I thought the whole point was that there was not the massive dose of MAOI directly hitting the GI mucosa?
In theory it's great! But it's more complicated in practice -especially medicolegally - at least according to
the Carlat Report back in 2006.
TCPR, November 2006, Vol 4, Issue 11, The Use of MAOIs
From The Carlat Report:
The Early History
EMSAM is the reformulation of an oral MAOI, selegiline, into a skin patch form. Selegiline was discovered in the 1960's and has been available in the U.S. since 1989 through Somerset Pharmaceuticals under the brand name Eldepryl, approved to treat Parkinson's Disease.
Although selegiline was never FDA-approved as an antidepressant in this country, there has been ample clinical experience and research data demonstrating that it is an effective antidepressant at doses between 30 and 60 mg a day (Bodkin et al, Psychiatric Annals 2001; 31:385-391). In fact, those of us who have prescribed it for depression have found it to be a useful drug with fewer nuisance side effects such as weight gain, sexual dysfunction and edema than other MAOIs such as Nardil (phenelzine). Consistent with this more benign side effect profile was a study by Sunderland et al (Arch Gen Psychiatry 1994;51:607-15) in which selegiline successfully treated major depression in treatment-refractory geriatric patients.
So why wasn't oral selegiline marketed to psychiatrists? At low doses, up to 10 mg/day (the dose used to treat Parkinson's Disease), selegiline inhibits only one of the two isoforms of monoamine oxidase enzymes, MAOI-B. Most research has shown that MAO-A inhibition is also necessary to treat depression, and while at higher doses selegeline does inhibit MAO-A, this comes with the disadvantage of requiring the same MAOI dietary limitations as conventional MAOIs. Therefore, there was little economic incentive for Somerset Pharmaceuticals to seek a depression indication for a "me-too" MAOI drug that would likely be prescribed by few psychiatrists.
The MAOI diet and EMSAM
So why does the EMSAM 6 mg patch not require the MAOI diet? And why are low doses in patch form therapeutic when higher doses are required when taken orally? Absorption through the skin sends selegiline directly into the blood stream and toward the brain, sidestepping the liver, where some of the oral MAOI is spent in blocking the breakdown of ingested tyramine. Thus, the patch is able to generate higher levels of MAO-A and MAO-B inhibition in the brain at lower doses with much less inhibition of gut and liver MAO-A. There is enough inhibition of MAO in the brain to produce a therapeutic antidepressant effect, and the absence of MAOI in the liver allows tyramine to be inactivated by intestinal MAO, thereby minimizing the danger of a hypertensive reaction.
The FDA Ruling
Let's return to the FDA decision to limit the removal of MAOI dietary restrictions for the 6 mg patch only, thus creating the complicating situation for clinicians in which pushing the dose to 9 mg or 12 mg requires instructing patients to initiate the MAOI diet. (The FDA hearings on this issue, in all of its 243-page glory, can be viewed at
http://www.fda.gov/ohrms/dockets/ac/05/transcripts/2005-4186T2.pdf)
How did the FDA determine that 6 mg was the only safe dose? Somerset presented results of a "tyramine pressor test" in which patients were fed tyramine under experimentally controlled research conditions. (In one study, research subjects were asked to eat a few pounds of cheddar and blue cheese over a two hour period!) The increase in blood pressure was only slightly greater for subjects gorging on tyramine with the 6 mg EMSAM patch than for those who ingested tyramine while taking the control drugs, 20 mg fluoxetine or 10 mg oral selegiline. There was enough research data and patient experience to satisfy the FDA that subjects on the 6 mg patch could eat all the tyramine they wanted without incurring any hypertensive risk.
But what did the research data say about the risk of tyramine at the higher doses of EMSAM, such as 9 mg? While there was evidence of a greater potential of a hypertensive effect, the tyramine risk was still much less than found with the comparator classic MAOI, Parnate. However, far fewer subjects were tested at this higher dose than at the 6 mg dose. Thus the manufacturer opted to play it safe in not requesting the lifting of dietary restrictions on the 9 mg dose, even though their naturalistic data set included about 800 people who were on either the 9 or 12 mg patch, had not followed an MAOI diet, and had no problems with hypertension.
From a medico-legal perspective, pending more data, we clinicians may feel equally compelled to recommend an MAOI diet for patients on the 9 and 12 mg patches.
At all doses, EMSAM carries the same medication restrictions as other MAOIs. But here as well some data endorses the cardiovascular safety of sympathomimetics combined with EMSAM (Feinberg, J Clin Psychiatry 2004; 65:1520-1524) and, in particular, Sudafed (pseudoephedrine) in combination with the 6 mg dose of EMSAM (Patkur et al, CNS Spectr 2006;11:363-375).
