
The Y in Psychiatry
"The Y in Psychiatry" – a pragmatically endearing podcast talking to the med students, residents, fellows, and attendings of the medicine world about the nuances of psychiatry.
Each episode features focused discussions that explore the intersection of the mental health, medicine, and the human experience.
Together, we'll uncover the hidden "Y" – the compelling reasons, profound insights, and groundbreaking discoveries shaping the psychiatric landscape.
So grab a seat, warm beverage, tune in, and let's embark on this journey to unlock the mysteries of the human psyche, only on "The Y in Psychiatry."
The Y in Psychiatry
E13 - Kidneys don't Kid Around with Antidepressants
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In this episode, Dr. Handratta and Dr. Amayo explore the importance of the kidney in psychiatry and discuss the impact of renal disease on medication management. They provide insights on dosing adjustments for various medications and highlight the role of the kidney in drug excretion. Tune in to unlock the mysteries of the human psyche on The Y in Psychiatry.
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So why is cytochrome P450 called cytochrome P450?
Dr. Amayo:What? That
Dr. Handratta:Enzymes are so named because. There are bound to memories within a cell and contain a heme pigment. Yeah, and because of heme it gets chrome, the name, and because of the pigment. The first letter is p. that absorbs light at a wavelength of 450 nano more when exposed to carbon monoxide.
Dr. Amayo:That's a weird reason to give an enzyme name. You must be fun at parties. I will.
Thanh:Welcome to the Y in Psychiatry!
Dr. Amayo:Hi, this is Dr. Amayo C/L fellow.
Thanh:Where we delve into the intricate nuances of psychiatric topics.
Dr. Handratta:My name is Dr. Handratta attending psychiatrist. I did my residency from University of Connecticut and then I did my fellowship from Georgetown University in consultation and liaison.
Thanh:Each episode features interview style discussions that explore the intersection of the mind medicine and the human experience. Together we'll uncover the hidden why and the groundbreaking discovery shaping the psychiatric landscape. So grab a seat, warm beverage, tune in, and let's embark on this journey to unlock the mysteries of the human psyche. Only on The Y in Psychiatry.
Dr. Amayo:Welcome back to the Y in psychiatry. Today we'll be continuing our series depression in special population, and we'll be focusing on renal disease as usual. I'm your host, Dr. Amayo, consult and liaison fellow. And I have Dr.
Dr. Handratta:Hi. And this is Dr. Handratta attending psychiatrist.
Dr. Amayo:And so today, last time we talked about the liver. Today we're talking about the kidney. And the question is, why is the kidney important in psychiatry? Yeah. Why should we talk about the kidney?
Dr. Handratta:So now for psychiatrists, brain is the primary organ.
Dr. Amayo:What is life?
Dr. Handratta:Yes. And cardiologists will say, heart is life. I didn't. Yeah. So we all like, actually, like there will be a tough war on this. But we need to know about kidney because as we talked about in the previous episode, how liver plays an important role in drug metabolism. Kidney also plays a very important role, especially in excretion of the drugs, right? Majority of our medications, not all after they are metabolized in the liver, are conjugated and made water soluble and excreted through the kidney, right? So the drug can be excreted either in the feces or in the, your right. So patients who have renal disease, there will be a problem in the way our body handles the drug. And plus patients with renal disease also have increased comorbidity with depression. Again, actually the incidence rate actually of depression is, it's a huge range actually, but it's usually like around 30 to 40%, especially patients who are on dialysis.
Dr. Amayo:Okay. So the kidney is important for excretion. And again, we see there's a lot of comorbidities with depression and kidney failure and treating the depression improves outcome. And so what specific role or what specific way does the kidney excrete our medications?
Dr. Handratta:So kidney plays an important role with the medication excretion. We know that, right? So when in renal disease, there's a decrease in the urine output and there's a decrease in the glomerular filtration rate. So the medications, which goes through the kidney, is going to accumulate in a systemic circulation causing toxicity, right? Patients with renal disease, they also excrete a large amount of albumin so patients can have hypoalbuminemia. And we know that a lot of our psychiatric medication bounds to albumin
Dr. Amayo:By the last time.
Dr. Handratta:Exactly. And then it's a pre form of the medication that is active. Yeah. And then patients with renal disease, there is also an increase in the level of urea and urea will now compete with albumin with the medication. So further increasing the free form of the medication causing more toxicity. So these are the three reasons why people with renal disease can experience toxicity when antidepressants are not dosed in a proper way.
Dr. Amayo:Okay. And I know there's a nomenclature for grading kidney failure or kidney disease using the creatinine clearance. Can you. Can you remind me of those number of questions and are those important for us? Let knowing like when should we prescribe this medication?
Dr. Handratta:Yes so there is an app where you can calculate the estimated creatinine clearance. Don't ask me the formula. Yeah. So you put in the, you punch in the numbers actually in the, prelbuadmin clearance calculator and based on the number they didivide into when is normal function, so we have to talk about normal, right? Yeah. So normal estimated creatinine clearance is more than or equal to 80 ml per minute, okay? Mild is in the range of 51 to 80 ml per minute. Okay? Moderate is from 31 to 50 ml per minute. Severe is less than or equal to 30 ml per minute. And end stage renal disease is when you require dialysis is less than 10 ml per minute. Basically for simplicity, we say normal functioning, mild, moderate, severe kidney disease or end stage renal disease.
Dr. Amayo:Yeah. Okay. And what medications should we, what medications can we give or should we stay away from towards the severe and ESRD?
Dr. Handratta:Umm, there are a lot of medications that we can talk about, but the ones that I want to stress about in this particular podcast. Some of them I'm gonna name. So Venlafaxine, vex, right? Metabolic of venlafaxine. That is desvenlafaxine. Then we have duloxetine, uh, we have Bupropion and we have levomilnacipram. I hardly use it levomilnacipram, but there are psychiatrists who do use levomilnacipram. So we have to be careful with these four medications in patients with renal disease. So let's look at venlafaxine. Like how do we dose venlafaxine in patients with renal disease? So it's not like renal toxic, but it's excreted by the kidney. More than 80% of venlafaxine goes through the kidney and excreted out, right? So in patients who are mild, moderate, and severe renal disease, we decrease the dose of venlafaxine by 25 to 50%. So you can still use it, but you decrease the dose to prevent the toxicity and accumulation, and in patients with stage renal disease, you drop down the dose of 50% and wait till the dialysis,
Dr. Amayo:So you dose after the dialysis.
Dr. Handratta:Okay. You give one time dose, wait till the dialysis is done, and then give the second dose, which is 50% or before the renal toxicity. Okay? Then you have desvenlafaxine, which is a metabolite of venlafaxine. Again, more than 80% is excreted by the kidney. So with desvenlafaxine, you can get away with mild renal disease, you can dose it exactly the way you dose it, right? Whereas in patients with moderate renal disease, you don't go above 50 milligram every day, right? And in patients with severe and end stage renal disease, you dose it at 50 milligram every other day, right? So you can still use this medication, but you have to be careful how you dose them.
Dr. Amayo:And for the desvenlafaxine, does it matter when they have the dialysis all done? Do you It doesn't matter. Okay. It doesn't matter.
Dr. Handratta:Yeah. As long as you give it 50 milligram every other day. Yeah. Okay. And then you all got duloxetine. So this is a medication that will be used actually by physicians, even if the patient is in severe or end stage renal disease. And there's a common mistake that I see again and again while I do consultation/ liaison psychiatry. So duloxetine, once your estimated clearing creatinine clearance is less than 30 ml per minute, you stay away from duloxetine. Interesting. The reason being is that the metabolite of duloxetine, the area under the curve, that is the amount of medication is about seven to nine times higher in patients with renal diseases compared to healthy control. And that itself can be toxic. Plus it can also cause hepatotoxicity. Yeah. So you have to be careful with duloxetine.
Dr. Amayo:So once they reach severe stop duloxetine. Yes. And do a different medication.
Dr. Handratta:Exactly. And again, I'll say, don't stop it cold Turkey. Yeah. Because duloxetine has a very short half-life and is one of the medication which has really bad serotonin withdrawal. So whenever I'm prescribing patients duloxetine or venlafaxine or desvenlafaxine, I tell the patient, keep at least a week supply in your office so that if you forget it at home, at least you have a medication in your office which you can take because the withdrawal is bad. You feel the withdrawal by the end of the day. Yeah. Okay. Then you got bupropion. Bupropion. So Bupropion is a medication we extensively use in psychiatry. Yeah. Because it's one of the medication which does not cause sexual side effects. Yeah. Plus it's one of the medication that does not cause hyponatremia. So people feel comfortable using it. Plus it gives you the boost of energy because in depression you have a decrease in the energy level. So with Bupropion you can actually improve it
Dr. Amayo:And it helps with apathy.
Dr. Handratta:Exactly. And it helps with apathy helps with smoking cessation. Oh, wow. It helps with ADHD. Yeah. Yeah. So it does though it's all not FDA approved. Yeah. So with Bupropion, it's broken down into a metabolite called hydroxy-bupropion, which has approximately 50% of the activity of bupropion. In a healthy individual, the concentration of the metabolite is 10 times that of a parent compound. Just imagine patients with renal disease, plus patients with renal disease will have problem with sodium if they have hyponatremia. You give bupropion, you're decreasing the seizure threshold, and you're increasing the risk of seizures, right? So Bupropion, you have to be careful. In mild and moderate bupropion extended release, you can dose normally. Okay? But in severe and end stage renal disease, you give them 150 milligram every third day, right? So you have, be careful. And if you're using an immediate release, bupropion mild, you're fine. Be a little careful. Start low, go slow. Yeah. And then in moderate severe, at end stage, 75 milligram per day. So you have to be careful with Bupropion because you don't want to induce seizure in these patients, right? Levomilnacipram, I don't use it, but that does not mean that it's not a good medication. I do not have too much experience with it. buT it has a relative contraindication in in patients with end stage renal disease. So when you're using it, be careful in end stage renal disease.
Dr. Amayo:iS there any medication that has your approval? No, it seems like we, we hit all the SNRI. How about the SSRIs is it relatively good in renal disease.
Dr. Handratta:So most there are two SSRI which are, relatively safe It says safer in patients with renal disease, which we commonly use. One is sertraline and there is one, one property of sertraline in that makes it actually the medication of choice is because it prevents post dialysis hypotension. Do not ask me why. I do not know. I tried to look up for that and I could not find anything.
Dr. Amayo:Post dialysis apathy. Prevents that.
Dr. Handratta:Yes, it prevents that. And we do not know how does it do it. And then the other medication that is safer in patient renal disease fluoxetine flux. But one caution with fluoxetine is that it has a lot of drug interaction. Yeah. Please look up the drug interaction before you prescribe fluoxetine because patients with renal disease will be on polypharmacy.
Dr. Amayo:And fluoxetine has a long half-life.
Dr. Handratta:Yes.
Dr. Amayo:Is it cleared renally or
Dr. Handratta:Fluoxetine it's metabolized in the liver and then it does actually but it does not accumulate in the system does.
Dr. Amayo:Yeah. Okay. Okay. And so just to recap so kidneys are very important. They help with excretion and the biggest way that we can lead to toxicity is toxicity, is because of the reduced albumin in nephrotic syndromes. The increase in urea, which fights with, which reduces the plasma protein binding capacity of medications leading to high. Free medications and so this, so in kidney disease there's a higher risk of toxicity in these patients. We estimate creatinine clearance using the mild, moderate, severe method. And we talked about this. Five medications, desvenlafaxine, bupropion, levomilnacipram. And, and in venlafaxine, it's okay to reduce the dose by 25 or to 50% in mild, moderate, severe. And then in ESRD you give 50% of what you normally give and you give it after dialysis. In does venlafaxine, it's okay to reduce the dose around mild and moderate by severe. And ESRD give 50 milligrams every other day. Duloxetine, I would say stay away from. Because you accumulate a lot of the metabolites and increases, increases chance for both liver damage and as well as just as toxicity for bupropion. There's an increase in the metabolite as well and increases risk for seizures. So stay away with severe or ESRD and levomilnacipram has a relative contraindication in ESRD. Yeah. Sertraline and fluoxetine is relatively safe in this patient population. But be careful for fluoxetine drug-drug-interactions. Sertraline helps with post dialysis hypotension Yes, but our guru doesn't know why. So that's all we have on today for the Y Psychiatry.
Dr. Handratta:Thank you. Thank you.
Katrina:Thank you for joining us on today's episode. Our tireless team is already hard at work, cobbling together another potpourri of fascinating discussion for next week, so be sure to tune in, visit our website and our podcast feed and let us know your thoughts on the episode. Subscribe so you don't miss our releases every Wednesday. Until next time, keep smiling, keep shining, and stay curious.