70. Anxiety that has failed 2 SSRIs: How to switch and which med to choose next with Dr. Strawn

SSRI Switching in Pediatrics: When to Try a Third SSRI, When to Use Luvox, and Key Metabolism Pearls

Dr. Elise Fallucco continues her discussion with child psychiatrist Dr. Jeffrey Strawn (University of Cincinnati; co-author of Stahl’s DePrescribing) on practical tips regarding how to stop/decrease an SSRI and switch to another SSRI (or SNRI) for pediatric anxiety. 

Highlights from the Episode:

• After trying 2 different SSRIs for pediatric anxiety, in most cases, it makes sense to try a third SSRI as opposed to an SNRI
  • Rationale: SSRIs tend to be more effective and have fewer side effects than SNRIs
• "We Don't Talk about LUVOX": Luvox can be a great option for youth with OCD OR anxiety (generalized, social, separation)
  • Dosing strategy: start at 25mg with the plan to titrate up to a target dose of 150-200mg
• Consider grouping 3 of the SSRIs by their similar metabolic pathways (2C19): Sertraline, Citalopram, and Escitalopram
  • If your patient develops significant side effects on a low dose of one of these 3 meds, they MIGHT be a 2C19 poor metabolizer, which means that you may want to avoid trials of the other 2C19 meds in the group
• Fluoxetine has a LOOOOONg half-life: and it's related 2D6 inhibition will persist 4–5 weeks after stopping Fluoxetine - and affect the metabolism of other 2D6-metabolized meds during that time
  • The 2D6 group includes meds like Fluoxetine, Paroxetine and 2 of the SNRIs: Duloxetine and Venlafaxine

-- And Check Out  Dr. Jeffrey Strawn's new book which I highly recommend - Stahl's Deprescriber's Guide available on Amazon!

00:00 Introduction of Dr. Jeffrey Strawn

00:38 Preview of Episode: Switching SSRIs, when to use FluVOXamine or SNRIs, plus 2D6 and 2C19 metabolism of antidepressant medication

01:59 Try 2 different SSRIs or Duloxetine?

03:45 CYP 2D6 Inhibition with Fluoxetine

04:28 Clinical Pearl: Fluoxetine 2D6 inhibition continues 4-5 weeks after stopping

05:05 2D6 Metabolized Antidepressants: Venlafaxine, Duloxetine, Paroxetine

05:31 Choosing a Third SSRI

05:48 SSRIs generally more effective, fewer side effects than SRNIs in youth

06:49 Only 1 SNRI for child anxiety

07:27 People forget about Fluvoxamine

08:30 Sertraline and Es/Citalopram 2C19 metabolism

09:32 Fluoxetine to FluVOXamine cross-titration

11:16 Gratitude for Dr. Strawn

11:31 Check out Stahl's DEPrescribing Guide

12:23 Recap of Advanced SSRI and SNRI case discussion

Check out our website PsychEd4Peds.com for more resources.
Follow us on Instagram @psyched4peds

Transcript

Introduction of Dr. Jeffrey Strawn

Dr. Elise Fallucco 0:21

Welcome back to Child Mental Health for pediatric clinicians helping you, health kids. I'm your host, Dr. Elise Fallucco, child psychiatrist, and mom, it is a great honor and a joy to be able to continue talking with Dr. Jeffrey Strawn. Child psychiatrist extraordinaire, professor of psychiatry at the University of Cincinnati. College of Medicine and co-author of the new book Stalls, DEPrescribers Guide. Which is an incredibly user-friendly manual to help us figure out the best ways to take patients off of various psychotropic medications and or switch them from one medication to the other. And today we're continuing our conversation. About SSRI medication. We're gonna talk about the most popular and famous SSRIs, fluoxetine, sertraline and e citalopram or citalopram, but also talk about in which cases we would use Fluvoxamine or Luvox, We will talk about when Dr. Strawn recommends switching to an SNRI as opposed to an SSRI and the latest science clinical applications. About varying metabolism of medications through the cytochrome system, the 2D sixes, the two C nineteens, and what that means for us as we're prescribing and de-prescribing meds. But most importantly, while this is a lot of advanced technical talk. We wanted to ground it in a discussion of real clinical cases. Without further ado, let's continue our conversation with Dr. Jeffrey Strawn. So let's go back to another fun clinical example to test our knowledge.

Dr. Jeffrey Strawn 1:59

All right, let's do it

Dr. Elise Fallucco 2:00

The patient who failed sertraline 150 got switched to Fluoxetine, titrated up to, let's say, 30 or 40 now has failed that trial of a second SSRI. So the question is, do you switch the patient to a third SSRI or do you move to an SNRI for their anxiety?

CYP 2D6 Inhibition with Fluoxetine

Dr. Jeffrey Strawn 2:20

This is for anxiety. so I, I would probably still try another SSRI. Um, there's probably some caveats there or some asterisks or asterices, uh, that I would, would add. One is that, if, if there are a lot of physical symptoms, I might move towards something like a duloxetine. Let's say they'd had a high dose of sertraline in an earlier trial, and not had any tolerability concerns and not had any benefit, I probably wouldn't go to e citalopram or citalopram, just because I'm thinking is there a possibility that that patient may be an ultra rapid metabolizer in terms of two C 19? So maybe I'm not going to another two C 19 metabolized medication. But I love this example of Fluoxetine because I think this is one of the few medications that we've actually studied in child psychiatry in terms of relapse prevention studies. Those older studies by Graham Emsley and, and colleagues,, and Taryn Mays and others. It's also one where its kinetics make things a little bit more challenging or actually maybe a little bit easier depending. So let's take a second, maybe unpack that. So in the case of fluoxetine, as we know, we can certainly discontinue that relatively rapidly. And if we look at the pediatric studies that have stopped it, they've generally from doses of 40 milligrams, decreased to 20 milligrams per week and then stopped it. I think that is certainly very, very reasonable.

Dr. Elise Fallucco 3:54

And just as a quick reminder, you know, because Fluoxetine has such a long half-life, the medication almost self tapers, and so you can go from 40 to 20 for about a week before stopping.

Clinical Pearl: Fluoxetine 2D6 inhibition continues 4-5 weeks after stopping

Dr. Jeffrey Strawn 4:06

Absolutely. Now, the other issue where this becomes a little bit more important is if I'm going to a medication, let's say even something that's not an antidepressant that is metabolized via 2D six. Remember, fluoxetine and nor fluoxetine are pretty significant inhibitors of 2D six, and so that effect will persist over that time period when the medication is self tapering. So I'll still have Prozac related 2D six inhibition over those four or five weeks after I've stopped the medication, and that may have some implications in terms of what's going on with the new medication that I'm starting.

2D6 Metabolized Antidepressants: Venlafaxine, Duloxetine, Paroxetine

Dr. Elise Fallucco 4:50

I just wanna highlight what you just said because it's an incredible clinical pearl. What you're reminding our listeners is that even after stopping Fluoxetine, it'll still be in your system for another four to five weeks, which means that the related Cytochrome 2D six inhibition will also be in effect for that long. So practically speaking, this means that if you start a new medication that's metabolized by 2D six, after stopping fluoxetine, a low dose of the new medication is gonna feel more like a medium or even high dose due to the ongoing 2D six inhibition as fluoxetine is leaving your system.

Dr. Jeffrey Strawn 5:26

Exactly.

Choosing a Third SSRI

SSRIs generally more effective, fewer side effects than SRNIs in youth

Dr. Elise Fallucco 5:27

And for those of our listeners who might need a quick refresh on which of our commonly used antidepressants are metabolized by 2D six. Just a reminder, this would be the SNRIs, venlafaxine marketed as Effexor and Duloxetine marketed as Cymbalta. As well as an SSRI that we don't commonly use Paroxetine or Paxil. So, i wanna go back to a couple things. One is that in most cases, if somebody's tried two SSRIs for anxiety, your preference would be to try a third SSRI as opposed to switching to an SNRI first, I wanna say I agree and I I am glad to hear that, that you're,

Dr. Jeffrey Strawn 6:06

it's so nice when two psychiatrists agree, isn't it?

Dr. Elise Fallucco 6:09

While I always give patients the opportunity and talk about the different options, my personal clinical experience has been, and also based on research, it seems like the SSRIs tend to be more effective, and to have fewer side effect burden than the SNRI options in our teens and children. Is that why you do it or what's your rationale?

Only 1 SNRI for child anxiety

Dr. Jeffrey Strawn 6:30

It's exactly the same. Um, I think when we're talking about efficacy, you know, and we look at several of the meta-analyses that have been published in this area in pediatric anxiety, the SSRIs really win the race. From a tolerability standpoint. I think the, the SNRIs are pretty heterogeneous. So we have some SNRIs, like venlafaxine that are just notoriously. Not well tolerated. And I think the issue there is that, you know, I, I tend not to use venlafaxine, if, if I can ever avoid it. And so in, in that situation. You know, when we're just saying SNRIs, we're grouping a lot of things together. So for me, when I'm thinking SNRIs in child psychiatry, there's probably only one, that I might use for, anxiety and that would really be duloxetine.

People forget about Fluvoxamine

Dr. Elise Fallucco 7:21

Yes, I completely agree with that. Yeah, and I'm, I'm class of throwing her around the category, like we have so much from which to choose, so many SNRIs and I really just meant duloxetine.

Dr. Jeffrey Strawn 7:30

Right,

Dr. Elise Fallucco 7:31

But back to the case of somebody's on Fluoxetine 40, you're saying we could easily decrease to 20 for a week. And then off, what would be your third SSRI that you would choose?

Dr. Jeffrey Strawn 7:42

So this is a situation depending on what's there. I might go to Luvox or Fluvoxamine. I think a lot of people forget about fluvoxamine and it can be a really effective SSI both for OCD where it's approved in the pediatric population, but also for run of the mill generalized separation and social anxiety disorders.

Sertraline and Es/Citalopram 2C19 metabolism

Dr. Elise Fallucco 8:05

I love hearing that because I think a lot of people have steered away from that medication and kind of focus more on the big three, you know, fluoxetine, sertraline, and e citalopram and maybe citalopram has a little bit of a role there, but either one. And while we've moved away from paroxetine, I think people also have slowly moved away from, fluvoxamine or Luvox. But I'm interested to hear that that would be your third one. And before you had said some of your rationale might be, you know, let's say they've tried a high dose of sertraline. Which is metabolized by two C 19 and there wasn't a really good effect. Then it makes you think that maybe they're an ultra rapid metabolizer, that we might run into the same problem with citalopram and escitalopram. Is that why you wouldn't choose those or is there a different reason?

Dr. Jeffrey Strawn 8:51

That's precisely it, and maybe put that another way. If I have a patient that had very, very significant side effects at a low dose of sertraline. That I was pretty convinced were related to sertraline. I might not go with e citalopram or citalopram as my next line intervention'cause there's a possibility that that patient may be a poor metabolizer for two C 19. Obviously these are labs that we could check if we wanted to, but here I think we're trying to really use the clinical evidence and, and, and make our best guess, in terms of inferring.

Fluoxetine to FluVOXamine cross-titration

Dr. Elise Fallucco 9:27

I like how you're, organizing those three meds together, you know, citalopram, e citalopram, and sertraline because of the way they're metabolized and also informed by a lot of the s pharmacogenomic studies that you guys have led looking at the wide range of variability found in how quickly people metabolize those particular meds, based on their own two C 19 polymorphisms. Okay. So if they were fluoxetine 40, you would. Decrease the 40 to 20 milligrams while starting Luvox at that point, or would you wait for the Prozac to get out of the system before starting Luvox?

Gratitude for Dr. Strawn

Dr. Jeffrey Strawn 10:05

In this situation, I think it would be, depending on timing and other practical issues, I would probably start the Luvox, the. the day that the fluoxetine stopped, I would probably start at 25 milligrams. I know that there are some that do start at 50 milligrams. I tend to just because these are still different, SSRIs still titrate, as opposed to just starting at, you know, say my goal dose, which would be around 150 to 200 milligrams. I would never start at that dose. The other thing that I think is really interesting. When we look at how Fluvoxamine is dosed across these individual pediatric studies that we have, uh, if we look at things like the POTS study, again, this is OCD, they titrated this fairly aggressively. And similarly we can look at the adult COVID studies, where they titrated this incredibly quickly, much faster than I would ever do. Essentially getting to a couple hundred milligrams of fluvoxamine over several days. I would not recommend that. the other thing is that when, we look at the, the pediatric OCD study, the the pot study, what we do find is that there was a higher incidence of side effects in that study. And I, I have certainly wondered, if, if that was probably related to the rate at which it was titrated

Check out Stahl's DEPrescribing Guide

Dr. Elise Fallucco 11:27

that maybe it was aggressively titrated and so they ended up on a higher dose perhaps than they needed, which increased the side effect burden.

Dr. Jeffrey Strawn 11:35

Mm-hmm.

Dr. Elise Fallucco 11:36

Okay. Oh my goodness. could talk to you about clinical cases all day, but I need to let you go and see patients. This is

Dr. Jeffrey Strawn 11:42

fine. This is great. So,

Recap of Advanced SSRI and SNRI case discussion

Dr. Elise Fallucco 11:43

Well, sadly I have to say goodbye to you and we have to end our conversation. as I mentioned before, I'm gonna keep a link to your book on our website, psyched the number four Ps. I highly recommend it to our listeners. I think it's fantastic how you organize, organize it by medication name and medication type. And so you can literally use it as a reference and flip to, you know. Bupropion or Atomoxetine or whatever it is, and there's a very systematic way of going through what should you look for as you're coming off of this med, how to approach it, and even things like what dose should you decrease it to and over how many weeks? So it is a fantastic reference. It's available on Amazon. And, highly recommended. And as a final thanks, I just wanna say thank you so much Dr. Strawn, for being able to translate all of your wisdom, not only into this book, but into clinical discussions to be able to help other pediatric clinicians.

Dr. Jeffrey Strawn 12:35

Thank you so much for those kind words. And it's great as always to continue that work here on your podcast.

Dr. Elise Fallucco 12:42

Oh, thank you. That's the goal. Alright, listeners, we covered a lot today, but I wanted to have a chance to do a broad recap. Some of the highlights from our conversation. We talked about when you've got a child or a teenager with anxiety who has not responded or failed trials of two different SSRIs. Dr. STR recommended switching to a third SSRI typically, and the rationale for that being that the SSRIs tend to be more effective than the SNRIs, and also typically with fewer side effects. When we were talking about which SSRI to choose with a patient who's not responded to fluoxetine or sertraline, Dr. STR surprised me by saying that he would seriously consider Fluvoxamine or Luvox in that case. And as a side note. I keep thinking about how we actually don't talk about this medication and perhaps don't use it very often, which reminded me in my weird train of thought about that movie Encanto and the song we don't talk about Bruno. We don't talk about LUVOX. Anyway, back to the recap. Dr. Str mentioned that he really likes Luvox not only for OCD, but for our big three anxiety disorders, generalized anxiety, social anxiety, and separation anxiety. He talked about starting at 25 milligrams and then titrating up to a target dose of around one 50 to 200 milligrams. Another big clinical pearl from today's episode. Was the idea that you can mentally organize three of the SSRIs in a similar category based on their metabolism. So in this case, we're talking about the three SSRIs that are all metabolized by two C 19. So that would be Sertraline or Zoloft s Citalopram, or Lexapro and Talopram or Celexa. So Dr. Str mentioned that if your patient developed pretty bad side effects on a fairly low dose Then that might be a clue that they're a really poor metabolizer through two C 19. So you'd wanna avoid other meds that are in the two C 19 class. Another big clinical pearl. While we all know that Fluoxetine or Prozac tends to have a really long half-life and so does its active metabolite nor fluoxetine, Dr. STR reminded us. That even after stopping Fluoxetine, that you're gonna have the Fluoxetine related 2D six inhibition for an additional four to five weeks after stopping the med. So something to keep in mind if you've got a patient who you're starting on another 2D six Med. Like duloxetine or venlafaxine or potentially peroxetine, although we don't use that one that much. Whoof lots of information. I. And as it may be really hard to remember all of this technical information about dosing strategies as you come off of meds or as you come onto meds, I do wanna strongly recommend stalls, d prescribers guide, available on Amazon, co-authored by Dr. Jeffrey str. As a helpful reference tool so that you can just alphabetically flip to whichever medication that you're planning on switching from or switching to and you'll be able to find really helpful dosing tables and information about, you know, when would you decrease the dose? By how much, for how long, and then at what point would you start the next med? All right. That brings us to the end of this episode. Thank you so much for listening, and as always, please check out our website, psyched the number four peds.com, and sign up to become a friend and colleague. Of the podcast so that you can get our regular free newsletter with recaps from episodes, helpful, downloadable resources, and other tools. Until next time, take care.