How a Keto Diet Impacts Psychiatric Meds: Insights from Metabolic Psychiatry with Dr. Deanna Kelly

Deanna: 
Quetiapine, which is the antipsychotic, for example, has an XR extended release version. And so, if you give that with a high-fat meal, it actually increases the absorption. You can dump the whole XR and you can get like a high peak, and you might have some side effects. So, that’s one example where with that, a medication absorption can be real, can be changed.

Bret: 
Welcome to the Metabolic Mind Podcast. I’m your host, Dr. Bret Scher. Metabolic Mind is a nonprofit initiative of Baszucki Group where we’re providing information about the intersection of metabolic health and mental health and metabolic therapies such as nutritional ketosis as therapies for mental illness.

Thank you for joining us. Although our podcast is for informational purposes only and we aren’t giving medical advice, we hope you will learn from our content and it will help facilitate discussions with your healthcare providers to see if you could benefit from exploring the connection between metabolic and mental health.

Dr. Deanna Kelly is a Doctor of Pharmacy and a Professor of Psychiatry at the University of Maryland School of Medicine. And she’s an expert on the pharmacokinetics and pharmacodynamics of psychiatric medications, and you’re going to hear more about that. But how does the food we eat impact the way our bodies absorb and metabolize medications?

What do we have to be aware of if we’re eating a low-carb, high-fat ketogenic diet and how that’s going to impact the medication so many of our patients take, whether they’re psychotropic medications or others? So let’s hear from Dr. Kelly about this very important, but yet very specific and often overlooked issue.

Deanna Kelly, so great to see you. Thank you for joining me live here. 

Deanna: 
Yeah, absolutely. My pleasure to be here to see you again, yes. 

Bret: 
So, we had you on before talking about this study that you’re doing, which we’ll get to for sure today. But what I want to talk to you about is really dig into your knowledge as a pharmacist with that background about how our diet can change the way drugs are absorbed and drug levels and how they impact our body.

Because it’s something that I think maybe people don’t think a lot about. As you increase the fat in your diet and transition to a low-carb, high-fat diet, that can actually impact the way your body metabolizes medicine. So, tell us some of the details of that. 

Deanna: 
Yeah, good point. So, there’s a lot I probably have to say about this, but I think we think about drug interactions to be two drugs when they interact. And the food and drug interaction, we don’t think about a lot. So, you’re right. There’s a lot of things that can impact our, the way that our body handles medications or that the way the medications affect our body.

So, there’s really two things at play when we think about these interactions. There’s the idea of pharmacokinetics, and that’s actually what the body does to the drug. And then there’s pharmacodynamic interactions, and what the drug does to the body.

So, there’s two kinds of things at play when we think about pharmacokinetics, what the body does to the drug, we think about how it might be drugs might be absorbed and how that could change. So, the interaction of absorption of high-fat diets could change. It could change the amount of drug that actually gets into the body, but there’s two ways here. So, this is bidirectional, and we don’t think about that often as well.

It’s the idea that the medication could change the efficacy of the ketogenic diet. But then there’s also the high-fat food coming in and how that interacts with the medications. 

Bret: 
Okay. 

Deanna: 
So, there’s really a couple things at play here. And we know a little bit about some medications, especially psychiatric or psychotropic medications, in both the  pharmacodynamic and pharmacokinetic side of things that I could talk about. 

Bret: 
Yeah. So, let’s take them one at a time. So, when you talk about how your body absorbs the medication and how the medication gets into your body. What are some of the medications we have to be most aware of when we’re talking about eating a higher fat diet?

Deanna: 
Yeah, no, that’s a good. So, the thing is we think about being on a ketogenic diet and then in ketosis. And there’s that information. We know that, but in fact, we don’t have a lot of information about someone in a steady state of ketosis. But we do have a lot of information about when someone eats a fatty meal.

Bret: 
Okay. 

Deanna: 
So, they are two different things, so we just don’t know exactly. What’s interesting is that the Food and Drug Administration in the United States in the early two thousands started to require that new medications come to market, be tested in a high-fat condition and a high calorie condition.

So, prior to that, any medications we have, we don’t have a lot of good information. And I’ll get back to it. We have some, but at least there’s trials. And so you’ll find this funny, Bret, but what they actually, the FDA requires for the full fat meal is two eggs fried and butter, two pieces of toast with butter, two pieces of bacon, four ounces of hash browns, and eight ounces of whole milk. So, everyone does that. 

Bret: 
So, they have to eat this meal, and then take the medication. And then they measure how the levels are in your in your body. 

Deanna: 
Exactly. I am so interested how it all goes down at the, at when they’re actually, where they cook it at.

If it’s, but if it’s scrambled with fried, whatever. But in reality that, so then what they do is like half an, so it’s required, the FDA has it laid out, and they recommend this diet, actually they recommend this diet or this meal, and then 30 minutes after the meal, they test the medication availability.

So, the absorption can change in that time period. And some medications, it doesn’t make a difference with. And so if you look at the labeling, like the package insert or the labeling will often say, can take with regards without regards to meals. So, a lot of medications don’t, it doesn’t matter if they’re taken with or without food, but some of them they are.

And some of it just depends on calories and some of it depends on fat. Not a lot, but a few. So, this is for medications that have been brought to market since 2002. So, a couple of things. For example, in in the antipsychotic world, we have the medication lurasidone and ziprasidone.

Now, they’re both medications that should be taken with food because they’re more available, and you get better blood levels. So, there are two things and they specifically, one is specifically with 350 calories or more, and one was a 500 calories or more. So, you have to pay attention. But neither one of them are really matter if it’s fatty or not.

And so, there’s not a lot of, in the class of antipsychotics, we can talk about others, but for the absorption with other antipsychotics, there’s not a lot of interactions, except a couple of things. And so these are kind of like clinical pearls, that are not really out there but you, we can read about it and, you learn about this. But quetiapine, which is the antipsychotic for example, has an XR extended release version.

And so if you give that with a high-fat meal, it actually increases the absorption. You can dump the whole XR and you can get like a high peak, and you might have some side effects. So, that’s one example where with that a medication does absorption can be real, can be changed. But there, the one that I’m really paying attention to right now. So, this is going to be interesting for us, is the new medication that’s out, which is the xanomeline–trospium combination.

And we all knew that this became available, or FDA approved, I think the last week of September. So, it’s only been on a couple weeks. I don’t think it’s hit the market. It hasn’t been, it is not even the pharmacies yet. It’s going to be in a couple of weeks. So, we don’t know what this is what’s going to happen. 

Bret: 
But they’re sure are doing a lot of advertising and promotion for something that’s not even available.

Deanna: 
They are, and so it’s, but what’s what? We have a lot of hope for this medication in our field because it’s the first antipsychotic in my lifetime, in all antipsychotics to be non-dopaminergic. So, it’s a muscarinic. So, it’s involved the cholinergic receptor, so acetylcholine, but it hit on the muscarinic.

So, muscarinic receptors are one type of cholinergic receptor, and this is a medication that’s an agonist. Instead of blocking the receptor, it gives the muscarinic receptor acetylcholine. And we think that this is a mechanism by which could be important for schizophrenia. But when you do that, when you, when you agonize, when you’re an agonist for the receptor, that then, you could have side, you could have these muscarinic or cholinergic side effects like diarrhea, stomach pain, vomiting, et cetera, which is why the medication’s not approved by itself.

Because there’s too many GI side effects. We knew long ago this worked, but it had too many GI side effects. So ,you give it with this other medication called TROs, which blocks these cholinergic receptors in the peripheral but not the brain. 

Bret: 
Yeah. 

Deanna: 
So, if you, so like it’s a combination because we want to get the effective one, but we want to save on the side effects.

The whole reason I’m telling you this is there’s two pieces, there’s two medications involved in. Both of them need to be working at the right dose and the right combination so we don’t get too many GI side effects, et cetera. What we know about this medication is if you look at the package labeling, it’s really impacted by a fatty meal.

And so in it in both, and it sort, I think of it as a potential double whammy here. So, we’re going to have to pay attention because there’s two medications and both of those medications are impacted by a fatty meal. So, not just one or the other. 

Bret: 
Yeah. 

Deanna: 
So, for example, if you give, and it shows you in the labeling, if you give this medication with a high-fat meal, you are going to increase the levels of the main ingredient by 30%.

It’s a lot. 30 % is a lot. But you’re going to decrease the blocker that’s going to help you on your side effects by 70 to 85%. That’s what it says. 

Bret: 
Yeah. 

Deanna: 
Theory, in theory, that could mean you’re raising the blood levels of the one, you’re lowering the levels of the other during a high-fat diet, and you could have a lot of these GI side effects that you’re not anticipating.

And so that’s a long example, long explanation, but it’s a new medication coming to market. And it’s one of the medications, and I’ve talked only about antipsychotics that really could be impacted by fat intake. 

Bret: 
Yeah, so you said it’s a long example, but such an important example. Can you imagine if you didn’t know that and you started taking the medication while you’re eating a high-fat ketogenic diet, and you say, why isn’t this working?

Why am I having so many side effects? It makes complete pharmacokinetic sense. 

Deanna: 
Right? Yeah, we just have to pay attention to it, and how it’ll play out when we go to use it. Could be a little different, but we do have to pay attention to that. Now, there are, you mentioned, the absorption issue. So, in the antiepileptic field, when we’re looking at treatments for bipolar disorder or in epilepsy seizure disorder, there’s several that could be decreased with, their absorption could be decreased.

So, we could actually have breakthrough seizures or breakthrough symptoms potentially, like valproic acid, which is a fatty acid in and of itself. Carbamazepine, lithium are all examples of antiepileptics or meds that we use that actually could have, you could have some breakthrough symptoms because the ketogenic diet might not be as effective with those medications, or they might, their levels might be lowered actually from, yeah.

Bret: 
Lithium’s such an interesting example because practically everybody who’s had an episode of mania is on lithium it seems. So, then if you transition that person to a ketogenic diet, which in theory is going to also help the mania. But maybe in that transition period, if you’re decreasing the lithium before you’ve seen the full benefit of the ketogenic diet, and we talk about how hypomania is a risk in that transition period. I wonder if that has something to do with it, the pharmacokinetics? 

Deanna: 
I think it could very well be. Lithium’s interesting because it’s actually a salt and when we’re dealing with a ketogenic diet, we have to worry about our salt a little bit, too.

And the excretion of lithium is dictated by the kidneys and by the salt intake. There’s literature that kind of goes both ways on a lot of these medications. There’s a lot of controversy because there’s not a lot of well done studies. But lithium’s interesting because in the early weeks, I think that it’s possible when your salt imbalance and water imbalance is off, you could actually have higher lithium levels potentially in some people.

But, so that’s interesting because you’re trying to regulate your salt intake and so that becomes then like a pharmacodynamic or a pharmacokinetic interaction there. So, you could have higher levels, but there’s some evidence also that on the ketogenic diet, longer term you might have decreased absorption. So, fat might decrease the absorption of lithium.

Okay, so there’s a paper out. It’s from 1993. So, this is long time ago, but what it did show us is on a, I think it was eight or nine people on a high-fat diet, you could see that lithium levels were significantly lower when you were on, when you’re eating it with a high-fat meal. But again, we’ve had this medication used for a long time, but people might see that. They might see lower level differences right at first, but then lower levels or low, but that could be an absorption issue from the fat. 

Bret: 
Yeah, and it always goes back to what’s happening clinically as well. Because just because the level’s changing doesn’t mean you necessarily need to react to the level if you’re not having any clinical issues.

And presumably if someone’s doing better with a lower level, that’s a victory, right? 

Deanna: 
Yeah, absolutely. And that, and I think that’s a point, important point that you’re making is that we need to be checking the medications that have a therapeutic window where we have to get the blood levels, we have to pay attention and get those upfront and then monitor them because that’s just it.

It’s going to matter clinically, but we should also have a baseline. We should know what’s happening before so that we could check those levels if we need to. Valproic acid, for example, and lithium are good examples, of just making sure we know, or carbamazepine, making sure we know what it is. And then once we treat with a ketogenic diet, and we can see if that’s changing, we need to do anything different with the dose as well. Yeah, that’s important. 

Bret: 
Alright. So, we’ve talked a lot about how high-fat diets can impact the medication. So, now let’s talk about how the medications can impact the state of ketosis. 

Deanna: 
Yeah, so there’s, high-fat diet could actually lead to, so you have less carb in, and carbs can actually make a difference.

Sugar, changes in sugar can make a big difference in some of your side effects and some of your outcomes with the ketogenic diet. For example, if you had a liquid cough medication preparation, for example, and had lots of carbs in that, and you take that, you could actually have, take yourself out of ketosis, right?

That’s one example. We have other medications, i’m thinking about some of the steroid medications or some of the blood pressure medications like beta blockers, for example. When they raise carb levels, they raise glucose levels in the blood. We don’t think about that all the time, but there’s several classes of medication that can raise glucose.

When that happens, that can bring us out of ketosis. So, then we have that bidirectional. So. The opposite is happening here where the state of ketosis is impacting the medication. So that’s, yeah. 

Bret: 
Yeah, that’s interesting. So, a lot of people who might also have metabolic dysfunction, might have high blood pressure, might be on a beta blocker for that, they have to pay attention to how all those medications can impact your blood sugar. 

Deanna: 
And like some of the antipsychotics that cause weight gain and cause insulin resistance also may make it more challenging to get into ketosis. 

Bret: 
Yeah. 

Deanna: 
And even in, we can come back to my study, but even in my study, for example, the experience I had when wev were trying to get people into ketosis. We had levels of maybe 0.7, 0.8, 0.9, and I was talking to some the other day thinking we should with, what we were that diet were giving me, we should be around 1.0. We should have higher, and maybe that’s such that we’re giving them in combination with antipsychotics that do cause insulin resistance or they all do have some degree of insulin resistance. So we, those are, there’s a lot of things to learn there. 

Bret: 
Yeah, interesting. Because it can make it more challenging, but makes it that much more important as well to try and combat that insulin resistance.

So, I wonder if you find that there’s a point that once you’ve treated that insulin resistance, that now the medication doesn’t impact it quite as much or will that sort of always be a potential side effect of that? 

Deanna: 
Yeah, I don’t know that, but I would hope that we would improve insulin resistance, and then we don’t have to worry even so much about that kind of interaction, yeah. 

Bret: 
Yeah. So, it’s a lot to think about. So when a doctor wants to start a patient on ketogenic therapy and look at their med list and decide how to do this, like you can see how they make it dizzy trying to think of all this. 

Deanna: 
Absolutely, and yeah, a couple things I haven’t even mentioned as there are some medications that have been out for a long time before.

We now have guidance from the FDA for, in the realm of ADHD, i’m thinking of a couple. Adderall, which is methamphetalate, some of these salts, for example, not in the package label at all. So, you can’t, the physicians and treatment teams can’t go and say, oh, this information’s there. They have to find this in the literature.

So, sometimes it’s not, there’s not a lot of good information out there. But like Adderall XR, for example, the levels are decreased when you give it with a high-fat diet, significantly so, I think. That’s an important and sometimes up to, I think, it’s like 50, 60% differences. 

Bret: 
Big difference.

Deanna: 
And so that’s a big difference. And there’s another medication called guanfacine, which is a nonstimulant but often used for ADHD. And that’s one more example that I’m thinking, and I know this is one of the most profound, but it’s a 75% increase under a fatty diet condition. There are, like you said, I’m just trying to round it out and make sure we’re covering all these topic areas.

But those are some examples where you can have profound differences. 

Bret: 
So, this is so interesting because I think your average physician, primary care doctor, psychiatrist probably isn’t going to know this, right? I can’t imagine most people are looking that deep into it because they probably don’t have that many patients in ketosis.

Hopefully that’ll change, but do you think most pharmacists will know this? 

Deanna: 
I think that pharmacists have a lot of knowledge on drug interactions, yeah. And, but I do think that we’ve done a poor job in education systems, in general, around the food and the drug interactions. And I think keto is one area, the whole fat area.

But there are other drug interactions with food. For example, I’m just giving one example, but like charcoal broiled beef induces the metabolic enzymes in the system called the cytochrome P450, and this specifically in this 1A2, which metabolizes meds like olanzapine or clozapine or some of the SSRIs, for example.

And if you eat charbroil meat, you can speed up the metabolism. So, we don’t think about how our diet can impact medications a lot of time. And I think it’s variable probably on training and understanding about that. 

Bret: 
Yeah, no. That one sounds interesting and maybe concerning because it would be intermittent, but how much charbroil meat are we talking about? 

Deanna: 
Yeah, no, exactly. I just gave you an example because it is the first thing that came to mind when I’m thinking diet. But there’s lots of things that could impact, for example, if you drink milk with certain medications, you can, like antibiotics for example, you can, what to cause this chelate. That’s a chelate that forms so they can, it doesn’t become active anymore.

So, it’s just an example. But yeah, we do have to pay attention to everything we put in our body makes a difference potentially in how the drug or how the medication or how the diet’s going to go. 

Bret: 
So, I think the big takeaway would be if you are eating a low-carb, high-fat diet or aren’t or are in ketosis, it’s something that your physician and your pharmacist probably needs to know to make sure there aren’t any other considerations you need to know about with your medications.

Deanna: 
Absolutely, I think it’s all about communication. I think it’s all about talking and being part of a team because one person alone doesn’t have the, all the knowledge, one person alone doesn’t have all the time to be focused on these things. So, when we’re in a team-based approach or you utilize all the people around you to help, I think it’s important to talk about it. Talk to your pharmacist about it and say, hey look, I am on a ketogenic diet.

Is there anything I need to be concerned about with my medications? And they might say, oh, I didn’t even think to look about that. Thanks for bringing that up. And so even bringing up to your physician and he might say, talk to your pharmacist. But that communication, so advocating and just think, as someone taking a ketogenic diet, I would encourage people to make sure that their healthcare team members know that.

It’s important. And then, like I said, it’s important for us to be monitoring the medication blood levels that might have important ranges to keep in mind, yeah. 

Bret: 
And as were talking about earlier offline, the pharmacist, I guess, is maybe like an underutilized part of the healthcare team.

Not really thought about as part of the healthcare team as much, but could be such an amazing resource, especially for something like this. 

Deanna: 
No, absolutely. And the thing is that most people are going to come face-to-face with their pharmacists more often than they’re going to see other members of the treatment team.

So pharmacists, and I’m talking community pharmacists now become an important member of their team, asking them questions. They’re trained clinically. Now, all pharmacists come out with their doctors. They’re trained clinically. They’re not in like in days past, just learn how to dispense medications.

They know how medications work, right? They know side effects of medications, and they learn a lot about patient care. So they’re really trained in helping to answer those questions, helping to understand like what’s important to know. So, I like utilize their brains and the resources that they have.

Bret: 
Yeah. 

Deanna: 
And then the other thing is, my specialty is psychiatric pharmacy. So, there’s about 3000 of us specifically trained and board certified in psychiatric pharmacy practice. And if someone was lucky enough to come across a psych pharmacist, there’s this specialty and advanced knowledge that they have, but they’re on a lot of treatment teams.

They’re on a lot of care teams in community mental health centers, et cetera. They have a lot of knowledge and they actually help physicians often understand these interactions. And pharmacists are, yeah, important to keep involved. 

Bret: 
Very important. 

Deanna: 
Yeah. 

Bret: 
Alright. Now that was a wonderful discussion, but now let’s circle back to the study that you were doing at, Maryland, at University of Maryland at the inpatient study on ketogenic intervention for schizophrenia. A basically sort of landmark study, which showed so much promise and so encouraging, which was then shut down by the health board. We have a whole other episode, not for any clear reason that we can see.

So, what’s been the fallout? What’s been the reaction and the fallout and where does that stand now? 

Deanna: 
Yeah. No, this was a whirlwind of a spring and very unfortunate that we had our studies initially shut down by the Department of Health for no cause at all. I think it was just making sure that everything was in order.

Lots of other things at play. But, then were allowed to have all of our clinical trials continue that were federally funded. There was a lot of pressure from the federal government, but also those were allowed to go. , This left us with the closure, continued closure of the ketogenic diet study, unfortunately, which is really unfortunate because physicians recommended this medication.

All patients got a chance to be on a ketogenic diet, and there was an initial, double our initial, randomized phase where it was a regular diet or keto. But then, everyone got eight weeks of a keto diet. So, those were opportunities that people just don’t have regularly and in a controlled environment where we have, we can make changes through diet, et cetera.

So I did, the field really rallied to the support. I’ve just been like really humbled by the community. The community and so there was a petition that Dr. Chris Palmer developed, and if you haven’t seen it, I think it’s around 21,000 signatures. That’s no small tat. I was blown away. This is the community rallied and when you look through and you read what people have to say, what’s happening is our patients and people out there with severe mental illness, bipolar, schizophrenia, are saying, you know what?

Medications haven’t worked. I’ve had side effects. I deserve a chance to have a treat, to be treated with the ketogenic diet. We deserve to have these, this science out there. And so people, so it was not only the medical community, but the lived experience community all rallied. I did submit an appeal in August, an official appeal requesting to the governor’s office and to the Secretary of Health in the mental, in the Department of Health requesting, and I have not heard back yet.

I will move forward somehow because it’s really important and this, the science is really emerging. So, whether we need to change that and move to outpatient or do something different. But right now, I’m still not giving up hope, and we’ll continue to fight for this study. 

Bret: 
Yeah, i’m glad you’re not giving up, that you’re as committed as ever and looking for alternatives. But I think it is just such a wonderful example of the community and everybody recognizing the importance of a study like this and how it could change so many lives. If the science is there, if it proves to do what we think it can, the impact would be tremendous. So, it’d be ashamed to not see this through.

Deanna: 
I agree completely.

Bret: 
Yeah, wonderful. Thank you for all your work and everything you’re doing. And I hope one day, we’ll have you back to talk about the results of that study, which will happen and should happen.

Deanna: 
I would love to. Thanks so much for having me. 

Bret: 
Alright, thank you. Thanks for listening to the Metabolic Mind Podcast.

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