MAOI

[sujalneuro]

MAOI are potent Alpha blockers causing hypotension. How is that excess with tyramine causes hypertensive crisis.

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[MacDonaldTriad]

Hypertensive crisis
Inactivation of intestinal MAO impairs the metabolism of tyramine. Tyramine can act as a false transmitter and displace norepinephrine from presynaptic storage granules. Therefore, large amounts of dietary tyramine can result in a hypertensive crisis in patients taking MAOIs because increased amounts of norepinephrine are displaced from adrenergic terminals, resulting in profound adrenergic activation. This reaction has also been called the "cheese reaction" because tyramine is present in relatively high concentrations in aged cheeses.

plagerized from APA text

 

[st2205]

Speaking of MAOIs, how much experience does everyone have with them?

 

[PistolPete]

I think I've only seen one patient on a selegeline patch, and that's it... have seen lots on low-dose TCA's for sleep from PCP's, but MAOI's have been few and far between.

 

[Jalapeño King]

Same here. I rarely see patients on MAOIs, though I saw a patient in clinic this week who has been on tranylcypromine (Parnate) for years and years and years.

 

[MacDonaldTriad]

They work when nothing else does sometimes. Especially Panic. Generally better tollerated than TCAs, until they really aren't of course.

 

[Doctor Bagel]

Speaking of MAOIs, how much experience does everyone have with them?

Never prescribed them and never treated anyone on them except for selegiline for Parkinson's. I'm reading a lot about them for the purpose of boards because from question banks, they seem like a popular topic. I remember looking this up a while ago and came up with the fact that something like less than 2% of psychiatrists use them (and honestly that number seems a little high).

 

[hamstergang]

MAOI are potent Alpha blockers causing hypotension. How is that excess with tyramine causes hypertensive crisis.

You should learn how to search for the answers to your questions. While it's nice to discuss these things here, I find it an important skill in life to be able to find information on your own, especially when it's actually very easy to find. Wikipedia is a good place to start, imo.

 

[vistaril]

Speaking of MAOIs, how much experience does everyone have with them?

Have several pts on Maois now. Now they aren't getting better of course, but things like dosing it and side effects/interactions haven't been an issue

 

[notdeadyet]

I've used them a fair bit with good results for refractory depression (better luck than I've had with other medications). There are risks but they tend to be less than the risk of suicide for the sort of patients I prescribe MAOIs for, to say nothing of quality of life.

 

[jettavr6]

I treated one patient 6 months ago with Nardil after nothing else had worked, and she was headed for ECT. Two weeks later, she was at least 75% better according to her. The treatment was suggested to me by an old mentor; I'm still afraid to use it on others.

 

[st2205]

I treated one patient 6 months ago with Nardil after nothing else had worked, and she was headed for ECT. Two weeks later, she was at least 75% better according to her. The treatment was suggested to me by an old mentor; I'm still afraid to use it on others.

My follow-up question (before the above comment) is when would people (practically speaking) reach for an MAOI before ECT? At my institution we do a lot of ECT (and by a lot I mean that we do them 3x/wk and it's not uncommon). On the other hand, I haven't had any experience with MAOI, which I'd like to be comfortable with coming out of training.

 

[freaker]

I had a mentor who had an algorithm for treating depression that went something along the lines of SSRI (usually tried several before getting to su) -> SNRI -> Nortriptyline -> Another TCA based on symptoms (usually either amitriptyline or clomipramine) -> Isocarboxazid. I definitely saw a progression where subsequent medications would be more heplful, and I definitely saw patients who responded to Marplan when they hadn't responded to anything else. Sure, we'd occasionally augment, but it was a fairly quick progression. If results weren't meaningful, it meant moving along.

A lot of patients still ended up getting ECT, but maintenance might be less frequent or with fewer sessions on an MAOI. I also saw several patients who exhibited refractory depression who suddenly became manic on a MAOI and then responded splendidly to a combo of lamotrigine and an atypical.

 

[slappy]

I treated one patient 6 months ago with Nardil after nothing else had worked, and she was headed for ECT. Two weeks later, she was at least 75% better according to her. The treatment was suggested to me by an old mentor; I'm still afraid to use it on others.

That's too bad because they are excellent drugs for treatment-resistant depression (and anxiety), as your experience probably illustrated to you. It seems to me like much of the fear stems from misconceptions, and perhaps also from seeing it too frequently on PRITEs and boards questions, and automatically associating "MAOIs" to "doom"! Here's a good primer written by Grady and Stahl on their drug-drug interactions, and how to safely use them: http://www.ncbi.nlm.nih.gov/pubmed/22790112

 

[slappy]

Selegiline does appear to be better tolerated than the older drugs. I never use the patch because it's so expensive. The problem with the pills is they only seem to come in 5mg doses and you need at least 30-60mg for depression so 6-12 pills a day. at these doses you do need the same dietary restrictions as it irreversibly binds to both MAO-A and -B. bear in mind that selegiline, like Parnate (tranylcypromine) is metabolized to amphetamine! also with the older drugs the pharmacies may not have them in stock immediately.

Yep, it's about $500 a month for the patch. But, with co-pay, and comparing it with the cost of multiple ECTs, and therapy sessions, a case could still be made for the patch. Especially considering the very low risk of tyramine reactions with the patch compared to the oral form because of the absence of MAO-A inhibition in the GI tract.

 

[whopper]

I've only had maybe around 5 patients total on an MAO-I ever and 2 of them shouldn't have been on one.

One guy, I had for example, as an inpatient and severe anxiety and depression. He was placed on an MAO-I after several failed trials of SSRIs and only mild improvement on venlafaxine. He was placed on Selegeline by his outpatient psychiatrist but hospitalized because his depression and anxiety were too severe.

I placed him on a B-Blocker and within a few hours was significantly better so I upped it, more improvement, so I upped it again, he felt fine. All of this was through a course of 3 days. Turned out his depression was secondary to his anxiety. Turned out his anxiety was due to his adrenergic system being chronically activated. His psychiatrist, while I agree she did nothing wrong (other than not figure out the problem, her decision making was based on an algorithm that was sound), if she had her way it would've taken months to figure out the MAO-I course was a dead-end. She told me if that didn't work she wanted him to have ECT.

While I agree that MAO-Is should be considered for use, you have to bear in mind that just starting one on it could take several weeks if previously on another antidepressant and will take weeks before it gets to a sufficient dosage to rule out it if works or not.

Also bear in mind that just like life, medicine, and in this case psychiatry isn't a straight line. It's simply not a course of failure--> failure ---> failure --> MAO-I ---> ECT. If one spent adequate time thinking about the guy's case, the obvious chicken/egg argument would've arisen. Is his depression from the anxiety? Will knocking out one fix the other? Shouldn't one then consider treating the anxiety before having the guy wait several weeks to even start an MAO-I?

I imagine in some alternate universe, this guy would've gotten ECT when propranolol fixed him fine.

 

[MacDonaldTriad]

That's too bad because they are excellent drugs for treatment-resistant depression (and anxiety), as your experience probably illustrated to you. It seems to me like much of the fear stems from misconceptions, and perhaps also from seeing it too frequently on PRITEs and boards questions, and automatically associating "MAOIs" to "doom"! Here's a good primer written by Grady and Stahl on their drug-drug interactions, and how to safely use them: http://www.ncbi.nlm.nih.gov/pubmed/22790112

Speaking of Dr. Stahl....


http://youtu.be/0rm5p3DTyE8

 

[PistolPete]

The above link didn't work for me

 

[MacDonaldTriad]

try this

 

[hamstergang]

Turned out his anxiety was due to his adrenergic system being chronically activated.

How did you determine this?

 

[slappy]

Oh my! That's so goofy! What was he thinking! Thanks for sharing. I hadn't seen this before.

 

[ketosisevangelist]

PITS

S=maob. The others are maoa

 

[Doctor Bagel]

PITS

S=maob. The others are maoa

So mnemonics don't work for me, but ? What does PITS stand for? Why is S=maob. If S is serotonin, isn't that maoa?

I feel like I missed out in residency because I trained at a non-Stahl liking place.

 

[whopper]

How did you determine this?

Because he was fine on the B-Blocker alone. No pathological depression or anxiety. Was fine for a year later still only on propranolol. He did also have HTN. A better and more exhaustive look into the case would've also warranted ruling out pheochromocytoma and perhaps blood and urine levels of catecholamines, but he was fine and did not warrant hospitalization after he got better. He stayed another 1-2 days because I was freaked out how good he got. I kept tabs on him because his outpatient doctor was part of the same department, but she never went further to look into my theory that it really was possibly a endrocrinological problem presenting as a psychiatric one.

So I'm convinced he did not have an Axis I depression in the real sense, that is unless propranolol somehow treats depression that I'm not aware of; if anything it causes depression.
One could argue, however, there was no endocrine issue and that it was simply an anxiety problem, albeit severe that was treated with propranolol that caused a comorbid depression.

 

[slappy]

So mnemonics don't work for me, but ? What does PITS stand for? Why is S=maob. If S is serotonin, isn't that maoa?

I feel like I missed out in residency because I trained at a non-Stahl liking place.

I don't know that mnemonic either but my guess would be that S stands for Selegiline as it's an MAO-B inhibitor, while the MAO-A inhibitors "PIT" would be Phenelzine, Isocarboxazid, and Tranylcypromine.

 

[Doctor Bagel]

I don't know that mnemonic either but my guess would be that S stands for Selegiline as it's an MAO-B inhibitor, while the MAO-A inhibitors "PIT" would be Phenelzine, Isocarboxazid, and Tranylcypromine.

Ah, that might make sense. I spend more time trying to figure out the mnemonic than actually learning. Aren't the others non-selective, though, rather than purely A?

Speaking of mnemonics, the ones for things like delirium seem entirely useless to me -- if everything is included in the mnemonic (which is kinda true for something like delirium), it's not a useful mnemonic.

 

[slappy]

Aren't the others non-selective, though, rather than purely A?

That's right. I don't think any of the MAO-A selective inhibitors are available in the US. I guess the mnemonic just points out that selegiline is the odd one out since it's selective for MAO-B and does not act on MAO-A unlike the others. I agree with you - mnemonics are a poor (although efficient) way to learn. Understanding concepts and letting the facts register on their own accord is far superior.

 

[notdeadyet]

Yep, it's about $500 a month for the patch. But, with co-pay, and comparing it with the cost of multiple ECTs, and therapy sessions, a case could still be made for the patch. Especially considering the very low risk of tyramine reactions with the patch compared to the oral form because of the absence of MAO-A inhibition in the GI tract.

Keep in mind that the risk of tyramine reactions is an issue when you use it beyond the starting dose (6mg?). You can only safely ignore the food restrictions at the lowest dose with the Emsam, which isn't a high enough dose for many folks.

I still think MAOIs are a good choice when appropriate. Some places seem to foster a no-no list for certain medications, which seems based on the idea you'll never see any truly refractory cases. That doesn't hold water if you're going to have a long career, or even a short one at an academic center.

MAOIs have their place, despite their reputation. So does nefazodone. Just because the Step I uses drugs like these as whipping posts doesn't mean they aren't useful meds in the right cases. They can work miracles when needed.

 

[OldPsychDoc]

Oh my! That's so goofy! What was he thinking! Thanks for sharing. I hadn't seen this before.

I like this one better:

 

[clubdeac]

I have a pt on Nardil who I'm treating for lbp. As you are probably all aware depression and anxiety are very common comorbidities in the pain population. Any specific pain meds I need to avoid other than the obvious I.e. TCAs and SNRIs? What are the most common side effects I need to be aware of and any good references you'd recommend? Thanks for the help!

 

[HarryMTieboutMD]

I like this one better:

As much as we like to trash Stahl (while we surreptitiously use his books in practice bc they are easy reference and understandable), he does do Gilbert and Sullivan justice (from a huge G&S fan).
Also: "MAOIs are good for borderlines because it gives them something to worry about" -one of my attendings

 

[splik]

I have a pt on Nardil who I'm treating for lbp. As you are probably all aware depression and anxiety are very common comorbidities in the pain population. Any specific pain meds I need to avoid other than the obvious I.e. TCAs and SNRIs? What are the most common side effects I need to be aware of and any good references you'd recommend? Thanks for the help!

Personally I would be consulting the literature and discussing with a pharmacist before prescribing pain meds to a patient on Nardil and documenting this carefully including the risks and benefits and rationale for using a particular agent. There are a number of excellent papers written on the topic, here is one that specifically focuses on opioids.

btw TCAs with the exception of clomipramine are not contraindicated as a combination with MAOIs. In general the patient should be on a TCA first and then a MAOI added (as the TCA may block the uptake of tyramine from the gut), rather than the other way round. The risk is more in terms of hypertensive crisis not serotonin syndrome if adding a TCA to an MAOI. The exception here would be using low doses of nortriptyline. That said, I think you would brave to do this as a pain doc, and would consult with the patient's psychiatrist and discuss the risks and benefits in detail with the patient. You need to monitor or have patient monitor their blood pressure after initiation. Also remember that because of the synergistic effects, patients need much lower doses of a TCA when on an MAOI than they would otherwise. In the limited literature available, the combination is not typically well tolerated but it certainly was not uncommon in the past.