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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 14 of 14. This is the beginning of the thread.
Posted by matze on April 20, 2001, at 12:46:47
Hi,
Is there anyone, who had success with selegiline for the treatment of major depression or dysthymia?
What doses of selegiline are effective?Thanks for response
matze
Posted by SalArmy4me on April 20, 2001, at 13:48:36
In reply to selegiline for depression, posted by matze on April 20, 2001, at 12:46:47
This is still the authoritative discussion on selegiline: http://www.dr-bob.org/tips/split/Selegiline-for-depression.html
60 mg of selegiline is said to be as effective as 30 mg of phenelzine for depression.
I tried it myself but didn't stay on it long enough to notice anything.
> Hi,
> Is there anyone, who had success with selegiline for the treatment of major depression or dysthymia?
> What doses of selegiline are effective?
>
> Thanks for response
> matze
Posted by Neal on April 21, 2001, at 0:06:15
In reply to selegiline for depression, posted by matze on April 20, 2001, at 12:46:47
I'm starting low-dose Selegiline 5mg as an adjunct to Amisulpride, a European drug. So far, it's working well. A nice, even, energy enhancer.
Posted by JohnL on April 21, 2001, at 4:59:01
In reply to selegiline for depression, posted by matze on April 20, 2001, at 12:46:47
> Hi,
> Is there anyone, who had success with selegiline for the treatment of major depression or dysthymia?
> What doses of selegiline are effective?
>
> Thanks for response
> matzeI haven't seen Adam here in a while, but he used to be a regular here all the time. He had success with Selegiline in treating his depression. If I recall correctly I believe his therapeutic dose was in the 20mg range? He originally had success in a clinical trial where he was given a selegiline patch. When the trial was over, he had no choice but to switch to oral selegiline. Last I heard he was still doing well with it.
It's not for everyone though. When I tried it, I felt almost immediate improvement, which then pooped out super fast, like within a couple days. Increasing the dose actually made me feel worse and also made me impotent as well. As with everything, mileage varies considerably from one person to the next.
John
Posted by AndrewB on April 23, 2001, at 1:03:26
In reply to Re: selegiline for depression, posted by Neal on April 21, 2001, at 0:06:15
Selegiline can be quite effective for major depression, comparable to Parnate or Nardil. That is, at high dosages, selegiline acts as an MAOI inhibitor (of both MAO-A and MAO-B), like a Nardil or Parnate would. Selegiline, as an MAO-I is used at doses ranging from 20 to 60mg/day. Being in general stimulating, it is more akin to Parnate. The delivery of selegiline in a patch form is preferable, lower doses being able to be used and side effects significantly diminished. There is some controversy concerning whether you may have a compounding chemist produce selegiline in the patch form.
As JohnL pointed out, Adam is a poster who has been on both the patch and (currently) the oral form for a long time. He is very knowledgeable on the subject and if you search the archive for his posts concerning selegiline you will come up with a wealth of information including information concerning compounding chemists and the patch.
Now, to change the subject a bit, selegiline at doses below 15mg./day acts quite differently than it does at high doses. Specifically, it inhibits only MAO-B and not MAO-A. At dosages of 2.5mg-10mg./day people will frequently experience increased motivation, mental vigilance, sexual vigor and (as Neal has noted) increased energy.
The most common side effect at these dosages is agitation or anxiety. It seems though that taking amisulpride may lessen or eliminate the possibility of this side effect.
Keeping the dosage low as possible also seems to lessen the likelihood of such side effect. One study has stated that complete MAO-B inhibition can be achieved with doses of 2.5 mg. a day. My belief at this point is that there is no added benefit in using 10mg. of selegiline a day versus 5mg. If one experiences a positive effect at 5mg./day, a person should then try 2.5mg. and see if the same effect can be achieved.
The reason behind this suggestion is somewhat speculative, but let me explain. Selegiline, via its MAO-B inhibition, can give one increased energy and the other effects noted above. However it also has a powerful antioxidant action by greatly increasing the action of SOD, one the body’s three major antioxidant systems. The other 2 antioxidant systems are catalase, which selegiline increases slightly, and glutathione peroxidase, which it has no action on. Antioxidants disarm free radicals in the body. These radicals if not disarmed cause cellular damage or celular death. The body’s antioxidant system becomes less effective as we age. Selegiline, probably due to its enhancement of SOD activity, is able to slow the progression of certain diseases (i.e. Alzheimer’s and Parkinson’s) and, when taken in the right dosage, may quite possibly extend one’s life span. However, the life span studies have all been done on animals. And it should be noted, for example, that while selegiline significantly increased the life span of male beagle dogs, females experienced no such effect. Ironically this has been speculated to be due to the fact that selegiline increases SOD activity in females much more so than males. Speculation is that too much SOD activity can be harmful also, creating free radicals of its own.
The suggestion therefore is to 1) keep your selegiline dose to a minimum (i.e. 2.5mg./day) and 2) balance your body’s antioxidant system by increasing the gluthione peroxidase activity, which will ‘quench’ SOD produced free radicals. Specifically, take 1000mg. of the nutritional supplement N-Acetyl-Cysteine (NAC) per day. This will raise the body’s gluthione peroxidase levels. If possible, divide your NAC into 2 or 3 doses a day.
Can low doses of selegiline (2.5 to 5mg.) improve mood. Yes and no. By itself selegiline is not effective against depression. Similarly, by itself the nutritional supplement L-phenylalanine is not effective against depression. However when combined together, there is significant evidence that they can be very effective in treating depression, especially dysthymia. L-phenylalanine (and D-phenylalanine) is metabolized into PEA, a natural compound in the body, with an amphetamine like structure, that is proposed to enhance mood and energy. PEA however is quickly broken down in the body into another substance by MAO-B. Therefore, an MAO-B inhibitor, namely selegiline, is required for phenylalanine supplements to be effective in raising the body’s level of PEA. Unlike manmade amphetamines, PEA’s mood enhancing and energizing effect does not diminish over time. The most common side effect of phenylalanine supplementation probably is a sense of inner tension. Again, it is my best guess, that cocommitment use of amisulpride lessens or eliminates the likelihood of such a side effect.
In sum, if you are taking low dose selegiline, you may well benefit by l-phenylalanine or d-l-phenylalanine supplementation. Dosage would be approximately 1,500mg. to 6,000mg./day, taken three times a day. For example, 1,000mg. in the morning, 1,000 at noon, the last 1,000mg. in the afternoon. Take at least 30 minutes before a meal.
BTW: Neal how is the amisulpride going- what symptoms has it helped you with. I am on selegiline and amisulpride also.
Best wishes,
AndrewB
Posted by Lorraine on April 23, 2001, at 9:20:44
In reply to Re: Matze, Neal- selegiline for depression, posted by AndrewB on April 23, 2001, at 1:03:26
Andrew: I'm on Selegiline (10 mg day) and Neurontin (400 mg 3x day). I tried going down to 5 mg on the Selegiline, no go. It dipped my mood too much and energy level. Thought about going to 5 and augmenting with an amphetamine--tried dexedrine (2.5 mg) with 5 mg Selegiline--too many hyperventilating types of symptoms plus heart arryhhmia. I too have the anxiety, agitation or fear side effects. My question to you is two fold. Have you tried a beta-blocker like pinodlol for the anxiety side effects? Also have you augment Selegiline successfully with amphetamine? I am seeing a pdoc and under his care with respect to combining drugs but curious about your opinion.
Posted by Adam on April 23, 2001, at 11:18:06
In reply to selegiline for depression, posted by matze on April 20, 2001, at 12:46:47
Hi there!
Sad to say, don't have a lot of time to post at the moment. But...
I have done very well on selegiline. I have been pretty much depression-free (at least by my standards) for about a year and a half. Prior to that, I was severely depressed, probably my whole life. It got worse as I got older, and six months before trying selegiline, I had to be hospitalized (though the reasons for that little episode are probably a bit complex).
Anyway, as others have mentioned, I first tried selegiline as a participant in a clinical trial of the Selegiline Transdermal System (SDS) for major depression. Many here, including myself, have fondly referred to the SDS as "the patch". I had a HAM-D score in the mid-to-high twenties going into the study, which went down to about six once I had a robust response. In my case, the antidepressant effect was fast, and highly efficacious. Your milage may vary, as they say.
The patch is currently not available for marketing. I hope it will be soon, but have no idea when. The date which the investigators running the trial had hoped for approval has long past, which fits my prediction that the much-anticipated time is still well in our future, if it comes at all. The benefits of the patch are many, but include more even and sustained dosing, a reduction in metabolite levels (the metabolites include the "left-hand" versions of methamphetamine and amphetamine, which are about an order of magnitude weaker than their "right-hand" isomers), and a greater blood level of the parent compound per dose, due to the avoidance of "first-pass" matabolism in the GI tract. Perhaps the most significant benefit of the patch to most users may be the lack of dietary restrictions at a dose effective for major depression in at least some patients.
I took "the patch" at 20mg/day. After the trial was over, I moved eventually to 30mg/day orally, and I'm still doing well, as I mentioned above. I do find insomnia to be more of a problem on the oral form, though I did have this difficulty also on the patch. On this dose, I have to observe drug and diet restrictions. The former I am scrupulous about, the latter...well, I cheat quite a bit, and seem to be OK, though I never go overboard - no fondue for me, though I'll sneak a slice or two of pizza (not gourmet, but the mass-produced, pseudo-imitation-rubberized-faux-mozzarella-topped variety) now and then. The fact I am on a relatively low dose (for depression) may have something to do with my ability to be all right without draconian diet restrictions. My guess is there's a little room for error when you're on an MAOI. Stay away from the forbidden drugs, though!
As I said, I'm on a relatively low dose for depression. The common dose ranges for that indication that I have seen have been 30 or 40 to 60 (or higher) mg/day, usually split into two doses, morning and afternoon, to avoid too many sleep problems.
I think many people who have done well on one MAOI might do well on selegiline, and it should be just as useful for refractory patients who have failed other first and second-line treatments as the other MAOIs, though the best drug for each person can only be found by trial and error. If one had to pick another MAOI on the market that selegiline is similar to, it might be Parnate (tranylcypromine), which also has some stimulant properties. Its generally thought that Nardil and Marplan (phenelzine and isocarboxazid) are better for those with anxiety and depression, especially the dual diagnosis of depression and social phobia, while Parnate is a better fit for those with "anergic" symptoms. All MAOIs are said to be good for those with "atypical" depressions, characterized by symptoms like mood-reactivity and severe rejection sensitivity.
The truth, of course, is that these are only broad guidelines, with no hard and fast rules for which drug is best for whom. I think selegiline is a good choice for anyone with depression, and (as I have experienced) has fairly mild side-effects at efficacious doses. However, the other MAOIs are also worth a try, if you haven't already given them a go. Some doctors prefer to use the more "tried and true" antidepressants (selegiline isn't approved as a treatment for depression, and is only used so as an "off-label" therapy - some doctors have never used it in their practice as a result), and its true that the older MAOIs have a richer history to draw from to inform your doctor's decisions.
All that said, I went through many different drugs, with little or no success, before I found selegiline. I wish someone suggested it, or another MAOI, a long time ago. I think many doctors are too reticent to use the MAOIs. They do have their hazards, but the benefits, as far as I'm concerned, far outweigh them, if they prove effective for an individual.
Best of luck to you!
> Hi,
> Is there anyone, who had success with selegiline for the treatment of major depression or dysthymia?
> What doses of selegiline are effective?
>
> Thanks for response
> matze
Posted by Leighwit on April 23, 2001, at 11:36:56
In reply to Re: Matze, Neal- selegiline for depression, posted by AndrewB on April 23, 2001, at 1:03:26
Hi Andrew,
Wow. What a post. I had to print it so I could re-read it several times. I think I'll take it to my next Pdoc appointment as a basis for discussion. (There's no way I'd remember every issue/fact you addressed. I'm feeling a bit "foggy" lately.)
I was doing quite well on Wellbutrin augmented by Celexa and Aricept. The Celexa has caused major weight gain and against my doctors previous thoughts & recommendations about it, I've stopped taking Celexa this week. I wasn't sure the Celexa was the culprit for the weight gain, but after laying out an objective history, I am now sure that it is. I stopped the Aricept also, for different reasons. I'm surprised that after only a few days, I'm not feeling so great. I'll begin the Aricept again, but I know that it doesn't influence depression - it merely helps offset the side effects of the WB (which for me, are mental confusion and short term memory problems.)
I usually have a "position" put together before Pdoc appointments, but right now I'm at a loss for one. Until your post on selegiline there wasn't even anything I was particularly curious about that I hadn't tried before. I have never taken MAOIs because they're contraindicated (or so I've been advised) for Type I (insulin-dependent, juvenile-onset) diabetics. Selegiline, however, might be an exception to the rule.
Could you profile your own use of selegiline for us? What is your experience with it? What else are you taking and why? If this is somewhere else, just let me know and I'll go search again -but it didn't come up on my first search attempt.Thanks Andrew,
LBW> Selegiline can be quite effective for major depression, comparable to Parnate or Nardil. That is, at high dosages, selegiline acts as an MAOI inhibitor (of both MAO-A and MAO-B), like a Nardil or Parnate would. Selegiline, as an MAO-I is used at doses ranging from 20 to 60mg/day. Being in general stimulating, it is more akin to Parnate. The delivery of selegiline in a patch form is preferable, lower doses being able to be used and side effects significantly diminished. There is some controversy concerning whether you may have a compounding chemist produce selegiline in the patch form.
>
> As JohnL pointed out, Adam is a poster who has been on both the patch and (currently) the oral form for a long time. He is very knowledgeable on the subject and if you search the archive for his posts concerning selegiline you will come up with a wealth of information including information concerning compounding chemists and the patch.
>
> Now, to change the subject a bit, selegiline at doses below 15mg./day acts quite differently than it does at high doses. Specifically, it inhibits only MAO-B and not MAO-A. At dosages of 2.5mg-10mg./day people will frequently experience increased motivation, mental vigilance, sexual vigor and (as Neal has noted) increased energy.
>
> The most common side effect at these dosages is agitation or anxiety. It seems though that taking amisulpride may lessen or eliminate the possibility of this side effect.
>
> Keeping the dosage low as possible also seems to lessen the likelihood of such side effect. One study has stated that complete MAO-B inhibition can be achieved with doses of 2.5 mg. a day. My belief at this point is that there is no added benefit in using 10mg. of selegiline a day versus 5mg. If one experiences a positive effect at 5mg./day, a person should then try 2.5mg. and see if the same effect can be achieved.
>
> The reason behind this suggestion is somewhat speculative, but let me explain. Selegiline, via its MAO-B inhibition, can give one increased energy and the other effects noted above. However it also has a powerful antioxidant action by greatly increasing the action of SOD, one the body’s three major antioxidant systems. The other 2 antioxidant systems are catalase, which selegiline increases slightly, and glutathione peroxidase, which it has no action on. Antioxidants disarm free radicals in the body. These radicals if not disarmed cause cellular damage or celular death. The body’s antioxidant system becomes less effective as we age. Selegiline, probably due to its enhancement of SOD activity, is able to slow the progression of certain diseases (i.e. Alzheimer’s and Parkinson’s) and, when taken in the right dosage, may quite possibly extend one’s life span. However, the life span studies have all been done on animals. And it should be noted, for example, that while selegiline significantly increased the life span of male beagle dogs, females experienced no such effect. Ironically this has been speculated to be due to the fact that selegiline increases SOD activity in females much more so than males. Speculation is that too much SOD activity can be harmful also, creating free radicals of its own.
>
> The suggestion therefore is to 1) keep your selegiline dose to a minimum (i.e. 2.5mg./day) and 2) balance your body’s antioxidant system by increasing the gluthione peroxidase activity, which will ‘quench’ SOD produced free radicals. Specifically, take 1000mg. of the nutritional supplement N-Acetyl-Cysteine (NAC) per day. This will raise the body’s gluthione peroxidase levels. If possible, divide your NAC into 2 or 3 doses a day.
>
> Can low doses of selegiline (2.5 to 5mg.) improve mood. Yes and no. By itself selegiline is not effective against depression. Similarly, by itself the nutritional supplement L-phenylalanine is not effective against depression. However when combined together, there is significant evidence that they can be very effective in treating depression, especially dysthymia. L-phenylalanine (and D-phenylalanine) is metabolized into PEA, a natural compound in the body, with an amphetamine like structure, that is proposed to enhance mood and energy. PEA however is quickly broken down in the body into another substance by MAO-B. Therefore, an MAO-B inhibitor, namely selegiline, is required for phenylalanine supplements to be effective in raising the body’s level of PEA. Unlike manmade amphetamines, PEA’s mood enhancing and energizing effect does not diminish over time. The most common side effect of phenylalanine supplementation probably is a sense of inner tension. Again, it is my best guess, that cocommitment use of amisulpride lessens or eliminates the likelihood of such a side effect.
>
> In sum, if you are taking low dose selegiline, you may well benefit by l-phenylalanine or d-l-phenylalanine supplementation. Dosage would be approximately 1,500mg. to 6,000mg./day, taken three times a day. For example, 1,000mg. in the morning, 1,000 at noon, the last 1,000mg. in the afternoon. Take at least 30 minutes before a meal.
>
> BTW: Neal how is the amisulpride going- what symptoms has it helped you with. I am on selegiline and amisulpride also.
>
> Best wishes,
>
> AndrewB
Posted by Lorraine on April 24, 2001, at 9:31:02
In reply to Re: Matze, Neal- selegiline for depression, posted by Leighwit on April 23, 2001, at 11:36:56
I think that the diabetes problems with MAOs would exist with Selegiline--I assume it has to do with the risk of a hypertensive crises because of the dietary restrictions. If so, you might try flying under the radar using less than 15 mg of Selegiline. I use 10 mg/day, but it did combat the depression, just energized me and helped my thinking and helped with orgasm. Then we added Neurontin--at 600/mg a day, it didn't do anything for my mood. When we upped it to 900 mg a day, an antidepressant effect kicked in (my pdoc had told me it would). The Selegiline gives me a side effect of agitation (eating my cuticles) and anxiety (more fearful than usual). To help combat these we upped the Neurontin to 1200 mg day. I have been playing with adding Mirapex to the mix. The results have been that at 1/2 of .125 mg I get sedated. Yesterday I decreased the Neurontin to 900 mg and added 1/2 of .125 mg--still too sedated. Today I'm going to do the same thing but with 1/4 of .125 Mirapex. The Mirapex takes away the edginess and aids sexual "arousal" if anesthesia has been a problem.
Posted by KS on April 24, 2001, at 14:37:22
In reply to Re: selegiline for depression, posted by Neal on April 21, 2001, at 0:06:15
> I'm starting low-dose Selegiline 5mg as an adjunct to Amisulpride, a European drug. So far, it's working well. A nice, even, energy enhancer.
Hi there Neal, are you ONLY taking 5mg of selegiline because you get the desired effect at this dose or becuase you want to avoid MAOI negative phenomena. I'm dead keen to start selegiline myself and would, therefore, be interested in your progress. In South Africa we do not have Amisulpiride. Instead we have a drug called sulpiride. Do you think it's the same thing? Can you get me any more information?
Cheers, KS
Posted by KS on April 24, 2001, at 14:52:20
In reply to Re: Matze, Neal- selegiline for depression, posted by AndrewB on April 23, 2001, at 1:03:26
.
>
> Can low doses of selegiline (2.5 to 5mg.) improve mood. Yes and no. By itself selegiline is not effective against depression. Similarly, by itself the nutritional supplement L-phenylalanine is not effective against depression. However when combined together, there is significant evidence that they can be very effective in treating depression, especially dysthymia. L-phenylalanine (and D-phenylalanine) is metabolized into PEA, a natural compound in the body, with an amphetamine like structure, that is proposed to enhance mood and energy. PEA however is quickly broken down in the body into another substance by MAO-B. Therefore, an MAO-B inhibitor, namely selegiline, is required for phenylalanine supplements to be effective in raising the body’s level of PEA. Unlike manmade amphetamines, PEA’s mood enhancing and energizing effect does not diminish over time. The most common side effect of phenylalanine supplementation probably is a sense of inner tension. Again, it is my best guess, that cocommitment use of amisulpride lessens or eliminates the likelihood of such a side effect.
>
> In sum, if you are taking low dose selegiline, you may well benefit by l-phenylalanine or d-l-phenylalanine supplementation. Dosage would be approximately 1,500mg. to 6,000mg./day, taken three times a day. For example, 1,000mg. in the morning, 1,000 at noon, the last 1,000mg. in the afternoon. Take at least 30 minutes before a meal.
>
THANKS FOR THE ABOVE INFO ...It's not the first time I've seen this combo (i.e., selegiline plus DLPA) advocated. Has anyone tried it? I'm quite to do so, but would prefer more input from you guys.
Cheers, KS
Posted by shelliR on June 9, 2001, at 17:52:35
In reply to Re: Matze, Neal- selegiline for depression, posted by Lorraine on April 24, 2001, at 9:31:02
>
Lorraine, how did the combination of selegiline and mirapex work for you? Maybe you have a post on this on another thread that I missed; if so I am sorry for the repetition. On Tuesday I am going to start selegline but am a bit less than optimistic because I hate drugs that stimulate me. I am unable to take neurotin because of huge retention of fluid (15 lbs worth--same as on lamictal). So I was wondering if the selegiline and mirapex together cut your anxiety. Also if it was helpful, what were the doses of each?Thanks. I'm going into the hospital tomorrow late afternoon , so if I don't respond back it's because I may not have internet access, although I am bringing a laptop.
Shelli
Posted by Lorraine on June 9, 2001, at 22:42:57
In reply to Re: selegiline mirapex for depression » Lorraine, posted by shelliR on June 9, 2001, at 17:52:35
Shelli--we are all different, but I could not tolerate Mirapex--even on a miniscule dosage. I found that I was just completely slammed down and stoned on it. It wasn't unpleasant just I couldn't function with it. I did not think that it helped the anxiety--my anxiety is strictly physical--hyperventilating and so forth. The sex on it was great though--it was kind of tough to give it up because of that. I thought well maybe I'll just augment with Mirapex on those special nights, but I found that I had a big rebound depression the next day when I would stop taking the drug. So Mirapex is out for me.
I don't want to go on benzos for the anxiety (although it is such an obvious thing to do). So having tried non-benzo meds, I am now starting neurofeedback to help control my anxiety. What I was told at my first appointment was interesting. They said (and showed me on my QEEG) that I was having subthreshold seizure activity in my brain waves. (Another QEEG Neurologist had told me the same thing last November.) I was told that this subthreshold activity could manifest itself in migraines (which I have a history) or mood imbalances. Pretty interesting stuff, but, you know, scientifically neurofeedback is considered experimental. So who knows? Maybe I am buying snake oil. Only time and trying the training will tell. It's pricey ($90/ session) and you need at least 10-12 sessions to know if it is going to work for you. Then they say 20-40 sessions to really lock in the training. I'll let you know if it is snake oil if you are curious in two or three weeks. The neurologist was putting me on mood stabilizers and anti-convulsants, but I am VERY medication sensitive. Side effects kill most meds for me at the get go. (Lomictal, Depokote are both out. I won't try Lithium because of the cognitive side effect and hair loss profile. Tegretal--cognitive side effect profile and so forth). So to me, if I can find a way of getting the anxiety under control without a med, it will make my life much easier.
Good luck with whatever you try.
Posted by shelliR on June 10, 2001, at 0:06:30
In reply to Re: Shelli Cam Elizabeth, posted by Lorraine on June 9, 2001, at 22:42:57
Hi Lorraine.
Thanks for the feedback about your experience with mirapex. Sounds disappointing. I don't have any problems with using benzos for my anxiety--depression is the much difficult issue for me.
It's strange. I talked to the pdoc who did a large study with selegiline on geriatric patients at NIH and he said there was no problem with added anxiety. Yet I think everyone I've read or communicated with on the board has gotten more anxious or jittery. I am also very sensitive to meds, so I'm feeling not exactly overly optimistic.
Good luck with the neurofeedback program. Let us know how you are doing.
Shelli
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