PsychEd4Peds: child mental health podcast for pediatric clinicians

30. When an SSRI doesn’t work for depression with Dr. John Walkup

• Elise Fallucco and John Walkup • Season 2 • Episode 30

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What do you do when your patient doesn’t tolerate or doesn’t respond to an SSRI for depression? Join us as we discuss this issue and talk about non-SSRI medication‘s for depression.

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Dr. Elise Fallucco:

Welcome back to psyched for paeds, the child mental health podcast for pediatric clinicians, helping you help kids. I'm your host, Dr. Elise Fallucco, child psychiatrist and mom. So today we're continuing the conversation with Dr. John walkup about medication treatment for depression. What is the best SSRI for depression? And what do you do if the first SSRI doesn't work? Particularly, if you're going to go out of class to a non SSRI, which medications do you choose and why? Thanks for joining us. As we jumped back into the conversation with Dr. John walk up. So do you have a favorite medication for depression? Assume let's just assume there's no comorbid anxiety in this case. Let's say we're lucky and the kid doesn't have a past history of loss. It's just depression, elevated PHQ 9. What's your med?

Dr. John Walkup:

I think they all work. Even the ones that have quote unquote failed clinical trials. I think they all work like all the S. s. R. I. S. You mean all the S. s. I. R. I. S. Work. The S. N. R. I. S. Work. They just work better in some people than in others. And, So they all work. I've gotten past this idea that the ones that have been had a positive clinical study are the only ones that work. And so then what you're left with is what was the first to market? And are you one of those people who only use something that's been on the market for 30 years? Okay, then you're using fluoxetine. If you're... Like me, I'm not a big fan of medicines that have nonlinear pharmacokinetics.

Dr. Elise Fallucco:

You talked about fluoxetine having nonlinear pharmacokinetics, what's like an easy way of describing that and why you wouldn't like it?

Dr. John Walkup:

Yeah. Okay. So linear pharmacokinetics, when you go from 25 to 50 to 75, you go to X. 2X, 3X. With medicines like fluoxetine and paroxetine, you go from X to 5X to 15X to 20X when you go from 10 to 20 to 30 to 40. And because fluoxetine particularly has a super long half life, so let's say you go 10 for two weeks and 20 for two weeks and 30 for two weeks. And then by week eight, you just start 40. You won't reach steady state of 40 milligrams for another six to eight weeks. So you're now out 12 weeks and all of a sudden the kid has a weird side effect. And the reason he's having a weird side effect is because he became toxic. Going from 10 to 20 to 30 to 40. The kid's body was going from from X to five X to 10 X to 15 X to 20 X. And so all of a sudden you get late onset side effects that you weren't anticipating. Plus If you add many of our other psychotropics, then you get drug- drug interactions because many of our psychotropics are metabolized through 2D6 and fluoxetine interacts with 2D6. So I like drugs that I have linear pharmacokinetics 25-50-75-100 123 Me. Yeah. Yeah. And and I like drugs that don't have drug interactions. So low 2d6 drugs uh, escitalopram is a beauty. It doesn't really have, it, it has drug interactions, but not with most of our psychotropics. Right. Um, And you know, escitalopram is the Goldilocks. It's got a little of this and a little of that, but not too much of anything. I worry a little bit about it for weight gain. So I'm particularly sensitive with escitalopram for kids where there might be a weight gain issue. I don't think my experience with Sertraline suggests that there's a predictable pattern of weight gain. There are some kids that get flatter on escitalopram than on Sertraline. And we've talked about this before where you get the sertraline sparkle and you get the kind of the mellowing with escitalopram, but these are such subtle differences. And then, so there's, and then there are people who only want FDA approved, right? So then

Dr. Elise Fallucco:

you've got fluoxetine and escitalopram,

Dr. John Walkup:

assuming that's what you got. Yeah. And there are people who feel handcuffed to that. I'm trying to teach people, they all work. They're all part of a class. You just have to pick and choose about what matters to you, what's important to you and match it up with your patient. You should be empowered to pick as opposed to feel stuck with either FDA approval or first to market or something like that.

Dr. Elise Fallucco:

Super helpful. Let's say somebody's depression, let's say they didn't tolerate their first SSRI. Would you give them another trial of an SSRI or would you move to an SNRI for depression only?

Dr. John Walkup:

Yeah, it depends on what the tolerating problem was Those who get activated. And they, I gave them 25 of sertraline and they couldn't tolerate that. So the activation side effect that for me is a showstopper and I go to non activating antidepressants. Anything

Dr. Elise Fallucco:

else? Great. So just if they could get activation on one SSRI, then you'd move them to an SNRI? Or just in the case if they get activation from a an SSRI that's not as likely to be as activating as fluoxetine.

Dr. John Walkup:

There, there are people who will disagree with me but there is just such a characteristic pattern. It's that Benadryl reaction. When I see that Benadryl reaction, either at 25 or 50 of sertraline, for example or going from 10, 10 on fluoxetine, and I go to 20 and within 24, 72 hours, all of a sudden, they just have this agitated kind of discomfort. It usually comes with a fair amount of dysphoria. I see that. I trust that. I believe in that. I don't think there's any way to sneak up on that by starting low and going slow, but people will actively disagree with me on that. So I just switch out. I just go to something that's non activating. I say every one of them, every one of the meds works. So I just pick an antidepressant that doesn't activate. I use duloxetine. I'll even use mirtazapine if I can have the right kid in the right way with the kind of right side effect profile with mirtazapine. I use, believe it or not, I go back to tricyclics. So I do some of that stuff. I don't just jump to a bupropion though, because if there's any anxious feature in many of these kids, there was a pre existing history of anxiety. I don't go to the bupropion.

Dr. Elise Fallucco:

If somebody has depression and anxiety, I try not to use bupropion because it can sometimes make the anxiety worse. is that what you were saying why you would not use for the same reason?

Dr. John Walkup:

Yeah so this is where I get a little nuance for people. But if I have a kid with clinical depression, nuance at age 17. I expect that child to be anxious about their loss of function. I expect that anxiety to be proportional, understandable. Expectable in response to the fact that they're beginning, they've experienced a substantive mood change that is not anxiety disorder. That is a normal anxious reaction to a change in mood that person. No previous history of anxiety. That's a good bupropion case where I'm shooting for mood elevation and energizing of that patient. The other patient is the anxious kid who at age 17 finally comes to care because they're demoralized by their anxiety and the clinician calls that depression. That is the worst kid to give bupropion to because the underlying disorder is anxiety and the low mood is demoralization secondary to the condition of anxiety. That's the worst kid to give bupropion to.

Dr. Elise Fallucco:

Okay, so that's helpful. So SSRIs, if one SSRI fails because of activation, then you'd think about non activating meds like an SNRI, which would be Duloxetine probably, potentially Mirtazapine if somebody wants to have an increased appetite and sleep more because those are the known side effects, and then less likely Bupropion, it would have to be that specific candidate that you described before who's really More depression. Very low anxiety.

Dr. John Walkup:

Yeah.

Dr. Elise Fallucco:

And one of your messages to the pediatric clinicians would be that if somebody develops activation on an SSRI, then you would jump ship, get away from the SSRI class and switch to a medicine outside of the class that is non activating. But let's consider a slightly different scenario. Let's say I have a kid who tries their first SSRI and they don't seem to respond fully or tolerate the first SSRI, but it's not an activation issue. It's just, they're not getting a robust response. I definitely would switch to try another SSRI. Before moving out of the class, is that what you would do to?

Dr. John Walkup:

Yeah What tends to happen though, is you have a kid who's demoralized and has a clinical depression, you give them the med, their clinical depression begins to lift pretty substantially. They're coping better with their demoralization, but their demoralizing circumstances are still there. There are some people who their depression goes away and their life still is extraordinarily difficult and adverse. And we got to be able to do that figure ground thing and kind of talk with patients. Your general mood is so much better, but your life circumstances still extremely challenging. I would expect that you would still be challenged by your life circumstances. But that you have, would have greater reserve, greater capacity to problem solve and to think your way out of whatever challenges that you're facing. But you may not. It's still, your life still may be difficult.

Dr. Elise Fallucco:

So something to keep in mind when we're treating kids with depression, is that our expectation is not that the medication is going to make them feel fantastic and make all of the problems in their life going go away. We really have to be focused on, is the medication helpful for the symptoms of depression? And if they still have, you know, some low mood or some frustration, Is that really the depression? Or could that be the demoralization, that an appropriate response to some of the ongoing stressors in their life? And it's also reassuring to hear your take on this idea that all of the SSRIs are very helpful, can be helpful for depression, the SNRIs as well, and that it's a matter of thinking about side effect profile and what's the best match for the kid's particular symptoms.

Dr. John Walkup:

Yeah, the idea that only one works, really, they're all the same, they have slight differences, they have slight differences but they built them and brought them to market because they shared similar characteristics, right? So why would one work? And the other not work. There's some SSRIs that are going to work better for some than another SSRI.

Dr. Elise Fallucco:

So to summarize, you would say first-line treatment for depression in teens would be an SSRI. And in your mind, all the SSRI. Are effective. And it's just a matter of finding the right med for the right person. If they don't tolerate the first SSRI or you don't get a robust response, but you're not experiencing activation, then you could consider another SSRI. If, however they get activation, then you consider nonactivated meds. Like do locks, the teen, which is Cymbalta. Or potentially bupropion. Only if they don't have significant anxiety. And possibly you could consider something like Mirtazepine. If you have somebody who really needs the increased appetite, increased sleep. Thank you again for joining us as always. These conversations are fantastic. And for our psyched for paeds listeners, if you have any questions or any ideas or clinical conundrums, please feel free to email us at info at site. The number four paeds.com. Visit our website, psyched for paeds.com or message us on Instagram. Take care and see you next week.