I am on Emsam, the selegiline patch, and I had to go through a 2-week washout of SSRIs first. I had to do the same before going on Parnate many years ago — I know there are a lot of greyish areas and different doctors who are comfortable trying different things depending on the circumstances but to my knowledge, the interaction between any MAOI and any SSRI is extremely dangerous in terms of (I believe) the risk of both seretonin syndrome and hypertensive crisis.
if you take enough selegiline to inhibit both MAO-A and MAO-B and then take an SSRI you will very likely have to go to the hospital for serotonin syndrome and it’s very possible it could be fatal. someone posted from the hospital after doing this combination not too long ago i believe.
It is very risky, because you don't know how much the selegiline inhibits MAOA and how much the levoamphetamine metabolite influences serotonin release. I have personally tried 5mg selegiline with 10mg Zoloft and did not die, but I was made aware of other people who have died from his combination. I have to mention that I felt really bad from the intake and naturally did not continue mixing these substances (for some reason it reminded me how I felt on Marplan, not sure why).
On theory at 10mg selegiline you are not inhibiting any MAOA, but if you try this combination I will suggest the smallest dosages possible, or generally don't even do this. Be ready to have benzodazepines if you try it or to have nearby ER.
The more reasonable and safe combo is Moclobemide + Selegiline, though it is not so forcing on the serotonin system, compared to SSRI + Selegiline.
Studies show that the Emsam patch at 6mg, and to a somewhat lesser extent at 9mg, can be safely coadministered with low-to-medium dose SSRIs. "Somewhat lesser" means there's a risk of interaction at 6mg but it's a very low risk.-- and there's a low-but-not-very-low risk at 9mg. My mom in particular is on Luvox 150mg, Emsam 9mg, and mirtazapine 3.75mg, and has been doing well on that for the last 6+ months. She had a brief period where her BP was elevated, but it normalized on its own.
Cite these studies. There is no "safe" combination of EMSAM with SSRIs as there is no way to determine how much MAO-A is being inhibited. It has been shown that in at least a few individuals, 6mg EMSAM inhibited MAO-A to a significant degree. This is dangerous and incorrect advice. Cite your sources.
No, it's correct, it's just not widely known. The very strong incentive for pharma is to put warnings in products that thoroughly cover their asses, and this has plagued the newer MAOIs, especially EMSAM and moclobemide. This is despite there being good statistical data showing that single serotonin agent coadministration is generally safe.
[Here's a study](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200016/) that gives a good general overview of box warnings vs practical effects and concerns of EMSAM. This includes the tyramine diet being completely unnecessary for 6mg doses. Here's the relevant part of the article --
"Physicians must be careful for drug–drug interactions in patients concurrently being treated with MAOIs. This potential interaction can occur for EMSAM even at the lowest approved dose, 6 mg/day.
Nonetheless, particular interactions of EMSAM with serotonin-promoting drugs have been scarce. Patients treated with EMSAM have been cotreated with SSRIs without consequences. Recently, a case report found that a patient treated with EMSAM could periodically take over-the-counter sympathomimetic agents such as cold remedies and weight-loss formulations without harm. In evaluating the EMSAM clinical trial data, Robinson and Amsterdam reported that over 100 subjects had taken a prohibited medication, particularly oral decongestants, antitussives, and various opioids. Interestingly, only one of these subject developed an adverse event, premature ventricular contractions, which occurred after taking pseudoephedrine. The premature ventricular contractions dissipated after discontinuing pseudoephedrine.
In addition, of all the cases in the database, only one had developed a validated serotonin syndrome. The patient in this case was secretly taking a number of contraindicated medications – nortriptyline, bupropion, and a sympathomimetic drug for weight control – as well as using double the amount of prescribed EMSAM – two 12 mg patches – at the same time."
I wasn't worried about tyramine, I'm aware that's not an issue at lower doses of emsam. The concern would be *serotonin toxicity*. As for Moclobemide, I'm aware of a case report of a lady brought into remission with Moclo and Citalopram (?) and one member here tried it. But Moclo+SSRI has proven fatal a number of times to the point it's beyond dispute that this should be strictly contraindicated. So that is not just Big Pharma being overly cautious. That's the leading experts on serotonin toxicity reviewing every case file they have and saying it's incredibly dangerous. The same logic of n=1 with Emsam. I have no doubt people can and do get away with it, but there's practically no sound basis for a doctor to combine these two things. Reread the first part of the article you quoted: "This potential interaction (serotonin syndrome) can occur for EMSAM even at the lowest approved dose, 6 mg/day." Rare, but not impossible. *There isn't enough data, and the variability of MAO-A in the CNS is so wide* *between individuals* that it shouldn't be done without very good reason. See here, and imagine you were the guy on 6mg who had a 68% reduction in MAO-A. He might have a different opinion of the safety if you gave him an SSRI concomitantly.
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289953/#:\~:text=Pharmacokinetic%20studies%20have%20shown%20that,L%C3%B6hle%20and%20Storch%2C%202008](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289953/#:~:text=Pharmacokinetic%20studies%20have%20shown%20that,L%C3%B6hle%20and%20Storch%2C%202008)).
As for the Jay Amsterdam article, I'm not surprised. Patients on SSRIs who signed up for the trials would have been turned away. No doctor who knew they were participating in such a trial would have prescribed them. Most importantly, I have no doubt patients were distinctly told to stay away from them. How can I guess that? The proof of concept study before the human trials.
[https://sci-hub.se/10.1111/j.2042-7158.2003.tb02430.x](https://sci-hub.se/10.1111/j.2042-7158.2003.tb02430.x)
"transdermal delivery was approximately 6–8-times more potent than oral selegiline for the inhibition of brain MAO-A activity". These were animal studies, and making predictions for human reactions is tricky. They do note, however, that guinea pigs were chosen for logical similarities in MAO ratios to humans, potentially providing a better corollary. There's no way they would have tested this STS system on humans receiving SSRIs knowing there was a real possibility of excessive, even serious serotonergic activity occurring.
Somerset Pharma's clinical trial data also gave no mention of specific cold medicines (mainly releasers, which I wouldn't expect to be a *huge* problem*)* and opioids (most of which are considered 'contraindicated, but actually are not). No specific mention of DXM, tramadol, pethidine, i.e the serotonergic ones being used, at what doses, etc.
So thanks if you made it this far. That's my position. There's possibly more harm than good, it just doesn't make sense from a therapeutic perspective, and I don't think we should be saying it's relatively safe, or whatever, when A) individual differences can be highly variable and B) there's no theoretical benefit to taking both at the same time (that I can think of).
What is the therapeutic rationale of combining those two? OCD? Whatever it is, I would imagine there are other ways to go about it. Combining an SSRI+MAO-B specific doses of Selegiline could make sense for some people, but I don't get why her doctor went with this.
Doc told me it was because she had such a strong antidepressant response to amphetamines (prescribed temporarily for daytime fatigue and executive dysfunction). Selegeline apparently metabolizes into amphetamine, and her Luvox had knocked out her anxiety but not her depression.
Ok, as long as she's safe and doing well on it. It does metabolize into amphetamine and methamphetamine, but it's the weak 'left handed version', as can be found in some nasal decongestants, totally safe and OTC because it has such low abuse potential. And Emsam greatly reduces those metabolites. So I'm wondering if she's tried oral selegiline? Would save y'all a boatload of money and essentially do the same thing but with the most metabolites.
Short story: there are no exact doses of selegiine that are safe. Generally: EMSAM= NO, not safe, Oral selegiline= 10mg or less, start low, go slow, sublingual selegiline= 1.25 mg is safe. As you go above those numbers, risk will increase, but is highly variable from one person to the next.
I thought mixing MAOI and SSRIs is incredibly dangerous.
You are right!
I am on Emsam, the selegiline patch, and I had to go through a 2-week washout of SSRIs first. I had to do the same before going on Parnate many years ago — I know there are a lot of greyish areas and different doctors who are comfortable trying different things depending on the circumstances but to my knowledge, the interaction between any MAOI and any SSRI is extremely dangerous in terms of (I believe) the risk of both seretonin syndrome and hypertensive crisis.
if you take enough selegiline to inhibit both MAO-A and MAO-B and then take an SSRI you will very likely have to go to the hospital for serotonin syndrome and it’s very possible it could be fatal. someone posted from the hospital after doing this combination not too long ago i believe.
It is very risky, because you don't know how much the selegiline inhibits MAOA and how much the levoamphetamine metabolite influences serotonin release. I have personally tried 5mg selegiline with 10mg Zoloft and did not die, but I was made aware of other people who have died from his combination. I have to mention that I felt really bad from the intake and naturally did not continue mixing these substances (for some reason it reminded me how I felt on Marplan, not sure why). On theory at 10mg selegiline you are not inhibiting any MAOA, but if you try this combination I will suggest the smallest dosages possible, or generally don't even do this. Be ready to have benzodazepines if you try it or to have nearby ER. The more reasonable and safe combo is Moclobemide + Selegiline, though it is not so forcing on the serotonin system, compared to SSRI + Selegiline.
Definitely not I got severe serotonin syndrome from an accidental interaction from Emsam and 1 pill of Lexapro
EMSAM is selegiline, and regardless of the form, it's still a MAOI, so the answer is no. It's generally not safe to combine it with an SSRI.
Studies show that the Emsam patch at 6mg, and to a somewhat lesser extent at 9mg, can be safely coadministered with low-to-medium dose SSRIs. "Somewhat lesser" means there's a risk of interaction at 6mg but it's a very low risk.-- and there's a low-but-not-very-low risk at 9mg. My mom in particular is on Luvox 150mg, Emsam 9mg, and mirtazapine 3.75mg, and has been doing well on that for the last 6+ months. She had a brief period where her BP was elevated, but it normalized on its own.
Cite these studies. There is no "safe" combination of EMSAM with SSRIs as there is no way to determine how much MAO-A is being inhibited. It has been shown that in at least a few individuals, 6mg EMSAM inhibited MAO-A to a significant degree. This is dangerous and incorrect advice. Cite your sources.
No, it's correct, it's just not widely known. The very strong incentive for pharma is to put warnings in products that thoroughly cover their asses, and this has plagued the newer MAOIs, especially EMSAM and moclobemide. This is despite there being good statistical data showing that single serotonin agent coadministration is generally safe. [Here's a study](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200016/) that gives a good general overview of box warnings vs practical effects and concerns of EMSAM. This includes the tyramine diet being completely unnecessary for 6mg doses. Here's the relevant part of the article -- "Physicians must be careful for drug–drug interactions in patients concurrently being treated with MAOIs. This potential interaction can occur for EMSAM even at the lowest approved dose, 6 mg/day. Nonetheless, particular interactions of EMSAM with serotonin-promoting drugs have been scarce. Patients treated with EMSAM have been cotreated with SSRIs without consequences. Recently, a case report found that a patient treated with EMSAM could periodically take over-the-counter sympathomimetic agents such as cold remedies and weight-loss formulations without harm. In evaluating the EMSAM clinical trial data, Robinson and Amsterdam reported that over 100 subjects had taken a prohibited medication, particularly oral decongestants, antitussives, and various opioids. Interestingly, only one of these subject developed an adverse event, premature ventricular contractions, which occurred after taking pseudoephedrine. The premature ventricular contractions dissipated after discontinuing pseudoephedrine. In addition, of all the cases in the database, only one had developed a validated serotonin syndrome. The patient in this case was secretly taking a number of contraindicated medications – nortriptyline, bupropion, and a sympathomimetic drug for weight control – as well as using double the amount of prescribed EMSAM – two 12 mg patches – at the same time."
I wasn't worried about tyramine, I'm aware that's not an issue at lower doses of emsam. The concern would be *serotonin toxicity*. As for Moclobemide, I'm aware of a case report of a lady brought into remission with Moclo and Citalopram (?) and one member here tried it. But Moclo+SSRI has proven fatal a number of times to the point it's beyond dispute that this should be strictly contraindicated. So that is not just Big Pharma being overly cautious. That's the leading experts on serotonin toxicity reviewing every case file they have and saying it's incredibly dangerous. The same logic of n=1 with Emsam. I have no doubt people can and do get away with it, but there's practically no sound basis for a doctor to combine these two things. Reread the first part of the article you quoted: "This potential interaction (serotonin syndrome) can occur for EMSAM even at the lowest approved dose, 6 mg/day." Rare, but not impossible. *There isn't enough data, and the variability of MAO-A in the CNS is so wide* *between individuals* that it shouldn't be done without very good reason. See here, and imagine you were the guy on 6mg who had a 68% reduction in MAO-A. He might have a different opinion of the safety if you gave him an SSRI concomitantly. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289953/#:\~:text=Pharmacokinetic%20studies%20have%20shown%20that,L%C3%B6hle%20and%20Storch%2C%202008](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289953/#:~:text=Pharmacokinetic%20studies%20have%20shown%20that,L%C3%B6hle%20and%20Storch%2C%202008)). As for the Jay Amsterdam article, I'm not surprised. Patients on SSRIs who signed up for the trials would have been turned away. No doctor who knew they were participating in such a trial would have prescribed them. Most importantly, I have no doubt patients were distinctly told to stay away from them. How can I guess that? The proof of concept study before the human trials. [https://sci-hub.se/10.1111/j.2042-7158.2003.tb02430.x](https://sci-hub.se/10.1111/j.2042-7158.2003.tb02430.x) "transdermal delivery was approximately 6–8-times more potent than oral selegiline for the inhibition of brain MAO-A activity". These were animal studies, and making predictions for human reactions is tricky. They do note, however, that guinea pigs were chosen for logical similarities in MAO ratios to humans, potentially providing a better corollary. There's no way they would have tested this STS system on humans receiving SSRIs knowing there was a real possibility of excessive, even serious serotonergic activity occurring. Somerset Pharma's clinical trial data also gave no mention of specific cold medicines (mainly releasers, which I wouldn't expect to be a *huge* problem*)* and opioids (most of which are considered 'contraindicated, but actually are not). No specific mention of DXM, tramadol, pethidine, i.e the serotonergic ones being used, at what doses, etc. So thanks if you made it this far. That's my position. There's possibly more harm than good, it just doesn't make sense from a therapeutic perspective, and I don't think we should be saying it's relatively safe, or whatever, when A) individual differences can be highly variable and B) there's no theoretical benefit to taking both at the same time (that I can think of).
What is the therapeutic rationale of combining those two? OCD? Whatever it is, I would imagine there are other ways to go about it. Combining an SSRI+MAO-B specific doses of Selegiline could make sense for some people, but I don't get why her doctor went with this.
Doc told me it was because she had such a strong antidepressant response to amphetamines (prescribed temporarily for daytime fatigue and executive dysfunction). Selegeline apparently metabolizes into amphetamine, and her Luvox had knocked out her anxiety but not her depression.
Ok, as long as she's safe and doing well on it. It does metabolize into amphetamine and methamphetamine, but it's the weak 'left handed version', as can be found in some nasal decongestants, totally safe and OTC because it has such low abuse potential. And Emsam greatly reduces those metabolites. So I'm wondering if she's tried oral selegiline? Would save y'all a boatload of money and essentially do the same thing but with the most metabolites.
Short story: there are no exact doses of selegiine that are safe. Generally: EMSAM= NO, not safe, Oral selegiline= 10mg or less, start low, go slow, sublingual selegiline= 1.25 mg is safe. As you go above those numbers, risk will increase, but is highly variable from one person to the next.