Mixed Antidepressants, 3 Ways I Start My Day | Episode 198

Today's topic is antidepressants and the 3 things I do when I start in the morning that make a difference.

Monoamine Oxidase Inhibitors (MAOIs)

Let's start with MAOIs - Monoamine oxidase inhibitors. These are the original ones from the 1950’s. To give us a timeline, we started with this as an anti tuberculosis drug, and people got a little giddy on the drug and they felt good. And tuberculous is a tough course to go through. 

MAOI inhibitors came along from this drug that was supposed to treat tuberculosis, and we found out that in fact, those that had tuberculosis who were getting this drug felt better. Hence the evolution to the discovery of an effect that was positive. Not all side effects are negative, and it was applied.

MAOI inhibitors had a lot of baggage. You must be really careful with certain foods, such as fermented foods, wine, cheeses the like please go back and review that podcast. The important thing about MAOI inhibitors is they're still valuable and they're useful in clinical settings, but they must be monitored by a healthcare professional.

Don't go out and seek pain relief without understanding exactly what's going on in you!  

I think Demerol is pretty much historical. Unfortunately, it's a really good drug. But that was our big risk drug. People got these biochemical reactions that led to thermal genesis in the body. There were a lot of problems with mixing MAOI inhibitors with certain commonly used meds, sometimes not expected. Clinicians that weren't schooled, or they did not know that somebody was on an MAOI inhibitor. 

Tricyclic Antidepressants

So the next step was tricyclic antidepressants, and then the later development of “four” cyclic antidepressants. 

The tricyclic antidepressants are still used to stay. They're really good drugs. The MAOIs and the tricyclics may not be first line, but they are there, and were in the sixties, seventies, eighties. I use them today. They help with sleep, they help with muscle pain, and there's a very narrow therapeutic window for depression. 

But I must tell you, in a general sense, if somebody is having a little trouble with sleep, they're a pretty good drug, but the side effects and baggage of course, are there. Dry eyes, dry mouth, constipation, et cetera.

Newer Antidepressants

The newer drugs are:

• SSRI, the serotonin reuptake inhibitors. 
• The norepinephrine reuptake inhibitors, the SNRIs, which have come along, are on the timeline a little bit later. They're very beneficial drugs. 

Now, these drugs take a while to work, they can take a significant time to work and some don't work. It's been suggested that with major depressive disorder (MDD) these drugs are good first line drugs, but they can take five weeks. I call it “mixed” depressive disorder because usually anxiety, situational, depression, and other problems are so common, even postpartum depression, that it's “mixed”, and maybe major, 

To refresh our memory:

• MAOI inhibitors
• amitriptylines and the like, as a tricyclic drug
• imipramine drugs came along 
• SSRIs:
• Citalopram, which is Celexa
• Escitalopram, which is Lexapro
• Fluoxetine, which is Prozac
• Paroxetine, which is Paxil
• Sertraline, which is Zoloft

Those came along, and they're VERY good drugs.

We then moved on and we developed these mixed drugs that affect serotonin, norepinephrine, epinephrine, dopamine, and it can be any one of a combination. They can affect the noradrenergic system, the depressive systems, dopaminergic. 

The point is, we're always in a desirous mode to develop incredible adjuncts that come on quickly, and that help more than 50 to 60 percent of the population. This is a generalized population problem - situational depression and anxiety.

SNRIs, Serotonin and norepinephrine reuptake inhibitors

The SNRIs did a little better than the SSRI. The SNRIs are:

• Desvenlafaxine (Pristiq)
• Duloxetine (Cymbalta) - love this drug. It's been labeled by the FDA for fibromyalgia, situational depression, anxiety. A lot of people use it for headaches. It's a good drug. I don't necessarily have a favorite, but it comes on fast, it's predictable, and I like it. 
• Venlafaxine (Effexor) -  I started using this in the nineties because I noticed that people with pain, especially muscle pain, fibromyalgia-like symptoms, and trouble with sleep and the like get a little better on that one. There's lots of different pronunciations for this one.

Then kind of these other drugs that you hear a lot about and are used a lot that have a kind of a mixed effect. Remember, it's serotonin, norepinephrine, epinephrine and dopamine. 

• Remeron (Mirtazapine) is a good example of that. Remeron works on the noradrenergic system. It's specific serotonergic. It blocks norepinephrine. So Remeron is a good drug and a lot of people use it for sleep. 

• Bupropion (Wellbutrin). It helps a lot with anxiety and kind of a spinoff, off-label use is it helps craving for cigarettes. It works on norepinephrine, dopamine and it's widely available. It's generic. And its side effect profiles are pretty reasonable. I like that drug. It's a good, good drug for a lot of people that have very high sensitivity to some of these antidepressants. Talk it over with your healthcare provider.

• Vortioxetine (Trintellix)
• Trazodone (Desyrel), a very common drug. It's often used for sleep.

Side Effects of Antidepressants

So what are the side effects? Well, with all antidepressants, in most every drug: headache, nausea, vomit. Sleepiness or insomnia, and mania - sometimes. Blood pressure changes either up or down. You must follow that with your healthcare provider. It can cause situational depression, anxiety, you can be allergic to it, or have side effects that are often mistaken for allergy. 

Suicide and Antidepresants

Suicidality has been attributed to these drugs and we talked about that. I don't know what it is. Is it from the situational depression and anxiety? Is it from the drug? Or is it one plus one equals three? I don't know. And many times we have to really monitor the start of these drugs. Henceforth, do not get these drugs on the internet. Go to a healthcare provider who has a responsibility to follow you from all standpoints, of not only your vital signs, but your response to the drug. 

You will know if you're sitting longer, taking less medicine, better restorative sleep, less anxiety, better mood. You can go longer, go to the grocery store, play with the grandchildren, whatever it is. You're responding to these drugs, and it might be subtle, it might be very subtle. So keep an inventory for your healthcare provider. That is very important, so they know what’s up. And you know what's up. 

You can get a health and history form at https://paininformation.com. Forms are helpful. They're not complete, and they're not the medical history that fits everybody. Not one shoe fits all, but it's a start. And it has some of those things that are so important to make comments on regarding function and quality of life. 

My 5 Rules for Healthcare Providers

Number one: Pain is a description. This includes anxiety, depression, and addiction. 

Number two: The reality is very different based on diagnosis. 

Number three: If you don't believe in it and you think it's entirely psychosomatic, you can't treat it. You must refer to it out. Get it to somebody that can make a difference. It can be lifesaving. Same with situational depression, anxiety, and pain. 

Number four: You must know your drugs. Know thy drugs, five classes, five deep. 

Number five: From a compassionate standpoint, you want to get everybody better. I want to get them symptom free or just grin on their face, like those marketing photos. But from a realistic standpoint, you want to improve function and quality of life. 

My Morning Rituals

These are the three ways that I start my day, and I've done this for years. I don't know if it's right or wrong, it helps me, so I'll share them with you.

What helps me to decrease anxiety, improve quality of life and function? My morning routine.

Number One. I'm aware. I'm grateful and thankful that I got up. It's important to be grateful and understand that you have a day in front of you. 

One of my favorite sayings is from Samuel Clemens (Mark Twain). I’ll paraphrase. He said that if you're thinking about the day and you don't want to get out of bed, and you have a terrible day ahead of you, go eat a frog. Make it a live frog. Make it one of the most unpleasant things you can do with that squishy, slimy thing. Because no matter what happens the rest of the day, the worst things have already happened to you. 

Number Two. I've tried yoga. Yoga really works for people and there's a lot of good science that says it will help you. Any stretching, and include something with your neck, then with your torso. Rotational. Also, do something with your lower extremity. If you have to sit in a chair, move your legs a little, maybe 30 or 60 seconds. And when you're starting to get mindful and you're thinking, this is a good day, and you're progressing through your routine, you become much more aware.

Does this type of approach do much? Well, I'll tell you what does - cognitive behavioral therapy. We use that a lot in Western medicine to help with situational depression and anxiety. We also use some other brain awareness techniques and focused guided imagery, being mindful with this awareness and acceptance. I didn't always know what the name of it was, I've just always tried to be mindful in the morning. I didn't know it was called mindfulness.

Number Three. If you can, if you're so inclined, acknowledge a higher power. That's not necessarily religious. Take this back to a lot of the folks in the addiction world or in the anxiety and depression worlds. A higher power can be anything. It can be your enjoyment of a certain song that takes you to a better place. It can be a person. It can be spiritually oriented, but it's a higher power for you. 

Be mindful of that every day and learn acceptance. This higher power can help you do that. We do know from the science of all this, especially through meditation, that it may take time, but it does seem to enhance synaptogenesis and neurogenesis in the brain - that's the process of brain derived neurotrophic factor. 

But that is fundamental in order to understand that we can see proof through the functional MRI, and other methods that we have seen experimentally. We can see that the brain actually goes from kind of sick and unhealthy to healthier. 

Whatever technique you use, it can be yoga, it can be physical exercise. It can be through strength training, either very light or heavy strength training. It can be anything you choose that takes you through a guided and mindful approach to brain health and brain awareness and a focus on the things that matter. It helps to make you calm. It helps with observation, thoughtfulness, it helps with emotion and sleep. It helps you tolerate pain, it helps you tolerate anxiety, it helps you tolerate stresses and cravings that are so important with depression, anxiety, and addiction. 

There's emotion, and that is the cornerstone to improving your quality of life that has so much to do with actual brain activity and brain function. 

A Few More Newer Antidepressants

We also have some newer antidepressants coming out just within the past year or two that I'll want to expand on:

• Bupropion (Wellbutrin)
• Dextromethorphan (Zuranolone), which works on the NMDA receptor
• Some of the newer formulations of drugs that are coming out. One with ketamine, esketamine. Psilocybin, which is happy magic mushrooms, a big push on that one. I'm not sure I've fallen into the favor on that one. 
• Allopregnanolone. During pregnancy hormones are affected and a new drug is coming out that's a derivative of steroid, of course, because that has a lot to do with hormones. It's coming out as a drug called Brexanolone that may help postpartum depression. And it kind of wails on the GABA aminobutyric acid A receptor, GABA A receptor. (There's two, GABA A and GABA B. GABA A is the one that benzo's love, and B is the one that baclofen loves, which is a muscle relaxer.

All these drugs, of course, can cause the same side effects as all the rest of them. Where we've also noted, when you push the doses, you get cardiovascular issues such as akathisia. That's a general restlessness of your legs and that sort of thing. You must move.

The drugs that have great promise, especially some of them that are coming down the pike, they work pretty fast. And that's important. If we can get something that works faster than one to four weeks, instead in a matter of days, we're winning. This is why I love ketamine. Also, I understand the science of ketamine and I've used it for years. So go back in some of the podcasts and look at the Ketamine, and the psilocybin. I've done some other podcasts on these drugs, and it's worth taking a listen.