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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by ExcellentCamper on December 13, 2005, at 21:58:02
I just added Selegiline two weeks ago along with Lamictal (150mg). I decided to add it for foggy brain/anhedonia/difficulty focusing, etc. I'm up to 10mg, along with 1000mg of DLPA (first thing in the morning 30-60 minutes before eating). No detectable difference so far.Does Selegiline require the 4-6 weeks of an SSRI to take effect? Or is it more of a matter of the dose being too low?
Who has taken larger doses with good results? Did it result in increased energy or focus? Side-effects?
Will
Posted by ExcellentCamper on December 23, 2005, at 22:17:16
In reply to How much selegiline do you take?, posted by ExcellentCamper on December 13, 2005, at 21:58:02
No takers on this one the first time ... thought I'd refresh the post.Anyone out there doing well on high doses? What do you do if you slip up on the diet?
I checked with the maker of the patch, and it still doesn't have FDA approval.
Posted by RobertDavid on December 24, 2005, at 0:06:20
In reply to Selegiline, posted by ExcellentCamper on December 23, 2005, at 22:17:16
EMSAM will be approved (or not) by Feb 26th. My doc has been hired by the drug co. to write labeling info. He tells me they feel strongly it will be approved. Probably take a few more months to become available.
I'm anxious to try it. I asked my doc about taking oral selegiline now, but he said to wait. And if EMSAM is not approved he suggested Nardil would be a better choice than oral selegiline.
He claims that with the patch delivery not only are the side affects and food restrictions significantly reduced, but it works much better for both anxiety and depression. I've wonered why it the same drug would be so different with patch delivery vs oral, but that's what he says and what I have heard from others. We'll see.
Posted by Tomatheus on December 24, 2005, at 3:51:45
In reply to Re: Selegiline, posted by RobertDavid on December 24, 2005, at 0:06:20
> He claims that with the patch delivery not only are the side affects and food restrictions significantly reduced, but it works much better for both anxiety and depression. I've wonered why it the same drug would be so different with patch delivery vs oral, but that's what he says and what I have heard from others. We'll see.
RobertDavid,
I'm definitely no expert in psychopharmacology, so please keep in mind that my thoughts on this topic should be taken with a grain of salt. But if I were a researcher or a doctor, I would hypothesize that the Emsam patch will likely be both more effective and more tolerable (in terms of side effects) than oral selegiline because it has been shown to be much more consistent in its inhibition of MAO (types A and B) than the pill form. According to a graph on page 5 of Dr. Gregory M. Dubitsky's (2005) PowerPoint presentation on Emsam's tyramine safety, the selegiline blood concentration reaches 2000 pg/mL within an hour after 10mg of the drug is administered in its pill form, and then the concentration appears to sharply drop off until it reaches 0 pg/mL after six hours. With 20mg x 20 sq cm of Emsam, however, the selegiline blood concentration only varies slightly; it remains relatively close to 1000 pg/mL from the moment it is administered until the patch is due to be removed 24 hours later (Dubitsky, 2005).
I don't have any hard data to support what I am about to say next, but I am beginning to suspect that the brain's serotogenic, noradregenic, and dopaminergic systems actually adjust the production rates of their respective neurotransmitters to compensate for changes in MAO-A and MAO-B activity. So, if my suspicion is correct, inhibiting MAO-B for example, would allow more dopamine to be *released* (since MAO-B is located *inside* dopaminergic neurons). Then, as more dopamine accumulates in the synapses at the times when it is *released*, it triggers the feedback mechanisms that control the *production* of dopamine, and less is produced as a result. So, in my view, MAO inhibition allows the brain to release more neurotransmitters at the times when it is supposed to (e.g., when environmental stimuli prompt it to) instead of relying more heavily on constantly creating more neurotransmitters. With every MAOI that I have tried (moclobemide, Parnate, and Nardil), I've always noticed mood elevations immediately after starting the drugs and after dose increases. Based on messages posted on this board, it appears that others have had similar experiences with MAOIs. What I suspect happens during these periods of mood elevation is that the drugs inhibit MAO at a relatively fast rate while the neurotransmitters are still being produced as quickly as they were before the MAO inhibition took place. So, with new, higher levels of neurotransmitter *release* and non-adjusted levels of neurotransmitter *production*, synaptic neurotransmitter levels are high, and mood elevation takes place. Eventually, though, the neurotransmitter feedback systems kick in, and neurotransmitter production levels adjust themselves to compensate for the higher level of neurotransmitter release triggered by MAO inhibition. If more MAO is inhibited each day over a period of several weeks as it is with Nardil and Parnate, neurotransmitter production levels keep adjusting themselves until the level of MAO inhibition begins to flatten out. It is often around this time that the "true" effects of MAOIs begin to be felt (at least at the given dose).
Now, keep in mind that everything I described in the previous paragraph is highly speculative. So, the viability of my hypothesis depends on the validity of the ideas that I just described above, which very well may not hold much water. But if there is some truth to what I described in the previous paragraph, inhibiting MAO-A and MAO-B at a consistent level would be critical to the effectiveness of MAO-inhibiting drugs. If the level of MAO inhibition varies considerably over a 24-hour period, then it is doubtful that neurotransmitter production levels would ever be able to properly adjust themselves. Although moclobemide, a reversible inhibitor of MAO-A, has been found to be as effective as SSRIs in comparative research studies, real-world reports from doctors and patients (including here on this board) suggest that the drug is relatively ineffective in practice. Even in the comparative research studies, it has been found to be less effective than both Nardil and Parnate (Lotufo-Neto et al., 1999). There are obviously a lot of factors that could be used to explain moclobemide's relative lack of effectiveness, but I have suspected for some time that the drug's inconsistency in its MAO-A inhibition is a big part of the reason why it tends not to be very effective. Moclobemide is rapidly absorbed after it is taken, and the drug reaches its maximum plasma concentration within an hour (Nair et al., 1993). The drug is also rapidly eliminated from the body, and its inhibition of MAO-A typically lasts no longer than eight to 10 hours (Nair et al., 1993). On the other hand, MAO-A and MAO-B levels typically take about two weeks to return to 100 percent after the administration of a single dose of Nardil or Parnate. Even with Nardil, one of the complaints about the "new" Pfizer formulation has been the bioequivalency test only demonstrated that Pfizer reached the bloodstream in a timely fashion. It did not demonstrate whether or not plasma levels of the "new" Nardil were just as consistent (over time) as those of the "old Nardil."
So, we know that moclobemide tends to be less effective than the irreversible MAOIs (Nardil and Parnate), and we also know that it does not inhibit MAO-A as consistently as the irreversible drugs. From what I've read, there also seems to be a consensus that the "new" Pfizer formulation of Nardil is generally less effective than the "old" formulation. Of those who have taken both formulations, some have said that the "old" formulation was clearly more effective than the "new" one, and others have said that there is little to no difference. I have yet to read a report from someone who actually found the "new" Nardil to be superior to the "old" Nardil. So, in addition to knowing that some individuals have found the "old" Nardil to be superior to the "new" Nardil (but not vice versa), we are now also aware of the possibility that the inactive ingredients of the "new" Nardil may not allow phenelzine to inhibit MAO-A and MAO-B as consistently as the "old" Nardil did (of course, this needs to be confirmed). Finally, we know that some doctors have said that the Emsam patch is supposed to be more effective at treating depression and anxiety than oral selegiline, and we also know that the plasma concentration of selegiline is much more consistent when the drug is taken in patch form than in pill form. So, what I'm beginning to see is a positive correlation between consistency of MAO inhibition and effectiveness. Does this mean that consistent MAO inhibition actually *causes* a drug to be more effective? Of course not. My hypothesis obviously needs some hard data to support it, but I think it's something to consider.
Before I finish (I know, it seems like this message will never end), I would like to point out that I am somewhat skeptical of Emsam's potential as an antidepressant. Even though I like the idea of delivering an MAO-inhibiting drug to the bloodstream via a transdermal patch (because of the fact that it allows for greater consistency of MAO inhibition than pill form), selegiline is still primarily an MAO-B inhibitor. It is believed to lose some of its selectivity for MAO-B at higher doses, but the fact remains that it still inhibits MAO-B more than it does MAO-A. Even though some individuals may benefit from Emsam's relative preferentiality to MAO-B, the results of research studies support the idea that MAO-A is more central to antidepressant activity than MAO-B (Thase et al., 1995). Should this dissuade a treatment-resistent depressive from trying Emsam? Of course not. It does hold a lot of promise. I may even try it myself, depending on how I ultimately respond to Nardil. But I have my doubts.
Tomatheus
==
REFERENCES
Dubitsky, G. M. (2005). Tyramine safety with Emsam. Retrieved Dec. 9, 2005, from http://www.fda.gov/ohrms/dockets/ac/05/slides/2005-4186S2_02_FDA-Dubitsky.ppt
Lotufo-Neto, F., Trivedi, M., & Thase, M. E. (1999). Meta-analysis of the reversible inhibitors of monoamine oxidase type A moclobemide and brofaromine for the treatment of depression. Neuropsychopharmacology, 20, 226-47.
Nair, N. P. V., Ahmed, S. K, & Ng Ying Kin, N. M. K. (1993). Biochemistry and pharmacology of reversible inhibitors of MAO-A agents: Focus on moclobemide. Journal of Psychiatric Neuroscience, 18, 214-25.
Thase, M. E., Trivedi, M. H., & Rush, A. J. (1995). MAOIs in the contemporary treatment of depression. Neuropsychopharmacology, 12, 185-219.
Posted by RobertDavid on December 24, 2005, at 13:42:31
In reply to Re: Selegiline » RobertDavid, posted by Tomatheus on December 24, 2005, at 3:51:45
Wow, a plethora of info to ponder in your post! I'm not sure that the scientists that make these drugs have the answers to some of your hypothisis, but it's very interesting.
Because I have had so many poor responses to anti depressants and other meds to treat my SAD/GAD with mild depression I too am skeptical of EMSAM. But, I'm done with "30 day trials" of other meds until it comes out. My last trial was with Remeron and it was about the worst so far.
My doctor has always thought that if he only had once shot, one try to prescribe a med for me (even before trying all the others) it would have been Nardil. Now he wants me to wait and try EMSAM first. The klonopin has helped greatly with my primary issue of anxiety, but it's my hope that EMSAM will supplement it or perhaps even replace it.
All I'm hoping for with EMSAM is some help with mild depression, cognitive clarity, brighten my mood, and additional anxiety relief (in reading that it looks like a lot to ask for).
Though I can't wait to try it and it seems as promising as anything that's out there, I too am skeptical. I've just had my hopes up too many times. Hopefully it will be a breakthrough med. Perhaps other meds will work better via a patch delivery. We'll see.......
Posted by Tomatheus on December 27, 2005, at 0:23:50
In reply to Re: Selegiline » Tomatheus, posted by RobertDavid on December 24, 2005, at 13:42:31
RobertDavid,
I'm sorry for taking so long to respond to your post. My responses to various sections of your post are below.
> Wow, a plethora of info to ponder in your post! I'm not sure that the scientists that make these drugs have the answers to some of your hypothisis, but it's very interesting.
Thanks for the kind words. I too am uncertain as to whether whether the scientists that make MAOIs actually have the evidence to either support or confirm my hypothesis. I would like to point out that even though I've already put some time into thinking about the relationship between the efficacy of MAOIs and the consistency of MAO-A and MAO-B inhibition, I've only scratched the tip of the iceberg, so to speak, in terms of the amount of research that has actually been done regarding the relationship between serum concentrations of various meds and the efficacy of these meds. I intend to keep doing more research (probably a lot more) for a variety of purposes. So, hopefully some of my future posts about the relationship between the consistency of MAO inhibition and the efficacy of MAOIs will be less speculative and more fact-based.
> Because I have had so many poor responses to anti depressants and other meds to treat my SAD/GAD with mild depression I too am skeptical of EMSAM. But, I'm done with "30 day trials" of other meds until it comes out. My last trial was with Remeron and it was about the worst so far.
I'm sorry to hear that. :(
> My doctor has always thought that if he only had once shot, one try to prescribe a med for me (even before trying all the others) it would have been Nardil.
Wow! Finally a doctor who thinks on the same wavelength as I do. Nothing against my pdoc (I do think that he's highly intelligent and willing to think "outside the box" a little more than most psychiatrists), but I never thought I'd actually hear of a doctor saying that he should have just prescribed a patient Nardil to begin with. It shows that your doctor is interested actually finding the med that's the best fit for a patient from the very beginning and that he (?) is sympathetic to the painful frustration of the trial-and-error process of psychiatric treatment that we have to endure as treatment-resistant patients.
> All I'm hoping for with EMSAM is some help with mild depression, cognitive clarity, brighten my mood, and additional anxiety relief (in reading that it looks like a lot to ask for).
It may sound like you're asking for a lot, but I don't think that it's unreasonable or even unrealistic to have the goal of getting some relief from your most bothersome symptoms. You deserve better than the inadequate responses that you've received from most meds, and I do think that it's possible that you can do better -- or at least will be able to do better at some point. Now, whether or not any of the meds that are currently available (or soon to become available, in Emsam's case) will do the trick is another question. But even if you don't get the response you're looking for from Emsam or Nardil (and I'm not saying that you won't), it's always possible that the best med for you will be the next one to be developed. And also, please be aware that if you do end up taking Nardil at some point, many long-term Nardil users in the U.S. (are you in the U.S.?) consider the current Nardil formulation to be inferior to an older formulation that was used until the fall of 2003. If you don't respond favorably to the current Nardil formulation, it's always possible that you might respond better to the older formulation if it ever becomes available again (and that's a possibility that I would not rule out). So, I guess the point that I'm trying to make is that the possibility of achieving remission will always be there, even if you end up exhausting all of your current options.
> Though I can't wait to try it and it seems as promising as anything that's out there, I too am skeptical. I've just had my hopes up too many times. Hopefully it will be a breakthrough med.
I hope you're right. It looks like you've got the right combination of skepticism and optimism.
> Perhaps other meds will work better via a patch delivery. We'll see.......
That is actually something that I considered but never got around to saying when I read your post about making your own Emsam. If we could actually figure out a good way to make our own transdermal meds, then I guess those options will become available, even if no drug company ever wants to pursue them. So, if it's true that MAOIs could become more effective by using a delivery system that allows for a more consistent inhibition of the MAO enzymes, maybe we should consider making our own Nardil, or even our own moclobemide. Of course, the scenario I'm describing is not the most desirable one and should not be attempted by just anybody (personally, I wouldn't feel comfortable making my own meds), but it's something to think about if all else fails.
Tomatheus
This is the end of the thread.
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