Posted by Ktemene on July 16, 2004, at 15:28:27
In reply to Selegiline Anti-Depressant Dose, posted by stalwart on July 16, 2004, at 4:00:55
> My pdoc<well respected physician in NY> admits not prescribing this drug for years. Vaguely, he recalls 20mg oral dose.
>
> My research here and on the web indicates a dose in the 30-60mg oral dose range.
>
> It has been two weeks, I am taking 15mg...10 in the morning and 5mg at noon. Frankly, and perhaps thankfully, I have no side-effects BUT also no anti-depressant effect.
>
> Any anecdotal accounts using Selegiline as an anti-depressant...oral form.
>
> Thank you.Hi Stalwart,
I’m glad you posted; I was wondering how you are doing. I was very interested in your post a couple of weeks ago saying you were beginning a trial of selegiline because I also started selegiline recently (about 6 weeks ago). I take 5 mg per day, and I also take Adderall (10-20 mg) and Provigil (200-400 mg).
As I recall you started selegiline at 5 mg per day. I am guessing that you stayed at 5 mg for a few days, perhaps a week, before raising the dose to 15 mg? If so, you have only been at the 15 mg level for a week or so. In that case the absence of antidepressant effect is pretty much what is to be expected, at least according to what I have read, and I take it your own research indicates this as well. E.g. the Harvard Med School doctors who wrote the article on MAOI’s in Current Psychiatry a couple of years ago (June 2002) said that selegiline is not a good antidepressant below the 20 mg level, and they recommend aiming for 45 mg per day. Selegiline could still be a great med for you with a little more time and at a higher dose. Also, precursor loading (DLPA or LPA or even chocolate/Chocamine) could make a difference for you, if you have not already tried that. (Some pdocs recommend precursor loading in the Tips section of Psycho_Babble.) Of course some people do respond to tiny doses of selegiline, but that is really quite rare. One of my favorite posters, Adam, had a great response to the selegiline patch, but did not respond well to oral selegiline until he reached the 30 mg level. He hardly ever posts any more, for the best possible reason: 30 mg oral selegiline (as a solo med) put his severe depression into more or less complete remission. In the ten years before he hit on selegiline he had tried lots of other meds that did not help him. Of course, selegiline may not be the med for you. But then again selegiline may be exactly the right med for you. There is really no reason to be discouraged at this point. Just keep hanging in there and see what happens.
Have you noticed any effects from selegiline at all? I think you mentioned in your earlier post that you were taking a med to help you sleep. Do you usually have insomnia? Or did your pdoc prescribe a sleeping med because selegiline often has insomnia as a SE? Have you had any increased insomnia, increased energy, increased jitteriness etc? If your pdoc has not prescribed selegiline in 20 years it sounds as if your pdoc did not suggest selegiline to you. Was selegiline your idea? Why did you decide to try selegiline?
My own experience with selegiline over the last six weeks has been complicated by the horrible flu that I had for more than three of those weeks. But selegiline has certainly given me insomnia and has been very activating (my depression is of the anergic anhedonic sort). I really am puzzled that selegiline should have this effect on me. Adderall does not have this effect on me at all. Adderall makes me feel more calm and focused, and I can actually sleep after taking 10 mg Adderall if I want to. Maybe this isn’t surprising since I have ADD. But why should 5 mg selegiline activate me so much that I can’t sleep and don’t want to sleep? Selegiline cannot be having this effect on account of its levo-amphetamine metabolites, since the amphetamines in larger doses of Adderall don’t have this effect. It makes no sense to me at all. However, I should say that after six weeks the insomnia has moderated a bit. Now I can take 5 mg selegiline in the morning (three weeks ago I was only taking half of my prescribed 5 mg dose because of the insomnia) and still sleep 5 or 6 hours a night, and that seems to be all the sleep I need. And just in the last few days I am beginning to notice some antidepressant effect in addition to the energizing effect; my mood is brighter, more hopeful, more resilient. Of course, this may be just placebo effect, but I am hoping my pdoc will increase the selegiline dose to 10 mg in a couple of weeks or so. (Or maybe add a little Wellbutrin, which worked well for me before and might be synergistic with selegiline? I don’t know…)
There’s one more thing I wanted to mention on the off chance that it might be useful to you. My pdoc’s prescription was for 5 mg selegiline hydrochloride capsules. When I started taking selegiline and got the massive insomnia I asked my pdoc if I could break open the caps and just take half of the med. He agreed, and then an idea occurred to me. I had heard about a new formulation of selegiline, Zydis Selegiline, designed for “buccal absorption”. The advantage is that some portion of the selegiline does not go into the gut but is absorbed into the blood stream and so the first pass effect (which is apparently massive in the case of selegiline) is avoided for that portion of the dose. So Zydis Selegiline has, although to a lesser degree, some of the advantages that the selegiline patch has (greater bioavailability, fewer SE’s, less danger of hypertensive crisis). Unfortunately, Zydis Selegiline is not yet available in the U.S. (where I live). But I noticed that Zydis Selegiline has the same active chemical as that in my capsules, selegiline hydrochloride. So now I open the cap, and pour the powder directly into my mouth, and try to hold it there for as long as I can before I swallow. I feel a little silly doing it, but it definitely doesn’t hurt, and I may be getting greater bioavailability from my 5 mg dose on account of it. I have copied the abstract of the article on Zydis Selegiline below.
Good luck, and let us know how you are doing.
Ktemene
Comment in:
* J Neural Transm. 2003 Nov;110(11):1273-8.
A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition.
Clarke A, Brewer F, Johnson ES, Mallard N, Hartig F, Taylor S, Corn TH.
Scherer DDS, Swindon, United Kingdom. aclarke@cephalon.com
Seven randomised comparative studies were conducted in healthy volunteers to compare the pharmacokinetic and pharmacodynamic profiles of selegiline hydrochloride in a new formulation designed for buccal absorption "Zydis Selegiline" (1.25-10 mg) with conventional selegiline hydrochloride tablets "conventional selegiline tablets" (10 mg). A total of 156 healthy volunteers participated in these studies. Plasma concentrations of selegiline and its primary metabolites, N-desmethylselegiline (DMS), l-amphetamine (AMT), and l-methamphetamine (MET) were measured using Gas Chromatography Mass Spectrometry (GCMS) and gas liquid chromatography (GLC) assays. Inhibition of monoamine-oxidase type B (MAO-B) and monoamine oxidase type A (MAO-A) activity was determined by measurement of as beta-phenylethylamine (PEA) by GCMS and 5-hydroxyindoleacetic acid (5-HIAA) by High Performance Liquid Chromatography (HPLC) assays. Almost a third (2.96 mg) of a 10 mg selegiline dose in Zydis Selegiline was absorbed pre-gastrically (predominantly buccally) within 1 minute. Mean [SD] area-under-the curve (AUC(0- infinity)) values following Zydis Selegiline 10 mg (5.85 [7.31] ng.h/mL) were approximately five times higher than those following conventional selegiline tablets 10 mg (1.16 [1.05] ng.h/mL). In contrast, plasma concentrations of metabolites were significantly ( p<0.001) lower following Zydis Selegiline 10 mg than following conventional selegiline tablets 10 mg. Plasma concentrations of selegiline and its metabolites increased in a dose-dependent manner over the dose-range Zydis Selegiline 1.25-5 mg. Bioavailability was determined using AUC and peak plasma concentrations (C(max)). The C(max) of selegiline was similar following administration of Zydis Selegiline 1.25 mg (1.52 ng/mL) or conventional selegiline tablets 10 mg (1.14 mg/mL). The range of values for AUC(0- infinity) and C(max) following Zydis Selegiline 1.25 mg were entirely contained within the range following conventional selegiline tablets 10 mg, with a much higher variability of plasma selegiline concentrations occurring after conventional selegiline tablets than after Zydis Selegiline. As expected, peak plasma concentrations for DMS, AMT and MET were consistently lower after Zydis Selegiline 1.25 mg (1.19, 0.34, 0.93 ng/ml, respectively) than after conventional selegiline tablets 10 mg (18.37, 3.60, 12.92 ng/ml, respectively). A significant (r=0.0001) correlation between daily PEA excretion (a measure of brain MAO-B inhibition) and the log-transformed AUC((0-t)) for selegiline was demonstrated. Mean daily PEA excretion was similar following Zydis Selegiline 1.25 mg and conventional selegiline tablets 10 mg (13.0 microg versus 17.6 microg). In contrast, there was no correlation between PEA excretion and selegiline metabolites, indicating that selegiline metabolites do not significantly inhibit MAO-B. Urinary excretion of 5-HIAA (used as a marker for MAO-A inhibition) was unrelated to plasma concentrations of selegiline or DMS following single or repeat dosing of Zydis Selegiline 1.25 mg or conventional selegiline tablets 10 mg. However, comparison of treatment groups revealed a significantly lower excretion of 5-HIAA in the conventional selegiline tablets 10 mg group than in the Zydis Selegiline 1.25 mg group after repeated administration over 13 days. In summary, by reducing the opportunity for first-pass metabolism, the absorption of selegiline from Zydis Selegiline was more efficient and less variable than from conventional selegiline tablets. Compared with conventional selegiline tablets 10 mg, Zydis Selegiline 1.25 mg yielded similar plasma concentrations of selegiline and degree of MAO-B inhibition, but markedly reduced concentrations of the principal metabolites. Thus, the lower but equally MAO-B inhibitory dose of selegiline in Zydis Selegiline 1.25 mg, which is associated with lower concentrations of potentially harmful metabolites, could offer a safer and more predictable treatment in the management of patients with Parkinson's disease.
Publication Types:
* Clinical Trial
* Randomized Controlled Trial
PMID: 14628189 [PubMed - indexed for MEDLINE]> My pdoc<well respected physician in NY> admits not prescribing this drug for years. Vaguely, he recalls 20mg oral dose.
>
> My research here and on the web indicates a dose in the 30-60mg oral dose range.
>
> It has been two weeks, I am taking 15mg...10 in the morning and 5mg at noon. Frankly, and perhaps thankfully, I have no side-effects BUT also no anti-depressant effect.
>
> Any anecdotal accounts using Selegiline as an anti-depressant...oral form.
>
> Thank you.
poster:Ktemene
thread:366762
URL: http://www.dr-bob.org/babble/20040714/msgs/366896.html