bipolar depression and MAOIs?

[randomdoc1]

Has anyone explored this or have any feelings about this? There aren't exactly plentiful options for bipolar depression and some have not the greatest side effects, weight gain and sedation being some of the more common. Although I thought I read that MAOIs may be less prone to causing the switching over to mania? Especially if there is a good mood stabilizing agent on board, what are your thoughts? From some of the literature I've encountered, for bipolar patients with ADHD, patients seem to do alright on stims as long as they have a mood stabilizing agent too.

Also, most of my experience with MAOIs currently are with the transdermal formulation. From what I gather so far, in particular, there is a guide about prescribing MAOIs in Current Psychiatry (Vol 16, No 12, from December 2017). It says a good rule of thumb is that tyramine is hardly a concern if a patient sticks to fresh foods (with the exception of some things like fava beans?). It also says these days most people rarely ingest over 25mg of tyramine in a meal. It also said those on 6mg/day of emsam, those who consumed a meal with 400mg of tyramine did not notice significant pressor response but tyramine doses in capsules as low as 8-10mg can increase SBP by 30mm Hg. Article says when ingested as food, tyramine less than 50mg are unlikely to cause major BP changes but some can be as sensitive to 10-25mg. They recommend hospital evaluation if patient ingested over 100mg of tyramine which these days would just about need to be intentional as well as BP cuff if pt has concerns or symptoms. Based on data from 1960-1964, it says about 1.5 million patients took MAOIs, no dietary guidelines, and 14 deaths were reported. So, in a reliable and appropriate patient, you could give them dietary guidelines of high tyramine foods to avoid and recommend they have a BP cuff for rare instances where a dietary indiscretion may have occurred or they may be experiencing a headache. Thus far I have been working with registered dietitians to help patients, but this is cumbersome. Do a lot of psychiatrists mostly provide a list of foods to avoid, recommend a medical bracelet too (in rare event of emergency so other medical providers know they are on an MAOI), and go from there?

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[whopper]

All the data showing that antidepressants don't work for Bipolar Disorder-Depressed-I'm not finding that to be true with many patients. When the data first emerged years ago I told all of my stabilized Bipolar Disordered patients to stop their antidepressants and most of them became depressed within weeks, we restarted the antidepressants and their depression stabilized again.

With Bipolar Disorder-Depressed patients I do follow evidenced-based guidelines starting with Latuda, Lamotrigine, Quetiapine or Olanzapine/Fluoxetine again I'm not finding the evidence supporting what I'm seeing in real-life either. Many patients I've tried Latuda on for Bipolar Depression don't experience benefit with it. Now my sample size isn't huge, about 15 patients, but only about 2 of them experienced benefit with Latuda with depression.

So how sure am I that they really had Bipolar Disorder? Very sure. Most of them I've seen manic or they met the criteria of it very well with family members or friends saying they saw the person manic and it met DSM criteria while they were not using illicit substances.

Due to the above I have a theory but I don't know how it can be tested. That with people with Bipolar Disorder, there's a mechanism specific to Bipolar Disorder that makes them depressed hence this is true Bipolar Disorder Depressed Type, or they happen to be someone with Bipolar Disorder who gets depressed under the usual circumstances someone without Bipolar Disorder gets depressed. How I can test this theory I don't know.

My bottom line is I am willing to prescribe antidepressants, but I will follow the evidenced-based guidelines first for Bipolar Disorder Depressed type. When I've tried about 2-4 meds with the solid data, then I'll resort to an antidepressant.

As for MAO-Is, I'd consider trying them too but there's so many things to try before it gets to MAO-Is.

Mood stabilizers, antipsychotics? Forgot the name of the study but a recent study showed that when patients were on a mood stabilizer or antipsychotic that was found to be useful for the patient, antidepressants pretty much didn't raise the risk of mania with a huge sample size. I forgot the number but I recall it being over 1000. Bear in mind this just wasn't simply using a mood stabilizer or antipsychotic but one where it was found to work well for the patient over a long duration. (As we all know sometimes the meds don't work or the dosage isn't high enough).

 

[randomdoc1]

All the data showing that antidepressants don't work for Bipolar Disorder-Depressed-I'm not finding that to be true with many patients. When the data first emerged years ago I told all of my stabilized Bipolar Disordered patients to stop their antidepressants and most of them became depressed within weeks, we restarted the antidepressants and their depression stabilized again.

With Bipolar Disorder-Depressed patients I do follow evidenced-based guidelines starting with Latuda, Lamotrigine, Quetiapine or Olanzapine/Fluoxetine again I'm not finding the evidence supporting what I'm seeing in real-life either. Many patients I've tried Latuda on for Bipolar Depression don't experience benefit with it. Now my sample size isn't huge, about 15 patients, but only about 2 of them experienced benefit with Latuda with depression.

So how sure am I that they really had Bipolar Disorder? Very sure. Most of them I've seen manic or they met the criteria of it very well with family members or friends saying they saw the person manic and it met DSM criteria while they were not using illicit substances.

Due to the above I have a theory but I don't know how it can be tested. That with people with Bipolar Disorder, there's a mechanism specific to Bipolar Disorder that makes them depressed hence this is true Bipolar Disorder Depressed Type, or they happen to be someone with Bipolar Disorder who gets depressed under the usual circumstances someone without Bipolar Disorder gets depressed. How I can test this theory I don't know.

My bottom line is I am willing to prescribe antidepressants, but I will follow the evidenced-based guidelines first for Bipolar Disorder Depressed type. When I've tried about 2-4 meds with the solid data, then I'll resort to an antidepressant.

As for MAO-Is, I'd consider trying them too but there's so many things to try before it gets to MAO-Is.

Mood stabilizers, antipsychotics? Forgot the name of the study but a recent study showed that when patients were on a mood stabilizer or antipsychotic that was found to be useful for the patient, antidepressants pretty much didn't raise the risk of mania with a huge sample size. I forgot the number but I recall it being over 1000. Bear in mind this just wasn't simply using a mood stabilizer or antipsychotic but one where it was found to work well for the patient over a long duration. (As we all know sometimes the meds don't work or the dosage isn't high enough).

Seeing this comes from whopper, I feel so much better. My experiences are exactly the same! I often wondered about that. Not great robust responses to the evidenced based regimens, the weight gain side effects are especially bothersome. And my bipolar patients tend to respond to antidepressants as well and I've observed little switching.

 

[Stagg737]

Isn't there a major question as to whether SSRIs cause patients to "flip/switch into mania" at all? I thought the evidence of that was still shaky at best.

 

[randomdoc1]

Isn't there a major question as to whether SSRIs cause patients to "flip/switch into mania" at all? I thought the evidence of that was still shaky at best.

I believe that has indeed been a debated question. Although I have no doubt that SNRIs, that I have for sure seen cause switching. Another reason I'm thinking MAOI is that after a number of SSRIs, pretty unlikely trying another SSRI is going to work (and many of the bipolar patients have already tried at least a couple). SNRI is dicey, so maybe MAOI is less dicey when it comes to the mania? One of the psychopharm lecturers who is an absolute guru here just shrugs his shoulders and says "american diets really don't have that much tyramine, it's a lot easier than you think, give parnate a whirl." Then he rolls his eyes and says psychiatrists need to stop being so scared of MAOIs. I just laugh and say, sure, easy for him to figure out, lol.

 

[clausewitz2]

I believe that has indeed been a debated question. Although I have no doubt that SNRIs, that I have for sure seen cause switching. Another reason I'm thinking MAOI is that after a number of SSRIs, pretty unlikely trying another SSRI is going to work (and many of the bipolar patients have already tried at least a couple). SNRI is dicey, so maybe MAOI is less dicey when it comes to the mania? One of the psychopharm lecturers who is an absolute guru here just shrugs his shoulders and says "american diets really don't have that much tyramine, it's a lot easier than you think, give parnate a whirl." Then he rolls his eyes and says psychiatrists need to stop being so scared of MAOIs. I just laugh and say, sure, easy for him to figure out, lol.

The old data showing manic switching was largely based on TCAs and people just sort of analogize from that.

Worth remembering some people have really severe insomnia if they take an MAOI too late in the day but this is not mania.

 

[Lorijones]

Has anyone explored this or have any feelings about this? There aren't exactly plentiful options for bipolar depression and some have not the greatest side effects, weight gain and sedation being some of the more common. Although I thought I read that MAOIs may be less prone to causing the switching over to mania? Especially if there is a good mood stabilizing agent on board, what are your thoughts? From some of the literature I've encountered, for bipolar patients with ADHD, patients seem to do alright on stims as long as they have a mood stabilizing agent too.

Also, most of my experience with MAOIs currently are with the transdermal formulation. From what I gather so far, in particular, there is a guide about prescribing MAOIs in Current Psychiatry (Vol 16, No 12, from December 2017). It says a good rule of thumb is that tyramine is hardly a concern if a patient sticks to fresh foods (with the exception of some things like fava beans?). It also says these days most people rarely ingest over 25mg of tyramine in a meal. It also said those on 6mg/day of emsam, those who consumed a meal with 400mg of tyramine did not notice significant pressor response but tyramine doses in capsules as low as 8-10mg can increase SBP by 30mm Hg. Article says when ingested as food, tyramine less than 50mg are unlikely to cause major BP changes but some can be as sensitive to 10-25mg. They recommend hospital evaluation if patient ingested over 100mg of tyramine which these days would just about need to be intentional as well as BP cuff if pt has concerns or symptoms. Based on data from 1960-1964, it says about 1.5 million patients took MAOIs, no dietary guidelines, and 14 deaths were reported. So, in a reliable and appropriate patient, you could give them dietary guidelines of high tyramine foods to avoid and recommend they have a BP cuff for rare instances where a dietary indiscretion may have occurred or they may be experiencing a headache. Thus far I have been working with registered dietitians to help patients, but this is cumbersome. Do a lot of psychiatrists mostly provide a list of foods to avoid, recommend a medical bracelet too (in rare event of emergency so other medical providers know they are on an MAOI), and go from there?

I am 49 years old and have been suffering from treatment resistant bipolar II disorder, ADHD, anxiety and panic attacks since childhood. My first suicide attempt took place in the sixth grade. Most recently I suffered from agoraphobia for almost three years after stopping all my meds out of total frustration. I have been hospitalized several times, tried ECT, TMS,CBT,DBT, you name it.
After my husband threatened to leave me if I didn’t get help, I found a new Psychiatrist and shortly after started an intense outpatient program at the hospital. It was de ja vu once again with all the same meds that wasted decades of my life.
I finally got to a point where I was so frustrated being prescribed the same medications over and over again. I looked back on my med history and did my own research on what has worked and what hasn't worked. The only thing that really stood out was and emsam. But, that only lasted for about seven or eight months. Finally I came across parnate. It took me going 3 three different doctors, with my hand filled with research, including the hospital’s doctor, who finally agreed to prescribe the MAOI for me. Within less than two weeks I started feeling happy, energized, joy from hearing a song on the radio, peace from the beauty of nature. Simply having the energy and desire to do things, wanting to leave the house. After suffering from agoraphobia for almost three years, that was huge.
With another handful of research, I convinced my doc to prescribe ADHD meds. Last, I rejected his recommendation of a mood stabilizer in a pretty free sample packet and researched my own. Most of my MAOI research came from Dr. Ken Gillman psychotropical.com.
Here is a bonus treatment idea. My mood stabilizer is Topiramate Sprinke. One of its side effects is weight loss. It has also eased my Fibromyalgia pain by 95%. I have seen research that shows parnate (GABA) + Topiramate reduces inflammation in cytokines, which I really think needs to be looked at more in depth. My gut is telling me this is somehow key to solving treatment resistant bipolar. I am not qualified, but I at least want to throw that out there.
I am very glad you are starting these discussions. I wish more Doctors were more willing to think outside the box. I believe that is the only way to make a difference with treatment resistant patients. Please continue along these lines. There are so many people like me. Just go on the bp magazine Facebook support group page and read through some of the posts re frustrations with meds, then realize 1 out of 5 will attempt suicide. That might be a good lesson for your students.

 

[Lorijones]

Here is a very similar story. Don't cast aside an effective antidepressant just because it's old

Thank you so much for your time!!!

 

[Sushirolls]

I've had plenty of true bipolar I patients on some mood stabilizer be it lithium/neuroleptic/antipschotic + antidepressants do well.

ECT before MAOI.

All the Emsam cases I've seen in residency had no benefits. High Axis II population if people were to formally spend the time to diagnosis it, most likely.

American diet is MAOI worst nightmare: Cheese, wine, beer, meat heavy.

I don't prescribe MAOIs.

 

[Lorijones]

As far as the diet goes, I started out careful, but now I rarely pay attention to it anymore. My bp is great, even with adderral. In my opinion, the diet restrictions are a bit exaggerated for these days. Food is processed with less Tyramine. I won't eat aged cheese or aged sausage, but a sausage mcmuffin is fine.
I realize we are wired different. My life has changed, I have one. That should say something. I have a 2 1/2 page list of meds that didn't work for me. It is a difficult illness to treat.

 

[Lorijones]

I overlooked bipolar 1, I am bipolar II. I dont know if an MAOI would be good for them because of full blown Mania. Hypomania is less of a risk.

 

[BorderlineQueen]

I am 49 years old and have been suffering from treatment resistant bipolar II disorder, ADHD, anxiety and panic attacks since childhood. My first suicide attempt took place in the sixth grade. Most recently I suffered from agoraphobia for almost three years after stopping all my meds out of total frustration. I have been hospitalized several times, tried ECT, TMS,CBT,DBT, you name it.
After my husband threatened to leave me if I didn’t get help, I found a new Psychiatrist and shortly after started an intense outpatient program at the hospital. It was de ja vu once again with all the same meds that wasted decades of my life.
I finally got to a point where I was so frustrated being prescribed the same medications over and over again. I looked back on my med history and did my own research on what has worked and what hasn't worked. The only thing that really stood out was and emsam. But, that only lasted for about seven or eight months. Finally I came across parnate. It took me going 3 three different doctors, with my hand filled with research, including the hospital’s doctor, who finally agreed to prescribe the MAOI for me. Within less than two weeks I started feeling happy, energized, joy from hearing a song on the radio, peace from the beauty of nature. Simply having the energy and desire to do things, wanting to leave the house. After suffering from agoraphobia for almost three years, that was huge.
With another handful of research, I convinced my doc to prescribe ADHD meds. Last, I rejected his recommendation of a mood stabilizer in a pretty free sample packet and researched my own. Most of my MAOI research came from Dr. Ken Gillman psychotropical.com.
Here is a bonus treatment idea. My mood stabilizer is Topiramate Sprinke. One of its side effects is weight loss. It has also eased my Fibromyalgia pain by 95%. I have seen research that shows parnate (GABA) + Topiramate reduces inflammation in cytokines, which I really think needs to be looked at more in depth. My gut is telling me this is somehow key to solving treatment resistant bipolar. I am not qualified, but I at least want to throw that out there.
I am very glad you are starting these discussions. I wish more Doctors were more willing to think outside the box. I believe that is the only way to make a difference with treatment resistant patients. Please continue along these lines. There are so many people like me. Just go on the bp magazine Facebook support group page and read through some of the posts re frustrations with meds, then realize 1 out of 5 will attempt suicide. That might be a good lesson for your students.

Okay SDN is not for medical advice.

 

[clausewitz2]

I've had plenty of true bipolar I patients on some mood stabilizer be it lithium/neuroleptic/antipschotic + antidepressants do well.

ECT before MAOI.

All the Emsam cases I've seen in residency had no benefits. High Axis II population if people were to formally spend the time to diagnosis it, most likely.

American diet is MAOI worst nightmare: Cheese, wine, beer, meat heavy.

I don't prescribe MAOIs.

The typical American diet actually does not have very much tyramine in it because we eat a lot less spoiled food than we did in the 60s. Unless the typical diet is cave-aged parmesan with jamón ibérico topped with kimchi in a soy sauce reduction.

Mozzarella had basically no tyramine. You can eat a whole pizza on parnate and be fine. Same is true of pretty much any cheese that's not deliberately aged.

Beer in the bottle is fine, unless it is bottle-conditioned. Draft beer is a problem only because you don't know if something funky is growing in the lines. I haven't seen data yet but I'd be leery of the more trendy 'hazy' beers popping up all over the place as well as farmhouse style ales. Pound your favorite west coast IPA or Miller High Life or whatever and it's not the Marplan that is going to cause problems.

It's all very well to say ECT before MAOIs but I know that you know that ECT is not accessible everywhere and the data for bipolar disorder are not fantastic.

Why cut yourself off completely from another useful class of medications (in addition to BZDs/BZD receptors agonists as I recall)?

EDIT: I have the same impression of Emsam, but this hardly surprising as it produces a much attentuated version of the physiological effect of an irreversible MAOI. It is also often dosed very cautiously because of overblown tyramine concerns aa above.

Also remember that you can have significant personality dysfunction and also still be depressed. Especially if depression is treated repetitively and ineffectively - is it surprising that some people fall into really dysfunctional interpersonal patterns and struggle with emotion regulation? Dismissing a class of medications because a lot of the people you encountered on it had characterological issues comes dangerously close to dismissing all the people with characterological issues.

 

[Lorijones]

Okay SDN is not for medical advice.

I am not here for advice. I feel a duty to those suffering as I was. I was complimenting the author who started this thread.

 

[Sushirolls]

The typical American diet actually does not have very much tyramine in it because we eat a lot less spoiled food than we did in the 60s. Unless the typical diet is cave-aged parmesan with jamón ibérico topped with kimchi in a soy sauce reduction.

Mozzarella had basically no tyramine. You can eat a whole pizza on parnate and be fine. Same is true of pretty much any cheese that's not deliberately aged.

Beer in the bottle is fine, unless it is bottle-conditioned. Draft beer is a problem only because you don't know if something funky is growing in the lines. I haven't seen data yet but I'd be leery of the more trendy 'hazy' beers popping up all over the place as well as farmhouse style ales. Pound your favorite west coast IPA or Miller High Life or whatever and it's not the Marplan that is going to cause problems.

It's all very well to say ECT before MAOIs but I know that you know that ECT is not accessible everywhere and the data for bipolar disorder are not fantastic.

Why cut yourself off completely from another useful class of medications (in addition to BZDs/BZD receptors agonists as I recall)?

EDIT: I have the same impression of Emsam, but this hardly surprising as it produces a much attentuated version of the physiological effect of an irreversible MAOI. It is also often dosed very cautiously because of overblown tyramine concerns aa above.

Also remember that you can have significant personality dysfunction and also still be depressed. Especially if depression is treated repetitively and ineffectively - is it surprising that some people fall into really dysfunctional interpersonal patterns and struggle with emotion regulation? Dismissing a class of medications because a lot of the people you encountered on it had characterological issues comes dangerously close to dismissing all the people with characterological issues.

The side effects cannot be discounted from MAOIs. In this modern error, these are archaic meds that not only carry the dietary restrictions, which we need to counsel patients on per the literature, not our present day synopsis of less tyramine then days of old. The other issue with these medicines are their drug/drug interactions. No one prescribes this class of medicines anymore, and certainly the ARNPs don't which is the rising tide of psychiatric providers. The drug drug interactions become an issue too, because primary care, ED, and Anesthesiology seldom see these meds either. That in itself is an additional risk we don't think about.

I'll nope your jab, "dangerously close to dismissing all the people with characterological issues" this is a logical fallacy, hasty generalization, that follows the BZDs comment, suggesting another possible logical fallacy, genetic fallacy. As elucidated in other posts I am averse to benzos for a list of reasons that speak for themselves - we disagree on your presumption of their broader usefulness. But I do dismiss all my patients with characterlogical issues at the end of the appointment - with a positive salutation - and they typically offer a courteous thank you - and I see them again at their next appointment to continue their journey towards their recovery goals.

The risk profile of MAOIs clearly deserve a second look at diagnosis before initiation, if Axis II really is the driving pathology of symptoms, then lets emphasize a course of DBT, and educate on the diagnosis (which I've found provides a sense of relief for patients once they know what's going and why they have the symptoms they do).

Limited ECT accessiblity? Agreed.

Data for ECT and bipolar depression as "not fantastic"? Disagree with my sample sizes in my career, and here's a fresh off the press Swedish Registry study that even suggests the opposite, it is fantastic.

 

[clausewitz2]

The side effects cannot be discounted from MAOIs. In this modern error, these are archaic meds that not only carry the dietary restrictions, which we need to counsel patients on per the literature, not our present day synopsis of less tyramine then days of old. The other issue with these medicines are their drug/drug interactions. No one prescribes this class of medicines anymore, and certainly the ARNPs don't which is the rising tide of psychiatric providers. The drug drug interactions become an issue too, because primary care, ED, and Anesthesiology seldom see these meds either. That in itself is an additional risk we don't think about.

I'll nope your jab, "dangerously close to dismissing all the people with characterological issues" this is a logical fallacy, hasty generalization, that follows the BZDs comment, suggesting another possible logical fallacy, genetic fallacy. As elucidated in other posts I am averse to benzos for a list of reasons that speak for themselves - we disagree on your presumption of their broader usefulness. But I do dismiss all my patients with characterlogical issues at the end of the appointment - with a positive salutation - and they typically offer a courteous thank you - and I see them again at their next appointment to continue their journey towards their recovery goals.

The risk profile of MAOIs clearly deserve a second look at diagnosis before initiation, if Axis II really is the driving pathology of symptoms, then lets emphasize a course of DBT, and educate on the diagnosis (which I've found provides a sense of relief for patients once they know what's going and why they have the symptoms they do).

Limited ECT accessiblity? Agreed.

Data for ECT and bipolar depression as "not fantastic"? Disagree with my sample sizes in my career, and here's a fresh off the press Swedish Registry study that even suggests the opposite, it is fantastic.

An anesthesiologist who can't recognize an MAOI and what should not be given with that is borderline incompetent. Again, the list of actual medications that have ever had reports of toxicity is not that long. It is important to counsel about this, of course. But if we are talking about drug-drug interactions MAOIs are vastly less likely to affect the levels of other prescription medications; meanwhile things that get handed out like candy, such as Prozac, interact with a vast array of common medications in ways that can be very problematic. The idea that you have to eliminate vast swathes of the pharmacoepia when taking an MAOI is based on the erroneous idea that because a medication interacts in some way with a serotonin receptor it must have the effect of increasing extracellular serotonin levels. This is why you see very silly assertions such as avoiding mirtazapine with an MAOI, when in fact there is no reason or evidence to do this.

I don't have to guess at the tyramine content of foods and the amounts consumed that have a chance of being clinically relevant. We have a lot of physiological data on the tyramine pressor response and it is fairly well-characterized. It also turns out unsurprisingly that food regulatory agencies are rather interested in how spoiled things they regulate are and so a wealth of empirical lab data on tyramine contents of common food is out there.

You absolutely have to counsel patients on what to avoid but that does not mean you have to base this on ideas from the 60s. There have also been several review articles and commentaries in the recent past in peer-reviewed articles addressing these concerns as well as urging more use of these medications. It is not at all difficult to find a 'respectable minority" of physicians prescribing them and I would respectfully suggest that this may be an area where your confidence exceeds your knowledge (we all have them, that's why there's that whole life-long learning thing).

EDIT: Remember, at one time a very typical regimen for TRF was nortriptyline + MAOI. They are less restrictive than you think.

I am interested to read the Swedish study you mention and if there is more reason to believe ECT will treat especially bipolar ii I am thrilled. But ECT for depression has unmedicated relapse rates of approaching 90% in a year in some studies so you have to prescribe something for prophylaxis anyway. And the best-studied and validated combination is nortriptyline and lithium, which are hardly benign!

If someone did okay on medications that are relatively benign (or at least have the side effects that it is hard to get sued for) they probably would not need ECT or an MAOI.

I would personally take Parnate over Seroquel in a heartbeat if it came down to it, no diabetes for me, thanks.

EDIT EDIT: just a couple months ago, another one, speaking of Ken Gillman...

Revitalizing monoamine oxidase inhibitors: a call for action | CNS Spectrums | Cambridge Core

Revitalizing monoamine oxidase inhibitors: a call for action - Volume 25 Issue 4

www.cambridge.org

 

[NickNaylor]

Has anyone explored this or have any feelings about this? There aren't exactly plentiful options for bipolar depression and some have not the greatest side effects, weight gain and sedation being some of the more common. Although I thought I read that MAOIs may be less prone to causing the switching over to mania? Especially if there is a good mood stabilizing agent on board, what are your thoughts? From some of the literature I've encountered, for bipolar patients with ADHD, patients seem to do alright on stims as long as they have a mood stabilizing agent too.

Also, most of my experience with MAOIs currently are with the transdermal formulation. From what I gather so far, in particular, there is a guide about prescribing MAOIs in Current Psychiatry (Vol 16, No 12, from December 2017). It says a good rule of thumb is that tyramine is hardly a concern if a patient sticks to fresh foods (with the exception of some things like fava beans?). It also says these days most people rarely ingest over 25mg of tyramine in a meal. It also said those on 6mg/day of emsam, those who consumed a meal with 400mg of tyramine did not notice significant pressor response but tyramine doses in capsules as low as 8-10mg can increase SBP by 30mm Hg. Article says when ingested as food, tyramine less than 50mg are unlikely to cause major BP changes but some can be as sensitive to 10-25mg. They recommend hospital evaluation if patient ingested over 100mg of tyramine which these days would just about need to be intentional as well as BP cuff if pt has concerns or symptoms. Based on data from 1960-1964, it says about 1.5 million patients took MAOIs, no dietary guidelines, and 14 deaths were reported. So, in a reliable and appropriate patient, you could give them dietary guidelines of high tyramine foods to avoid and recommend they have a BP cuff for rare instances where a dietary indiscretion may have occurred or they may be experiencing a headache. Thus far I have been working with registered dietitians to help patients, but this is cumbersome. Do a lot of psychiatrists mostly provide a list of foods to avoid, recommend a medical bracelet too (in rare event of emergency so other medical providers know they are on an MAOI), and go from there?

Since I work on a team that primarily assesses and treats treatment-resistant depression, we use MAOIs all the time.

What you’re describing with selegiline isn’t surprising - at the lowest dose of the transdermal patch, there isn’t enough peripheral MAO blockade to actually cause the tyramine-related effects that we worry about with the MAOIs. UpToDate has a great “patient education” sheet outlining the dietary restrictions for patients taking MAOIs. That’s what I will typically give patients when we start a MAOI. Partially for your own medicolegal liability, partially because tyramine-induced hypertensive crisis does actually happen, I would still advise all patients to follow a tyramine-free diet, regardless of what various studies regarding tyramine ingestion amounts show. That’s not going to be defensible in the off chance that you have a case where someone has a hemorrhagic CVA due to a hypertensive crisis. One thing to remember, though, is that hypotension tends to be the most intolerable side effect of MAOIs. These agents can cause significant orthostasis. Just a couple of weeks ago I had a patient on a total of 30 mg of tranylcypromine who got lightheaded shortly after getting out of bed, fell, and broke his ankle. The tranylcypromine was causing such significant hypotension that his long-standing anti-hypertensive was actually stopped by his PCP.

As far as affective switching, it’s a real thing but seems to vary significantly by antidepressant class. The way that I very roughly think about is that the more monoamines a drug screws around with, the greater the risk for affective switching. This isn’t a completely accurate framework but is “good enough” without having to go and dig through the data. I get less ornery about patients being on SSRIs or even SNRIs with a bipolar disorder diagnosis - as long as there is a true “mood stabilizer” on board - compared to TCAs and MAOIs. I agree that “no antidepressants ever in someone who has been diagnosed with bipolar disorder” is probably too broad - if that were actually true, why would the olanzapine/fluoxetine combination get approved? - but I do think it would be prudent to be cautious about starting an antidepressant in these patients - and do so carefully - because the evidence is what it is. There are some international guidelines that do include antidepressants relatively early in the treatment algorithm for bipolar depression, though.

 

[clausewitz2]

Since I work on a team that primarily assesses and treats treatment-resistant depression, we use MAOIs all the time.

What you’re describing with selegiline isn’t surprising - at the lowest dose of the transdermal patch, there isn’t enough peripheral MAO blockade to actually cause the tyramine-related effects that we worry about with the MAOIs. UpToDate has a great “patient education” sheet outlining the dietary restrictions for patients taking MAOIs. That’s what I will typically give patients when we start a MAOI. Partially for your own medicolegal liability, partially because tyramine-induced hypertensive crisis does actually happen, I would still advise all patients to follow a tyramine-free diet, regardless of what various studies regarding tyramine ingestion amounts show. That’s not going to be defensible in the off chance that you have a case where someone has a hemorrhagic CVA due to a hypertensive crisis. One thing to remember, though, is that hypotension tends to be the most intolerable side effect of MAOIs. These agents can cause significant orthostasis. Just a couple of weeks ago I had a patient on a total of 30 mg of tranylcypromine who got lightheaded shortly after getting out of bed, fell, and broke his ankle. The tranylcypromine was causing such significant hypotension that his long-standing anti-hypertensive was actually stopped by his PCP.

Yeah people forget that MAOIs were used for a while as antihypertensives. Just like reserpine, which got this lore about causing depression because in the 50s people were not very good at picking up on akathisia, which if you read the old studies is what was driving the suicidal ideation. Literally the first RCT in psychiatry was a demonstration of the antidepressive efficacy of reserpine, in fact.

As far as legal defensibility goes, I think the consensus statement I linked goes a long way towards helping to meet a "respectable minority" standard, signed as it is by 130 psychiatrists including the late Donald Klein, Jonathan Stewart (not the daily show guy) and Stephen Stahl. Of course the input of the forensic folks here would be appreciated.

EDIT: of course tyramine-induced hypertensive crisis happens, but of the up-to-date table, if I am looking at the same one you are talking about, the "avoid" column is reasonable but the others are not based more empirical evidence than randomly selecting things in grocery store shelves would be.

 

[splik]

Yeah people forget that MAOIs were used for a while as antihypertensives. Just like reserpine, which got this lore about causing depression because in the 50s people were not very good at picking up on akathisia, which if you read the old studies is what was driving the suicidal ideation. Literally the first RCT in psychiatry was a demonstration of the antidepressive efficacy of reserpine, in fact.

I would disagree with this characterization. My own clinical experience of VMAT inhibitors and familiarity with the history of psychopharmacology underscores that patients can and do become catastrophically depressed with drugs like reserpine and tetrabenazine. Depression in hypertensives treated with reserpine was known before or at the same time as it was being studied for in neurotic and psychotic disorders. It is definitely not just akathisia driving suicidality in these patients as it can occur in the absence of this. The first controlled study in psychopharmacology was Dub and Lurie's study of benzedrine in melancholic patients (the first controlled study in psychiatry may have been Kopeloff and Cheney's study in 1922 of removing the teeth and tonsils for institutionalized patients on the theory that psychosis was caused by infection). The RCT of reserpine was published in 1955. The paper shows that lower doses of reserpine may have outperformed placebo in the treatment of anxious/depressive symptoms but the drug is mildly sedative and may have had non-specific effects that would unmask it from placebo. In that paper, patients treated with higher doses (i.e. the doses we would use in schizophrenia) did not improve, and in fact developed parkinsonism.

 

[Lorijones]

Clausewitz2: Two questions:
1) Is there any evidence that a spike a blood pressure may be an indicator of shift from a depressive episode to hypomania?
2. When measuring a MAOI patient's blood pressure, are you most interested in laying, sitting or standing?
Thanks

 

[clausewitz2]

Clausewitz2: Two questions:
1) Is there any evidence that a spike a blood pressure may be an indicator of shift from a depressive episode to hypomania?
2. When measuring a MAOI patient's blood pressure, are you most interested in laying, sitting or standing?
Thanks

1) not that I'm aware of
2) what matters is measuring the change between blood pressures taken in different positions, so just having one blood pressure is not very helpful. The hypotension from MAOIs is usually troublesome as orthostatic hypotension, i.e. a failure to adequately adjust to the shift between lying/sitting or sitting/standing.

 

[clausewitz2]

I would disagree with this characterization. My own clinical experience of VMAT inhibitors and familiarity with the history of psychopharmacology underscores that patients can and do become catastrophically depressed with drugs like reserpine and tetrabenazine. Depression in hypertensives treated with reserpine was known before or at the same time as it was being studied for in neurotic and psychotic disorders. It is definitely not just akathisia driving suicidality in these patients as it can occur in the absence of this. The first controlled study in psychopharmacology was Dub and Lurie's study of benzedrine in melancholic patients (the first controlled study in psychiatry may have been Kopeloff and Cheney's study in 1922 of removing the teeth and tonsils for institutionalized patients on the theory that psychosis was caused by infection). The RCT of reserpine was published in 1955. The paper shows that lower doses of reserpine may have outperformed placebo in the treatment of anxious/depressive symptoms but the drug is mildly sedative and may have had non-specific effects that would unmask it from placebo. In that paper, patients treated with higher doses (i.e. the doses we would use in schizophrenia) did not improve, and in fact developed parkinsonism.

Fair point about tetrabenazines and clinical experience thereof; I imagine the fact that reserpine is also hitting VMAT1 and having neuroendocrine effects probably means that it's action is not quite idéntical to more selective VMAT2 inhibitors, though. I don't doubt a lot of the efficacy was due to nonspecific effects, but then most psychotropic drugs are not disease-modifying agents to begin with.

Dub and Lurie (1937) was a double-blinded, placebo controlled trial but assignment was not randomized to different treatment arms. Strictly a within-subjects cross-over design and while investigators and patients were blinded to precisely which drug was being received when there was no randomization of sequence involved. Thus not really an RCT. I don't fetishize RCTs above all else but still.

EDIT: I don't know, looking at some of the earlier reserpine literature I kind of still think a lot of this was akathisia. From Achor et al. 1955 on the mood effects on the majority of their subjects:

"At the conclusion of the study nearly every patient expressed the wish to continue the medication even at his expense and despite the rather frequent occurrence of annoying side-effects. Subjectively, the principal benefit described was a feeling of well-being, freedom from much of the former tenseness, and the ability to relax. It was our impression that many patients reacted less strongly to environmental stimuli while taking the active drugs than they had prior to treatment. "

And re: the negative emotional side effects in 10/58 subjects:

"Emotional upsets developed in 10 of the 58 patients during the course of study, and these concerned us a great deal. The mildest form of upset consisted of increased tenseness, restlessness, insomnia, and a feeling of being very uncomfortable."

They note that three of the 58 had depressive episodes that were classified as quite severe and needed ECT; at least one of these people resumed reserpine again later and did not become depressed.

I think overall I buy that it probably can tank the mood of some proportion of the people who take it. At the same time, it is not hard to find case series involving mania induced by, say, lurasidone, and I am sure we have all encountered someone with ADHD who gets sleepy when they use caffeine/stimulants. Idiosyncratic effects can be very real while at the same time being very rare. It is simply not the case that we can predict strongly from similarities in mechanism or even group-level responses what the individual experience will be.

EDIT EDIT:

Holy cow, I had never read the original Davies and Shepherd paper in detail, but it's no wonder that they did not find an effect of higher doses of reserpine comparable to the effect observed at lower doses. The lower-dose group was 54 outpatients receiving 0.5 mg per day or placebo while the higher dose group was 4 (!!!!) inpatients who got high doses (like 10 or 15 mg) for three weeks and then had treatment stopped abruptly for a week before receiving ECT instead (!) by design.

Of course the higher dose group with more severe depression didn't show a similar effect! The intervention is a mess conceptually and there is almost no statistical power. I'm not sure you can firmly conclude anything from the second group in this paper. They also don't report any data on group B or how they assessed their depressive symptoms, just stating they didn't get better. They do note that the doses they gave these people had, in other patients not included in the study ,induced frank parkinsonism, so just maybe the dose was way too high.

The mild-moderate depression group is recognizable as an RCT but the severe group is not.

 

[Lorijones]

1) not that I'm aware of
2) what matters is measuring the change between blood pressures taken in different positions, so just having one blood pressure is not very helpful. The hypotension from MAOIs is usually troublesome as orthostatic hypotension, i.e. a failure to adequately adjust to the shift between lying/sitting or sitting/standing.

Thank you. Who is this masked man? I really enjoy reading all your posts. Brilliant.