![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 7 to 31 of 47. Go back in thread:
Posted by Jakeman on June 11, 2006, at 22:11:09
In reply to Re: EMSAM doses too low to effect depression ?, posted by notfred on June 11, 2006, at 21:08:36
What you are saying is in opposition to the studies conducted my Somerset and others which indicate that transdermal delivery by-passes first-pass metabolism resulting in higher exposure to selegline and less dietary restrictions as well as less exposure to metabolites. How are they wrong?
Warm regards, Jake
MSAM does not inhibit MAO-A at lower doses. This alone and not its transdermal delivery system accounts for the lack of dietary restrictions.
>
Posted by Jakeman on June 11, 2006, at 23:16:44
In reply to Re: EMSAM doses too low to effect depression ?, posted by notfred on June 11, 2006, at 21:10:24
>>
> Its a dirty drug; it has many effects.
>
In what way is it a dirty drug? Please explain.warm regards, Jake
Posted by notfred on June 11, 2006, at 23:54:31
In reply to Re: EMSAM doses too low to effect depression ? » notfred, posted by Jakeman on June 11, 2006, at 22:11:09
> What you are saying is in opposition to the studies conducted my Somerset and others which indicate that transdermal delivery by-passes first-pass metabolism resulting in higher exposure to selegline and less dietary restrictions as well as less exposure to metabolites. How are they wrong?
>
I am not saying they are wrong. They played it safe to get the dietary restrictions removed. There was quite a bit of wrangling with the FDA to get this one on the market. There is limited clinical experience with the transdermal delivery system and avoidance for the "cheese reaction", just a few studies. So they stuck to doses that were already established as safe for Selegline/Deprenyl by mouth. There is quite a bit of clinical experience there.At the doses of EMSAM indicted to be safe, you could just as well take an equivalent amount by mouth and still not have the "cheese reaction".
The safe doses for EMSAM are in the low part of the range for effective treatment of depression in Selegline/Deprenyl. Unfortunately Somerset did not get approved for higher levels of EMSAM w/o dietary restrictions. But their research does bear out that the delivery system avoids the side effect in question. Higher doses should be OK.
EMSAM's potential is limited unless docs are willing to prescribe higher doses. It would be nice to have a MAOI that is free of dietary restrictions and can be used throughout its therapeutic range.As to the metabolites, the exclusion of the amphetamines may not be a good thing. They also have MAOI activity and legit use as psyco meds. The levels were really low to begin with. The MAOI's are effective partly because the effect many things, a dirty med, adding a bit of meth/amphetamine may be of benefit.
Posted by notfred on June 12, 2006, at 10:41:21
In reply to Re: EMSAM doses too low to effect depression ? » notfred, posted by Jakeman on June 11, 2006, at 23:16:44
> In what way is it a dirty drug? Please explain.
>
> warm regards, JakeIt effects multiple NT's. As apposed to the SSRI's which are very specific. TCA's are dirty drugs. In this case dirty is often a good thing, among psyco meds the dirty drugs (or polypharacology) make for more effective drugs or drug regimens.
Posted by notfred on June 12, 2006, at 11:02:12
In reply to Re: EMSAM doses too low to effect depression ?, posted by cecilia on June 11, 2006, at 21:40:49
> In Dr. Bob's "tips' (written long before Emsam) some of the doctors say they get good results for depression on 40-60 mg day of oral selegiline. The largest "patch" 12mg/24 h is supposedly equivalent to 40 mg oral,
The mon0graph indicates something different:
EMSAM systems are transdermal patches that contain 1 mg of selegiline per cm2 and deliver approximately 0.3 mg of selegiline per cm2 over 24 hours. EMSAM systems are available in three sizes: 20 mg/20 cm2,30 mg/30 cm2, and 40 mg/40 cm2 that deliver,
on average, doses of 6 mg, 9 mg or 12 mg, respectively, of selegiline over 24 hours.
Pharmacokinetics
Absorption
Following dermal application of EMSAM to humans, 25%-30% of the selegiline content on average is delivered systemically over 24 hours (range ~ 10%-40%).Consequently, the degree of drug absorption may be 1/3 higher than the average amounts of 6 to 12 mg per 24 hours.So not more than 12 mg a day on the largest patch,
& that requires ditary restrictions:To further define the likelihood of hypertensive crises with use of EMSAM, several Phase I tyramine challenge studies were conducted both with and without food (see PRECAUTIONS, Drug Interactions, Tyramine). In its entirety, the data for EMSAM 6 mg/24 hours support the recommendation that a modified diet is not required at this dose. Due to the more limited data available for EMSAM 9 mg/24 hours, and the results from the Phase I tyramine challenge study in fed volunteers administered EMSAM 12 mg/24 hours (see PRECAUTIONS, Drug Interactions, Tyramine), patients receiving these doses should follow Dietary Modifications Required for Patients Taking EMSAM 9 mg/24 hours and 12 mg/24 hours.
Posted by Jakeman on June 12, 2006, at 20:38:39
In reply to Re: EMSAM doses too low to effect depression ?, posted by notfred on June 11, 2006, at 23:54:31
>But their research does bear out that the delivery system avoids the side effect in question. Higher doses should be OK.
> EMSAM's potential is limited unless docs are willing to prescribe higher doses. It would be >nice to have a MAOI that is free of dietary >restrictions and can be used throughout its therapeutic range.Over time docs may be willing to prescribe higher dosages without imposing the FDA recommended dietary restrictions after they look at the studies and get patients reporting no problems. There's always going to be some guy who will say I ate a big bowl of sauerkraut with a glass of wine and felt fine. People are going to experiment (hopefully cautiously) and maybe not even inform their doctors.
> As to the metabolites, the exclusion of the amphetamines may not be a good thing. They also have MAOI activity and legit use as psyco meds. >The levels were really low to begin with. The MAOI's are effective partly because the effect many things, a dirty med, adding a bit of >meth/amphetamine may be of benefit.It can be a good thing especially if you are lacking in energy and drive. But my hope was that the reduction of amphetamine metabolites would also reduce the oft mentioned side effect of insomnia and irritability. The Emsam data sheet has a chart showing very significant reductions in amphetimine metabolites compared to oral dosing. However many people on this board using Emsam still report those side effects.
warm regards, Jake
Posted by cecilia on June 13, 2006, at 1:41:42
In reply to Re: EMSAM doses too low to effect depression ? » notfred, posted by Jakeman on June 12, 2006, at 20:38:39
I don't know how much is actually absorbed from the patch (it probably varies from person to person), but the Emsam patch is STRONG. I haven't noticed anyone on Psychobabble who's gotten to the 40 mg patch-people seem to either have good results or intolerable side effects on a much lower dose. Cecilia
Posted by notfred on June 13, 2006, at 16:21:35
In reply to Re: EMSAM doses too low to effect depression ?, posted by cecilia on June 13, 2006, at 1:41:42
I haven't noticed anyone on Psychobabble who's gotten to the 40 mg patch-people seem to either have good results or intolerable side effects on a much lower dose. Cecilia
deprenyl has been on the market for years so there is clinical experiance with it at higher doses.
EMSAM/Deprenyl is a whole different AD at higher doses. At lower doses it does not directly effect
serotonin nor norepinephrine. So I do not think one can draw conclustions from the lower doses as to how the higher doses will work.not work.
Posted by notfred on June 13, 2006, at 19:25:09
In reply to Re: EMSAM doses too low to effect depression ?, posted by notfred on June 13, 2006, at 16:21:35
http://www.dr-bob.org/babble/20020301/msgs/96388.html
http://www.dr-bob.org/babble/20020313/msgs/97853.html
Posted by Psydoc on March 13, 2002, at 21:42:38
In reply to Re: Just look. Take it or leave it. SELEGLINE COMBO!!!, posted by Eloy on March 5, 2002, at 4:35:30
Here are a few MEDLINE abstracts on Selegline:
1: Arch Gen Psychiatry 1994 Aug;51(8):607-15
High-dose selegiline in treatment-resistant older depressive patients.
Sunderland T, Cohen RM, Molchan S, Lawlor BA, Mellow AM, Newhouse PA, Tariot PN,
Mueller EA, Murphy DL.Section on Geriatric Psychiatry, National Institute of Mental Health, Bethesda,
Md.BACKGROUND: We examined the effect of high-dose selegiline in 16
treatment-resistant older depressive patients. We hypothesized that selegiline,
at a dosage of 60 mg/d, would be at least partially effective but that the
higher doses would not maintain the monoamine oxidase B selectivity observed
with the lower doses of selegiline. METHODS: Sixteen treatment-resistant
subjects (mean [ SD] age, 65.6 9.3 years) entered a double-blind,
randomized, crossover study of placebo vs 3 weeks of selegiline at a dosage of
60 mg/d. Objective measures of mood and behavior were obtained in all subjects,
and 10 of the subjects underwent repeated lumbar punctures for analysis of
monoamine metabolites in the cerebrospinal fluid. RESULTS: Objective measures of
mood and behavior revealed significant improvement in the Hamilton Depression
Rating Scale score (37.4% decrease), the Global Depression score (22.7%
decrease), and the Brief Psychiatric Rating Scale score (19.3% decrease);
subjective behavioral measures, however, did not show significant improvement
during the 3-week medication trial. Cerebrospinal fluid values revealed a
statistically significant drop in 3-methoxy-4-hydroxyphenylglycol (51%) and
5-hydroxyindoleacetic acid (17%) levels, and there was a significant lowering of
systolic blood pressure on standing (15%), but these changes were not
accompanied by clinical side effects. CONCLUSIONS: Our results suggest that
high-dose selegiline can be an effective antidepressant in treatment-resistant
older depressive patients. While the selegiline dose required has nonselective
monoamine oxidase effects and thus would not be free of possible tyramine
interactions, other advantages suggest that further investigations with
selegiline are warranted in this population.Publication Types:
Clinical Trial
Randomized Controlled TrialPMID: 7519005 [PubMed - indexed for MEDLINE]
2: Arch Gen Psychiatry 1989 Jan;46(1):45-50
A controlled study of the antidepressant efficacy and side effects of
(-)-deprenyl. A selective monoamine oxidase inhibitor.Mann JJ, Aarons SF, Wilner PJ, Keilp JG, Sweeney JA, Pearlstein T, Frances AJ,
Kocsis JH, Brown RP.Department of Psychiatry, Cornell University Medical College, New York, NY
10021.Monoamine oxidase (MAO) inhibitors are effective antidepressants whose use is
limited because of unwanted side effects and the possibility of a
tyramine-induced hypertensive crisis (cheese reaction). (-)-Deprenyl (the
official nonproprietary name for this substance is selegiline), a selective MAO
type B inhibitor, may be safer and have fewer side effects, but its
antidepressant efficacy is uncertain. A double-blind placebo-controlled study
was carried out in depressed outpatients who were treated with (-)-deprenyl in
an MAO type B selective dose range and at a higher nonselective dose range.
(-)-Deprenyl did not have a statistically significant antidepressant effect
after three weeks of treatment at doses of 10 mg/d. However, after six weeks and
at higher doses (averaging about 30 mg/d for the second three weeks),
(-)-deprenyl was superior to placebo in antidepressant effect with a positive
response rate of 50% vs 13.6% and with a 41% reduction in the Hamilton
Depression Rating Scale mean score vs 10% in the placebo-treated group. No
hypertensive crises were seen. The rate of occurrence of side effects with
(-)-deprenyl was no greater than with placebo. It was concluded that
(-)-deprenyl is an effective antidepressant in a dose range where it is
distinguished by the absence of many of the side effects typical of nonselective
MAO inhibitors.Publication Types:
Clinical Trial
Controlled Clinical TrialPMID: 2491941 [PubMed - indexed for MEDLINE]
3: Biol Psychiatry 1985 May;20(5):558-65
Biochemical effects of L-deprenyl in atypical depressives.
Liebowitz MR, Karoum F, Quitkin FM, Davies SO, Schwartz D, Levitt M, Linnoila M.
To examine the biochemical effects of 10-30 mg/day L-deprenyl, measurement of
24-hr urinary output of phenylethylamine (PEA), 3-methoxy 4-hydroxy
phenylethyleneglycol (MHPG), and L-deprenyl's amphetamine metabolites were
carried out before and during the treatment of atypical depressives. Platelet
monoamine oxidase (MAO) activity was also assessed. With L-deprenyl 10-30
mg/day, the expected MAO B inhibition occurred, as indicated by significant
increase in urinary PEA excretion and virtual disappearance of platelet MAO
activity. Twenty-five to 33% of the daily dose of L-deprenyl was recovered as
urinary methamphetamine or amphetamine. Excretion of MHPG was significantly
decreased with L-deprenyl 10-20 mg/day. Overall, the results suggest that
L-deprenyl's antidepressant effects are mediated by some mechanism other than,
or in addition to, MAO B inhibition.Publication Types:
Clinical TrialPMID: 3921065 [PubMed - indexed for MEDLINE]
4: Br J Psychiatry 1983 May;142:508-11
L-Deprenil, a selective monoamine oxidase type B inhibitor, in the treatment of
depression: a double blind evaluation.Mendlewicz J, Youdim MB.
In a double blind controlled study, 14 affectively ill patients (2 bipolars, 12
unipolars) were randomly allocated to L-Deprenil treatment (an irreversible
selective MAO-B inhibitor without "cheese effect") and 13 patients (3 bipolars,
10 unipolars) to placebo only. Patients on L-Deprenil showed a significantly
greater clinical improvement than placebo patients. A positive relationship was
found between clinical improvement and degree of platelet MAO inhibition in
patients treated with L-Deprenil.Publication Types:
Clinical Trial
Randomized Controlled TrialPMID: 6409196 [PubMed - indexed for MEDLINE]
Best regards . . .
Ivan
%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
Posted by Jakeman on June 13, 2006, at 20:00:10
In reply to Selegline posts on psycobabble, 2002, posted by notfred on June 13, 2006, at 19:25:09
Thanks for the info. If I'm not mistaken the Somerset studies on transdermal selegline contradict the conclusions of the study cited below. They said antidepressant effect WAS significant at lower doses, (6mg) based on patient responses on the Hamilton Scale.
warm regards, Jake
> (-)-Deprenyl did not have a statistically significant antidepressant effect
> after three weeks of treatment at doses of 10 mg/d. However, after six weeks and
> at higher doses (averaging about 30 mg/d for the second three weeks),
> (-)-deprenyl was superior to placebo in antidepressant effect with a positive
> response rate of 50% vs 13.6% and with a 41% reduction in the Hamilton
> Depression Rating Scale mean score vs 10% in the placebo-treated group. No
> hypertensive crises were seen. The rate of occurrence of side effects with
> (-)-deprenyl was no greater than with placebo. It was concluded that
> (-)-deprenyl is an effective antidepressant in a dose range where it is
> distinguished by the absence of many of the side effects typical of nonselective
> MAO inhibitors.
>>
Posted by endof90 on June 13, 2006, at 23:21:36
In reply to Re: EMSAM doses too low to effect depression ?, posted by notfred on June 13, 2006, at 16:21:35
Hi, I started Emsam on April 13, after coming off of Nardil 2wks. prior. As many others on this board I have been on multiple AD's w/various augmentors over the past 16yrs., due to refractory depression and social phobia. The ones that have helped eventually lose their effect, while others (mainly SSRI's) do not help @ all. Nardil was always my lifesaver, and I have been on and off of it for various periods since 1992. This past year it only really helped me for about 4 mos. but stayed on it anyway trying the addition of Lithium (didn't help)and then Lamictal which I really don't feel made much of a difference, though I continue to take 200mg daily. My first week on Emsam 6mg was intolerable due to excessive anxiety and insomnia. I would of welcomed the extra energy if I weren't so damned depressed and unmotivated,as my depression can usually have me sleeping @ least 15hrs/day @ times. I was increased to the 9mg patch after 7 days as my psydoc. stated the excessive anxiety was due to the MAO-B inhibition, whereas I respond best to the inhibition of MAO-A which only occurs @ the higher doses. Ativan and Ambien also helped me get thru this time. After 4wks. on 9mg I was better than I had been before starting this med. but in noway did it come close to the releif I felt w/Nardil when it was working for me. So I was increased to the 12mg patch on May 24. I have not noticed any significant improvement since, and am very worried that I am going down to where I've been too many times. I'm able to function still but it takes a tremendous effort to motivate myself. Stayed in bed from Wed. to Sun. this past week. Suddenly I'm tired again, w/absolutely no problem sleeping. Have been seeing my therapist twice a week so I can try to keep myself from completely isolating from the world again. If I don't try to fight it I'd never leave the house. Life is not supposed to be so hard. Just trying to hold on and not give up yet. Maybe something can be added. I'm also in the process of finding a new psydoc. b/c I'm not really happy w/the one I have for various reasons. Live in NJ, trying to find someone w/more experience in treatment resistant depression. Tried ECT in 2001, think it made me worse. I am truly happy for everyone that Emsam has helped so far and I wish you all continued success. Wish I could have a better response, but we're all different. I'm not ready to give up trying just as yet.
Posted by cecilia on June 14, 2006, at 0:13:37
In reply to Re: EMSAM doses too low to effect depression ? » notfred, posted by endof90 on June 13, 2006, at 23:21:36
That's interesting, Endof90, that you actually felt LESS insomnia and anxiety at the higher doses. I'm just too afraid to go any higher, not just because of the insomnia but mainly because of the eye pain, which keeps getting worse. Did you have that, and did the dose affect it? I hope you can find something that works for you. All these new meds-it's like a tease-maybe this will be the one, but of course it never is. Cecilia
Posted by Declan on June 14, 2006, at 2:30:38
In reply to Re: EMSAM doses too low to effect depression ? » notfred, posted by endof90 on June 13, 2006, at 23:21:36
How old are you? (you sleep so well)
No problems sleeping on the 12mg patch? Would it make sense to try a higher dose?
2mg sublingual deprenyl/d disturbed my already bad sleep.
But then you've come off Nardil 2 months ago, which might....?
Declan
Posted by Declan on June 14, 2006, at 2:32:48
In reply to Re: EMSAM doses too low to effect depression ?, posted by cecilia on June 14, 2006, at 0:13:37
Hey Cecilia
I haven't read all the thread, but what's all this eye pain business? Do you know what causes it? Dry eyes?
Declan
Posted by endof90 on June 14, 2006, at 6:02:39
In reply to Re: EMSAM doses too low to effect depression ?, posted by cecilia on June 14, 2006, at 0:13:37
Hi, I have fortunately not experienced any eye pain but have had frequent headches that are sometimes unrelenting no matter what I try, ever since I started this med. Sorry to hear you are experiencing this, I can just imagine how uncomfortable it must be. Have you had an eye exam recently? They routinely do a glaucoma test to see if there might be increased intraoccular pressure. Might be a good idea to be checked just to be sure. What we have to go thru w/some of these medications is really terrible. Besides the headaches, I have had the worst constipation I have ever had on a med, and sometimes experience alot of epigastric discomfort which feels like my stomach is being twisted into a knot. Might be from taking so many damn analgesics for the headaches. Zantac usually helps though, and this particular side effect has become less frequent. It was really bad when I first started the Emsam. I really don't understand the sudden tiredness either, having felt not sleeping so much was one of the positive aspects of this med. initially. My sleeping usually increases when a med. starts losing it's effect. Anxiety is still there but not as bad. I only have to take an Ativan when going out in the world b/c of the social anxiety. The only med that really ever helped w/this was Nardil,(until it stopped working again) The Emsam hasn't really helped in this area. Seem to feel uncomfortable in my own skin and less @ ease around people than I had been. Only difference is I don't need to take it when I'm home and feel safe I guess. The first weeks I needed to take it all the time. I was really hoping for better results w/this med.
Posted by endof90 on June 14, 2006, at 7:30:26
In reply to Re: EMSAM doses too low to effect depression ? » endof90, posted by Declan on June 14, 2006, at 2:30:38
> How old are you? (you sleep so well)
> No problems sleeping on the 12mg patch? Would it make sense to try a higher dose?
> 2mg sublingual deprenyl/d disturbed my already bad sleep.
> But then you've come off Nardil 2 months ago, which might....?
> Declan
I am 47. My problems started w/panic attacks @ 16. Completely ruined me @ 30, but is a long story. Have you heard of anyone going higher than the 12mg patch? My last months on the Nardil were really bad, and my somnolence increased as well as the isolation. I was put on Lamictal about the 4th month on the Nardil, when it seemed to be losing it's effect. A few weeks into taking Lamictal, I began having heart palpitations and pressure in my chest soon after taking my usual Nardil dose. I had to take sublingual Procardia whenever this occurred because my B/P would shoot up. Anyway the Nardil had to be lowered to 45mg from 90mg/day. My psydoc. insisted the Lamictal had nothing to do w/this. I had never experienced this w/Nardil before nor had any history of any cardiac problems. I had been on it for 6 mos. in 2003 where it was working well, but in Dec. of that year I had a hypertensive crisis that seemed to hit me out of nowhere. It occurred after eating a peice of chocolate, which I had never had a problem with previously. It had come as a gift and was from a place that made their own confections, so that might have been the reason. It was a terrible, frightening experience. This happened during the time Pfizer was apparently in the process of changing the formula, and @ the time it was very difficult getting Nardil anywhere. I remember having to write to the company to get a emergency supply b/c all pharmacies were out of it, and having a difficult time obtaining it. I now wonder if this had something to do w/it, as I now see alot of people have had problems w/Nardil since then. Problem is, after having such a good response to a med. and then having it lose it's effect is so discouraging. When it worked I felt as if I had experienced a miracle. Had been hoping for this w/Emsam, but just don't know now. Terrible thing also is when something does finally help, I feel like I am always looking over my shoulder for it's eventual failure. Guess I should just be grateful for the respites I have had in my life dealing w/this ugly disease. My Dr. wanted me to add a small dose of Lexapro while on the Nardil, but I was too scared to try. Maybe if he had offered to supervise the experiment in his office, I would have tried it. Then Emsam became available and he decided to go w/that. Did you ever hear of combining a MAO w/Lexapro? I haven't been able to find any info on such a combination. Would have been willing to try it if there had been some evidence of it being used w/out dying of a hypertensive crisis.
Posted by notfred on June 14, 2006, at 10:33:34
In reply to Re: EMSAM doses too low to effect depression ?, posted by cecilia on June 14, 2006, at 0:13:37
> That's interesting, Endof90, that you actually felt LESS insomnia and anxiety at the higher doses.
EMSAM has totally different actions at higher doses.
Posted by Pops_1 on June 14, 2006, at 13:22:24
In reply to Re: EMSAM doses too low to effect depression ?, posted by notfred on June 14, 2006, at 10:33:34
Your original speculation - that EMSAM doesn't require dietary restrictions b/c it is essentially equivalent to sub-therapeutic oral selegline dose levels - is interesting but incorrect on two points.
(See http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=400 for excellent overview of MAO Inhibitors and EMSAM's pharmokinetics).
1. Transdermal delivery has very different pharmokinetics than oral delivery. Since it enters the bloodstream directly, it has much stronger effect than oral dose, which much of which is metabolized before it can reach brain to inhibit MAO A & B.
"The bioavailability of selegiline is ~75% following STS compared with 4.4% after oral administration due to first-pass metabolism. Therefore, STS produces higher and more sustained steady-state levels compared with oral selegiline."
"STS also was 10–20 times more potent than oral selegiline in producing its antidepressant-like effect and inhibiting cortical MAO-A."
2. Dietary restrictions aren't require despite the higher potency of transdermal selegiline because transdermal delivery doesn't inhibit the MAO-A in the gut to the extent oral selegline dose. If your gut MAO-A are OK, you can still eat tyramine-rich foods.
"Doses of [Selegiline Transdermal System] that inhibit brain MAO-A and MAO-B by 60% and 90%, respectively, do not alter [gastro intestinal] MAO-A activity."
Hope that explanation is clear...
Posted by notfred on June 14, 2006, at 14:11:55
In reply to EMSAM stronger than oral selegline, posted by Pops_1 on June 14, 2006, at 13:22:24
> Your original speculation - that EMSAM doesn't require dietary restrictions b/c it is essentially equivalent to sub-therapeutic oral selegline dose levels - is interesting but incorrect on two points.
>Reread a bit and you will see that is not what I was saying.
(See http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=400 for excellent overview of MAO Inhibitors and EMSAM's pharmokinetics).
The manufacture says there is "limited clinical experience" with this.
Posted by SFY on June 14, 2006, at 15:53:13
In reply to Re: EMSAM doses too low to effect depression ? » cecilia, posted by endof90 on June 14, 2006, at 6:02:39
> Hi, I have fortunately not experienced any eye pain but have had frequent headches that are sometimes unrelenting no matter what I try, ever since I started this med. Sorry to hear you are experiencing this, I can just imagine how uncomfortable it must be. Have you had an eye exam recently? They routinely do a glaucoma test to see if there might be increased intraoccular pressure. Might be a good idea to be checked just to be sure. What we have to go thru w/some of these medications is really terrible. Besides the headaches, I have had the worst constipation I have ever had on a med, and sometimes experience alot of epigastric discomfort which feels like my stomach is being twisted into a knot. Might be from taking so many damn analgesics for the headaches. Zantac usually helps though, and this particular side effect has become less frequent. It was really bad when I first started the Emsam. I really don't understand the sudden tiredness either, having felt not sleeping so much was one of the positive aspects of this med. initially. My sleeping usually increases when a med. starts losing it's effect. Anxiety is still there but not as bad. I only have to take an Ativan when going out in the world b/c of the social anxiety. The only med that really ever helped w/this was Nardil,(until it stopped working again) The Emsam hasn't really helped in this area. Seem to feel uncomfortable in my own skin and less @ ease around people than I had been. Only difference is I don't need to take it when I'm home and feel safe I guess. The first weeks I needed to take it all the time. I was really hoping for better results w/this med.
Have you checked your blood pressure? Headaches from Emsam could be a sign of a potentially dangerous hypertensive crisis.
Posted by Pops_1 on June 14, 2006, at 17:22:25
In reply to Re: EMSAM stronger than oral selegline, posted by notfred on June 14, 2006, at 14:11:55
> > Your original speculation - that EMSAM doesn't require dietary restrictions b/c it is essentially equivalent to sub-therapeutic oral selegline dose levels - is interesting but incorrect on two points.
> >
>
> Reread a bit and you will see that is not what I was saying.
>
> (See http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=400 for excellent overview of MAO Inhibitors and EMSAM's pharmokinetics).
>
> The manufacture says there is "limited clinical experience" with this.Um, sorry if I interpolated your posts incorrectly, but I took from your following two statements...
"Deprenyl and EMSAM contain the same active ingredient. The doses for depression are far higher that those mentioned on this board."
"Yes, that is fundamental and well known as to why there are no dietary restrictions at lower doses. EMSAM does not inhibit MAO-A at lower doses. This alone and not its transdermal delivery system accounts for the lack of dietary restrictions."...that you assumed:
a. EMSAM & deprenyl dosing were equivalent (e.g., if you needed 40mg-60mg oral dose for AD, you would need 40-60mg EMSAM dose for AD)
b. MAO-A inhibition is what produces antidepressant efficacy
c. MAO-A inhibition is what creates dietary restrictions
d. Since EMSAM 20mg doesn't have dietary restrictions, it must not inibit MAO-A
What did you actually mean to suggest?
As indicated in the article I linked, EMSAM 20mg achieves cortical MAO-A inhibition equivalent to 60mg-120mg of oral deprenyl (way beyond doses required for AD efficacy) without impacting GI MAO-A levels sufficiently to warrant dietary restrictions. "STS allows inhibition of brain MAO-A and MAO-B enzymes with reduced effects on GI MAO-A, thereby reducing the risk of possible interactions with tyramine-rich foods at therapeutic doses."
If you read the full article, you'll see that even the 30mg & 40mg patches are likely to not cause dietary problems, but that data from the test trials indicated that the most tyramine-sensitive patient could in theory have a hypertensive crisis at these doses if they ate a really, really tyramine rich meal, which is probably why Somerset was OK with the dietary restrictions on labelling for the higher doses.
Posted by notfred on June 14, 2006, at 17:50:40
In reply to Re: EMSAM stronger than oral selegline, posted by Pops_1 on June 14, 2006, at 17:22:25
>
> b. MAO-A inhibition is what produces antidepressant efficacyI have already posted studies to bear out this.
>
> c. MAO-A inhibition is what creates dietary restrictions
>see http://www.biopsychiatry.com/pressor.htm
Monoamine oxidase inhibitors
and pressor response to dietary amines
by
Tipton KF
Department of Biochemistry,
Trinity College Dublin, Ireland.
ktipton@tcd.ie
Vopr Med Khim 1997 Nov-Dec;43(6):494-503"Because gastro-intestinal monoamine oxidase (MAO) effectively prevents dietary pressor amines, typically tyramine, from entering the tissues, a marked hypertensive response (the "cheese reaction") can occur when subjects treated with antidepressant MAO inhibitors ingest foods or beverages rich in such amines. Although tyramine is a substrate for both MAO-A and -B, it is only inhibitors of the former enzyme"
Posted by endof90 on June 14, 2006, at 18:07:05
In reply to Re: EMSAM doses too low to effect depression ?, posted by SFY on June 14, 2006, at 15:53:13
You are right, it was one of the first things I thought of as I have unfortunately been thru 2 incidents of hypertensive crisis in the past while on Nardil. The circumstances of one of them I had posted on this thread earlier today in response to a question from Declan. Today is the first time I've had the nerve to post anything so I really don't even know if I am using this board correctly. The first hypertensive crisis I experienced was while I was taking Dexedrine as an augmentor to the Nardil in 1999. I had been on the Dexedrine for @ least 2 mos. w/out any problem before it happened. Beleive me when it happens it is a headache you will never, ever, forget. I usually run a low B/P, 90/60, and since starting the Emsam it has not really changed, even w/the headaches. It went up to 200/90 during the hypertensive crises. The 2 incidents I experienced really knocked me for a loop because I was always very vigilant w/the MAO diet. As much as I loved cheese it was worth giving up,( as well as other some other foods )not to be depressed. The first time I was put on it was in 1992 and @ the time I had been not too long out of eating disorder treatment for bulemia ( which started @ age 16). So I was pretty much used to being on somewhat of a restricted diet as it was. Unfortunately I've struggled w/bulemia again in recent years when falling back into depression, usually when whatever med. that has helped suddenly stops working. Despite this, I have always continued to avoid the forbidden foods during these times. Sadly, it is probably b/c of such an ingrained fear of potentially dying in such a humiliating way. Thank you for your concern regarding the headaches though.
Posted by Jakeman on June 15, 2006, at 1:22:28
In reply to Re: EMSAM stronger than oral selegline, posted by notfred on June 14, 2006, at 17:50:40
>
> >
> > b. MAO-A inhibition is what produces antidepressant efficacy
>Other studies have shown that antidepressant efficacy for transdermal selelinge is provided at lower doses(6 mg) See below. Which may indicate that transdermal delivery has a stronger effect. Maybe its hitting both A and B. I don't know.
http://www.rxlist.com/cgi/generic4/emsam_cp.htm
Clinical Efficacy TrialsThe efficacy of EMSAM as a treatment for major depressive disorder was established in two placebo-controlled studies of six and eight weeks duration in adult outpatients (ages 18 to 70 years) meeting DSM-IV criteria for major depressive disorder. In both studies, patients were randomized to double-blind treatment with EMSAM or placebo. The 6-week trial (N=176) showed that EMSAM 6mg/24hours was significantly more effective than placebo on the 17-item Hamilton Depression Rating Scale (HAM-D). In an 8-week dose titration trial, depressed patients (N=265), who received EMSAM or placebo at a starting dose of 6mg/24hours, with possible increases to 9mg/24hours or 12mg/24hours based on clinical response, showed significant improvement compared with placebo on the primary outcome measure, the 28-item HAM-D total score.
In another trial, 322 patients meeting DSM-IV criteria for major depressive disorder who had responded during an initial 10-week open-label treatment phase for about 25 days, on average, to EMSAM 6mg/24hours, were randomized either to continuation of EMSAM at the same dose (N=159) or to placebo (N=163) under double-blind conditions for observation of relapse. About 52% of the EMSAM-treated patients, as well as about 52% of the placebo-treated patients, had discontinued treatment by week 12 of the double-blind phase. Response during the open-label phase was defined as 17-item HAM-D score <10 at either week 8 or 9 and at week 10 of the open-label phase. Relapse during the double-blind phase was defined as follows : (1) a 17-item HAM-D score ³ 14, (2) a CGI-S score of ³ 3 (with at least a 2-point increase from double-blind baseline), and (3) meeting DSM-IV criteria for major depressive disorder on two consecutive visits ³ 11 days apart. In the double-blind phase, patients receiving continued EMSAM experienced a significantly longer time to relapse
Posted by Pops_1 on June 15, 2006, at 12:44:48
In reply to Re: EMSAM stronger than oral selegline, posted by notfred on June 14, 2006, at 17:50:40
>
> >
> > b. MAO-A inhibition is what produces antidepressant efficacy
>
> I have already posted studies to bear out this.> >
> > c. MAO-A inhibition is what creates dietary restrictions
> >
>
> see http://www.biopsychiatry.com/pressor.htmBoth of these statements are correct and are confirmed in the monograph I cited. I was trying to clarify that your OTHER two apparent assumptions were incorrect, and hence dispel any suggestion that EMSAM 20mg doesn't require dietary restrictions because it doesn't inhibit cortical MAO-A.
- "a. EMSAM & deprenyl dosing were equivalent (e.g., if you needed 40mg-60mg oral dose for AD, you would need 40-60mg EMSAM dose for AD)"
- "d. Since EMSAM 20mg doesn't have dietary restrictions, it must not inibit MAO-A"
Is this what you were suggesting? If not, what is your point about EMSAM 20mg?
I provided the quotes from the monograph to demonstrate that EMSAM 20mg achieves its status as "MAOI without dietary restrictions" by producing therapeutic inhibition of brain MAO-A without impacting GI MAO-A, not because it only inhibits MAO-B.
I think this is important to clarify, since someone currently on a traditional MAOI might infer from your post that they would have to go to the dietary-restricted EMSAM doses to get the same benefits, which is probably not the case.
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