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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 19 of 19. This is the beginning of the thread.
Posted by Craig Allen on February 14, 2003, at 19:16:05
i am a treatment resistant, atypical depression guy. most of the time i am sleepy and bored. i am on adderall (20mg, 3x per day) because it keeps me awake which enables me to stay employed. at first, the adderall was mood elevating. now it makes me feel flat and dull. i've read on this board that people have had a good response to selegeline (eldepryl). i have a few questions:
1) is there a rebound effect with selegeline, as there is with stimulants?
2) how long before it starts to work?
3) what drugs can, or can't, be combined with selegeline?
4) taken orally, what dosages are people finding to be effective? how long does it take to build to that dose?
5) before starting on selegeline, do you have to be off all meds for 2 weeks, as with other MAOI's?
anything else about your selegeline experiences would be greatly appreciated. thanks for your help in advance.
Posted by JohnL on February 15, 2003, at 7:18:14
In reply to ANYONE ON SELEGELINE? QUESTIONS..., posted by Craig Allen on February 14, 2003, at 19:16:05
I have tried selegeline, though only in the 5mg to 10mg range.
Most psychiatric drugs actually make me feel worse instead of better. But selegeline was one of the few good ones. Oddly though, it made me impotent. It is supposed to be pro-sex, but it wasn't for me.
I actually felt good effects from selegiline the very first day. It was sort of like stimulant. But very quickly tolerance builds up and that stimulant feeling goes away.
I did not experience a rebound effect.
For me it started to work the first day, but I've heard others say it can take a few weeks.
When the selegeline dosage is 10mg or lower, there isn't much problem combining it with other meds. But above 10mg it starts to act like a full fledged MAOI, in which combinations demand a more cautious "low and slow" approach.
Some people find benefits in the 5mg to 10mg range. Others have had to go up to 40mg. You'll just have to experiment.
As long as you start out in the 5mg range, you won't need to do a washout.
> i am a treatment resistant, atypical depression guy. most of the time i am sleepy and bored. i am on adderall (20mg, 3x per day) because it keeps me awake which enables me to stay employed. at first, the adderall was mood elevating. now it makes me feel flat and dull. i've read on this board that people have had a good response to selegeline (eldepryl). i have a few questions:
> 1) is there a rebound effect with selegeline, as there is with stimulants?
> 2) how long before it starts to work?
> 3) what drugs can, or can't, be combined with selegeline?
> 4) taken orally, what dosages are people finding to be effective? how long does it take to build to that dose?
> 5) before starting on selegeline, do you have to be off all meds for 2 weeks, as with other MAOI's?
> anything else about your selegeline experiences would be greatly appreciated. thanks for your help in advance.
Posted by Craig Allen on February 15, 2003, at 7:26:45
In reply to Re: ANYONE ON SELEGELINE? QUESTIONS..., posted by JohnL on February 15, 2003, at 7:18:14
thanks for all the info john l. after you stopped getting a stimulant effect from the selegeline, were you getting any benefit from it or was it a complete poop out?
Posted by JohnL on February 15, 2003, at 8:21:59
In reply to Re: ANYONE ON SELEGELINE? QUESTIONS... » JohnL, posted by Craig Allen on February 15, 2003, at 7:26:45
> thanks for all the info john l. after you stopped getting a stimulant effect from the selegeline, were you getting any benefit from it or was it a complete poop out?
I wasn't actually on selegeline long enough to be able to tell. Only about 2 weeks. I think it was more of an issue of tolerance than it was poopout. If not for the strange impotence (that shouldn't have happened on selegeline), I would have given it more time.
Posted by SLS on February 16, 2003, at 10:46:48
In reply to Re: ANYONE ON SELEGELINE? QUESTIONS... » JohnL, posted by Craig Allen on February 15, 2003, at 7:26:45
Hi.
Selegiline, once called l-deprenyl, was initially researched and developed as an antidepressant. Quite a bit of money was poured into getting it approved as such. Selegiline is different from the other irreversible MAOIs (Parnate, Marplan, and Nardil) in that it binds to the MAO-B form of monoamine-oxidase much more strongly than it does to MAO-A. MAO-B metabolizes dopamine (DA). MAO-A metabolizes both norepinephrine (NE) and serotonin (5-HT). At low dosages, it was found that selegiline was selective for the MAO-B enzyme. Generally speaking, it is the MAO-A enzyme that seems to be the more important when treating depression.
Selegiline is *selective*, but not *specific*. At dosages above 10mg, selegiline begins to inhibits MAO-A in addition to MAO-B. At the low dosages used initially, it proved to be a disappointment. However, it was subsequently studied to evaluate its utility in treating Parkinsons Disease , a disorder involving the degeneration of neurons that utilize dopamine as their neurotransmitter. Selegiline demonstrated enough efficacy to be approved by the FDA for Parkinsons, but not depression.
In order to work as an antidepressant monotherapeutically in severe depression, it seems that the dosage of selegiline must be greater than 10mg per day. No longer being selective, it inhibits both MAO enzymes similar to Parnate and Nardil. At the point where MAO-A becomes significantly inhibited, the same dietary restrictions that must be followed for Parnate and Nardil apply with selegiline as well. This is true for oral administration. However, when used as a patch (transdermal delivery), the MAO-A along the digestive tract is bypassed, preventing the hypertensive food-reaction. Another advantage of the transdermal patch is that it maintains a constant blood level of selegiline throughout the day. People often report that the quality of their antidepressant response is significantly better and qualitatively different than that they experience with oral selegiline.
Selegiline can make a good augmentor of standard antidepressants. It can do so at dosages lower than what are necessary for its use as monotherapy. On Psycho-Babble, I see quite a few people report success using 5.0mg of selegiline in this fashion. Low dosages might also be effective for dysthymia, ADD / ADHD, chronic fatigue syndrome, and perhaps Alzheimers Dementia. My guess is that the reason low dosages of selegiline are effective for the former three is that it is metabolized into methamphetamine in the body, and that it methamphetamine that produces the improvements in mood, energy, and attentional deficits.
I forgot what the question was. :-)
- Scott
Posted by Craig Allen on February 16, 2003, at 11:31:02
In reply to Re: ANYONE ON SELEGELINE? QUESTIONS..., posted by SLS on February 16, 2003, at 10:46:48
thanks for the info scott. at low doses, is selegiline safe to use in combination with standard anti depressants? also, for anyone with first hand experience using this drug, does it have the same rebound depession and poop out tendencies that amphetemines have?
Posted by hok on February 16, 2003, at 12:53:03
In reply to Re: ANYONE ON SELEGELINE? QUESTIONS..., posted by SLS on February 16, 2003, at 10:46:48
Scott-
Interesting synopsis. Thanks for the info.
I am currently deciding whether to try use the selegiline tablets or the subligual form as an augmentor. Until this point, I assumed the sublingual form was the obvious choice since it bypasses the 1) GI tract, 2) keeps more of the active form in the bloodstream and less of its metabolites floating around -- so hopefully less side effects. But your theory on the antidepressant effects being due to the methamphetamine metabolite instead of the MAO-B inhibitory effect makes me think I should try the tablet form. On a side note, I've been a smoker in the past, and I always believed that the strong anti-anhednonic effect I've always gotten from it was due to the MAO-B inhibition involved.Have a couple of questions, if you don't mind. Would like to hear more of your thought on the biochemical details of the atypical/anhedonia issue if possible, and what implications this has for taking either form of the drug.
Also, what is the downside of the sublingual form? Does its pharmacokinetics fade very fast so frequent dosing is needed? Besides not having to administrate multiple doses throughout the day, what will be tha advantage of the patch over the sublingual form?
And lastly, have you had experience with either one personally? If so, can you relate your conclusions to us all? It would be much appreciated.Thanks,
HK
> Hi.
>
> Selegiline, once called l-deprenyl, was initially researched and developed as an antidepressant. Quite a bit of money was poured into getting it approved as such. Selegiline is different from the other irreversible MAOIs (Parnate, Marplan, and Nardil) in that it binds to the MAO-B form of monoamine-oxidase much more strongly than it does to MAO-A. MAO-B metabolizes dopamine (DA). MAO-A metabolizes both norepinephrine (NE) and serotonin (5-HT). At low dosages, it was found that selegiline was selective for the MAO-B enzyme. Generally speaking, it is the MAO-A enzyme that seems to be the more important when treating depression.
>
> Selegiline is *selective*, but not *specific*. At dosages above 10mg, selegiline begins to inhibits MAO-A in addition to MAO-B. At the low dosages used initially, it proved to be a disappointment. However, it was subsequently studied to evaluate its utility in treating Parkinsons Disease , a disorder involving the degeneration of neurons that utilize dopamine as their neurotransmitter. Selegiline demonstrated enough efficacy to be approved by the FDA for Parkinsons, but not depression.
>
> In order to work as an antidepressant monotherapeutically in severe depression, it seems that the dosage of selegiline must be greater than 10mg per day. No longer being selective, it inhibits both MAO enzymes similar to Parnate and Nardil. At the point where MAO-A becomes significantly inhibited, the same dietary restrictions that must be followed for Parnate and Nardil apply with selegiline as well. This is true for oral administration. However, when used as a patch (transdermal delivery), the MAO-A along the digestive tract is bypassed, preventing the hypertensive food-reaction. Another advantage of the transdermal patch is that it maintains a constant blood level of selegiline throughout the day. People often report that the quality of their antidepressant response is significantly better and qualitatively different than that they experience with oral selegiline.
>
> Selegiline can make a good augmentor of standard antidepressants. It can do so at dosages lower than what are necessary for its use as monotherapy. On Psycho-Babble, I see quite a few people report success using 5.0mg of selegiline in this fashion. Low dosages might also be effective for dysthymia, ADD / ADHD, chronic fatigue syndrome, and perhaps Alzheimers Dementia. My guess is that the reason low dosages of selegiline are effective for the former three is that it is metabolized into methamphetamine in the body, and that it methamphetamine that produces the improvements in mood, energy, and attentional deficits.
>
> I forgot what the question was. :-)
>
>
> - Scott
Posted by wingedcat on February 16, 2003, at 18:57:54
In reply to ANYONE ON SELEGELINE? QUESTIONS..., posted by Craig Allen on February 14, 2003, at 19:16:05
> i am a treatment resistant, atypical depression guy. most of the time i am sleepy and bored. i am on adderall (20mg, 3x per day) because it keeps me awake which enables me to stay employed. at first, the adderall was mood elevating. now it makes me feel flat and dull. i've read on this board that people have had a good response to selegeline (eldepryl). i have a few questions:
> 1) is there a rebound effect with selegeline, as there is with stimulants?
> 2) how long before it starts to work?
> 3) what drugs can, or can't, be combined with selegeline?
> 4) taken orally, what dosages are people finding to be effective? how long does it take to build to that dose?
> 5) before starting on selegeline, do you have to be off all meds for 2 weeks, as with other MAOI's?
> anything else about your selegeline experiences would be greatly appreciated. thanks for your help in advance.
I responded to another post of yours about selegiline here:http://www.dr-bob.org/babble/20030214/msgs/200983.html
but here are answers to these particular ?s:
1) I've tried Adderall before too and I didn't like the rebound. I haven't noticed any rebound with selegiline.
2) I noticed it the first day. I had been suicidal because of the anhedonia/numbness. The first day I started selegiline I was able to cry and let loose a lot of feelings I had been keeping inside. Crying doesn't *sound* good but it was theraputic for me because I hadn't been able to cry for a long time.
3) You can't take opiates in any form, especially Demerol, you could die. I think it's this way with all MAOIs. As for stimulants, you should take a lower dose. I read someone on here combining a low dose of Dexedrine with Selegiline and having good results.
4) I was fine with 5mg a day, but I am small. 10mg a day (divided into two doses) is what I think is normally used in depression.
5) I think selegiline reacts less with most drugs than other MAOIs. If all you are taking right now is Adderall, that gets out of your system very fast. I think that the 2 week rule refers more to SSRIs.
Posted by Craig Allen on February 16, 2003, at 21:04:54
In reply to Re: ANYONE ON SELEGELINE? QUESTIONS... » Craig Allen, posted by wingedcat on February 16, 2003, at 18:57:54
thanks for all the helpful info. in addition to adderall, i'm on effexor (225 mg per day). anyone know if i can augment the effexor with selegiline? i'm going to drop the adderall. i'm hoping that the selegiline will ease the nasty depression that comes with stopping the adderall. thanks again.
Posted by SLS on February 16, 2003, at 22:37:46
In reply to Re: ANYONE ON SELEGELINE? QUESTIONS... » SLS, posted by hok on February 16, 2003, at 12:53:03
Hi Hok.
(I didn't proofread this).
You've asked important questions for which I have no answers or understanding, but I'd like to clarify a few points.
> I am currently deciding whether to try use the selegiline tablets or the sublingual form as an augmentor. Until this point, I assumed the sublingual form was the obvious choice since it bypasses the 1) GI tract, 2) keeps more of the active form in the bloodstream and less of its metabolites floating around -- so hopefully less side effects.
I wasn't aware that there was a sublingual preparation available. It looks good to me on paper. Which side effects do you attribute to the metabolites? What type of dosing schedule would you use (dose x frequency)? Where do you get sublingual selegiline?
> But your theory on the antidepressant effects being due to the methamphetamine metabolite instead of the MAO-B inhibitory effect makes me think I should try the tablet form.
Actually, I tend to believe that it is the inhibition of MAO-A that occurs at dosages greater than 10mg that is most responsible for the type of global improvement that one looks for when treating moderate to severe depression. Unbeknownst to many is that MAOI-A metabolizes dopamine as well as norepinephrine and serotonin. As an augmentor of other antidepressant drugs, it would appear that certain people benefit from lower dosages of selegiline: 2.5 - 5.0mg.
Perhaps the inhibition of MAO-B is sufficient to complement the actions of the antidepressant drugs it supplements. However, I think it is important to recognize the extent to which selegiline is converted to stimulating metabolites, methamphetamine and amphetamine. N-desmethylselegiline is the third major metabolite of selegiline oxidation. Transdermal delivery yields a reduced amount of these metabolites combined as compared to the oral preparation. However, the metabolism of selegiline is shifted away from the inactive N-desmethyl product and toward the two amphetamines. I think these stimulants help account for the utility selegiline has in treating ADD/ADHD or CFS. In addition, stimulants sometimes function well as augmentors of antidepressants. I am not saying that MAO-B inhibition is without effect in the treatment of these illnesses, but I think it is more productive to take into account the presence of its metabolites and the ability of MAO-A to metabolize dopamine in order to understand the pharmacology of selegiline.
> On a side note, I've been a smoker in the past, and I always believed that the strong anti-anhednonic effect I've always gotten from it was due to the MAO-B inhibition involved.
Although smoking can reduce the activity of MAO-B located on blood platelets, I don't know to what extent such is reflected in the brain. As far as reducing anhedonia is concerned, I believe that this is explained by the observed increase in dopaminergic activity in regions of the brain involving reward (ie. nucleus accumbens) secondary to the stimulation of nicotinic ACh receptors by nicotine. Nicotine does not inhibit MAO-B.
---"Platelet monoamine oxidase B activity is inversely associated with plasma cotinine concentration."
---
"Smoking a single cigarette does not produce a measurable reduction in brain MAO B in non-smokers."
---
"An acute dose of nicotine does not inhibit MAO B in baboon brain in vivo."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9674950&dopt=Abstract
---
"Brain reward system activity in major depression and comorbid nicotine dependence."
---
"Selegiline for the Delivery of Small Doses of Amphetamine in Autism, ADHD and Mental Retardation"
http://www.personalconsult.com/articles/selegilinedelivery.html
---
> Have a couple of questions, if you don't mind. Would like to hear more of your thought on the biochemical details of the atypical/anhedonia issue if possible, and what implications this has for taking either form of the drug.Hmm. I have seen more than a few people here report that low dosages of oral selegiline have helped with anhedonia. However, I'm not entirely convinced that this anhedonia was integral to major depression or bipolar depression. It seemed to me that these reports came from people who were suffering from dysthymia or perhaps CFS. Soo... I don't know. However, for treating an episode of major depression or bipolar depression, I think it makes sense to regard selegiline as just another non-selective MAOI, and not to linger too long at lower dosages. If I were to give it a go, I would target somewhere between 40-60mg. Even if selegiline loses its selectivity at these dosages, it certainly does not make it a clone of Parnate or Nardil. It is a different drug that acts differently in the body, even if only subtly. For each of the irreversible MAOIs (tranylcypromine / Parnate, phenelzine / Nardil, isocarboxazid / Marplan, selegiline / Eldepryl), there are individuals for whom only one will work well.
> Also, what is the downside of the sublingual form? Does its pharmacokinetics fade very fast so frequent dosing is needed? Besides not having to administrate multiple doses throughout the day, what will be tha advantage of the patch over the sublingual form?Great questions! No answers. Sorry.
> And lastly, have you had experience with either one personally? If so, can you relate your conclusions to us all? It would be much appreciated.
I tried Eldepryl (oral selegiline) over ten years ago. It did nothing for me, good or bad. However, having stopped at 30mg still leaves open the possibility that it might work well at the higher dosages now used. I would prefer to take some pills a few times a day than wear a patch every day for the rest of my life. However, people with major depression that have tried both preparations describe them as feeling like entirely different drugs, with the patch being unequivocally superior.
I'm going to follow your posts to see what you and others come up with. I am interested in revisiting selegiline.
Good luck!
- Scott
Posted by SLS on February 16, 2003, at 23:26:08
In reply to Re: ANYONE ON SELEGELINE? QUESTIONS... » wingedcat, posted by Craig Allen on February 16, 2003, at 21:04:54
> thanks for all the helpful info. in addition to adderall, i'm on effexor (225 mg per day). anyone know if i can augment the effexor with selegiline? i'm going to drop the adderall. i'm hoping that the selegiline will ease the nasty depression that comes with stopping the adderall. thanks again.
That sounds like a reasonable idea. Why can't you simply taper the dosage of Adderall gradually enough to avoid the fatigue and depression associated with abrupt withdrawal? S-AMe might be worth trying.
Combining an MAOI with any drug that potently inhibits the reuptake of serotonin (5-HT) is generally contraindicated. Such combinations often produce a serious reaction called "serotonin syndrome".
See:
http://www.google.com/search?hl=en&ie=UTF-8&oe=UTF-8&q=%22serotonin+syndrome%22&btnG=Google+Search
Theoretically, at dosages lower than 10mg, selegiline does not inhibit the MAO-A enzyme that contributes to serotonin syndrome. Dosages of 2.5 - 7.5mg might be safe, but you should be carefully monitored for signs of a reaction. I did a quick search on Medline. Unfortunately, in those abstracts that addressed the combining of selegiline with serotonin reuptake inhibitors, there was no mention of the dosages used. The abstracts that described the incidence of serotonin syndrome as being rare involved the treatment of Parkinsons Disease, for which the dosages of selegiline used are generally no higher than 10mg.
I don't recall reading any personal accounts of using this drug combination. However, if my doctor were to suggest giving it a try, I don't think I would hesitate as long as the dosage used does not exceed 10mg AND I be provided with a list of the symptoms of serotonin syndrome I should monitor.
I hope there's someone here who has actually tried it to give you better feedback. Please post your progress with selegiline. Good luck.
- Scott
Posted by hok on February 17, 2003, at 12:22:04
In reply to Re: ANYONE ON SELEGELINE? QUESTIONS..., posted by SLS on February 16, 2003, at 23:26:08
Has anyone tried the Jumex sublingual form with success yet?
I'd like to know what form (e.g., tablets or sublingual form) as well what brand is best recommended. Would love to know before I order some. Thanks.
HK
Posted by Craig Allen on February 17, 2003, at 13:15:59
In reply to Re: ANYONE ON SELEGELINE? QUESTIONS..., posted by SLS on February 16, 2003, at 23:26:08
thanks for the helpful info scott. i took your suggestion on tapering off the adderall. as an experienced medication guy, you would think that i would know better than to go cold turkey. the adderall has me feeling so depressed and anxiety ridden at this point though, i just want to be done with it. your suggestion to taper is a good one - thanks for stating the obvious, i needed to hear it. today i dropped down to 17.5mg per dose, i had been at 20mg. i think i'll just take it slow and hopefully it won't be that bad. the adderall has me in such a bad way right now. my work week starts tomorrow and i am really frightened about getting through it feeling like this. anyhow, i see my doc tomorrow and i'll run the selegiline idea by him. i don't know what else to try. seems like i've tried them all and nothing addresses the anhedonia and fatigue. thanks for listening!
Posted by haese100 on February 19, 2003, at 23:50:16
In reply to Re: ANYONE ON SELEGELINE? QUESTIONS... » SLS, posted by Craig Allen on February 17, 2003, at 13:15:59
wingedcat, did you say you on Effexor? Whoever? I would have to say your anxiety is from Effexor not the adderall or maybe it's the combo. I was on 300mg daily of Effexor, Provigil (not unlike adderall) and Lexapro, bad, ooh bad combo. I tapered off the Lexapro, things got better, then the Effexor much, much better then the Provigil lastly. Much better, wiping sweat off my brow! I found this thread because I too am wanting to start a regiment of Selegeline. Dopamine pathway is the way to go I've read. Been on anti upon anti for 5 years and believe it was all a waste!
Posted by haese100 on February 19, 2003, at 23:53:54
In reply to Re: ANYONE ON SELEGELINE? QUESTIONS... » Craig Allen, posted by haese100 on February 19, 2003, at 23:50:16
By the way, does anyone know a good place outside USA to order Selegiline? Of course it would help if they were trustworthy!
Posted by Dr. Bob on February 20, 2003, at 19:48:03
In reply to Re: ANYONE ON SELEGELINE? QUESTIONS..., posted by haese100 on February 19, 2003, at 23:53:54
> By the way, does anyone know a good place outside USA to order Selegiline?
Please don't use this site to exchange information that could be used to import into the US prescription medication without a prescription:
http://www.dr-bob.org/babble/faq.html#illegal
Thanks,
Bob
PS: Follow-ups regarding posting policies should be redirected to Psycho-Babble Administration.
Posted by haese100 on February 21, 2003, at 3:20:04
In reply to Re: prescription medication without a prescription » haese100, posted by Dr. Bob on February 20, 2003, at 19:48:03
I retract the question. Thanks
Posted by wingedcat on February 21, 2003, at 3:37:32
In reply to Re: ANYONE ON SELEGELINE? QUESTIONS... » Craig Allen, posted by haese100 on February 19, 2003, at 23:50:16
> wingedcat, did you say you on Effexor? Whoever? I would have to say your anxiety is from Effexor not the adderall or maybe it's the combo. I was on 300mg daily of Effexor, Provigil (not unlike adderall) and Lexapro, bad, ooh bad combo. I tapered off the Lexapro, things got better, then the Effexor much, much better then the Provigil lastly. Much better, wiping sweat off my brow! I found this thread because I too am wanting to start a regiment of Selegeline. Dopamine pathway is the way to go I've read. Been on anti upon anti for 5 years and believe it was all a waste!
No I'm not on Effexor, they keep trying to give me it but I don't want it because I kept hearing horror stories from you and many others. My depression has lifted after a few weeks of Selegiline and I've stopped it for now. I've had severe anxiety since I was a small child and it's several panic attacks a day now and I can barely function. I finally saw a psychiatrist it was a disaster and I felt ignored and confused. The hunt for a doctor that I feel comfortable with continues. Selegiline did help better than anything else I've tried as far as depression goes, so hopefully soon it will be approved and you can let me know about your trial with it :)
Posted by Craig Allen on February 21, 2003, at 17:21:33
In reply to Re: ANYONE ON SELEGELINE? QUESTIONS... » haese100, posted by wingedcat on February 21, 2003, at 3:37:32
what is your dosage on the selegiline? how long did it take to start working for you? thanks.
This is the end of the thread.
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