February 9, 2024 • 17 mins
Is there a go-to medication to treat a child with both ADHD and anxiety? Join us as we continue the conversation with Dr. Jeffrey Strawn from Cincinnati Children's Medical Center to discuss how to approach medication treatment for a child with ADHD and anxiety.
We talk about which stimulants are better tolerated, when to use alpha 2 agonists (like clonidine and guanfacine), and finally what to know about the norepinephrine reuptake inhibitors, Viloxazine (Qelbree) and atomoxetine (Strattera).
Key Points:
1 – treat ADHD first, then address residual anxiety (unless anxiety is Severe)
2 – When treating ADHD, start with stimulants; Methylphenidate (MPH) stimulants are less likely to cause mood/anxiety sxs than mixed-amphetamine salts; MPH stimulants also have ½ incidence of appetite suppression relative to the mixed-amphetamine salts
3 – When to use alpha 2-agonists
o Clonidine is “a little messier” – hits multiple receptors (alpha 2a, 2b, 2c; hits imidazoline receptor), more likely to affect BP, sedation; best for problems initiating sleep
o Guanfacine – “much more selective for alpha 2 A receptor”,
o Guanfacine XR can be dosed once daily (vs. clonidine xr which is still BID)
o Dosing and titration of Guanfacine XR stay below 6mg, 0.1 mg/kg/day
o Guanfacine XR considered as adjunctive med in addition to SSRI for anxiety
o Good to help w/ impulsivity
4 – Viloxazine/Qelbree (NRI) “what’s hype vs. what’s clinically relevant pharmacology?”
o Works more rapidly than atomoxetine: Even within first couple of weeks, noticing improvement in symptoms
o Little 2D6 metabolism, but not affected by 2D6 metabolizer status like atomoxetine (did you know fda recommends different dosing/titration based on metabolizer status in atomoxetine)
o Potent CYP 1A2 inhibitor (which metabolizes caffeine/energy drinks) increase caffeine exposure (blood level over time) six fold
** ADR2A genetic polymorphism means 2/3 people do NOT experience anxiety when they consume caffeine
Dr. Jeff Strawn is a Professor of Psychiatry and Behavioral Neuroscience at the University of Cincinnati College of Medicine. Dr. Strawn directs the Anxiety Disorders Research Program and conducts clinical trials and neuroimaging studies in patients with anxiety and related disorders. He is an internationally recognized expert int he field of child and adolescent anxiety disorders.
Check out our website PsychEd4Peds.com for more resources.
Follow us on Instagram @psyched4peds
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Dr. Elise Fallucco (00:42):
Welcome back to PsychEd4Peds the child mental
health podcast for pediatricclinicians, helping you help
kids.
I'm your host, Dr.
Elise Fallucco, childpsychiatrist and mom.
This week, we're continuing theconversation with Dr.
Jeff Strawn about medicationtreatment for ADHD and anxiety.
We'll start by talking aboutstimulant medication.
(01:04):
Then we'll switch and talk aboutnon-stimulant options.
Like alpha agonists.
As well as the norepinephrinere-uptake inhibitors viloxazine
and Atomoxetine.
So let's jump back into theconversation.
With Dr.
Jeff Strawn.
is there a go to stimulant thatyou would use for a child with
ADHD and a positive familyhistory of anxiety to try to
(01:26):
minimize the likelihood ofworsening anxiety?
Dr. Jeffrey Strawn (01:30):
Now, this is where the guidelines probably
don't help us as much as theycould because these guidelines,
which are a bit old at thispoint, actually recommend
treating the primary disorder.
But if we actually look at theevidence, except in some rare
circumstances, the evidenceactually suggests treating the
ADHD first, and then seeing,what we're left with in terms of
(01:51):
those residual anxiety symptomsagain, situation where we had
severe anxiety and ADHD.
We might approach this a littlebit differently, but all other
things being equal, our datareally suggests that we should
treat the ADHD first.
So now to your question abouttreatment, which should we go
with?
So in terms of now we're talkingabout treating ADHD, and so I
(02:15):
think really the evidence thatwe have is for stimulants and
within that stimulant family, Itend to use the methylphenidate
based medications.
And I think that's, somewhatbased on some of the
tolerability meta analyses thatsuggests that they may not
worsen anxiety symptoms.
In fact, there's actually someevidence they improve anxiety
symptoms.
(02:35):
We can talk a little bit aboutthat, but I tend to avoid the
mixed amphetamine salts in thepediatric population, at least
as a first line medication, justbecause there is some evidence
that they can cause moreirritability and some other
symptoms, at least from metaanalyses.
Dr. Elise Fallucco (02:52):
I completely agree.
I also start with themethylphenidate products.
I clinically, I find them, thekids tend to tolerate them
better.
And then if they don't work,then we'll think about mixed
amphetamine salts., but I've hada lot of kids where you start on
mixed amphetamine salts andthey'll get irritability or
increased anxiety.
And so they're not my firstchoice,
Dr. Jeffrey Strawn (03:13):
right?
And also, I think, just in termsof tolerability.
We roughly have almost half theincidence of appetite
suppression and some of theseother side effects that we think
of outside of just the emotionalor neurobehavioral side effects
of stimulants with themethylphenidate based medicines
relative to the mixedamphetamine salts.
Dr. Elise Fallucco (03:33):
Backing up, sometimes when we're starting
treatment for ADHD, you can usefamily history to guide you, if
you One of the parents is doingor one of the siblings is doing
really well on a certainmedicine.
You might think about tryingthat one for the child, but
without any of that information,the go to medicine would be
something in the methylphenidateclass.
Dr. Jeffrey Strawn (03:53):
That would certainly be my approach.
It sounds like it's yours
Dr. Elise Fallucco (03:55):
as well.
Yes.
Shifting gears from talkingabout the stimulant medications.
Let's talk about thenon-stimulant medications for
ADHD.
So, of course, we've got the.
Older ones, the alpha twoagonists, like guanfacine and
Clonidine.
And in addition, we have the norepinephrin re-uptake inhibitors
like Atomoxetine which isStrattera and the newer one.
(04:19):
Viloxazine or Qelbree.
There's a lot of buzz, about nonstimulant medications for ADHD.
Are there any cases of kids withADHD where you would start ADHD
monotherapy treatment with a nonstimulant as opposed to a
stimulant?
Dr. Jeffrey Strawn (04:37):
There are probably a few.
The one may be in an olderadolescent who has a history of
perhaps stimulant misuse.
Now, again, I think, even inthose situations, that doesn't
necessarily rule out my using astimulant because, many of these
kids may have used it more as aSelf-help medication, but I
(04:58):
think other situations, would bewhere we've had significant side
effects with a stimulant.
I think you laid out some of theoptions in terms of the alpha
two agonists and also in termsof Viloxazine and atomoxetine.
With regard to the alpha twoagonists.
Really what we have here areclonidine and guanfacine and a
(05:20):
couple of things that I'd sayfirst of all, while they're both
alpha 2 agonists, they differ alittle bit in their pharmacology
and that's something that doesgive rise to differences in
terms of tolerability.
So when we're thinking aboutclonidine, we're thinking about
something that's a littlemessier.
So it's going to hit alpha, 2A,2B and 2C.
(05:40):
It's also going to hit theimidazoline receptor, which may
give rise to more of the bloodpressure related side effects,
as well as probably somesedation as well.
But it's a little bit of adirtier medication relative to
guanfacine, which is going to bemuch more selective for that
alpha 2a.
I tend to, for that reason, aswell as just in terms of ease of
(06:04):
dose, because if I'm using theextended release form, I can do
once a day with guanfacine,whereas I still have to do twice
a day with the extended releaseClonidine.
But I do tend to probably useguanfacine a little bit more
than clonidine.
Dr. Elise Fallucco (06:18):
Personally for kids with ADHD.
I really would just useclonidine for sleep.
I rarely use it during the dayto control impulsivity or ADHD
symptoms.
More often I would, like you, Iwould use the guanfacine or
particularly guanfacine XR.
We used to think aboutguanfazine XR or Intuniv as
1,2,3, and 4 milligrams.
(06:39):
But maybe about 5 to 10 yearsago, I started hearing about,
being able to titrate up to 5,6, or 7., do you have a ceiling
when you use guanfacine
Dr. Jeffrey Strawn (06:49):
XR?
I do.
I generally stay below sixmilligrams, but I think the
dosing is really important interms of guanfacine because if
we look at the ADHD studies,it's really not until you get to
0.
08 milligrams per kilogram withthe extended release guanfacine
that you really get the bigeffect.
(07:10):
And if you want to make the matheasier, it's actually 0.
08 to 0.
12, so I sometimes will just goby 0.
1 because I tend to not likemath and that way I can just
divide in terms of the patient'sweight in kilograms,
Dr. Elise Fallucco (07:24):
that's really helpful.
Obviously we're going to startat the lowest dose and even
though guanfacin is not as messyas clonidine, we still have the
potential for blood pressureside effects.
But the idea would be to titrateknowing that.
In clinical studies, getting agetting close to 0.
1 milligrams per kilogram perday dose is going to be where
(07:44):
you're going to see the effect.
Dr. Jeffrey Strawn (07:45):
Absolutely.
And in the one study that wehave, that's a placebo
controlled study.
In terms of disclosure, this wasone of our studies, but it was
not designed to be an efficacystudy.
We actually did go higher thanthat four milligrams in terms of
treating kids with anxiety.
Now, this is a populationwithout ADHD, but kids with
generalized separation or socialanxiety disorder, treating them
(08:08):
with Guanfacine.
Dr. Elise Fallucco (08:09):
I'm so glad you brought up that study
because I wanted to talk aboutit.
It's the one that was publishedin 2017.
You were first author and youguys looked at, as you said,
guanfacine in kids withdifferent types of anxiety, the
generalized separation socialanxiety who did not have ADHD.
And so at the time we'rethinking, Oh, this isn't ADHD
med, but they're looking at itin kids with anxiety.
(08:31):
And then you find out it's welltolerated, it's feasible.
And in fact, the kids showedsome improvement in their
clinical global impression.
on the medication.
And so could this be anadjunctive medication for
anxiety?
So how do you use guanfacine in,let's say a kid does not have
ADHD.
Do you consider guanfacine foranxiety treatment?
Dr. Jeffrey Strawn (08:54):
I do, but I think we generally have better
treatments as first or secondline.
As you alluded to, I often useit adjunctively uh, in those
patients, perhaps that I've notgotten a full response in terms
of my SSRI.
Or there's been sometolerability concern, et cetera.
Dr. Elise Fallucco (09:13):
What I would teach some of the pediatricians
around here is obviously startFirst line treatment for
anxieties, SSRIs, but if you'reclose, but we're not quite
there, the child may or may nothave ADHD, it's reasonable to
consider adding on guanfacine tosee if it can help with some of
the anxiety symptoms Shiftinggears a little bit from the
alpha two agonists, I wanted totalk about the new hot drug on
(09:38):
the market.
That's not actually that new andmaybe not that hot, it's called
viloxazine or Qelbree orsometimes I call it Quelbree
because I have no idea how tosay it.
I think they say
Dr. Jeffrey Strawn (09:47):
Qelbree, but I've heard both.
So I add
Dr. Elise Fallucco (09:50):
a U in there.
It seems like all of my Scrabbleintuition tells me that Qs have
to be followed by Us.
But moving on, so for whichcases, do you think that
Viloxazine or Qelbree is a goodoption?
Dr. Jeffrey Strawn (10:05):
So maybe taking a step back in terms of
Viloxazine and talking a littlebit about it.
So you know when this originallycame out, it was really
presented to me as somethinglike atomoxetine and certainly
reading through things, I lookedat it as another norepinephrine
reuptake inhibitor.
It does do a bit more, butagain, it's always hard to
(10:26):
figure out what's height versuswhat's actually clinically
relevant pharmacology.
I'm sure your experience issimilar to mine in terms of
atomoxetine.
We started.
We titrate, we wait.
Are you better?
Are you a little bit better?
You a little bit better?
Let's wait some more.
And for me, that's oftensomething that's very
frustrating because, during thattime, you may still be getting
(10:49):
side effects but you're notnecessarily seeing the efficacy.
And that for me is probably oneof the biggest drawbacks to
atomoxetine.
And so when I started usingViloxazine I was expecting.
A similar profile in terms ofjust that temporal course of
response and what patientsstarted telling me was even
(11:09):
within those first couple ofweeks, they had a much earlier
response.
They were noticing someimprovement in symptoms.
And so I think it probably isvery different relative to
atomoxetine.
The other issue is that we don'thave as much of an issue in
terms of variation inmetabolism.
We have a little bit of 2D6 withfiloxazine, but obviously with
(11:33):
atomoxetine, we have majordifferences in terms of how
folks metabolize the medicine.
And the FDA even recommendsdifferent titrations and
different dosing based onWhether a patient is a slow or
faster metabolizer forcytochrome 2D6.
Back to Viloxazine, a couplethings that are probably also
(11:54):
relevant certainly I do seeimprovement beyond what I
historically have seen even withan alpha 2 uh, or with
atomoxetine.
But the other thing that I'venoticed a couple of times,
especially when I forgot tomention it, is it's a pretty
potent inhibitor of cytochrome1A2.
And so a lot of my patients,like me, drink energy drinks and
(12:17):
coffee, and they've actually Incoming back and as I asked about
the medicine mentioned sometremulousness and as we started
really unpacking that what welearned was that it was directly
related their caffeine intake.
Viloxazine will actuallyincrease your caffeine exposure.
So blood level over time SIXFOLD.
(12:41):
Whoa.
Substantially.
So my cup of coffee that I'mdrinking right now becomes six
cups of coffee.
So that's probably veryclinically significant.
Dr. Elise Fallucco (12:50):
Six times exposure.
So basically like it's Theequivalent of ordering a tall at
Starbucks and getting threeVenti's instead of getting
exposure to three Venti's.
Yes.
Dr. Jeffrey Strawn (13:01):
and then we also back to our topic today
have that complex relationshipbetween caffeine and anxiety,
which again, I think we're alltaught in residency and
actually, quite frankly, inmedical school that caffeine
causes anxiety.
The reality is that it doesn'tfor about two thirds of
individuals.
(13:22):
So there's a geneticpolymorphism in the ADR2A gene
uh, that makes some peoplereally not experience any of
those symptoms with caffeine.
Dr. Elise Fallucco (13:32):
This makes sense.
I'll see somebody having acaffeinated beverage at five or
at 6 PM and I'm thinking, Areyou kidding?
If I had that, I would be up allnight and they swear it doesn't
affect them that they still cansleep and they're probably
right.
ADR2A polymorphism.
It explains it all now.
back to Qelbree.
This is really promising that inyour clinical experience, it
(13:54):
tends to be more effective thanatomoxetine or stratera.
Certainly it works more rapidlythat we don't have to worry as
much about the 2d6 polymorphismsthat can affect dosing depending
upon whether you're slow orrapid metabolizer.
And that the main thing to lookout for would be that it's gonna
increase your exposure to anycaffeine that you're drinking.
(14:16):
And so we have to be carefulabout that.
Dr. Jeffrey Strawn (14:19):
I think that was an excellent summary.
So the other thing that probablyis important to mention with
regard to Viloxazine, is thatsome of it is metabolized by
2D6.
And so what we'll see is about a20 percent bump in drug levels
of Viloxazine in patients thatare 2D6 poor metabolizers.
Now, in general, that's notthought to really be clinically
(14:40):
significant.
Dr. Elise Fallucco (14:41):
so there are some 2D6 effects, but unlike
with atomoxetine, we don't haveto be dose adjusting
significantly in response
Dr. Jeffrey Strawn (14:49):
I think that's very well put..
And we wouldn't necessarilycheck 2D6 metabolizer status at
baseline or pharmacogenetics forVIloxazine, whereas we would
want to with Atomoxetine.
I think that's also a very fairstatement.
Dr. Elise Fallucco (15:04):
Wow.
We've covered so much in just ashort period of time.
So I want you to do a quickrecap before shifting gears.
Dr Strawn.
You would recommend that insomebody with ADHD and anxiety,
we treat ADHD first and thenaddress residual anxiety.
Unless the anxiety itselfhappens to be incredibly severe.
And as far as treatment forADHD, you would start with the
(15:26):
methylphenidate stimulantproducts instead of the mixed
amphetamine salts, because theyseem to be better tolerated.
We talked about the role ofalpha two agonists and that
Clonidine is a little bitmessier, alpha, two agonists
that hits multiple receptors andis more likely to cause the
blood pressure changes andsedation.
Whereas guanfacine is much moreselective for the alpha two, a
(15:49):
receptor and the XR version canbe dosed once daily.
With a target dose of 0.1milligrams per kilogram, per
day.
To help with impulsivity.
And also to help manage some ofthe side effects with stimulant
medication.
And finally we discussed thenorepinephrine re-uptake
inhibitors and it sounds likeyou're a big fan of Viloxazine
(16:11):
which works more rapidly thanAtomoxetine I mean, is not
effected by two D sixmetabolizer status like
Atomoxetine is, but that we justhave to be careful about
Viloxazine because it's a potent1A2 inhibitor which can increase
caffeine exposure over time.
Six fold.
We are not done talking aboutADHD and anxiety with Dr.
(16:32):
Strawn.
So we hope you'll join us nextweek.
As we do some rapid fire Q anda.
Talk about an amazing resourceavailable for all pediatric
clinicians.
And finally discuss whymedication for ADHD and anxiety
is like peanut butter and jelly.
Thanks for joining hope to seeyou next week.
Welcome back to PsychEd4Peds the child mental
health podcast for pediatricclinicians, helping you help
kids.
I'm your host, Dr.
Elise Fallucco, childpsychiatrist and mom.
This week, we're continuing theconversation with Dr.
Jeff Strawn about medicationtreatment for ADHD and anxiety.
We'll start by talking aboutstimulant medication.
(01:04):
Then we'll switch and talk aboutnon-stimulant options.
Like alpha agonists.
As well as the norepinephrinere-uptake inhibitors viloxazine
and Atomoxetine.
So let's jump back into theconversation.
With Dr.
Jeff Strawn.
is there a go to stimulant thatyou would use for a child with
ADHD and a positive familyhistory of anxiety to try to
(01:26):
minimize the likelihood ofworsening anxiety?
Dr. Jeffrey Strawn (01:30):
Now, this is where the guidelines probably
don't help us as much as theycould because these guidelines,
which are a bit old at thispoint, actually recommend
treating the primary disorder.
But if we actually look at theevidence, except in some rare
circumstances, the evidenceactually suggests treating the
ADHD first, and then seeing,what we're left with in terms of
(01:51):
those residual anxiety symptomsagain, situation where we had
severe anxiety and ADHD.
We might approach this a littlebit differently, but all other
things being equal, our datareally suggests that we should
treat the ADHD first.
So now to your question abouttreatment, which should we go
with?
So in terms of now we're talkingabout treating ADHD, and so I
(02:15):
think really the evidence thatwe have is for stimulants and
within that stimulant family, Itend to use the methylphenidate
based medications.
And I think that's, somewhatbased on some of the
tolerability meta analyses thatsuggests that they may not
worsen anxiety symptoms.
In fact, there's actually someevidence they improve anxiety
symptoms.
(02:35):
We can talk a little bit aboutthat, but I tend to avoid the
mixed amphetamine salts in thepediatric population, at least
as a first line medication, justbecause there is some evidence
that they can cause moreirritability and some other
symptoms, at least from metaanalyses.
Dr. Elise Fallucco (02:52):
I completely agree.
I also start with themethylphenidate products.
I clinically, I find them, thekids tend to tolerate them
better.
And then if they don't work,then we'll think about mixed
amphetamine salts., but I've hada lot of kids where you start on
mixed amphetamine salts andthey'll get irritability or
increased anxiety.
And so they're not my firstchoice,
Dr. Jeffrey Strawn (03:13):
right?
And also, I think, just in termsof tolerability.
We roughly have almost half theincidence of appetite
suppression and some of theseother side effects that we think
of outside of just the emotionalor neurobehavioral side effects
of stimulants with themethylphenidate based medicines
relative to the mixedamphetamine salts.
Dr. Elise Fallucco (03:33):
Backing up, sometimes when we're starting
treatment for ADHD, you can usefamily history to guide you, if
you One of the parents is doingor one of the siblings is doing
really well on a certainmedicine.
You might think about tryingthat one for the child, but
without any of that information,the go to medicine would be
something in the methylphenidateclass.
Dr. Jeffrey Strawn (03:53):
That would certainly be my approach.
It sounds like it's yours
Dr. Elise Fallucco (03:55):
as well.
Yes.
Shifting gears from talkingabout the stimulant medications.
Let's talk about thenon-stimulant medications for
ADHD.
So, of course, we've got the.
Older ones, the alpha twoagonists, like guanfacine and
Clonidine.
And in addition, we have the norepinephrin re-uptake inhibitors
like Atomoxetine which isStrattera and the newer one.
(04:19):
Viloxazine or Qelbree.
There's a lot of buzz, about nonstimulant medications for ADHD.
Are there any cases of kids withADHD where you would start ADHD
monotherapy treatment with a nonstimulant as opposed to a
stimulant?
Dr. Jeffrey Strawn (04:37):
There are probably a few.
The one may be in an olderadolescent who has a history of
perhaps stimulant misuse.
Now, again, I think, even inthose situations, that doesn't
necessarily rule out my using astimulant because, many of these
kids may have used it more as aSelf-help medication, but I
(04:58):
think other situations, would bewhere we've had significant side
effects with a stimulant.
I think you laid out some of theoptions in terms of the alpha
two agonists and also in termsof Viloxazine and atomoxetine.
With regard to the alpha twoagonists.
Really what we have here areclonidine and guanfacine and a
(05:20):
couple of things that I'd sayfirst of all, while they're both
alpha 2 agonists, they differ alittle bit in their pharmacology
and that's something that doesgive rise to differences in
terms of tolerability.
So when we're thinking aboutclonidine, we're thinking about
something that's a littlemessier.
So it's going to hit alpha, 2A,2B and 2C.
(05:40):
It's also going to hit theimidazoline receptor, which may
give rise to more of the bloodpressure related side effects,
as well as probably somesedation as well.
But it's a little bit of adirtier medication relative to
guanfacine, which is going to bemuch more selective for that
alpha 2a.
I tend to, for that reason, aswell as just in terms of ease of
(06:04):
dose, because if I'm using theextended release form, I can do
once a day with guanfacine,whereas I still have to do twice
a day with the extended releaseClonidine.
But I do tend to probably useguanfacine a little bit more
than clonidine.
Dr. Elise Fallucco (06:18):
Personally for kids with ADHD.
I really would just useclonidine for sleep.
I rarely use it during the dayto control impulsivity or ADHD
symptoms.
More often I would, like you, Iwould use the guanfacine or
particularly guanfacine XR.
We used to think aboutguanfazine XR or Intuniv as
1,2,3, and 4 milligrams.
(06:39):
But maybe about 5 to 10 yearsago, I started hearing about,
being able to titrate up to 5,6, or 7., do you have a ceiling
when you use guanfacine
Dr. Jeffrey Strawn (06:49):
XR?
I do.
I generally stay below sixmilligrams, but I think the
dosing is really important interms of guanfacine because if
we look at the ADHD studies,it's really not until you get to
0.
08 milligrams per kilogram withthe extended release guanfacine
that you really get the bigeffect.
(07:10):
And if you want to make the matheasier, it's actually 0.
08 to 0.
12, so I sometimes will just goby 0.
1 because I tend to not likemath and that way I can just
divide in terms of the patient'sweight in kilograms,
Dr. Elise Fallucco (07:24):
that's really helpful.
Obviously we're going to startat the lowest dose and even
though guanfacin is not as messyas clonidine, we still have the
potential for blood pressureside effects.
But the idea would be to titrateknowing that.
In clinical studies, getting agetting close to 0.
1 milligrams per kilogram perday dose is going to be where
(07:44):
you're going to see the effect.
Dr. Jeffrey Strawn (07:45):
Absolutely.
And in the one study that wehave, that's a placebo
controlled study.
In terms of disclosure, this wasone of our studies, but it was
not designed to be an efficacystudy.
We actually did go higher thanthat four milligrams in terms of
treating kids with anxiety.
Now, this is a populationwithout ADHD, but kids with
generalized separation or socialanxiety disorder, treating them
(08:08):
with Guanfacine.
Dr. Elise Fallucco (08:09):
I'm so glad you brought up that study
because I wanted to talk aboutit.
It's the one that was publishedin 2017.
You were first author and youguys looked at, as you said,
guanfacine in kids withdifferent types of anxiety, the
generalized separation socialanxiety who did not have ADHD.
And so at the time we'rethinking, Oh, this isn't ADHD
med, but they're looking at itin kids with anxiety.
(08:31):
And then you find out it's welltolerated, it's feasible.
And in fact, the kids showedsome improvement in their
clinical global impression.
on the medication.
And so could this be anadjunctive medication for
anxiety?
So how do you use guanfacine in,let's say a kid does not have
ADHD.
Do you consider guanfacine foranxiety treatment?
Dr. Jeffrey Strawn (08:54):
I do, but I think we generally have better
treatments as first or secondline.
As you alluded to, I often useit adjunctively uh, in those
patients, perhaps that I've notgotten a full response in terms
of my SSRI.
Or there's been sometolerability concern, et cetera.
Dr. Elise Fallucco (09:13):
What I would teach some of the pediatricians
around here is obviously startFirst line treatment for
anxieties, SSRIs, but if you'reclose, but we're not quite
there, the child may or may nothave ADHD, it's reasonable to
consider adding on guanfacine tosee if it can help with some of
the anxiety symptoms Shiftinggears a little bit from the
alpha two agonists, I wanted totalk about the new hot drug on
(09:38):
the market.
That's not actually that new andmaybe not that hot, it's called
viloxazine or Qelbree orsometimes I call it Quelbree
because I have no idea how tosay it.
I think they say
Dr. Jeffrey Strawn (09:47):
Qelbree, but I've heard both.
So I add
Dr. Elise Fallucco (09:50):
a U in there.
It seems like all of my Scrabbleintuition tells me that Qs have
to be followed by Us.
But moving on, so for whichcases, do you think that
Viloxazine or Qelbree is a goodoption?
Dr. Jeffrey Strawn (10:05):
So maybe taking a step back in terms of
Viloxazine and talking a littlebit about it.
So you know when this originallycame out, it was really
presented to me as somethinglike atomoxetine and certainly
reading through things, I lookedat it as another norepinephrine
reuptake inhibitor.
It does do a bit more, butagain, it's always hard to
(10:26):
figure out what's height versuswhat's actually clinically
relevant pharmacology.
I'm sure your experience issimilar to mine in terms of
atomoxetine.
We started.
We titrate, we wait.
Are you better?
Are you a little bit better?
You a little bit better?
Let's wait some more.
And for me, that's oftensomething that's very
frustrating because, during thattime, you may still be getting
(10:49):
side effects but you're notnecessarily seeing the efficacy.
And that for me is probably oneof the biggest drawbacks to
atomoxetine.
And so when I started usingViloxazine I was expecting.
A similar profile in terms ofjust that temporal course of
response and what patientsstarted telling me was even
(11:09):
within those first couple ofweeks, they had a much earlier
response.
They were noticing someimprovement in symptoms.
And so I think it probably isvery different relative to
atomoxetine.
The other issue is that we don'thave as much of an issue in
terms of variation inmetabolism.
We have a little bit of 2D6 withfiloxazine, but obviously with
(11:33):
atomoxetine, we have majordifferences in terms of how
folks metabolize the medicine.
And the FDA even recommendsdifferent titrations and
different dosing based onWhether a patient is a slow or
faster metabolizer forcytochrome 2D6.
Back to Viloxazine, a couplethings that are probably also
(11:54):
relevant certainly I do seeimprovement beyond what I
historically have seen even withan alpha 2 uh, or with
atomoxetine.
But the other thing that I'venoticed a couple of times,
especially when I forgot tomention it, is it's a pretty
potent inhibitor of cytochrome1A2.
And so a lot of my patients,like me, drink energy drinks and
(12:17):
coffee, and they've actually Incoming back and as I asked about
the medicine mentioned sometremulousness and as we started
really unpacking that what welearned was that it was directly
related their caffeine intake.
Viloxazine will actuallyincrease your caffeine exposure.
So blood level over time SIXFOLD.
(12:41):
Whoa.
Substantially.
So my cup of coffee that I'mdrinking right now becomes six
cups of coffee.
So that's probably veryclinically significant.
Dr. Elise Fallucco (12:50):
Six times exposure.
So basically like it's Theequivalent of ordering a tall at
Starbucks and getting threeVenti's instead of getting
exposure to three Venti's.
Yes.
Dr. Jeffrey Strawn (13:01):
and then we also back to our topic today
have that complex relationshipbetween caffeine and anxiety,
which again, I think we're alltaught in residency and
actually, quite frankly, inmedical school that caffeine
causes anxiety.
The reality is that it doesn'tfor about two thirds of
individuals.
(13:22):
So there's a geneticpolymorphism in the ADR2A gene
uh, that makes some peoplereally not experience any of
those symptoms with caffeine.
Dr. Elise Fallucco (13:32):
This makes sense.
I'll see somebody having acaffeinated beverage at five or
at 6 PM and I'm thinking, Areyou kidding?
If I had that, I would be up allnight and they swear it doesn't
affect them that they still cansleep and they're probably
right.
ADR2A polymorphism.
It explains it all now.
back to Qelbree.
This is really promising that inyour clinical experience, it
(13:54):
tends to be more effective thanatomoxetine or stratera.
Certainly it works more rapidlythat we don't have to worry as
much about the 2d6 polymorphismsthat can affect dosing depending
upon whether you're slow orrapid metabolizer.
And that the main thing to lookout for would be that it's gonna
increase your exposure to anycaffeine that you're drinking.
(14:16):
And so we have to be carefulabout that.
Dr. Jeffrey Strawn (14:19):
I think that was an excellent summary.
So the other thing that probablyis important to mention with
regard to Viloxazine, is thatsome of it is metabolized by
2D6.
And so what we'll see is about a20 percent bump in drug levels
of Viloxazine in patients thatare 2D6 poor metabolizers.
Now, in general, that's notthought to really be clinically
(14:40):
significant.
Dr. Elise Fallucco (14:41):
so there are some 2D6 effects, but unlike
with atomoxetine, we don't haveto be dose adjusting
significantly in response
Dr. Jeffrey Strawn (14:49):
I think that's very well put..
And we wouldn't necessarilycheck 2D6 metabolizer status at
baseline or pharmacogenetics forVIloxazine, whereas we would
want to with Atomoxetine.
I think that's also a very fairstatement.
Dr. Elise Fallucco (15:04):
Wow.
We've covered so much in just ashort period of time.
So I want you to do a quickrecap before shifting gears.
Dr Strawn.
You would recommend that insomebody with ADHD and anxiety,
we treat ADHD first and thenaddress residual anxiety.
Unless the anxiety itselfhappens to be incredibly severe.
And as far as treatment forADHD, you would start with the
(15:26):
methylphenidate stimulantproducts instead of the mixed
amphetamine salts, because theyseem to be better tolerated.
We talked about the role ofalpha two agonists and that
Clonidine is a little bitmessier, alpha, two agonists
that hits multiple receptors andis more likely to cause the
blood pressure changes andsedation.
Whereas guanfacine is much moreselective for the alpha two, a
(15:49):
receptor and the XR version canbe dosed once daily.
With a target dose of 0.1milligrams per kilogram, per
day.
To help with impulsivity.
And also to help manage some ofthe side effects with stimulant
medication.
And finally we discussed thenorepinephrine re-uptake
inhibitors and it sounds likeyou're a big fan of Viloxazine
(16:11):
which works more rapidly thanAtomoxetine I mean, is not
effected by two D sixmetabolizer status like
Atomoxetine is, but that we justhave to be careful about
Viloxazine because it's a potent1A2 inhibitor which can increase
caffeine exposure over time.
Six fold.
We are not done talking aboutADHD and anxiety with Dr.
(16:32):
Strawn.
So we hope you'll join us nextweek.
As we do some rapid fire Q anda.
Talk about an amazing resourceavailable for all pediatric
clinicians.
And finally discuss whymedication for ADHD and anxiety
is like peanut butter and jelly.
Thanks for joining hope to seeyou next week.
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