E8 - Depression - Continuing the Serotonin Soiree: Fluoxetine and Fluvoxamine

Join us this evening for a soiree that will give Bridgerton a run for its money. But not really cause it'll be jiving to the conversation of fluoxetine and fluvoxamine: the twins of SSRIs that never were. Got that warm beverage ready yet for this episode?

Good.

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Transcript

Dr. Amayo: 0:00

Do you, Thanh, you guys eat whole fish like that with the head? I know some Americans get freaked out when they see the head.

Dr. Nguyen: 0:06

My, my mom used to like, try to get me to eat like the eyeballs of the fish. No mom, nothing, she, but she would just be like gnawing on the head of the fish as well. And I could never get into it.

Thanh: 0:20

Welcome to the Y in Psychiatry!

Dr. Amayo: 0:22

Hi, this is Dr. Amayo C/L fellow.

Thanh: 0:25

Where we delve into the intricate nuances of psychiatric topics.

Dr. Handratta: 0:28

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: 0:38

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: 1:05

Welcome back to the Y in psychiatry. Today we are going to be continuing our series of strategy for choosing an antidepressants. Just to give you a quick reminder, our last episode we talked about citalopram/escitalopram and sertraline, and why not to choose this antidepressants Today we'll be talking about more antidepressants with Fluvoxamine, fluoxetine, venlafaxine and duloxetine. As usual I'm your host, Dr. Amayo C/L Consultant/Liaison Psychiatry fellow, and we have Dr. V.

Dr. Handratta: 1:44

Hi, this is Dr. Handratta how are you guys doing?

Dr. Amayo: 1:49

Alright, so Fluvoxamine is a medication that I've always stayed away from, I don't think I've ever prescribed fluvoxamine. Seems like it has a lot of side effects. Seems like it's not that effective. As a matter of fact, I don't even think I knew fluvoxamine was a antidepressant to like my third year of residency. So why or why not should we take fluvoxamine?

Dr. Handratta: 2:09

That's a great question. So a lot of people have not either heard of fluvoxamine or they confuse it with Fluoxetine or they've not actually used it at all, right? They might have heard of it, but not gotten an opportunity to use it. With my experience and my practice, I've used fluvoxamine plenty of times. And especially I use fluvoxamine a lot in patients who have obsessive compulsive disorder. I sometimes combine fluvoxamine with clozapine, but you have to be very careful with that combination because it can increase the clozapine level. We'll talk about that. So fluvoxamine is an SSRI, right? But it also actually has a good potency towards 5HT3 receptors. And as we know, 5HT3 receptors are present in your gut as well as they're also present in your chemo receptor trigger zone. So when you stimulate the 5HT3 receptors, you can induce nausea and vomiting, right? And we have medications that block this receptor, which are used as antiemetics, like ondansetron, right? So fluvoxamine can stimulate 5HT3. So the common side effects that you see during the first one to two weeks is headache, nausea, and vomiting, right? So always tell the patients to take fluvoxamine with food, right? But the 5HT3 receptors will downregulate over a period of time, like in a week or two weeks and the side effects will subside. Right. Now fluvoxamine is a great antidepressant once you start tolerating it, you have to dose it in the evening. Because it's sedating, but because of the short half-life, you have to dose it twice a day. But now you have an extended release formulation of fluvoxamine, which you can give once a day in the evening. It's an SSRI safe in liver disease. You can prescribe it to patients with cirrhosis. It is safer in pregnancy. It's safer in cardiac disease as well as in renal disease. It's not the choice in renal disease. Renal disease the choice is going to be either sertraline or fluoxetine But the patient has not tolerated sertraline or fluoxetine and you don't have anything else you can use fluvoxamine. And as Dr. Amayo just mentioned, there's a lot of drug interaction. Three cytochromes: cytochrome 1A2, cytochrome 2C19, and cytochrome 3A4. So you have to be very careful when you're combining fluvoxamine in patients who are on a bunch of cardiac medications, right? Or they are on a bunch of anticonvulsants. Or if they're on a mood stabilizers. So you have to be a little careful. You have to look at the drug interaction. I'm not gonna go through each and every medications that it interacts with, right? But something to look for when you're prescribing fluvoxamine. Now there's also a study that was done where fluvoxamine is combined with clozapine to reduce the weight gain by Clozapine, right because it's an inhibitor of cytochrome 1A2. It prevents the breakdown of clozapine to a metabolite called norclozapine which is considered to be cytotoxic, which can also cause weight gain. But the problem here is that you have to be very careful and you need to monitor the clozapine level because if you do not monitor the clozapine level, you can reach a toxic level of clozapine and we know what happens if the clozapine level is too high, right? You can actually develop agranulocytosis as well as seizures. And also keep an eye on acute myocarditis with the clozapine, right? So these are board questions, side effects of clozapine, right? Acute myocarditis is something that is commonly missed by people actually when they are on clozapine. So you can combine fluvoxamine with clozapine. It's an off-label use to prevent the weight gain, but be careful monitor the clozapine level. Does it make sense?

Dr. Amayo: 5:51

Makes sense. A lot to come up with Fluvoxamine. I did not know it was that. It was that special. All right, so big highlights here. It's a 5HT3 agonist, so you get a lot of headaches and nausea when you're first starting. So take with food, take at night short acting medication, but there is a long acting version of it Inhibit 1A2, 2C19, 3A4. For that 1A2, you can use it in combination with clozapine to help reduce the metabolite of clozapine and hopefully that would help reduce the weight gain. But be careful, you might increase the level of clozapine. Good in liver. I was wondering with all this, with all these reactions with the CYP enzymes. Why is it still good with liver?

Dr. Handratta: 6:35

Because it does not go through first pass metabolism. Oh plus it doesn't have a too high a plasma protein binding. Okay, so it's much safer.

Dr. Amayo: 6:44

So even though liver doesn't do much with it, it still affects the enzyme to the liver, but it can be metabolized and excreted even if you have lower liver function. And it's safe in pregnancy, not too crucial in renal. Okay. So those are the highlights for Fluvoxamine. Now let's talk about fluoxetine. I think Fluoxetine is your favorite

Dr. Handratta: 7:06

hahahaha. Fluoxetine, it's a great medication. I don't use it a lot.

Dr. Amayo: 7:12

Does big pharma pay you for fluoxetine?

Dr. Handratta: 7:16

Fluoxetine is a great medication, don't get me wrong. Alright, so the thing with Fluoxetine is that it's is a long halflife, So on one hand it's good for patients who are non-compliant with treatment, right? But on the other hand it is very difficult to take the patient off the fluoxetine and start them on something that is inhibited by fluoxetine, right? So when you're doing a cross titration, it becomes a little bit tricky when you're using fluoxetine. So let's talk about fluoxetine, right? I do use fluoxetine. It's not that I don't use it, I do use it in younger population who are not on too many medications like cardiac medications or cholesterol lowering medications, or antidiabetic, things like that. Right now, the biggest advantage of fluoxetine is a long half-life, right? It stays in the system so you don't have to worry about patients withdrawing when they miss one or two doses. In psychiatry, we know that patients are non-compliant with medications, right? So we never actually ask the patient, Hey have you been forgetting your medication? The best question to ask is we all forget to do things. How many days in a week have you forgotten or to take your medication? That's a better way actually, to put it and the patients will come forth and say, hey, I've missed one or two dose. And that's very normal, right? So it's great actually in that situation. Patients are forgetting medications you cannot prescribe them fluvoxamine because it is a short half-lifethen they'll withdrawal, right? Or paroxetine. So that is the biggest advantage of fluoxetine. The long half life, even after you stop the fluoxetine, it takes five weeks for fluoxetine to be flushed out of the system. So again, the dose titration, you have to be careful, right? You have to titrate the dose once every four weeks because a steady state takes about four weeks. So if you do a very rapid titration, you can actually induce toxicity. Fluoxetine is safer in patients with renal disease. So the two antidepressants we prefer is fluoxetine or sertraline in patients with renal disease. In patients with liver disease, you can actually give it, but be a little careful, It's not like a total contraindication in patients with liver disease. Pregnancy: you can prescribe fluoxetine patients with pregnancy, right? The two plus fluoxetine is also considered to be safer in patients who have cardiac disease. You can actually give it to them, but also let's make sure that you look at the drug interaction. Okay? Because it can interact with a lot of cardiac medications, right? Fluoxetine. Fluoxetine also inhibits a bunch of cytochromes, okay? So it can inhibit cytochrome 2D6, 2C19 and 3A4 And we know that a lot of medications are metabolized by these many cytochromes, especially 2D6 is involved in the metabolism of a lot of cardiac medication. So you have to be careful with that particular interaction. Be very careful combining fluoxetine also with a medication called clopidogrel, right? Which is basically used in cardiac patients as well as stroke patients. Because clopidogrel is processed by 2C 19 and Fluoxetine inhibits it. So just make sure that you look at the drug interaction when you're prescribing fluoxetine.

Dr. Amayo: 10:29

That is it for Fluoxetine. So Fluoxetine seems like the big deal for Fluoxetine is this long half life. So take your time when you are titrating up and take your time when you're titrating down as well. And then, be careful for serotonin toxicity if you're gonna switch. Make sure you give enough time for the fluoxetine, to be out of the system. And also another big deal would be the drug interaction. Seems like it's a potent inhibitor of 2D6, 2C19, 3A4, and a lot of cardiac medications. Uses these enzymes, especially called clopidogrel which for it to be active, it needs to be metabolized by 2C19. So if fluoxetine is blocking this enzyme they might get to a stage where their platelets are functioning too well.

Dr. Handratta: 11:14

And there's one more thing actually, fluoxetine is that once you hit an 80 milligram dosage, the FDA requires that you get an EKG because it can be associated with QTC prolongation and fluoxetine. This is a board question for people. It can inhibit its own metabolism because fluoxetine is by cytochrome 2D6. It inhibits 2D6 so it can actually inhibit its own metabolism, increasing its plasma level. So those are the two things to be a little bit careful with fluoxetine.

Dr. Amayo: 11:44

That's good to know. And so even though it can prolong Q T C, this is not a problem to you get to 18 milligrams. Yes. Okay. I think that's it for Fluoxetine. Alright. Next we have. Duloxetine. This is my favorite medication.

Dr. Handratta: 12:03

Yeah. So duloxetine is a lot of people's favorite medication, right? It's used actually by internal medicine. It's used by rheumatology. It's used by pain medicine people. So it's a very, it's a favorite medication by a lot of specialties, right? So duloxetine is not an SSRI, it's an SNRI, right? It inhibits serotonin transporter, as well as norepinephrine transporter. So it'll increase two different neurotransmitters. Now, duloxetine, the one thing to be a little bit cautious about duloxetine is its short half-life. So duloxetine, if a patient misses a dose, they will feel the side effects by the end of the day or the next day, right? So I always tell the patients, actually keep few pills in your office drawer so that even if you forget to take it at home, when you're in your office, you have a prescription, few pills that you can take to prevent because the serotonin withdrawal can be pretty unpleasant. So that is one thing that I'll be careful with duloxetine, because a lot of patients will stop it if they start experiencing the withdrawal symptoms, right? Because a lot of times patients think if you have withdrawing, that means that you'll get addicted to it. That's not the situation here. We'll talk about the definition of addiction when we talk about substance use disorder. So duloxetine, few things about duloxetine right? It's great in patients with major depressive disorder. It also has some off-label uses. Duloxetine can also be used in patients who have major depressive disorder with stress incontinence. It's not F D A approved for it, but it works in patients with stress incontinence. Duloxetine can also be used in patients with chronic pain who have depression with chronic pain. Duloxetine can also be used in patients with depression, with fibromyalgia, because patients with fibromyalgia can have depression. Few things about duloxetine you should be careful in patients with liver disease. If patients have liver disease, you should not prescribe duloxetine to those patients, right? Patients have renal disease. You have to be careful actually prescribing duloxetine, right? If the creatinine clearance is less than 30 ml per minute, stop duloxetine right? Because it'll cause accumulation of its metabolite that can be toxic Otherwise it's a great medication to be used.

Dr. Amayo: 14:17

But yeah, so duloxetine is a great drug, so seems like it's a short acting one, so be careful for those withdrawal. It's an SNRI. So it helps with pain, chronic pain, fibromyalgia, neuropathic pain Be careful with liver disease and renal disease. So severely renal disease with creatine clearance less than 30, that's when you should probably stop using duloxetine

Dr. Handratta: 14:37

Another thing actually before we end is duloxetine also be careful with drug interaction because it's a moderate cytochrome 2D6 inhibitor, so be careful combining with medication that is metabolized by 2D6 especially cardiac medications. So pay some attention on the drug interaction when you're prescribing it.

Dr. Amayo: 14:52

What's QTC prolongation like?

Dr. Handratta: 14:54

The data is patients who have overdose on duloxetine because it's an SNRI can cause tachycardia, right? But the problem with a lot of the research article is that they've used Bazett's formula to calculate the Q TC interval. But when you use Bazett's and the patient has tachycardia, it'll overcorrect for the QTC. So you should not use Bazetts's, you should use other uh, formula for the for calculating the Q TC interval. So duloxetine can still be used, just make sure that the patient doesn't have an underlying cardiac condition. But if the patient has an underlying cardiac condition, I'll say just get an E K G. Just for the medical-legal purpose, right? You don't have to, but just for the medical-legal purpose, monitor the QTC and just monitor the patients while they're on duloxetine

Dr. Amayo: 15:38

And that's it for today's episode on the Y in psychiatry.

Dr. Handratta: 15:40

Thank you guys.

Katrina: 15:45

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.