69. How to Switch SSRIs with Dr. Jeffrey Strawn

3 Ways to Switch SSRIs in Kids: Direct Switch vs Taper vs Cross-Titration 

Dr. Elise Fallucco continues a conversation with child psychiatrist and anxiety GURU Dr. Jeffrey Strawn about evidence-informed ways to switch SSRIs in pediatric patients when an adequate trial hasn’t led to remission. 

They review 3 strategies:

1.    direct stop/start

a.    Stop SSRI#1 then start SSRI#2: best for patients with side effects on the 1st SSRI, but creates a gap in antidepressant coverage during the transition

2.    taper-then-switch

a.    Taper SSRI#1 off then start SSRI#2: best for patients who are highly sensitive to medication changes, but leaves a LONG time without effective antidepressant/SSRI coverage 

3.    cross-titration

a.    Continue SSRI#1 while adding SSRI#2 with the plan to later taper down on SSRI#1: best for patients without side effects on 1st SSRI as it allows for optimal SSRI coverage in the transition between meds; watch out with SEROTONERGIC SIDE EFFECTS (nausea, vomiting, diarrhea, flushing) while 2 SSRIs on board

Clinical Pearl: Dr. Strawn emphasizes that higher starting doses don’t speed time to steady state, so start the new medication at LOW doses

Clinical Case: Teen on sertraline 150 mg switches to fluoxetine

·      How to cross-titrate

·      How to monitor for serotonergic side effects 

·      How to taper sertraline

Bonus Psychopharm: They receptor pharmacology considerations and the need to distinguish withdrawal effects from new-medication side effects, illustrated by an atomoxetine (Strattera) -to- fluvoxamine (LUVOX) switch affecting ADHD symptoms.

Check out our website PsychEd4Peds.com for more resources.
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Transcript

Intro to Switching SSRIs with Dr. Strawn

Dr. Elise Fallucco 0:21

Welcome back to Child Mental Health for pediatric clinicians helping you help kids. I'm your host, Dr. Elise Fallucco, child psychiatrist, and mom. Today we're continuing our discussion with the illustrious Dr. Jeffrey Strawn, child psychiatrist and co-author of the new book Stalls DEPrescribers Guide. Which addresses the really important issue of what is the best way to come off of medicines or to switch from one medicine to another. In today's episode, we're focusing on the tricky issue of how do you switch between SSRI medications. So without further ado, let's get back to the conversation. Dr. Strawn, I often get asked about what is the best way to switch from one SSRI medication to another. Prior to the release of your book, we didn't have a lot of evidence-based guidance to tell us how could we safely transition patients from one medication to another. So let's start with the clinical case. Let's say we've got. A child who we've started on one SSRI for anxiety and titrated up to an appropriate dose, but there's no major improvement and we're thinking about switching to a different SSRI. In your book, you talk about three different approaches. To switching medications. Can you walk us through those three different Strategies and tell us what is the best way to do it?

Option #1 - The Direct Stop - Stop SSRI#1 and start SSRI #2

Option #2 - Taper then Switch

Dr. Jeffrey Strawn 1:39

And I, I think setting that up in the way that you did is really important because when we think about this situation where somebody has not responded, they've not gotten really to remission from an SSRI, there's actually good evidence that switching to another SSRI in anxiety disorders and in depression may produce benefit. Now in terms of that switching over, there are probably hundreds of ways that people have, have done this either intentionally or unintentionally. So thinking about this approach, maybe just to go through a couple of these. One would be the direct stop. So for example, I have a patient treated with sertraline and I'm switching to fluoxetine and I stop my first antidepressant and then start my second antidepressant. That can be helpful in some situations, perhaps when I'm having a side effect with one medication, for example, the first SSRI. but the issue is that oftentimes just in switching over directly. I am at a point now where I no longer have antidepressant one in my system, but I don't yet have antidepressant two fully on board, especially depending on the pharmacokinetics of the second antidepressant. And so that leaves me potentially a bit behind the eight ball if I now realize, oh. Antidepressant one was actually doing more than I thought it was doing. Now similar to that, is the taper then switch. So you imagine rather than just switching directly from antidepressant one to antidepressant two, I'm gonna taper antidepressant one and then slowly titrate antidepressant two. Same issue as we just described in terms of that first switching strategy.

Dr. Elise Fallucco 3:28

I think historically those two types that you described were the most common ways that I've seen people try to go from antidepressant number one to antidepressant number two in practice. So direct I agree.

Dr. Jeffrey Strawn 3:39

That's what I see as well.

Dr. Elise Fallucco 3:40

Yeah. The taper and switch. taper antidepressant one and then switch and start antidepressant two and gradually titrate it up always to me, felt incredibly slow And I think the reality is, as you described so well, that the patient is going for weeks, if not months, essentially untreated or inadequately treated with a relatively low blood level of any type of antidepressant in that case. And so while I think it it feels like a more conservative approach. I've always shied away from that. and I am much more of a fan of the direct stop, you know, stop antidepressant number one and start antidepressant number two. What I have taught pediatricians, but I'm gonna have to update it after you and I talk, is that I would usually stop antidepressant number one and then start antidepressant number two, not at the lowest possible dose, but at a sort of pharmacologically equivalent dose, slightly lower than whatever the pharmacologic equivalent would be. Which still runs you into the problem of, it's gonna still take four to six weeks for antidepressant number two to work, and antidepressant number one is gone.

Dr. Jeffrey Strawn 4:48

right. And I think the other issue is, you know, when we're talking about starting at a higher or lower dose of the second antidepressant, one of the issues is that that starting dose doesn't predict absorption, or time to steady state. And so unfortunately, those are immovable from a pharmacologic standpoint other than just, quite frankly, through the use of time. no way that I'm aware of really with an orally administered medication to get us to steady state faster. Now, again, I, as much as I'm emphasizing steady state, I do want to probably also make sure that people are, are pretty clear that steady state does not equal efficacy. And efficacy does not mean steady state, but it is still a very, very important pharmacologic principle.

Option #3 - Cross Titration

Dr. Elise Fallucco 5:35

So your point is well taken that regardless of what dose you start at, it's still gonna take the same amount of time to reach steady state and to be able to tell whether we're seeing a response in our patients. Okay, so we talked about two of the ways to switch SSRIs. You either do the direct stop and start, or the taper and then switch. You were about to tell us about the third way to switch SSRIs.

Summary of Cross-Titration (Option #3)

Dr. Jeffrey Strawn 5:56

That's right. I was moving on to the third way, which is probably what I do a bit more of recently, which is the cross titration. So in some form, I'm potentially beginning to decrease antidepressant one as I'm starting antidepressant two. But here's where it gets just a little complicated, not too complicated, but just a little bit more complicated. So this is where I really need to consider the individual antidepressants. So for example, if I'm looking at a short half-life antidepressant as being antidepressant one and antidepressant two is also a short half-life antidepressant. That titration strategy or cross titration strategy is going to be different than, say, for example, if I'm going from or to fluoxetine, which of course your savvy listeners know, is a very, very long half life. medication with a half-life of fluoxetine, probably somewhere around seven days and a half life of its active metabolite, nor fluoxetine being around 14 days.

Case 1: Switch from Sertraline to Prozac

Dr. Elise Fallucco 7:02

So you're saying the cross titration approach is start antidepressant two while continuing antidepressant one with the plan of gradually decreasing the dose of antidepressant one while titrating up on antidepressant two, which means you're on two meds at the same time. Which I have to tell you a lot of pediatric clinicians fear, in part, because of the theoretical risk of serotonin syndrome. let's work through clinical cases so we can talk about, you know, the practical implications of going from short half-life to long half-life and vice versa, and sort of work through that. let's say we have a teenager on sertraline, say 150 milligrams, for anxiety it has been really well tolerated, but for whatever reason, after a solid trial, the clinician is saying, I don't think this is really getting us where we need to be. We're not seeing any increased benefit as we continue to titrate up, we need to try a different SSRI. This is the only SSRI that the patient has tried. So let's say the choice is to switch to fluoxetine, which as you mentioned, has the very long half-life, especially relative to sertraline. So 150 milligrams to sertraline, to a new trial of fluoxetine. How do you approach it?

Serotonergic Side Effects with 2 SSRIs

Dr. Jeffrey Strawn 8:15

So here we're going from, as you pointed out, short half-life SSRI to long half-life, SSRI. So the issue here is that that fluoxetine is actually going to take quite a bit of time to actually get into the system. here again, steady state does not equal efficacy. Efficacy does not equal steady state, but still very important pharmacologically. So in this situation, what I would do. As you mentioned in the absence of side effects, is to start the fluoxetine while I still have the patient on that treatment dose of sertraline, so 150 milligrams, and then I would slowly increase the dose of fluoxetine over several weeks as I'm maintaining the dose of the sertraline. After I am at 20 or 30 milligrams of fluoxetine, that is the point when I would actually begin to decrease the dose of the sertraline. However, you mentioned the serotonin syndrome, and I'm gonna expand that in terms of just serotonergic side effects. So if I am running into side effects, for example, nausea, vomiting, diarrhea, flushing. Increased motor tension as well as perhaps some restlessness that's not attributable to the underlying anxiety or to psychomotor agitation associated with depression. That's where I would perhaps start decreasing that dose of sertraline a bit faster. Most of the time in terms of these serotonergic side effects, we'll see something much milder than what we would typically see with a serotonin syndrome.

Dr. Elise Fallucco 9:59

That's a really good point. When you're making the choice to have two SSRIs on board during this process of cross titration, you'd look out for GI side effects like nausea, vomiting, diarrhea, as well as flushing, restlessness, and make sure that these symptoms are not due to underlying exacerbation or underlying anxiety, depression, you know, other stressors

Dr. Jeffrey Strawn 10:18

exactly.

Dr. Elise Fallucco 10:19

So we're continuing sertraline 150 milligrams for a while, really until we feel comfortable that, we have increased up to about 20 or 30 milligrams of fluoxetine. To three weeks you said? I assume you're starting at 10 milligrams.

Dr. Jeffrey Strawn 10:34

I did in my mind, envision starting at 10 milligrams. I guess I should have asked a little bit more about the hypothetical patient.

Dr. Elise Fallucco 10:41

So this is a teenager with pretty poorly controlled anxiety, had not developed side effects to medication previously. No symptoms of depression. Some somatic symptoms of anxiety as well. Kind of chronic headaches, occasional stomach aches, but functioning pretty well in school and even in extracurriculars, but just having more psychological distress,

Dr. Jeffrey Strawn 11:04

yeah, so in this situation, I would probably still start at 10 milligrams and then would go to 20. And I know some people do go from 20 to 40. I tend to take a pit stop at 30, before going all the way up to 40 milligrams.

Peak Concentration is not Steady State

Dr. Elise Fallucco 11:17

I feel like what I've been telling my pediatric clinicians has been wrong in not starting at the typical starting dose, but just jumping up to a higher dose. Is there any case in which you would go ahead and start at 20 of fluoxetine? I do hear your point about, you know, it takes five half-lifes to reach steady state. and steady state is not the same thing as efficacy. So if we start at 10 or if we start at 20, it's still gonna take us the same amount of time to get to steady

Dr. Jeffrey Strawn 11:44

state. Absolutely, and I think that's such an important point because I've heard clinicians say, oh, I started a higher dose, so I get to steady state faster. That is not true. That doesn't happen. It gets to a peak concentration faster. Or you, you get a, a higher peak, a greater peak, peak concentration I should say. But really all that does is produce side effects. Unfortunately.

Dr. Elise Fallucco 12:07

Think this is a good time to remind our listeners that just because we had titrated up to a fairly high dose of sertraline and found that it didn't work or was only partially effective, that doesn't necessarily predict that the patient's gonna need a similarly high dose of a different SSRI.

How to Taper off of Sertraline 150mg - Decrease by 50mg per week

Dr. Jeffrey Strawn 12:24

That is absolutely correct.

Dr. Elise Fallucco 12:26

I like that you're only taking two to three weeks to get up to probably a therapeutic dose for anxiety, either 20 or 30 milligrams of the fluoxetine. And then once you're at that dose, then you would start decreasing the sertraline. Talk us through how you would decrease it and what's your timing to go from 150 milligrams to zero.

Dr. Jeffrey Strawn 12:46

So once I'm at the Fluoxetine, and again, if the patient is having side effects, that affects how quickly I would taper off. But let's say that the patient is actually doing great now that they're on 30 milligrams of Fluoxetine. At that point I would actually taper the sertraline off relatively quickly, probably over several weeks.

Dr. Elise Fallucco 13:08

The way that I've approached tapering off over the course of several weeks is, 150 milligrams down to, let's say a hundred for a week, down to 50 for another week. If we're okay, either stop at that point or can go down to 25. Do you have a different approach?

Dr. Jeffrey Strawn 13:27

That is exactly what I would do.

Dr. Elise Fallucco 13:29

Okay.

Dr. Jeffrey Strawn 13:30

And I like how you almost added an asterisk to the 25.

Dr. Elise Fallucco 13:34

I just to be extra conservative because you never know.

Detective Work During Switches

Atomoxetine to Luvoxamine Case Example

Dr. Jeffrey Strawn 13:38

I think the other piece too is in terms of when we're thinking about the receptor pharmacology of these different antidepressants, that's something that may also inform this cross titration, and this is less of an issue when we're talking about the antidepressants, but when we're talking about some other medications where we have. Say an antidepressant that has a lot of antihistaminergic effects or a lot of anticholinergic effects. We don't use paroxetine much anymore, although that would be the classic one in terms of these receptor profiles. But in that situation, again, just thinking about the receptor pharmacology. It helps us predict what we're going to see. So as I decrease the dose of paroxetine, so Paxil and I lose that antihistamine effect, I lose that anticholinergic. Effect. I may start to see rebound symptoms of that. One of the other issues that's really important for clinicians to distinguish, and I've run into this recently, just a couple of weeks ago in my own clinic, is that as I'm tapering from one antidepressant or one medication to another medication, it's really important that we try to distinguish what might be an effect of stopping the first medication versus a side effect of the new medication.'cause often what I find is that as a clinician, I'm likely to attribute it to the new medication And that's the same in terms of patients, and it's also the same in terms of their families. I recently ran into this with a patient that was switching from Atomoxetine. To, Luvox, or Fluvoxamine. Now this is a patient who was also treated with, a stimulant for A DHD. And what happened was some of his A DHD symptoms, in fact got a little bit worse, and the family and the patient initially attributed that to the fluvoxamine, when in reality it was the coming off of the Atomoxetine or Strattera.

Dr. Elise Fallucco 15:37

there was a reason you were coming off of the atomoxetine, I'm imagining it was due to perceived lack of efficacy or was there another reason?

Dr. Jeffrey Strawn 15:45

Lack of efficacy and it really wasn't doing anything in terms of touching the anxiety. So this is where again, we need to be the pharmacological or psychiatric detective, as we're trying to figure out to what medication to attribute a side effect or a change in efficacy.

Dr. Elise Fallucco 16:01

And so you're thinking Atomoxetine is not helping anxiety, it's really not doing much for the A DHD. So you're coming off of that, starting a new medication for anxiety. But as the A DHD gets worse, everybody thinks, oh, it's the new medication. Because that's the one thing that has changed.

Dr. Jeffrey Strawn 16:16

Exactly.

Dr. Elise Fallucco 16:17

And yet you go back and think, actually this medicine that I didn't think was very helpful was must have been doing something. It's, at the end of the day, it wasn't enough, but right. That's why, that's where it becomes really tricky, like looking at what are we coming off of? What was that supposed to help, what are we starting, what are the known side effects for that? In

Pros and Cons of 3 ways to Switch SSRIs

Dr. Jeffrey Strawn 16:35

that situation, what we ended up doing was adjusting the dose of the stimulant, which was now on board. So we had gone from trying to use atomoxetine to address both the anxiety and the A DHD to now using two more efficacious medications, the stimulant and the SSRI to address the anxiety and A DHD.

Dr. Elise Fallucco 16:55

Yeah. I like the idea of trying to use one medication. You know, I think this is why Atomoxetine was initially very popular when it first came to market because of the theoretical opportunity to, kill two birds with one stone or a, hit anxiety N-A-D-H-D.

Dr. Jeffrey Strawn 17:12

Absolutely.

Dr. Elise Fallucco 17:13

But as you point out, atomoxetine is often not as effective as stimulants for A DHD, and certainly Atomoxetine is less effective than SSRIs for anxiety, which means you end up using two different meds for A DHD and anxiety. Alright, listeners, we've covered a lot so far, so I wanna hit the pause button and also share the main things we discussed to help you remember three ways to switch SSRIs. One way is to taper down the first SSRI. Wait till it's out of your system and then start the second SSRI. This is the slowest option that has the most time without adequate SSRI coverage, The second way is the direct stop start, which is best for patients with side effects from the original SSRI. And is more rapid than that first way of tapering down entirely. But the drawback is that you lose antidepressant coverage during the transition while you wait for your new medicine to reach steady state. And Dr. STR introduced us to the fancy third way, which he calls the cross titration, where you keep the original SSRI ON while you start the second medication. And this is best for patients who have not had side effects to the original medication and where you want to ensure ongoing. Medication coverage for underlying anxiety or depression. The things to watch out for here are potential serotonergic side effects, which include nausea, vomiting, diarrhea, flushing, and restlessness. My big learning point from this episode was that just because we needed or tried a high dose SSRI for our first trial and didn't have a response, it does not necessarily mean that the patient is gonna need a high dose. Of the second medication that you try and knowing this, we should start low on the second trial to minimize new side effects on the new med and then increase weekly to achieve a target dose by around week two or three. So the great news is that we are not done this conversation. We're gonna continue next episode to talk through some more complicated cases with Dr. Strawn about switching medications. For kids in teens with anxiety. Thanks for listening, and we'll see you next week.