This episode of Psych News Special Report delves into the complexities of prescribing psychotropic medications for medically ill patients. Dr. Adrian Preda and Dr. Jim Levinson discuss the challenges faced by psychiatrists, including pharmacokinetics, drug interactions, and the importance of collaboration with other healthcare providers. They emphasize the need for careful medication management, especially in patients with complex medical histories, and highlight the risks of not addressing psychiatric symptoms in these individuals.

Transcript for Audio

[00:00:00] Dr. Adrian Preda: Hello, and, uh, welcome to Psych News Special Report, a monthly podcast from Psychiatric News produced for the APA Medical Minds channel. I'm Dr. Adrian Preda, Editor in Chief of Psychiatric News and Professor of Clinical Psychiatry and Human Behavior at the University of California, Irvine School of Medicine.

Each episode, we sit down with the authors of Psychiatric News Special Report, our deep dive into clinically relevant topics at the heart of psychiatry and mental health care. We are tackling a critical, yet often overlooked challenge, prescribing psychotropic medications for medically ill patients. We tend to think about medications in a straightforward way.

You take this pill for that problem, and that's it. But in reality, it's far more complex, especially when psychiatric medications interact with serious medical conditions. And that's exactly what we'll explore today. Joining me is a leading expert, Dr. Jim Levinson, one of the authors of our February 2025 special report on this very topic.

Dr. Levinson is the Rona Arenstein Professor of Psychiatry and Professor of Medicine and Surgery at Virginia Commonwealth University. Jim, welcome and thank you for being here today.

[00:01:35] Dr. Jim Levenson: Thank you for having me.

[00:01:37] Dr. Adrian Preda: Let's start with the big picture. Why is prescribing psychotropic medication so complex when dealing with medically ill patients?

[00:01:45] Dr. Jim Levenson: Well, there are several reasons. One is that patients who are medically seriously ill are more sensitive to side effects. They may metabolize. Drugs differently, uh, impairment of kidney or liver function in particular, uh, makes it more difficult for the body to get rid of medications. Medical illnesses can generate symptoms that can be mistaken for psychiatric disorders as well.

And so it's important that psychiatrists keep up on their general medical knowledge in order to be safe and effective in taking care of their patients. Even those who don't. Work in the medical setting like consultation. Leah and psychiatrists do, um, will have patients whose psychiatric problems are alongside a chronic or acute medical illnesses.

No one practice entirely healthy.

[00:02:44] Dr. Adrian Preda: So it's about the psychiatrist taking more of a traditional medical role in this, uh, high stake situations.

[00:02:52] Dr. Jim Levenson: Well, let me clarify. It's more a matter of keeping up one's knowledge. It doesn't mean taking over management of those other medical conditions. Making sure one understands the ways in which other medical conditions may require us to choose our medications more carefully, choose our doses more cautiously.

[00:03:19] Dr. Adrian Preda: You made a point that in medically complicated patients, Part of the complications is that drugs are processed differently. So you talked in your article about pharmacokinetics. Would you explain for our listeners what pharmacokinetics means?

[00:03:37] Dr. Jim Levenson: Sure, pharmacokinetics refers to the sequence of the absorption of a drug, because until it gets into the body it, of course, can't have any benefits or side effects.

Its distribution throughout the body, uh, its metabolism, its excretion, those are the components of pharmacokinetics, and each of those, each of those steps can be influenced by physical illness.

[00:04:08] Dr. Adrian Preda: In what way could physical illness change pharmacokinetics? Can you give us some examples?

[00:04:15] Dr. Jim Levenson: Sure. So, patients who have a decrease in their ability to absorb drugs, and examples would include Patients with chronic inflammatory bowel diseases, like Crohn's disease, or the increasingly large number of people who've had gastric bypass surgery for obesity in this country, they have less functioning absorptive surface on their small bowel.

And so it means it will be more difficult for patients to absorb medicines. It may mean that one can't use slow release. forms of a medicine and may even need to use liquid forms when they're available, and perhaps at higher doses than one would in somebody with a normally intact gastrointestinal tract.

[00:05:10] Dr. Adrian Preda: So this would be a situation where the same dose of medication would result in different levels in patients would have different levels of absorption. So in other words, in addition to considering the dosing, it's important to consider these other variables that could significantly influence the drug levels and thus its, uh, its effectiveness.

[00:05:34] Dr. Jim Levenson: Exactly. Another example would be. Patients with severe chronic liver disease, most often we would be talking about cirrhosis, will have more difficulty metabolizing some psychiatric drugs than other psychiatric drugs. For example, if one were to choose a benzodiazepine, three of the benzodiazepines require less metabolism by the liver than all the others.

And so they would be preferred because using one of the others risks buildup of toxic blood levels because The impairment of liver function makes the patient unable to effectively get rid of the drug,

[00:06:19] Dr. Adrian Preda: right? So these are examples of the effects of the drugs being changed because changes in the absorption or distribution or metabolism and you also mentioned changes in how the drugs could be eliminated.

So different medical conditions that would affect all these different stages of. let's call it drug processing, would significantly impact both how a drug will work and then its tolerability.

[00:06:48] Dr. Jim Levenson: Yes, exactly.

[00:06:50] Dr. Adrian Preda: Now, the other part about medically complicated patients is that in addition to the medical conditions that could then affect the drug effects as we discussed, these patients tend to take a lot of other medications.

How would you factor that in?

[00:07:05] Dr. Jim Levenson: Well, so this is another whole area that it's important for psychiatrists to keep up on to educate themselves because Our medications can have effects that we are otherwise not aware of on the effectiveness of non psychiatric medications. So I'll give you two examples.

There are drugs that, on their own, are inactive. They have to be metabolized by the body to become active. So one of those drugs is tamoxifen, a drug that's mainly taken by women who've had breast cancer. to prevent recurrence of breast cancer. Tamoxifen has no activity of its own. It has to be metabolized by two liver enzymes, one of which is 2D6.

Well, about two thirds of antidepressants inhibit 2D6, which means if somebody's on one of those antidepressants, much of their tamoxifen doesn't get converted to the active compound. And there's some reason to believe that women who've been on tamoxifen and the wrong antidepressants had an increase in cancer recurrence.

Certain opiate drugs, codeine is an obvious example, are also pro drugs. Codeine is inert until it's converted by 2D6, that same enzyme, into morphine. I've had patients whose doctors who were prescribing their opiate medicines thought the patient was a misuser because they were complaining that the opiate wasn't doing anything for them.

And it was my antidepressant that was preventing their, their codeine or other opiate from being effective. So it's important to understand how our drugs may affect the metabolism of other drugs too.

[00:08:59] Dr. Adrian Preda: And also, uh, other drugs could, uh, in turn affect the metabolism of the psychotropic drugs.

[00:09:06] Dr. Jim Levenson: Yes. Yes. It goes in both directions.

[00:09:09] Dr. Adrian Preda: Any, like, you know, sort of, let's go, uh, maybe what are the first, you know, I would say the first three other drugs interacting with psychotropic things that psychiatrists should pay attention to?

[00:09:23] Dr. Jim Levenson: Um, well, some of these are very familiar to psychiatrists. to most psychiatrists, but I'll, I'll, I'll mention one here, which is that lithium levels can be influenced to be increased or decreased by diuretics, depending on which diuretic it is, and various other antihypertensives.

[00:09:41] Dr. Adrian Preda: What about grapefruit juice?

[00:09:44] Dr. Jim Levenson: I love grapefruit juice. But I think anybody who's taking multiple medications. An occasional glass of grapefruit juice won't harm anything. And if they always drank the same amount of grape juice every day, then doses can get adjusted around that. But if somebody is intermittently drinking large amounts of grape juice, that can throw off the blood levels of a variety of medications.

[00:10:12] Dr. Adrian Preda: That brings me to the next question because there are so many drug drug interactions that could go in either direction and there are drug food interactions. Grapefruit juice is an example. And then there are the drug, you know, nicotine smoking interactions. I mean, that's a lot. That's a lot to kind of remember and.

When you have a patient coming in real time with a list that's, you know, 20 something medications long, how do you figure it out? How do you figure out this whole drug drug interaction problem? How do you do it?

[00:10:40] Dr. Jim Levenson: Well, it continues to be a real challenge. Any prescribing health care provider who's listening to this podcast has had the experience if they work somewhere that has an electronic medical record of being warned about all kinds of combinations.

As if they were dangerous that we routinely use and really are not a concern. So part of the challenge is that some of the theoretical problematic drug interactions in real life don't occur. And so I think one needs to be aware of the possibility, but one shouldn't become overly cautious. I think there are prescribers who become overly concerned about the risk of serotonin syndrome, for example.

Most software will warn us not to combine an SSRI with trazodone. And yet, we've been combining SSRI with trazodone for decades. High doses of tramadol, a synthetic semi opiate, that's more often problematic in terms of risk of serotonin syndrome. If a patient is doing well on an SSRI and tramadol, I would educate the patient about the symptoms to look for, but I wouldn't tell them they have to get off the

[00:11:56] Dr. Adrian Preda: SSRI.

These are important points. I think it's fair to say. It's all physicians right now in the U. S. probably have used some form of an electronic medical record. And most of these systems, while they have the challenges, there is also an opportunity, right? Because we can reconcile medications at real time and then at the click of a button run drug drug interactions.

And the point is that that should be informative, but not definitive. It should be done, right, because the knowledge is at our fingertips. However, some of those recommendations, as you are, as you are emphasizing, should be taken with a grain of salt. And the clinical context should matter. So we run the interactions and then we decide if it's appropriate to make any changes in the regimen based on the results that are going to be given to us.

[00:12:46] Dr. Jim Levenson: Yes, um, and as you know, about two thirds of the psychiatric drugs in the United States are prescribed by non psychiatrists. And they can tend to be overly cautious, both in dosing and in worry about drug drug interactions. If their patient also has a serious medical condition, they can become afraid to use the psychiatric drug at all, or maybe a psychiatrist has been prescribing the psychiatric drug, and the non psychiatric physician may, out of an excess of caution, tell the patient to stop taking the drug, which would usually be a mistake.

Certainly a mistake without conferring doctor to doctor. Just because somebody has a serious physical illness, does not mean there's no role for psychiatric medication.

[00:13:35] Dr. Adrian Preda: Yeah, that's, that's worth emphasizing. Absolutely right. So, Jim, let's talk about the, um, some of the severe drug reactions. What are the biggest dangers that psychiatrists need to look out when prescribing psychotropics specifically in medically ill patients?

[00:13:53] Dr. Jim Levenson: Well, psychiatrists are well aware of neuroleptic malignant syndrome. If the psychiatrist is following a patient who's on some non psychiatric medicines. They should be aware that our colleagues outside of psychiatry are not very knowledgeable about neuroleptic malignant syndrome and don't realize that it can be caused by some non psychiatric drugs like, uh, promethazine and prochlorperazine.

which are common anti emetics, or metoclopramide, another gastrointestinal drug. Those three drugs can cause all the same movement disorder side effects that antipsychotics do, including tardive dyskinesia and neuroleptic malignant syndrome. And I diagnosed tardive kinesia, tardive dyskinesia in patients I was treating in whom I had never prescribed an antipsychotic, only to find out they were on one of those gastrointestinal drugs.

And their GI prescriber had no awareness of the risk. So that's a way in which psychiatrists can help correct their patients. I think there are other reactions like serotonin syndrome, where if you're concerned about the risk, then move slowly, start with a lower dose of the second drug. than you normally would prescribe and increase it gradually and and monitor for signs of the adverse reaction.

[00:15:20] Dr. Adrian Preda: Uh, what about lithium toxicity? Are any of the more discreet medical ill patients at higher risk for that?

[00:15:30] Dr. Jim Levenson: Sure. So lithium There are difficulties with both toxicity and too low a blood level in a variety of medical conditions. So, in a patient with unstable heart failure, their kidney function is going to be variable.

And they're likely to be intermittently being given diuretics and both changes in kidney function and being on and off diuretics are going to cause lithium levels to yo yo up and down. It's pretty difficult, if not impossible to use it both safely and effectively in a patient with actively unstable heart failure.

Cirrhosis of the liver doesn't directly affect kidney function in most patients. But lithium can be difficult to use in an unstable patient with cirrhosis because their fluid and electrolyte status is actively changing. And they too may be intermittently administered diuretics because of the excess fluid that accumulates in people with cirrhosis.

So lithium can be very difficult to use in patients whose kidney function or fluid and electrolyte status is changing. actively changing. On the other hand, if someone has end stage renal disease, they have no working kidneys anymore. Some clinicians have been afraid to prescribe lithium and yet a patient who's on dialysis is an ideal patient for lithium because the lithium can be given on the day that they don't have dialysis.

And then it will stay on their body at an exact stable blood level until their next dialysis, which will remove most of the lithium, and then they can be given a dose again. And so it's important to not fear using lithium in someone who no longer has any functioning renal abilities.

[00:17:26] Dr. Adrian Preda: So you are emphasizing, uh, like at the level of principles.

In terms of, like, how to approach these populations, probably it's a good idea to start low and go slow, right? That was one of the things that you, you discuss and, and then it's important to maybe begin with the lowest effective dose and then very gradually advance, uh, and make sure that the drug is well tolerated and there are no dangerous, uh, interactions.

You also mentioned, uh, the very important consideration of the clinical context as opposed to saying this is a bad idea just because consider the clinical context and, and if there are opportunities and, uh, most times they're not, that's going to be the case, uh, follow things objectively, uh, through regular, uh, laboratory workup.

[00:18:14] Dr. Jim Levenson: Yeah, so let me add another general principle. It's, it's not specific to our topic. I think it really applies throughout life, but, but it has particular relevance here. And that's that it doesn't make sense to ask the question. Is prescribing this drug risky? Without asking the question, well, what are the risks of not prescribing it?

One of the issues in this realm is the prescription of antipsychotics or other drugs that can increase the corrected QT interval. It's a measure on the electrocardiogram. because of the risk of precipitating a ventricular arrhythmia. Several years ago, a group of psychiatrists and cardiologists published a resource document on the American Psychiatric Association website.

It's still there, it's in the process of being updated this year, to answer the question of which psychiatric drugs pose risks and when are they contraindicated. And one of the key conclusions we made Was that there's no absolute QT corrected QT interval that automatically precludes. Any psychiatric drug, you have to look at each case and ask, what are the risks of continuing this medicine?

What are the risks of stopping it? If there's a good alternative that's safer, of course, that's easy. But sometimes the patient has only responded to one drug in a class.

[00:19:46] Dr. Adrian Preda: I think that's such a great point because, of course, we need to be aware of the risks but there are also benefits that in the bigger context, you know, considering the bigger context, you would want to be not risk adverse, but you would want to be appropriately assessing the risk benefit ratio as opposed to just deciding that the medication is not recommended.

[00:20:08] Dr. Jim Levenson: I'll give you another concrete example. The question arises, if someone. is on a psychiatric medication and they're going to have an elective surgical procedure should the medication be stopped. There's a publication consensus document that says, uh, lithium should be stopped three days Before the surgery.

I think it's a mistake to treat that as an absolute rule because it really depends on the patient. There are patients whose bipolar disorder is so fragile that even a small decrease in their lithium may precipitate a an acute manic episode. And I can tell you surgeons are not happy for a patient to become acutely manic in the acute stage of recovery from surgery where they need the patient to be very cooperative.

And so. The question of when should you stop lithium before a surgical procedure depends on the patient's psychiatric history. It depends on the type of surgery. You really need to make an individualized decision and not follow a just a flat rule.

[00:21:14] Dr. Adrian Preda: That makes sense. And with that, actually, let's shift to special cases.

You discussed surgery. What about any special considerations about describing psychotropics during pregnancy?

[00:21:27] Dr. Jim Levenson: That's a complex subject because we don't have as much data as we would like. I think that there are some things we can say clearly. In a patient who has bipolar disorder, valproic acid is something that one would want to avoid if at all possible.

If that was the only medication that controlled the patient's symptoms, if one could avoid it in the first trimester. One would likely avoid teratogenic effects. There's some small risk with lithium. Again, if the patient really needs lithium, if you can, if you can get by without using it in the first trimester, then there wouldn't be a risk of any cardiac malformations.

Uh, lamotrigine is entirely safe in pregnancy. It's best for the more common. Uh, depressive and anxiety disorders. I think it's quite clear to most obstetricians that the risk of untreated depression or untreated anxiety exceed the risks of most antidepressants and, uh, most obstetricians don't want their patients to stop taking antidepressants during pregnancy.

[00:22:38] Dr. Adrian Preda: You know, I have patients who want to breastfeed and they're at risk for postpartum depression. Any specific recommendations to consider when in that type of situation, breastfeeding recommendations for antidepressants, mood stabilizers?

[00:22:53] Dr. Jim Levenson: Sure. So one thing is that I wouldn't ever make a unilateral recommendation.

I would either confer with the patient's child's pediatrician and or their obstetrician because um, it's important that the patient not be. Giving, uh, three different kinds of advice, that, that's pretty disconcerting to patients. There are some drugs that have been judged to be safe in breastfeeding because they appear not to get into breast milk to any significant degree.

There are others that do get into breast milk, but where there's not been any data of harm to infants. But, again, there's not sufficient data to always be able to answer all patients questions. Patients ask me, for example, who have attention deficit disorder, whether they can, you know, Continue or get back on their stimulant medicine and I encourage them to discuss it with the other two physicians.

I tell them what the limits of the data are that there are haven't really been many case reports of any harm, but it's also a somewhat unknown area. So some of them choose with full information to go ahead knowing that there, there may be some degree of unmeasurable risk and others choose not to take that risk.

[00:24:13] Dr. Adrian Preda: Yeah. And I think it's so important you are emphasizing, and you said that a few times, time and again, that first. You know, uh, we should very carefully consider the overall picture and, uh, there is a lot of value in working collab collaboratively. The psychiatrists should consult with the surgeon. The surgeon should consult with the psychiatrist, with the pediatrician, with the OB, GYN in the case of a pregnant woman.

So it sounds like, uh, you know, it would be fair to say that probably one of the most important principles. Uh, is that teamwork between psychiatrists, uh, other medical providers and pharmacists is really critical, uh, in this type of situations.

[00:24:55] Dr. Jim Levenson: For anyone who's in an academic medical center, it's likely that, uh, like I, I do here have expert pharmacists who specialize in psychiatric medications.

They've been very helpful to me and my colleagues when we have a more challenging case. I would also encourage providers to make their own discoveries. So, I'll share one that I basically sort of stumbled across. I was prescribing a patient a particular antidepressant. It doesn't really matter which antidepressant for this.

This story, and she was very stable on it, it had done very well, and it abruptly stopped working. So, of course, the first thing I asked her was whether she was taking any new medications. And then I asked her if she was taking any new non prescription medicines, and she answered no to both of those. And then she remembered that she started taking Metamucil, which, as you know, is a, it's just fiber for colonic regularity.

And that coincided with when she stopped responding to the antidepressants. So, I went to PubMed and typed in the name of the antidepressant and Metamucil. And found there were case reports in which it appeared that the fiber was binding the drug and interfering with its absorption. That's not anywhere in the regular literature.

It's not in our, it's in our latest, the latest edition of our textbook. It wasn't in the earlier editions. Because we just hadn't seen it. And if one keeps one, one's eyes open, one will discover these things. Sometimes when a drug isn't working, it's not the, that the patient is non adherent.

[00:26:38] Dr. Adrian Preda: Absolutely.

Before we wrap up, what's one key message you want listeners to remember?

[00:26:44] Dr. Jim Levenson: A key message is. Don't be afraid to prescribe a psychiatric medication in someone with a complex medical picture. It can be done safely and effectively, but do it carefully. Consult with other providers. Go to the many online resources that are available to all of us these days that make it much easier to practice than when probably you and I started out.

And you can safely and effectively treat patients. Don't assume that their symptoms are just a normal reaction to their medical illness because having a serious chronic medical illness increases your risk of developing affective conditions. Thank you. anxiety and other disorders.

[00:27:30] Dr. Adrian Preda: Jim, thank you for this fantastic discussion.

Thank you, our listeners, for tuning in to Psych News Special Report. If you enjoyed this episode, Please rate, review, and subscribe. And if you found today's discussion valuable, feel free to share it on social media or with your colleagues. You can read the full psychiatric news special report at psychnews.org.

We've also posted a link to the article in the episode description. We'll be back soon with more expert conversations. Until then, stay informed, stay compassionate, and take care.