiline wasn't great enough to warrant trying augmentation of any kind. (He agreed with you and your doctor about Melatonin being a bad idea BTW). Thus I begin the weaning and washout periods and end up back at Square One. I'm devastated - I had such high hopes for Selegiline. I've never had any kind of positive response to an AD with so few side effects before. And I will miss the orgasmic experience (trust me on this!).
My remaining options seem to be Remeron (which I can't decline more passionately because of the sedation); or a revisitation of Parnate combined with something (a player to be named later, I guess) combined to take the edge off. I'll find out what comes next when I'm "clean" of Selegiline.
Thanks for all your help (Everyone else too!)
Judy
Posted by Adam on January 4, 2000, at 21:58:19
In reply to Re: Selegiline, Estrogen, etc., posted by Judy on January 4, 2000, at 19:24:58
>
> Anyway, your salient points are unfortunately moot points.I'm really sorry to hear that, Judy. Is there no hope for Nardil? Just out of curiousity, what are the possible "players" to be used in conjunction with Parnate to take the edge off? When you find out what your doctor has up his sleeve, I'd like very much to hear about it.
Thanks!
P.S. I don't know if estrogen alone would be as much of a problem with selegiline as oral contraceptives (estrogen+progesterone, I assume). I can't figure out why the investigators didn't try to tease out this issue, since it would be very easy to do and could only add immensely to the value of the paper for minimal effort. If only one or the other "sex hormone" was the culprit, that would be important information. I'm also curious about other exogenous steroids: What about testosterone, or, say, finasteride? The latter is quite often prescribed for benign prostate hyperplasia, a common affliction of older men. Since Parkinson's and Alzheimer's also strike the elderly most often (and I'm not forgetting estrogen treatment for post-menopausal women), it seems reasonable to check for possible interactions, given this paper. Hopefully there will be followup studies.
Posted by michael on January 27, 2000, at 19:45:01
In reply to Re: Selegiline Expertise Needed Again - -JohnL, posted by Rick on December 21, 1999, at 15:06:11
> JohnL-
>
> I'm back to taking a small amount (10 mg -- no food restrictions!) of Selegiline orally with my 2.0 mg Klonopin and 5 mg. Pindolol. And, my sexual reaction sounds just like what Adam is seeing with the patch. Unbelievable sexual desire and "sensations", but maybe actually a tad less stamina (but that could very well be from one of the other meds, or the combo, rather than the Selegiline itself).
>
> Once again, everyone's prone to different side effects. For example, look at how many meds list BOTH hypertension and hypotension as possible side effects.
>
> Rick
> ----
> > JohnL
> >
> > It doesn't suprise me at all that sexual dysfunction is a side effect of selegiline. Different people respond differently, that's perhaps the only axiom I could trust, in regards to meds, and based on the stories I have read here. Perhaps the similarities in our responses to other drugs might be predictive, but I wouldn't count on that. Also, I'm currently taking selegiline in such a different manner (transdermally vs. orally) than most people here will be able too. Transdermal delivery changes the pharmicokinetics of selegiline quite a bit. I am, myself, scared sh#tless about what will happen in three months when the study I am in is over and I have to give up the patch. But this much I can say it true about me now: Sex is NOT a problem. I, um, just got more evidence of that last night (I am, as they say, a little giddy at the moment). Does it _enhance_? It sure doesn't hurt. I have spent so many previous years trying to deal with sexual dysfunction that it's hard to know anymore what my "normal" level of functioning is. I pretty much have to look back to my early twenties for that (I'm about 2.5 months shy of 30). I would say I am at that level now, but...(oh, what the hell), I have not experienced an almost ravenous sexual hunger like this in a LONG time. Actually, there's no "almost" about it. I would say performance is as good as ever (and I'm older now), and desire is, hooahh...words can hardly describe. If there is a problem, it might be that my stamina is a bit adversely affected. I'm hoping with a little concentration to deal with that. It's not a big concern, I don't think. We'll see.
> > >
> > > Adam, couple questions for you. Your experiences on serzone and remeron mirror mine almost exactly, which makes me wonder if I might have a high likelihood of responding to selegiline as you have. First, didn't you say selegiline boosts libido and desire? Is it still that way? Second, at any point did you have any male difficulties in sex? I was reading about selegiline side effects and one of them listed is 'sexual dysfunction'. I thought, huh? Better ask Adam bout that...Thanks. JohnLRick,
I've been looking over some of the selegiline info here, and re-read your post above. I was just wondering what the motivation was for adding the 10mg selegiline.
I thought that I'd seen it referred to for counering the effects of anorgasmia, etc. at that low dosage. Just wondering if there were any other uses/benefits at that dosage?
Thanks,
michael
Posted by Rick on January 28, 2000, at 1:34:01
In reply to Re: Selegiline Expertise Needed Again - -JohnL, posted by michael on January 27, 2000, at 19:45:01
> > JohnL-
> >
> > I'm back to taking a small amount (10 mg -- no food restrictions!) of Selegiline orally with my 2.0 mg Klonopin and 5 mg. Pindolol. And, my sexual reaction sounds just like what Adam is seeing with the patch. Unbelievable sexual desire and "sensations", but maybe actually a tad less stamina (but that could very well be from one of the other meds, or the combo, rather than the Selegiline itself).
> >
> > Once again, everyone's prone to different side effects. For example, look at how many meds list BOTH hypertension and hypotension as possible side effects.
> >
> > Rick
> > ----
> > > JohnL
> > >
> > > It doesn't suprise me at all that sexual dysfunction is a side effect of selegiline. Different people respond differently, that's perhaps the only axiom I could trust, in regards to meds, and based on the stories I have read here. Perhaps the similarities in our responses to other drugs might be predictive, but I wouldn't count on that. Also, I'm currently taking selegiline in such a different manner (transdermally vs. orally) than most people here will be able too. Transdermal delivery changes the pharmicokinetics of selegiline quite a bit. I am, myself, scared sh#tless about what will happen in three months when the study I am in is over and I have to give up the patch. But this much I can say it true about me now: Sex is NOT a problem. I, um, just got more evidence of that last night (I am, as they say, a little giddy at the moment). Does it _enhance_? It sure doesn't hurt. I have spent so many previous years trying to deal with sexual dysfunction that it's hard to know anymore what my "normal" level of functioning is. I pretty much have to look back to my early twenties for that (I'm about 2.5 months shy of 30). I would say I am at that level now, but...(oh, what the hell), I have not experienced an almost ravenous sexual hunger like this in a LONG time. Actually, there's no "almost" about it. I would say performance is as good as ever (and I'm older now), and desire is, hooahh...words can hardly describe. If there is a problem, it might be that my stamina is a bit adversely affected. I'm hoping with a little concentration to deal with that. It's not a big concern, I don't think. We'll see.
> > > >
> > > > Adam, couple questions for you. Your experiences on serzone and remeron mirror mine almost exactly, which makes me wonder if I might have a high likelihood of responding to selegiline as you have. First, didn't you say selegiline boosts libido and desire? Is it still that way? Second, at any point did you have any male difficulties in sex? I was reading about selegiline side effects and one of them listed is 'sexual dysfunction'. I thought, huh? Better ask Adam bout that...Thanks. JohnL
>
>
>
> Rick,
>
> I've been looking over some of the selegiline info here, and re-read your post above. I was just wondering what the motivation was for adding the 10mg selegiline.
>
> I thought that I'd seen it referred to for counering the effects of anorgasmia, etc. at that low dosage. Just wondering if there were any other uses/benefits at that dosage?
>
> Thanks,
>
> michaelBefore Klonnopin. I was taking 15mg. Selgiline alone for Social Phobia with no results except perhaps a slight INCREASE in anxiety and agitation. (Hardly a surprise to me, but my pdoc is an MAOI proponent and wanted to try it after Nardil pooped out while leaving the awful side effects intact.) When I switched to Klonopin, I kept the low-dose Pindolol he had prescribed for mildly-elevated blood pressure, and which has a nice calming effect. Then I asked if I could continue low-dose Selegiline with the Klonopin since the Selegiline was activating and sexually stimulating, and supposedly cognitively-enhancing (and life-extending??) -- and I had heard stories of cognitive impairment with Klonopin. I eventually ended up cutting back the Selegiline to 5 mg., but it's obvious that it's still having an effect, in terms of alertness, clear thinking, libido, and significantly enhanced sexual sensations (but not enhanced sexual stamina). YMMV!
Rick
Posted by michael on January 28, 2000, at 8:53:49
In reply to Re: Selegiline Expertise Needed Again - -JohnL, posted by Rick on January 28, 2000, at 1:34:01
> > > JohnL-
> > >
> > > I'm back to taking a small amount (10 mg -- no food restrictions!) of Selegiline orally with my 2.0 mg Klonopin and 5 mg. Pindolol. And, my sexual reaction sounds just like what Adam is seeing with the patch. Unbelievable sexual desire and "sensations", but maybe actually a tad less stamina (but that could very well be from one of the other meds, or the combo, rather than the Selegiline itself).
> > >
> > > Once again, everyone's prone to different side effects. For example, look at how many meds list BOTH hypertension and hypotension as possible side effects.
> > >
> > > Rick
> > > ----
> > > > JohnL
> > > >
> > > > It doesn't suprise me at all that sexual dysfunction is a side effect of selegiline. Different people respond differently, that's perhaps the only axiom I could trust, in regards to meds, and based on the stories I have read here. Perhaps the similarities in our responses to other drugs might be predictive, but I wouldn't count on that. Also, I'm currently taking selegiline in such a different manner (transdermally vs. orally) than most people here will be able too. Transdermal delivery changes the pharmicokinetics of selegiline quite a bit. I am, myself, scared sh#tless about what will happen in three months when the study I am in is over and I have to give up the patch. But this much I can say it true about me now: Sex is NOT a problem. I, um, just got more evidence of that last night (I am, as they say, a little giddy at the moment). Does it _enhance_? It sure doesn't hurt. I have spent so many previous years trying to deal with sexual dysfunction that it's hard to know anymore what my "normal" level of functioning is. I pretty much have to look back to my early twenties for that (I'm about 2.5 months shy of 30). I would say I am at that level now, but...(oh, what the hell), I have not experienced an almost ravenous sexual hunger like this in a LONG time. Actually, there's no "almost" about it. I would say performance is as good as ever (and I'm older now), and desire is, hooahh...words can hardly describe. If there is a problem, it might be that my stamina is a bit adversely affected. I'm hoping with a little concentration to deal with that. It's not a big concern, I don't think. We'll see.
> > > > >
> > > > > Adam, couple questions for you. Your experiences on serzone and remeron mirror mine almost exactly, which makes me wonder if I might have a high likelihood of responding to selegiline as you have. First, didn't you say selegiline boosts libido and desire? Is it still that way? Second, at any point did you have any male difficulties in sex? I was reading about selegiline side effects and one of them listed is 'sexual dysfunction'. I thought, huh? Better ask Adam bout that...Thanks. JohnL
> >
> >
> >
> > Rick,
> >
> > I've been looking over some of the selegiline info here, and re-read your post above. I was just wondering what the motivation was for adding the 10mg selegiline.
> >
> > I thought that I'd seen it referred to for counering the effects of anorgasmia, etc. at that low dosage. Just wondering if there were any other uses/benefits at that dosage?
> >
> > Thanks,
> >
> > michael
>
> Before Klonnopin. I was taking 15mg. Selgiline alone for Social Phobia with no results except perhaps a slight INCREASE in anxiety and agitation. (Hardly a surprise to me, but my pdoc is an MAOI proponent and wanted to try it after Nardil pooped out while leaving the awful side effects intact.) When I switched to Klonopin, I kept the low-dose Pindolol he had prescribed for mildly-elevated blood pressure, and which has a nice calming effect. Then I asked if I could continue low-dose Selegiline with the Klonopin since the Selegiline was activating and sexually stimulating, and supposedly cognitively-enhancing (and life-extending??) -- and I had heard stories of cognitive impairment with Klonopin. I eventually ended up cutting back the Selegiline to 5 mg., but it's obvious that it's still having an effect, in terms of alertness, clear thinking, libido, and significantly enhanced sexual sensations (but not enhanced sexual stamina). YMMV!
>
> RickRick,
Thanks a lot for the feedback, and for getting back to me so quickly - I'm going in to discuss my meds in a couple hours, & wanted to discuss selegiiline. More info is always better...
Thanks again,
michael
This is the end of the thread.
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