Using Pharmacokinetics and Pharmacodynamics to Prescribe Antipsychotics

With all the information available now on using antipsychotic levels and interpreting them, Jonathan Meyer, MD, voluntary clinical professor of psychiatry at the University of California San Diego, wanted to clear up some misconceptions and give some guidelines for using antipsychotics with patients with schizophrenia. Dr Meyer shares key takeaways from his Neuroscience Education Institute (NEI) Congress session, "Level Up: Using Plasma Levels, Pharmacokinetics and Pharmacodynamics to Guide Antipsychotic Prescribing." In this video, Dr Meyer discusses the importance of considering plasma levels rather than prescribed doses and emphasizes the need to understand the kinetics of long-acting injectables. However, newer technologies may improve real-time information availability, he suggests.

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Read the Transcript: 

Hi. I'm Dr Jonathan Meyer, voluntary clinical professor of psychiatry at the University of California San Diego, here to talk about my presentation, "Level Up: Using Plasma Levels, Pharmacokinetics and Pharmacodynamics to Guide Antipsychotic Prescribing." Yes, it's a very long title, but there were really a few core concepts that we're covering in this session.

I think the basic idea is that, because of variations in adherence with oral medications and also differences in drug metabolism, the best proxy for the biological outcome, typically treatment response, but also adverse effects, is the plasma level of the antipsychotic and not the prescribed dose. There's a lot of information out there now about how to use antipsychotic levels and interpret them, and I think this can be a very useful tool in managing patients. And specifically we're talking about patients with schizophrenia.

As you use agents such as long-acting injectables, you have to understand the kinetics. And that's really the second idea we cover in this session. There are many long-acting injectable forms, for example, of Aripiprazole or Risperidone or Paliperidone, all of which have subtle differences. You have to know the kinetics to know how to use that particular product effectively. The failure to do so often results in sometimes subtherapeutic levels and adverse clinical outcomes. And then, lastly, the aspect of pharmacodynamics really relates to the fact that the partial agonist antipsychotics, the ABCs, Aripiprazole, Brexpiprazole, Cariprazine, don't play well with other D2 antagonists. And sometimes clinicians, not understanding this, wonder why when they add Aripiprazole to a D2 antagonist like Risperidone cause maybe adverse psychiatric outcomes, because the Aripiprazole displaces it.

Or conversely, they have somebody on Cariprazine and they wonder why adding a D2 antagonist does not make it better. It's because those partial agonists are designed to have such high affinity and occupancy of the D2 receptor that other antagonists just don't work. Once you understand that principle, you'll never make that mistake again. So some of the challenges health care professionals face in implementing some of these personalized approaches really relate to the fact that, especially for antipsychotic plasma levels, you often don't get the result back right away the way we do for other drug levels. But what I tell people is, even if you don't get that level back right away, if you're suspecting your patient is non-ad adherent, and this is why she's not getting better with her oral antipsychotic, or maybe she's an ultra rapid metabolizer, draw the level.

Even if you don't get the result back for a week or 2, you'll do what you normally do, which is make your best guess, often increasing the dose, but once you get the level back, you'll have a much better sense of what is going on. And even in people on LAIs, there are folks who are ultra rapid metabolizers. If you're wondering why somebody's not getting better, get a level. There are benchmarks for what levels to expect for a given oral dose for most antipsychotics, for a given LAI dose, and this can help you figure out why your patient isn't getting better. Again, you don't get the information back often in real time, but we think with newer technologies that will change. For example, there's now a Clozapine assay, which can be added on to a standard laboratory analyzer, and many labs now can give you Clozapine results in the several hours the way we get for Lithium or Valproate.

I think the overall take home message is that, while we prescribe medications, we don't want to, so to speak, drive blind, especially when we're dealing with a serious mental disorder like schizophrenia. Having level information can be very, very helpful. We can't get it for all antipsychotics, but for many of those which are commonly used, it can be a great guide to help figure out the dosing and certainly why the clinical scenario does not seem to fit with the dose. And most importantly, you have to know the drugs you prescribe, not only the kinetics, but how they work and, most importantly, which antipsychotics don't play well together so you can best help your patient with schizophrenia. So this is Dr. Jonathan Meyer, thank you so much, and I hope you look at other videos posted on the NEI Newsroom and affiliated HMP sites.

Jonathan Meyer, MD, is a voluntary clinical professor of psychiatry at University of California, San Diego, and a distinguished life fellow of the American Psychiatric Association. Dr Meyer is a graduate of Stanford University and Harvard Medical School, finished his adult psychiatry residency at LA County-USC Medical Center and completed fellowships there in Consultation/Liaison Psychiatry and Psychopharmacology Research. Dr Meyer has teaching duties at UC San Diego and the Balboa Naval Medical Center in San Diego, and is a consultant to the first episode psychosis program at Balboa NMC.