The Meds...Part 1, MAOI and More... | Episode 195

Today's highlight is depression and medications with depressive disorders. It's interesting that we call it a disorder because everybody gets depressed. That's not a disorder, that's living, that is so natural, and it's so important that people understand that not every day is an Instagram day or a Facebook day. 

This incredibly stressful life we lead does not have all those moments, those social media moments. We have some dark days and we have some gray days. We have what I call gray hat days and we have black hat days. 

We don't want many black hat days, so we try to find the best thing we can do to improve function, quality of life, and restorative sleep capacities. We want to improve somebody's ability to just get up in the morning and enjoy things, so they can go to the grocery store, and be able to play with their grandchildren. Just have a better day where they don't feel like just going to bed all the time or laying down, saying that they are so exhausted that they can’t think clearly.

Depression is really normal 

Five percent of the world's population at any given moment is depressed. That's not a horrible thing, that's a normal thing when you think about it. We've all had our good moments and our bad moments, things we wish we wouldn't have sent in an email, or maybe a comment or two we wish we could have back.

It leads to melancholy. Melancholy is not organic depression. Organic depression is either something you're born with, or it's something that you just have, and you're noticing it as becoming more prevalent and it's becoming more problematic in your normal activities.

From young children to adolescents and teens in that area are very different from adults and older folks. Older folks are more suicidal. We really have to watch where we're headed with life, and we all have to look out after each other. 

The first psychopharm drug of the 50s that came out that was looking clinically relevant was monoamine oxidized inhibitors MAOI. Class A, and then later Class B. We still use them. Actually, they're good with mixed depressive disorders, as are some of these other agents.

These drugs are very important- they're life-saving for some people's lives and experiences. In other people, they really get them going.

The Evolution of Antidepressants (and TV Dinners)

Look at the timeline of TV dinners, starting with TV dinners in 1953. That's about when they were introduced by Swanson. Some of us remember this thing with aluminum foil with three separate containers and the potatoes, gravy, turkey and cobbler or brownies. 

What does that have to do with depression? Well, somewhere in that time frame came some of the first antidepressants. There was a pharmaco explosion during the 50s and 60s, and the first antidepressants really started to become available. 

Fun fact: These TV dinners came from a lot earlier, they were first used in the airline industry because they had to get these dinners flash frozen and then sent to the awaiting airline. That would be Pan Am. 

These TV dinners in the 50s were then starting a revolution that led to what are called frozen dinners in the 70s and 80s. Then came “How Do You Handle a Hungry Man" with Mean Joe Greene, the football player. After that, these multi-course frozen dinners came around that we love today. 

So there was an evolution from the 50s to now,  just like antidepressants where we have an evolution along the same time. And they're getting better and better.

MAOIs, Monoamine Oxidase Inhibitors

I'll start with MAOIs, monoamine oxidase inhibitors, because they started everything back about the time when psychopharm really started taking off, and we're just kind of starting to know what everything else is. 

Followed in the MAOI class, there’s norepinephrine and dopamine and serotonin and all these other agents including tricyclic antidepressants, the infamous serotonin reuptake inhibitors, selective serotonin, and selective norepinephrine reuptake Inhibitors. Also some of the mixed drugs and other classes that don't get a lot of attention, but can mean a lot in mood and other disorders. How does that mix into depression? Because neurobiologically it all is a big soup. 

It's all pain soup. It's all addiction and depression in kind of a primitive part of the brain.

The antidepressants are really getting better and better, but that does not discount the fact that some that are very useful alone historically, or together. MAOIs are a classic example. The MAOIs affect norepinephrine, a chemical in the brain, serotonin, a chemical in the brain, and dopamine, a chemical in the brain. They're important because of how they act on those neurotransmitters. 

They're very important and they affect how you move, think remember.  They're important because they are first of all by mouth, that's important, and they can be utilized by other delivery systems, but they are readily available. Why don't we just these? Why were there others? Because as with all drugs, MAOIs had side effects and those side effects can be significant in MAOIs. 

Consider drug interactions as happened with the Libby Zion case, which is public record. Her dad was an attorney in New York. This was in the 1980s. Libby had a lot of unknown issues and she had a couple of abnormal labs in the ER. Lo and behold a drug was given, and she died. She had been taking an MAOI and was given Demerol. They thought it was serotonin syndrome, which is high blood pressure, tachycardia, you get a little out of control with the vital signs, and that leads into other issues including seizures and eventual death. Serotonin syndrome is another talk for another day, but that was my era. 

How is that important? MAOIs, monoamine oxidase inhibitors, are a real problem if you like your fermented foods. They initiate tyramine, kind of a storm, and you have increased blood pressure, and a lot of these really horrible problems that can lead to significant deleterious outcomes.

So you stay away from salami, sauerkraut, beer, cheeses, certain cheeses, and you look out for serotonin syndrome. Even cold and allergy medications can significantly increase the blood pressure, making things worse. 

This drug, benignly introduced in the early 50s as a possible treatment for TB, was very popular between the mid to late 50s through the 70s when some of the other drugs started coming out. The most common MAOI in this area was Phenelzine (Nardil) and it's a good drug. It has multiple brand names associated with it. They all have to be used with caution. They cause sexual dysfunction, muscle jerking and they interfere with sleep, and they can cause too much sleep. They are associated with dry mouth, diarrhea, constipation, drowsiness, headache, dizziness. This is off the data insert.

The key here is you have to talk it over with your healthcare provider, these drugs are not necessarily benign.

If you look at the data inserts and you don't have a health care professional around, you'll go you'll go nuts because virtually every drug and side effect profile is reported to the FDA in the trials.Talk to your health care provider. 

Considering the broad brush stroke of these drugs, I've mentioned TB, it's been used for Parkinson's, and it's also been used for panic disorder, agoraphobia, the fear of places, and it has been abused. Overdose is real. It's been described as a problematic issue with this drug, but the safety profile is really pretty good. Never quit this drug without telling your doctor, there is withdrawal. 

What about Ambien? 

Everybody knows Ambien, it’s a z drug, that's a sleep drug. If  you look at the package insert it says that it may cause drowsiness. It's a sleep drug, so use these drugs with care and  caution and by the direction of a healthcare provider. 

The big issue is don't discount the older drugs, it has utility and it's still being used today. I used an analogy with TV dinners.  Folks, the fact of the matter is, we're still using this drug. 

Look at microwave ovens. We are still using microwave ovens. Our first microwave oven we called a radar range because it used microwaves over a very specific Hz profile. It was first introduced in 1933 at the World's Fair.  A lot of things are around for a long time, and that doesn't mean that they're necessarily bad, they just keep getting improved upon. MAOIs are going to fall in that category.  The point is these drugs are not without risk, they're not without potential side effects, they're not something straightforward -  you can’t just pop a pill and move on. They can take time to work, and let's face it some depressive disorders don't respond to any particular agent. We have to use combinations sometimes. And some people don't respond to oral agents, transdermal or whatever the delivery system is.

So we're constantly looking at the psychopharmacology of these drugs that started in the 50s and seeing if we just can't do it a little better, less side effects and still get that improved function and quality of life.

The next struggle we're going to talk about is tricyclic antidepressants, and a little bit on tetracyclines that came about in the 70s. The tricyclics came around, a little safer than MAOIs, but they have their issues too. I mentioned some of my favorite drugs, meperidine (or Demerol) being one of them. They just fell by the wayside and I just loved that drug, but it had some cardiac issues, and they were pretty rare. TCAs have their arrhythmic problem too. We're going to talk about that pharmacology in the next podcast. Then we’ll step forward and talk about some of the really cool newer drugs which are out there.