![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 35. This is the beginning of the thread.
Posted by SalArmy4me on March 13, 2001, at 16:03:37
I have been on Selegiline for only two days at a dose of 60 mg in three divided doses. (I do not have Parkinsons' disease, but rather Treatment-Resistant Depression. I have taken every other antidepressant known to mankind). So far, I have noticed a moderate antidepressant effect after one hour of ingesting it, which I could never get from a placebo. And that is why I'm writing this, to alert others.
Selegiline should be known as the "alternative" MAOI, in that it has less of the side-effects of phenelzine or tranylcypromine. The main side-effect that I have with it is a powerful stimulating effect similar to one caused by buproprion. I have been taking 10 mg oxazepam along with selegiline in order to counter the anxiety produced by selegiline.
Notes:
--I don't think that selegiline has an antidepressant effect under doses of 40 mg per day.
--I don't know if selegiline has any sexual side-effects yet.
--100 of the Generic 5 mg capsules (you need 240 capsules for a months antidepressant supply) costs US $240 at Sav-On Drug Stores. That is expensive. However, medical insurance covers it.
--You have to drop almost every other antidepressant in order to take the MAOI selegiline, although there is only one reported case in history of Serotonin Syndrome (that is fact).
--You have to follow the MAOI diet (I won't, though. I didn't on phenelzine or tranylcypromine and didn't have a hypertensive crisis).
Posted by Lorraine on March 13, 2001, at 18:36:07
In reply to Report of success: Selegiline: alernate MAOI, posted by SalArmy4me on March 13, 2001, at 16:03:37
{The main side-effect that I have with it is a powerful stimulating effect similar to one caused by buproprion. I have been taking 10 mg oxazepam along with selegiline in order to counter the anxiety produced by selegiline.}
I'm on 10 mg of Selegiline and 600mg of Neurontin (to control the anxiety). The sex is good if you don't mix it with a sexually dsyfunctional drug. Tell me about oxazepam.
Posted by Mr. Scott on March 13, 2001, at 18:55:13
In reply to Report of success: Selegiline: alernate MAOI, posted by SalArmy4me on March 13, 2001, at 16:03:37
> I have been on Selegiline for only two days at a dose of 60 mg in three divided doses. (I do not have Parkinsons' disease, but rather Treatment-Resistant Depression. I have taken every other antidepressant known to mankind). So far, I have noticed a moderate antidepressant effect after one hour of ingesting it, which I could never get from a placebo. And that is why I'm writing this, to alert others.
>
> Selegiline should be known as the "alternative" MAOI, in that it has less of the side-effects of phenelzine or tranylcypromine. The main side-effect that I have with it is a powerful stimulating effect similar to one caused by buproprion. I have been taking 10 mg oxazepam along with selegiline in order to counter the anxiety produced by selegiline.
>
> Notes:
> --I don't think that selegiline has an antidepressant effect under doses of 40 mg per day.
> --I don't know if selegiline has any sexual side-effects yet.
> --100 of the Generic 5 mg capsules (you need 240 capsules for a months antidepressant supply) costs US $240 at Sav-On Drug Stores. That is expensive. However, medical insurance covers it.
> --You have to drop almost every other antidepressant in order to take the MAOI selegiline, although there is only one reported case in history of Serotonin Syndrome (that is fact).
> --You have to follow the MAOI diet (I won't, though. I didn't on phenelzine or tranylcypromine and didn't have a hypertensive crisis).I'm on it too (first day 5mg), and your analogy to buproprion is Exactly what I was thinking today when It made me a little anxious. Glad things are working out so quickly.. Keep us posted
Posted by JohnX on March 14, 2001, at 2:09:48
In reply to Report of success: Selegiline: alernate MAOI, posted by SalArmy4me on March 13, 2001, at 16:03:37
> I have been on Selegiline for only two days at a dose of 60 mg in three divided doses. (I do not have Parkinsons' disease, but rather Treatment-Resistant Depression. I have taken every other antidepressant known to mankind). So far, I have noticed a moderate antidepressant effect after one hour of ingesting it, which I could never get from a placebo. And that is why I'm writing this, to alert others.
>
> Selegiline should be known as the "alternative" MAOI, in that it has less of the side-effects of phenelzine or tranylcypromine. The main side-effect that I have with it is a powerful stimulating effect similar to one caused by buproprion. I have been taking 10 mg oxazepam along with selegiline in order to counter the anxiety produced by selegiline.
>
> Notes:
> --I don't think that selegiline has an antidepressant effect under doses of 40 mg per day.
> --I don't know if selegiline has any sexual side-effects yet.
> --100 of the Generic 5 mg capsules (you need 240 capsules for a months antidepressant supply) costs US $240 at Sav-On Drug Stores. That is expensive. However, medical insurance covers it.
> --You have to drop almost every other antidepressant in order to take the MAOI selegiline, although there is only one reported case in history of Serotonin Syndrome (that is fact).
> --You have to follow the MAOI diet (I won't, though. I didn't on phenelzine or tranylcypromine and didn't have a hypertensive crisis).All,
Selegiline is on my list of things to try along
with Mirapex and some other more dopamnergic acting meds.A question about Selegeline:
People seem to be getting various responses at various doses, any thoughts?
Is the cutoff point for the MAOI diet restriction around 15 mg/day?
Also, I remember threads on the patch version, which didn't have the dietary restrictions. Is this version available for importation from overseas?
I did well on Adderall ~20mg/day to relieve anhedonia, but am finding it *much* harder to get a script for in the state I just moved too given I'm not ADD. Selegiline is not as restrictive, and the funny thing is that it is an MAO-B inhibitor, but you may not know that it also breaks down into meth-amphetamine.
Based on my Adderal response at 20mg/day, anyone want to venture a guess as to what dose I might get any response on Selegiline? (I'm also looking into atypical anti-psychotics such as Zyprexa and Ziprasidone, the 5ht-2 antagonism is cross-my- fingers good for the anhedonia I experience).
-John
Posted by AndrewB on March 14, 2001, at 3:09:35
In reply to Re: Report of success: Selegiline: alernate MAOI, posted by JohnX on March 14, 2001, at 2:09:48
Selegine can cause anxiety in some people. Some feedback indicates that amisulpride can counter the selegiline anxiety. Zyprexa, other antipsychotics, and Mirapex may also combine will with serlgiline. I say all this in reference to low dose selegiline. My experience with low dose selegilne is an increase in motivation and vitality. Over 15mg. and the drug has a different effect, most notably MOA inhibition. As noted, it can be stimulating. It converts into amphetamine. The conversion to amphetamine is not necessarilly a disireable effect since the the blood levels of this amphetamine metabolite can rise at the wrong times, such as in the middle of the night. Adam, an occassional poster, has the most expereince with high dose selegiline and the patch and his prior posts are very informative.
AndrewB
Posted by Lorraine on March 14, 2001, at 10:33:23
In reply to Re: Report of success: Selegiline: alernate MAOI, posted by JohnX on March 14, 2001, at 2:09:48
John:
I was on 5 mg day of dexedrine--probably could have moved up to 10 mg. I'm on 10 mg day of Selegiline--it has very pronounced puppy upper effects. I'm damping it down with Neurontin. But then I'm sensitive to meds as you can tell. It's worth trying. You may also be able to augment with Mirapex, which also has activating effects, but is not in the MAO category. They are compatible drugs according to RX. My pdoc is quite liberal and will let my try augmenting with dexedrine if I need to for anhedonia. We will see. What was the difference between dexedrine and Ritalin if you have tried them both?
Posted by Lorraine on March 14, 2001, at 10:36:34
In reply to Re: Report of success: Selegiline: alernate MAOI, posted by AndrewB on March 14, 2001, at 3:09:35
Andrew: Thanx for the post--informative as usual. I am thinking of adding Mirapex to the mix. I checked an saw that it is compatible. Do you know anyone who has tried this?
Posted by kazoo on March 15, 2001, at 1:17:30
In reply to Report of success: Selegiline: alernate MAOI, posted by SalArmy4me on March 13, 2001, at 16:03:37
> --100 of the Generic 5 mg capsules (you need 240 capsules for a months antidepressant supply) costs US $240 at Sav-On Drug Stores. That is expensive. However, medical insurance covers it.
^^^^^^^^^^^
"Expensive" isn't the word ... try "price gouging"!I had my nephew pick me up a box in Italy. It's called "Jumex" (selegilina) over there. For a box of 50 tabs, 5 mgs. each, he paid $11.00 bucks.
kazoo
Posted by AndrewB on March 15, 2001, at 10:21:57
In reply to Re: Report of success: Selegiline: Andrew, posted by Lorraine on March 14, 2001, at 10:36:34
Lorraine,
The selegiline/mirapex combo is used often by PD patients, so it should be safe. I have taken selegiline and neurontin together without problem. I'm weak on pharmacological interreactions between meds. but I researched carefully low dose selegiline interactions. Possible complications seem limited to selegiline and MAOIs and (very occassionally) serotenergic agents. I haven't heard any reports on the mirapex/selgiline combo on mood and anxiety so if you do try mirapex as an add-on I would very much like to hear what your response is.
I have one small suggestion. 5 mg/day (and possibly even 2.5mg./day) of selegiline is able to achieve full MAO-B inhibition. The only difference is it takes a number of days longer to achieve this steady state full inhibition with the lower doses. I mention this not only because it is a little cheapeer to use the lower doses, but because selegiline even at small doses converts to amphetamine. That is selegline metabolizes to amphetamine at all dosages but as the dosage is increased, the metabolite increases, possibly linearly. Anyway since amphetamine can cause anxiety, and the MAO-B inhibition is what results in the desired effect from low dose selegiline, taking a lower dose may be produce noticeably less anxiety but have the same positive effect on motivation and vitality. I take 5mg./day.
AndrewB
Posted by Adam on March 15, 2001, at 18:31:00
In reply to Report of success: Selegiline: alernate MAOI, posted by SalArmy4me on March 13, 2001, at 16:03:37
I'm sorry. A while ago I tried to post and couldn't due to maintainance of the site. Then I went on a two-week vacation in the Southwest US. Now I'm back.
I had a quick response to selegiline also. So quick, in fact, that I often wondered aloud if I was imagining the whole thing. I don't believe this was the case. I am still on selegiline, and doing very well, mood-wise. Your response does seem remarkably quick, even knowing what I know, but as the pharmacokinetics of selegiline may be influenced by a pharmacodynamic profile involving responses to the parent molecule and its metabolites that are independant of it's MAO-inhibiting function, I'm guessing your exprience could well be more than a figment of your imagination.
I would not be too cavalier about the dietary restrictions, and I would be very serious about the potential drug interactions. I think with diet, it's possible to cheat a little and be OK. Hypervigilance isn't necessary, and the usual restrictions recommended by doctors are clearly not necessary for everyone. However, caution is always warrented. Changes in blood pressure are not always easy to detect emperically, and full-blown hypertensive crisis isn't the only risk state one need consider.
I have had Neurontin (gabapentin) prescribed for selegiline-induced insomnia and anxiety. I think this is a reasonable choice, given Neurontin's relatively benign side-effects profile at low doses. I have chosen not to take it though, and have rather focused my efforts on "sleep hygene" and exercise. For those with similar concerns who care to know, I would endorse this approach first, and a pharmacological approach second. Another approach that might be worth exploring is low-dose risperidol.
I have heard mention of foreign pharmacies somehow formulating their own selegiline patches. I wouldn't trust such a source, if indeed it exists. There have been and continue to be numerous placebo-controlled pilot and phase-II and III trials of the selegiline transdermal system (STS) for various indications (Parkinsons, AIDS-related dementia, Alzheimers, Major Depressive Disorder...not all trials are at the same stage of advancement). The results appear promising, but I've yet to hear anything about the approval of the STS for any indication. This is not suprising, given the glacial pace of the FDA approval process. I'm sure there is still hope that the STS will be on the market in the US in a few years or less, and may be marketed in other countries earlier (most likely, for most pharmaceuticals), and could conceivably be obtainable through foreign channels, though this is an increasingly difficult means of obtaining drugs.
On selegiline's chemical properties: Selegiline is an L-phenylamine-class drug, and it's metabolites, which happen to include methamphetamine and amphetamine, are also, given their parent's enantiomeric identity, the "L" forms of these drugs. The designer-drug versions of methamphetamine and amphetamine are the "D" forms, the "mirror images" of selegiline's metabolites, if you will, and have more potent and somewhat different effects on the central and peripheral nervous systems. They shouldn't make you high, in other words, at least not at the doses seen in any clinical application I'm aware of. Clearly, these metabolites do something, though, and I believe (being a non-expert, mind you) that their effects are mostly a nuisance which is mitgated considerably by transdermal delevery, which moderates both the rate of dosing and eliminates first-pass metabolism, whence much of the L-methamphetamine (the precursor of the L-amphetamine in this case) is generated. I'm fairly convinced that the antidepressant action of selegiline is due in large part to the parent compound, given the rate of my positive response to the patch, which I obtained through a phase-III trail for MDD.
It would appear that sexual side-effects are uncommon on selegiline, even at high doses. I think this could be a function of selegiline's activating properties, which seem to stem from it's strongly dopaminergic action, a result not only of MAO-inhibition but also, apparently, blockage of DA reuptake. Tranylcypromine may also be similar in this regard, due to it's amphetamine-like structure (giving it more than one dopaminergic mechanism of action). When one contrasts this with phenelzine, one can consider the latter's hyrazine metabolite(s), which enhances GABA signaling, which in turn inhibits DA secretion in some parts of the brain, leading to such beneficial effects as decreased anxiety, but possibly also some adverse effects like sexual dysfunction. (NOTE: Sexual dysfunction may also be due to enhanced serotonin signaling, the effects of would not be counteracted in phenelzine's case, given the current theories about serotonergic drugs' affects on the dopamine system, and some of the pharmicological antidotes that appear to work for some individuals).
> I have been on Selegiline for only two days at a dose of 60 mg in three divided doses. (I do not have Parkinsons' disease, but rather Treatment-Resistant Depression. I have taken every other antidepressant known to mankind). So far, I have noticed a moderate antidepressant effect after one hour of ingesting it, which I could never get from a placebo. And that is why I'm writing this, to alert others.
>
> Selegiline should be known as the "alternative" MAOI, in that it has less of the side-effects of phenelzine or tranylcypromine. The main side-effect that I have with it is a powerful stimulating effect similar to one caused by buproprion. I have been taking 10 mg oxazepam along with selegiline in order to counter the anxiety produced by selegiline.
>
> Notes:
> --I don't think that selegiline has an antidepressant effect under doses of 40 mg per day.
> --I don't know if selegiline has any sexual side-effects yet.
> --100 of the Generic 5 mg capsules (you need 240 capsules for a months antidepressant supply) costs US $240 at Sav-On Drug Stores. That is expensive. However, medical insurance covers it.
> --You have to drop almost every other antidepressant in order to take the MAOI selegiline, although there is only one reported case in history of Serotonin Syndrome (that is fact).
> --You have to follow the MAOI diet (I won't, though. I didn't on phenelzine or tranylcypromine and didn't have a hypertensive crisis).
Posted by Lynne on March 15, 2001, at 21:10:51
In reply to Re: Selegiline Combos: Lorraine, posted by AndrewB on March 15, 2001, at 10:21:57
I am confused about dosages. At what doseage do you need to take for depression? I had tried Selegiline a year ago at 30mg with no success. After reading these posts I have decided to try it again. This time at 60mg. I have taken this doseage for 2 days. It has made me so sleepy and moody. Any advice?
Thanks so much,
Lynne>
> The selegiline/mirapex combo is used often by PD patients, so it should be safe. I have taken selegiline and neurontin together without problem. I'm weak on pharmacological interreactions between meds. but I researched carefully low dose selegiline interactions. Possible complications seem limited to selegiline and MAOIs and (very occassionally) serotenergic agents. I haven't heard any reports on the mirapex/selgiline combo on mood and anxiety so if you do try mirapex as an add-on I would very much like to hear what your response is.
>
> I have one small suggestion. 5 mg/day (and possibly even 2.5mg./day) of selegiline is able to achieve full MAO-B inhibition. The only difference is it takes a number of days longer to achieve this steady state full inhibition with the lower doses. I mention this not only because it is a little cheapeer to use the lower doses, but because selegiline even at small doses converts to amphetamine. That is selegline metabolizes to amphetamine at all dosages but as the dosage is increased, the metabolite increases, possibly linearly. Anyway since amphetamine can cause anxiety, and the MAO-B inhibition is what results in the desired effect from low dose selegiline, taking a lower dose may be produce noticeably less anxiety but have the same positive effect on motivation and vitality. I take 5mg./day.
>
> AndrewB
Posted by AndrewB on March 16, 2001, at 8:28:44
In reply to Re: Selegiline Combos: Doseage?Lorraine, posted by Lynne on March 15, 2001, at 21:10:51
Posted by Adam on March 16, 2001, at 11:20:23
In reply to Re: Selegiline Combos: Doseage?Lorraine, posted by Lynne on March 15, 2001, at 21:10:51
Selegiline begins to lose it's MAO-B specificity at around 10mg/day. At 20mg/day, one is advised to adhere to dietary restrictions (drug restrictions should be observed at all doses unless under close doctor supervision).
The pressor response to tyramine challenge for oral selegiline at 60mg/day is comparable to that of tranylcypromine. This indicates comparable levels of MAO-A inhibition (in other words, complete).
Early studies indicated selegiline was effective above placebo for depression at doses of 40-60mg (20-30mg b.i.d.)
I am having a robust response at 30mg/day.
The individual response to dosage, as with all antidepressants, will vary considerably.
Sleepyness is a somewhat paradoxical side effect for selegiline, though not unheard of. Just out of curiosity, have you ever taken or been prescribed psychostimulants (Ritalin, Dexedrine)? Have you ever tried Wellbutrin? If so, what was your response/side effect profile?
> I am confused about dosages. At what doseage do you need to take for depression? I had tried Selegiline a year ago at 30mg with no success. After reading these posts I have decided to try it again. This time at 60mg. I have taken this doseage for 2 days. It has made me so sleepy and moody. Any advice?
>
> Thanks so much,
> Lynne
>
>
>
>
>
> >
> > The selegiline/mirapex combo is used often by PD patients, so it should be safe. I have taken selegiline and neurontin together without problem. I'm weak on pharmacological interreactions between meds. but I researched carefully low dose selegiline interactions. Possible complications seem limited to selegiline and MAOIs and (very occassionally) serotenergic agents. I haven't heard any reports on the mirapex/selgiline combo on mood and anxiety so if you do try mirapex as an add-on I would very much like to hear what your response is.
> >
> > I have one small suggestion. 5 mg/day (and possibly even 2.5mg./day) of selegiline is able to achieve full MAO-B inhibition. The only difference is it takes a number of days longer to achieve this steady state full inhibition with the lower doses. I mention this not only because it is a little cheapeer to use the lower doses, but because selegiline even at small doses converts to amphetamine. That is selegline metabolizes to amphetamine at all dosages but as the dosage is increased, the metabolite increases, possibly linearly. Anyway since amphetamine can cause anxiety, and the MAO-B inhibition is what results in the desired effect from low dose selegiline, taking a lower dose may be produce noticeably less anxiety but have the same positive effect on motivation and vitality. I take 5mg./day.
> >
> > AndrewB
Posted by Lorraine on March 16, 2001, at 11:21:40
In reply to Re: Selegiline Combos: Lorraine, posted by AndrewB on March 15, 2001, at 10:21:57
{Anyway since amphetamine can cause anxiety, and the MAO-B inhibition is what results in the desired effect from low dose selegiline, taking a lower dose may be produce noticeably less anxiety but have the same positive effect on motivation and vitality. I take 5mg./day.}
You may be right about the lower dosage. I started with the lower dosage but moved up because it was not "supporting" me--but I was also on a low dose of Neurontin. Now I'm at 900 mg Neurontin and getting some mood support from it, I may be able to scale back the Selegiline. I'll try 7.5 and take it from there good tip. My anxiety, by the way, is purely physical--tightness in chest, difficultly taking in a deep breath, I've been trying Magnesium, Taurine and thinking about adding GABA to try to get it under control. I don't think that I could have done the Selegiline without the Neurotin, but with the two my physical anxiety is not worse than it was before the Selegiline, it just isn't better. I may need to add a beta blocker ultimately. The thing is I am able to function for the first time in a long time. My pdoc also said that I could add dexedrine to my Neurontin/Selegiline combo if I want. If scaling back the Selegiline doesn't work, I may try scaling back and adding 2.5 dexidrine to the mix. For some reason, dexidrine doesn't seem to worsen my anxiety symptoms. I'm just not clear which Dopamine receptors are being hit by the Selegiline and which would be hit by the dexedrine. I know that with Mirapex its D2 and D3, with the emphasis strongly on the D3 (8 to 1 or something like that). Thanx for the post.
Posted by Lorraine on March 16, 2001, at 11:35:46
In reply to Re: Report of success: Selegiline: alernate MAOI, posted by Adam on March 15, 2001, at 18:31:00
Wonderful post. Raises lots of questions. First off, I also had a very quick response to Selegiline--within an hour. It may be the amphetamine aspect of the drug that did this.
{ I have had Neurontin (gabapentin) prescribed for selegiline-induced insomnia and anxiety. I think this is a reasonable choice, given Neurontin's relatively benign side-effects profile at low doses. I have chosen not to take it though, and have rather focused my efforts on "sleep hygene" and exercise.}
Please tell me more about this. My sleep hygene is excellent, although without the Neurontin it might be a problem. On the other hand, maybe GABA alone could handle it. I stay on the Neurontin (900 mg a day divided into 3 doses) because it gives me a level of "mood support" I did not get from the Selegiline alone. What is your exercise component? Do you exercise each time you take a dose--although you are on the patch so perhaps your "ride" is smoother.
{a pharmacological approach second. Another approach that might be worth exploring is low-dose risperidol.}
Do you know anything about risperidol? Neurontin is not taking away my physical anxiety (tightness in chest, difficulty taking in a deep breath). I was thinking perhaps a beta blocker.
{Clearly, these metabolites do something, though, and I believe (being a non-expert, mind you) that their effects are mostly a nuisance which is mitgated considerably by transdermal delevery, which moderates both the rate of dosing and eliminates first-pass metabolism, whence much of the L-methamphetamine (the precursor of the L-amphetamine in this case) is generated.}
Does that mean that you are not "speeded up" on the patch?
Posted by Lorraine on March 16, 2001, at 11:41:11
In reply to Re: Selegiline Combos: Doseage?Lorraine, posted by Lynne on March 15, 2001, at 21:10:51
{ I am confused about dosages. At what doseage do you need to take for depression? I had tried Selegiline a year ago at 30mg with no success. After reading these posts I have decided to try it again. This time at 60mg. I have taken this doseage for 2 days. It has made me so sleepy and moody. Any advice?}
You are having one odd reaction to Selegiline. It is a puppy upper not a doggy downer. My goal is MAO w/o dietary restrictions, sexual side effects and weight gain if possible. So I am using a low dose (10 mg and I may lower it because I am pretty hyper on this dose) and augmenting that dose with Neurontin (at 900 mg a day) to give me "mood support". At 10 mg, Selegiline is a selective MAO somewhere above 15 mg, it becomes a non-selective MAO with dietary restrictions and I am sure has a very different effect on the system. good luck. Keep me up to date on your progress. I would definately tell your pdoc that you are reacting to a puppy upper as tho it were a doggy downer. Your system may be a bit different and require a different response than most.
Posted by Lynne on March 16, 2001, at 13:05:26
In reply to Re: Selegiline Combos: Doseage?Lynne, posted by Lorraine on March 16, 2001, at 11:41:11
Thank you for responding to my posts.I have taken Ritalin, Dexedrine,Adderall in the past. They seem to help a little but I still could go to sleep after taking any of these stimulants. What I hated the most was the very depressed feelings after these meds wore off. Wellbutrin seemed to have helped the most but I am allergic to it.
I have tried so many meds I think I will just give up. The thought of giving up on meds is very scary to me. But I have tried everything from Parnate to SSRIs. Anyway thanks again for the info.
One more question, how long did you take Selegiline before you noticed it was helping?
Thanks,
Lynne
Posted by Adam on March 16, 2001, at 16:23:08
In reply to Re: Report of success: Selegiline: Adam, posted by Lorraine on March 16, 2001, at 11:35:46
> Please tell me more about this. My sleep hygene is excellent, although without the Neurontin it might be a problem. On the other hand, maybe GABA alone could handle it. I stay on the Neurontin (900 mg a day divided into 3 doses) because it gives me a level of "mood support" I did not get from the Selegiline alone. What is your exercise component? Do you exercise each time you take a dose--although you are on the patch so perhaps your "ride" is smoother.
>I am not currently on the patch. In fact, it's been quite some time (getting close to a year now).
Sleep hygene: When the clock strikes twelve, I turn into a pumpkin. Period. Selegiline seems to have taken away my ability to discern night from day in any circadian sense. I just don't feel the effects of the close of the diurnal cycle like a used to, and pretty much have to force myself to go to bed. Once I get there, if sufficiently tired, I go to sleep. If I don't go to bed, I don't go to sleep, seemingly indefinitely. I have gone, on a couple of occasions, 48+ hours without sleeping, pretty much because I didn't feel like it, or, strangely, felt like going to sleep in the middle of the day when it wasn't feasible to do so. So, in the absense of a reliable innner clock, I have to consciously adhere to a self-imposed sleep schedule, and, interestingly, once I get horizontal, I do eventually go to sleep.
Exercise: Strenuous cardiovascular activity during the day, but not too late in the day, or I'm wired and won't sit down or shut up (in all seriousness - my poor girlfriend will fall asleep during conversations because she can't keep her eyes open any longer and I'm still gabbing away for ten minutes before I catch on...). My main problem is, I like to run. Nothing gets me tired like a run, but I'm hurting my legs, and have to call it quits, or find something else. I may have to < grimace >, join a _gym_. I hate gyms. But, a treadmill or an erg would be lower-impact. I like ergs. And, well, there's also sex (including the self-administered kind). Good for sleep. I highly recommend it. Caution: Can be habit forming.
>
> Do you know anything about risperidol? Neurontin is not taking away my physical anxiety (tightness in chest, difficulty taking in a deep breath). I was thinking perhaps a beta blocker.
>
Risperidol seems to have some rather brain-region specific effects on dopamine signaling (though it also affects serotonin signaling), and at low doses, should not antagonize the beneficial effects of selegiline. This is just conjecture, though. I think it's been tried as an antidote to selegiline-associated adverse effects, and has also been used to augment SSRIs to increase efficacy of antidepressant and/or antiobsessional response. This might be good for anxiety, or stimulant-induced obsessions or psychoses. Risp. does seem to have some bad side effects for some, but, at low doses, the risk of extrapyramidal symptoms is about nil.
>
> Does that mean that you are not "speeded up" on the patch?I was plenty "speeded up" shortly after beginning the patch, but in a kind of hypomanic way. Once I seemed to settle into the whole bona fide antidepressant response thing (a new experience for me, quite frankly, barring ECT, which was more transient), I found it less of an anxiety and insomnia inducer than oral selegiline has turned out to be. My explanation, again, is that the delivery is more even and the half life greatly increased (hence much lower rate of L-methamphetamine production). Must repeat my caution, though: This is just conjecture.
Posted by Adam on March 16, 2001, at 16:34:02
In reply to Re: Selegiline Combos: Doseage?, posted by Lynne on March 16, 2001, at 13:05:26
I noticed some benefit from selegiline in about a day, and in two or three days, I was actually euphoric and, as one doctor described me, "expansive". This response is, in my humble and grateful oppinion, well above and beyond the call of duty. I certainly would be happy for anyone if they also had such a response, but I do believe it is quite a lot to expect of any antidepressant. The main objective: not feeling so damn sad anymore. Focus on that. Keep working with your doctor. Don't give up on meds. It seems that you've gotten some positive responses (however imperfect) from some commonly-used drugs, and that's more than a lot of people can say, unfortunately.
Your relative lack of sensitivity to stimulants is interesting. Have you tried a COMT inhibitor, like Tolcapone, as an augmentation to selegiline or a stimulant?
> Thank you for responding to my posts.I have taken Ritalin, Dexedrine,Adderall in the past. They seem to help a little but I still could go to sleep after taking any of these stimulants. What I hated the most was the very depressed feelings after these meds wore off. Wellbutrin seemed to have helped the most but I am allergic to it.
> I have tried so many meds I think I will just give up. The thought of giving up on meds is very scary to me. But I have tried everything from Parnate to SSRIs. Anyway thanks again for the info.
> One more question, how long did you take Selegiline before you noticed it was helping?
> Thanks,
> Lynne
Posted by Mr. Scott on March 16, 2001, at 17:14:17
In reply to Re: Report of success: Selegiline: alernate MAOI, posted by Adam on March 15, 2001, at 18:31:00
> I'm sorry. A while ago I tried to post and couldn't due to maintainance of the site. Then I went on a two-week vacation in the Southwest US. Now I'm back.
>
> I had a quick response to selegiline also. So quick, in fact, that I often wondered aloud if I was imagining the whole thing. I don't believe this was the case. I am still on selegiline, and doing very well, mood-wise. Your response does seem remarkably quick, even knowing what I know, but as the pharmacokinetics of selegiline may be influenced by a pharmacodynamic profile involving responses to the parent molecule and its metabolites that are independant of it's MAO-inhibiting function, I'm guessing your exprience could well be more than a figment of your imagination.
>
> I would not be too cavalier about the dietary restrictions, and I would be very serious about the potential drug interactions. I think with diet, it's possible to cheat a little and be OK. Hypervigilance isn't necessary, and the usual restrictions recommended by doctors are clearly not necessary for everyone. However, caution is always warrented. Changes in blood pressure are not always easy to detect emperically, and full-blown hypertensive crisis isn't the only risk state one need consider.
>
> I have had Neurontin (gabapentin) prescribed for selegiline-induced insomnia and anxiety. I think this is a reasonable choice, given Neurontin's relatively benign side-effects profile at low doses. I have chosen not to take it though, and have rather focused my efforts on "sleep hygene" and exercise. For those with similar concerns who care to know, I would endorse this approach first, and a pharmacological approach second. Another approach that might be worth exploring is low-dose risperidol.
>
> I have heard mention of foreign pharmacies somehow formulating their own selegiline patches. I wouldn't trust such a source, if indeed it exists. There have been and continue to be numerous placebo-controlled pilot and phase-II and III trials of the selegiline transdermal system (STS) for various indications (Parkinsons, AIDS-related dementia, Alzheimers, Major Depressive Disorder...not all trials are at the same stage of advancement). The results appear promising, but I've yet to hear anything about the approval of the STS for any indication. This is not suprising, given the glacial pace of the FDA approval process. I'm sure there is still hope that the STS will be on the market in the US in a few years or less, and may be marketed in other countries earlier (most likely, for most pharmaceuticals), and could conceivably be obtainable through foreign channels, though this is an increasingly difficult means of obtaining drugs.
>
> On selegiline's chemical properties: Selegiline is an L-phenylamine-class drug, and it's metabolites, which happen to include methamphetamine and amphetamine, are also, given their parent's enantiomeric identity, the "L" forms of these drugs. The designer-drug versions of methamphetamine and amphetamine are the "D" forms, the "mirror images" of selegiline's metabolites, if you will, and have more potent and somewhat different effects on the central and peripheral nervous systems. They shouldn't make you high, in other words, at least not at the doses seen in any clinical application I'm aware of. Clearly, these metabolites do something, though, and I believe (being a non-expert, mind you) that their effects are mostly a nuisance which is mitgated considerably by transdermal delevery, which moderates both the rate of dosing and eliminates first-pass metabolism, whence much of the L-methamphetamine (the precursor of the L-amphetamine in this case) is generated. I'm fairly convinced that the antidepressant action of selegiline is due in large part to the parent compound, given the rate of my positive response to the patch, which I obtained through a phase-III trail for MDD.
>
> It would appear that sexual side-effects are uncommon on selegiline, even at high doses. I think this could be a function of selegiline's activating properties, which seem to stem from it's strongly dopaminergic action, a result not only of MAO-inhibition but also, apparently, blockage of DA reuptake. Tranylcypromine may also be similar in this regard, due to it's amphetamine-like structure (giving it more than one dopaminergic mechanism of action). When one contrasts this with phenelzine, one can consider the latter's hyrazine metabolite(s), which enhances GABA signaling, which in turn inhibits DA secretion in some parts of the brain, leading to such beneficial effects as decreased anxiety, but possibly also some adverse effects like sexual dysfunction. (NOTE: Sexual dysfunction may also be due to enhanced serotonin signaling, the effects of would not be counteracted in phenelzine's case, given the current theories about serotonergic drugs' affects on the dopamine system, and some of the pharmicological antidotes that appear to work for some individuals).
>
>
>
> > I have been on Selegiline for only two days at a dose of 60 mg in three divided doses. (I do not have Parkinsons' disease, but rather Treatment-Resistant Depression. I have taken every other antidepressant known to mankind). So far, I have noticed a moderate antidepressant effect after one hour of ingesting it, which I could never get from a placebo. And that is why I'm writing this, to alert others.
> >
> > Selegiline should be known as the "alternative" MAOI, in that it has less of the side-effects of phenelzine or tranylcypromine. The main side-effect that I have with it is a powerful stimulating effect similar to one caused by buproprion. I have been taking 10 mg oxazepam along with selegiline in order to counter the anxiety produced by selegiline.
> >
> > Notes:
> > --I don't think that selegiline has an antidepressant effect under doses of 40 mg per day.
> > --I don't know if selegiline has any sexual side-effects yet.
> > --100 of the Generic 5 mg capsules (you need 240 capsules for a months antidepressant supply) costs US $240 at Sav-On Drug Stores. That is expensive. However, medical insurance covers it.
> > --You have to drop almost every other antidepressant in order to take the MAOI selegiline, although there is only one reported case in history of Serotonin Syndrome (that is fact).
> > --You have to follow the MAOI diet (I won't, though. I didn't on phenelzine or tranylcypromine and didn't have a hypertensive crisis).Do you think there is a "SAFE" dosage to take selegeline WITH an SSRI?
Posted by Lorraine on March 16, 2001, at 20:28:34
In reply to Re: Selegiline Combos: Doseage?, posted by Lynne on March 16, 2001, at 13:05:26
{ One more question, how long did you take Selegiline before you noticed it was helping?}
It's pretty immediate; a day or two, but then I've added the Neurontin for mood support.
Posted by Lorraine on March 16, 2001, at 20:32:20
In reply to Re: Report of success: Selegiline: Adam, posted by Adam on March 16, 2001, at 16:23:08
Thanx
Posted by Adam on March 17, 2001, at 22:24:14
In reply to Re: Report of success: Selegiline: alernate MAOI, posted by Mr. Scott on March 16, 2001, at 17:14:17
> Do you think there is a "SAFE" dosage to take selegeline WITH an SSRI?
In theory, there shouldn't be a problem with doses where there is no inhibition of MAO-A, which one would think is 10mg or lower. From what I've read, there is complete or near-complete inhibition of MAO-B at doses around 5mg/day, and once you are up in the 10mg/day range, you've got complete inhibition of MAO-B, and a small amount of inhibition of MAO-A. You have to be mindful of the fact that the "specificity" of selegiline is really just a differential affinity for each isoform of MAO. Most dose-response curves for drugs are typically "sigmoidal", or S-shaped (and can be fit "parametrically" pretty well, in most cases, to the "Hill equation", though there are usually better models for specific drugs). You have a long range on the low and high ends of the curve where there is little or no added effect for an increase in dose, and then somewhere in between the effect shoots up, and in this dose range, you get a near linear increase of effect per increase in dose. So you want to know, what's the real EC50 (the dose where 50% of inhibition occurs) for MAO-A? That dose is one you want to stay away from, because anything close to that (within about a log or half a log), or much higher, could give you a pretty significant inhibition of MAO-A. The trouble is, I'm not sure if the answer to that is known. If someone has done a dose response curve for MAO-A in people, I'm not aware of it, and there's little real information for someone to work with to inform such a decision (to augment an SSRI with selegiline or visa versa), if there is no such info. And, unfortunately, that value (EC50 for MAO-A) could vary quite a lot from person to person, perhaps because they are taking a drug that inhibits selegiline metabolism, or they are deficient in a drug-metabolizing enzyme (neither of which may be easy to ascertain).
I was once under the impression that, at 5mg/day selegiline, one should have no problem taking an SSRI concurrently, and you would still see complete or near-complete inhibition of MAO-B. I've revised my thinking, especially since I've been experimenting with small-molecule drugs a lot a work, and seen some of the variation that can occur in dosing, even among inbred animals. It may be entirely possible (and I know some people do it, as there are a few papers from Europe describing the practice) to take low-dose selegiline and an SSRI concurrently, and suffer no ill effects. However, there may be real risk, which is impossible, as far as I can see, to assess beforehand, of serotonin syndrome, which, as we all know, could be deadly. Given even remote odds, I seriously doubt you will find a physician on American soil who would go along with the experiment. Maybe I'm wrong, but, given the risks, I don't think this is a viable approach, for both health and legal reasons.
Posted by shelliR on June 22, 2001, at 22:51:47
In reply to Re: Report of success: Selegiline: alernate MAOI, posted by Adam on March 17, 2001, at 22:24:14
I started selegiline about ten days ago and am up to 20mg. I am also taking oxycontin for the depression (10mg twice a day)--which I will post about at some other time. I started both around the same time in the hospital. I would have liked to see how the selegiline did by itself, but I was so depressed that I was barely hanging on. So I decided I would sort it out after. I don't feel much from the selegiline so far, but side effects are an internal shakiness and very sweaty (clammy) feelings in the eastern humidity--much more so than ever before--mostly on my arms and face. I am wondering if anyone has the experience that these side effects subside?
Shelli
Posted by Lorraine on June 23, 2001, at 10:52:29
In reply to Re: Report of success: Selegiline: alernate MAOI, posted by shelliR on June 22, 2001, at 22:51:47
I take 2.5 mg 2x day of Selegiline. It makes me shakey and anxious if I take more. I take Neurontin (300 3x day) and Adderral (7.5 mg 2 x day) as well. This combo is not truly satisfying so I'd be interested in the AD you are taking with the Selegiline. Selegiline increasing my cognitive functions (which have been impaired) and restores my sexual functioning as well. Good luck with it.
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