The Land of Anti-Psychotics

MondayI’ve been reasonably stable (or at least no one has complained loudly) over the past several years by taking Lamictal alone for bipolar.  However, my moods have gradually gotten out of control over the past year. I realized (and admitted) that I needed a meds adjustment, so I found a psychiatrist who believes in the teamwork approach to meds management.  Thus, she sent me on a quest for new medications; I’ve always been opposed to lithium, but she asked me to consider it and also to look into the anti-psychotics.  In fact, she loaned me a book that describes the mechanisms behind how (it is believed that) they work. Unfortunately, I returned the book before I got this idea of sharing with you how these medications work, so I will have to rely on my own notes and conclusions.

DISCLAIMER: I am not a psychiatrist, psychologist, M.D., D.O., medical student, or even a biologist, nor do I play one on TV.  I am not an expert, just an intelligent individual with an inquisitive mind.  Please keep this in mind as you read this post.

The book I read is called:  Psychosis and Schizophrenia: Thinking It Through.  It’s published by Neuroscience Education Institute, but it was written by Stephen M. Stahl.  It’s full of amusing pictures, informative descriptions, and lots of technical lingo.  Now, on to what I’ve learned (or think I’ve learned):

The theory is based on the idea that dopamine plays a major role in schizophrenia.  There are five basic dopamine pathways (DA) in the brain:
(1) mesolimbic pathway
(2) mesocortical pathway to DLPFC (dorolateral prefrontal cortex)
(3) mesocortical pathway to VMPFC (ventromedial prefrontal cortex)
(4) nigrostriatal pathway
(5) tuberoinfundibular pathway

I have no idea who names these things, but I think of them as a bunch of little roads that all come together in (more or less) a central location in the middle brain.  Some of them are long roads and some are short roads, some work just fine (#4,5) whereas others either don’t work well enough (#2,3) or they are working overtime (#1).  The consequence of this “out of tune” situation, as Stahl puts it, is delusions, cognitive impairment, and depression.

Dopamine and Seratonin Pathways

There are several main receptors involved in this dopamine dance: 5HT1A, 5HT2A, D2, D3, M1, H1, and α1.  Some of these need to be increased and others decreased to bring the flow back into order. Medications act on these receptors in a variety of manners: some act as blockades, others act as agonists (stimulating the receptors) while others work as antagonists (reducing cell action), and then there are those that are partial agonists, partial antagonists or partial blockades.  Many medications are combinations of these effects.

What’s this got to do with anything?  It has everything to do with side effects!

As I understand it, some of these receptor sites have to be blocked in order to get the traffic flowing at the correct rate.  Depending on which site you decide to block, you get a different set of side effects.  For example:

M1: constipation, blurred vision, dry mouth, drowsiness
H1: drowsiness, weight gain
α1: drowsiness, low blood pressure, dizziness

Now that we have gotten through all that… let’s look at the conventional v.s. atypical anti-psychotics.

Conventional anti-psychotics create a chronic D2 blockade.  What does that mean?  Normally your neurotransmitters latch on to a receptor site and pass the signals along, however, a D2 blockade cuts in and blocks the neurotransmitter from reaching the receptor. If we go back to our dancing analogy, it stole your dance partner and won’t give him or her back!

Atypical anti-psychotics only borrow the receptor sites.  So it’s more like square dancing; the medicine cuts in, twirls about for a bit, then wanders off letting things go back to normal. This interruption process provides a better “traffic flow”.  Most of the atypical anti-psychotics appeal to a variety of receptor sites, which creates a mixture of side effects.

Basically, it’s all a dance: activate this, deactivate that, fully or partially blocking, all in an effort to regulate the “traffic flow” of dopamine and serotonin.

That’s how it works for schizophrenia.  Why do the same medications work for bipolar?  Well, the experts are still working on that.

(Note: The University of Utah has a very nice website that discusses neurotransmitters and pathways with respect to addiction.  It is a great resource for understanding the principles of reward pathways in the brain.)

© Monday and A Canvas Of The Minds 2013. Unauthorized use and/or duplication of this material without express and written permission from this blog’s author and/or owner is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to Monday and A Canvas Of The Minds with appropriate and specific direction to the original content.

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9 thoughts on “The Land of Anti-Psychotics

  1. I noticed that they are often coupled. This often applies when we’re talking medication and neurological research.

    I had success with Lamictal alone for about a year and a half. But for some reason, I started having these very long depressive episodes. I’m famous for rapid cycling. So, that was very concerning. We threw some Wellbutrin at it. After I worked through the initial manic episode, I responded amazingly. Then, it seemed like my chemicals went nuts and nothing was right.

    I’m glad to know about the dopamine and the receptors. I know that Wellbutrin is a tricyclic that inhibits dopamine. What exactly does Lamictal do? And how do you know what is doing what when you’re on a ton of meds?

  2. It’s a very good point, Luna – how do they know what is going on when you are on a mixture of meds? I think the answer is: they don’t. I’ve had several doctors confess that the mechanisms aren’t known for many drugs but there are theories as to how a particular medication (or class of medications) works. I used to know the theory behind Lamictal (and other anti-seizure meds) but I’ve forgotten over the years. However, I did just order a couple of books on psychopharmacology, so once I’ve had a chance to go through some of that “light” reading, I may be able to give you a better answer. 🙂

    • Actually, the best way to find this out is to unwaveringly advocate and stick to the following treatment strategy: one medication at a time. You start with one med and spend a few days, weeks, or months on it, depending on how long it takes to reach a steady state in your system. Note its effects.

      Now you introduce your next medication and follow the method above. Unless it falls under the category of “known interactions” (in which case both drugs are culprits) it is almost certainly caused by the new med. Occam’s Razor.

      Rinse and repeat. It can be maddeningly frustrating to go so slowly when you feel like your life is at stake, but this is coming from a woman who at her peak was taking 15 prescription meds, two OTC drugs, and eight supplements and vitamins – 25 types of pill – each day. And then there were the “rescue meds” which I took additionally for migraine, anxiety, asthma, whatever. Sound like a lot? It was. And yet because I followed Ruby’s System Of Eliminating Confounding Variables (and kept extensive notes), I could tell you today with perfect certainty what each of those pills were doing for and to me.

      Does it offer a biochemical explanation? No. Does it make your life so much easier down the line, when you’re trying to make choices on medications? Hells yeah!

  3. this stuff just trips my trigger! I’m so glad you took the time to explain it to us. I love the study of the brain and hope to get more into after grad school. Most of my free time is spent reading and writing grad school stuff!

  4. I will confess here and now to being an information whore, Manic Monday. I love, love, love all of the finer points about the mechanisms these medications have on the brain which you included. And I also like that while one of your illustrations was very straightforward and explanatory, the other was slightly offbeat and (though I didn’t read the fine print) illustrates near perfectly the way I feel about anti-psychotics – I’m also a sucker for juxtaposition. 😉

    Eagerly awaiting what you post on next!

    • Thank you Always! I selected the second picture simply because I found it amusing, so I am glad you liked it. 🙂

      As for my post… I’ve got something in the works.

  5. Something that my psychiatrist has talked about is also the synergistic effect of medications. An antipsychotic alone or lithium alone may not do much of anything. But, put them together and voila, effective medication. The brain can be crazy weird that way, you never know quite what you’re going to get until you try it.

    I also second ruby’s approach. Only, for me, they did it in reverse. They put me on lithium and slowly tapered me off everything. Then we hit lamictal, which I thought was doing nothing. A few days after that, and I went into a depression that sent me to a psych ward and from there they put me on a dose of zyprexa again. Whether it’s doing something or not, I’m stuck with it and my depressions seem to move along faster with it coupled with lithium.

    Also, the H1 receptor site is a wonderful receptor. Most of the atypicals that I’ve looked at in some way work on it. That can make one drowsy, but it can also do wonders for allergies. It’s exactly the same site that zyrtec and claritin work on. So no more hay fever for me while on zyprexa.

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