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Stimulants In Treating ADHD

​This presentation will offer an overview of methylphenidate and amphetamine class medications used in ADHD, converting between the two stimulants class and clinical vignette questions.

  • Woman: Good afternoon, everyone. We are excited to have you join us today as part of our "Boys Town Physician Education Series" for June. We encourage you all to stay connected with us and take advantage of these free monthly CME opportunities for all physicians virtual style. Before we get started, I'd like to announce that this series is jointly provided by Boys Town National Research Hospital and Creighton University.

    Today's presenter is Dr. Yancheng Luo, board-certified neurologist here at Boys Town National Research Hospital. Dr. Luo joined Boys Town Hospital in 2021 and sees patients at two clinics, one here at Boys Town Medical Campus, Pacific Street, and the other in Sioux City, Iowa at our Boys Town Specialty Clinic.

    Dr. Luo earned his medical degree from the Xiangya School of Medicine at Central South University in China and completed his pediatric and pediatric neurology residencies at Massachusetts General Hospital and Brigham and Women's Hospital in Massachusetts, an affiliate of Harvard Medical School.

    Dr. Luo has a special interest in common pediatric epilepsy syndromes. Today, Dr. Luo will be discussing the use of stimulants in treating attention deficit hyperactivity disorder. Please welcome Dr. Yancheng Luo

    Dr. Luo: So, hi everybody. I'm YC Luo. I'm one of the neurologists here, general neurologist here at Boys Town. So, my interest is childhood epilepsy and also other, like, general child neurological conditions as well. So, when I did my training in Massachusetts, actually ADHD, a lot of them, they are managed by neurologists. It's probably there are, like, an abundance of child neurologists in Boston.

    And so that's where I had my training and experience, was using stimulants. Especially sometimes for patients with common childhood epilepsy such as absence as you know, that they are at risk for ADHD. There is some myth and sometimes people have believed that stimulant is contraindicated in patients with epilepsy due to the risk for breakthrough seizures.

    We really don't have strong evidence for that and because of that sometimes I do see patients with epilepsy and also comorbid ADHD. So, today I just wanna take this opportunity to talk about using stimulants, particularly stimulants. And so we are not gonna be talking about how to diagnose ADHD or using non-stimulants. And so let's just get to start...let's get started.

    So, first off, just to remind you about the diagnosis of ADHD. So, currently, we still have the DSM-V criteria. And so there are several different subtypes of primarily intensive hyperactive or combined type of ADHD. And the easiest way to do is to do the Vanderbilt form and...form for parents and another form for the teachers and then follow up with a follow-up format.

    So, if you meet more than 6 out of the 9 symptoms on the Vanderbilt form for kids up to 16 years of age, or more than 5 out of the 9 criteria for adolescents 17 and older and adults, then you meet the criteria for ADHD. So, one of the change in DSM-V is in DSM-IV, it used to be that the ADHD symptoms must be present before age of 6.

    Otherwise, after 6, it is a little bit hard to diagnose ADHD, sometimes need like a formal neuropsych testing to get a formal diagnosis, and DSM-V changed it to 12, which makes diagnosis much easier. So, one of the thing I wanna go through first is general suggestions for ADHD, particularly stimulants use. So, for prescribing stimulants, one of the thing is I do recommend to set, like, the root before you prescribe. As you probably know, that ADHD sometimes, they do run in the family.

    So, when the kids have ADHD, very likely the parents, they also do have ADHD. So, sometimes it can have some executive function problems, like some...forget appointments, forget to call for your refills. So, one of the thing is stimulants is a little bit different than, for example, seizure medication is. The stimulants refill, they are never emergency or urgency.

    And you should set the expectation that refill requests should be submitted at least, like, one to two weeks prior. So, like last minute, like, Friday night refill is not appropriate. And so by setting the boundary will definitely make your life much easier. And then in terms of the different classes of stimulants, there are two major classes. So, the methylphenidate class, or the Ritalin class, and the Adderall class or the amphetamine class.

    So, generally speaking, it's really a personal choice to start with either class, but my practice and also the people I learn from in Boston, we typically think a methylphenidate class is generally better tolerated than the amphetamine class. And another common mistake is sometimes when we prescribe, like, stimulants BID, it does not mean 7:00 in the morning and 7:00 at night because sometimes that can cause issues.

    One of the thing we run into is a lot of people, they are on long....extended-release stimulants baseline at home, and when they're admitted to the hospital, most of the time, the inpatient side do not carry the long-acting stimulants, probably it's because they're much more expensive. And then when you try to convert long-acting stimulants to like short-acting dosing, if you change it to BID, that actually means most of the time it is 7:00 in the morning and after lunch.

    So, please do not do like 8 p.m. dosing of stimulants. It's not very nice and it will definitely disrupt their sleep. And the other things is one of the things I like about stimulants is by the end of the day is kind of like it's performance-enhancing medications. So, almost always, kids, they will respond to stimulants and the stimulants do have a linear dose-response curve.

    And so most of the time you'll have more symptom reduction with higher doses. And however, obviously, that will come with higher side effect as well. And another thing about stimulants is it is always appropriate, always right to start at the lowest dose and go up because stimulants, it can actually go up very quickly every three days or every week.

    So, if you don't really know how much the kid can tolerate, you can always start at the lowest dose and just ramp up quickly. Usually, we can see the response that those filled up pretty quickly. And then another pro of stimulants prescribing is it's usually not really titrated according to a weight-based dosing. We do have a maximum dosing based on weight.

    We will get into that, but in terms of efficacy and the most beneficial dose for each patient, it is different. Everybody has their own, like, individual dose response curve. So, that basically means that it is always right to start in the lowest dose and just titer up based on their response. And then the last one I think is also very important, is longer-acting medication, the extended-release, they're always preferred than short-acting.

    And so, first of all, due to they're easier to administer, you only take it once a day, and sometimes stimulants to be given at school, they can be a hassle because depending on their policy, stimulants is is controlled substances, so they have to have lockbox for it, and the nurse needs to have a letter. And so it's actually not very easy to give it at school, in a school setting.

    And another thing about longer-acting is, generally speaking, longer-acting usually at higher dose has a less chance of causing more side effect and, therefore, increase adherence and compliance as well. The short-acting, obviously, can be used in younger kids, especially if they cannot swallow the extended-release pill or if there's no appropriate formulation with doses for those younger kids.

    And so in terms of the mechanism of stimulants, you know, right now we, for example, the graph on the left is the methylphenidate class. So, we think that the methylphenidate inhibits the dopamine reuptake from the synapse back to the presynaptic neuron. So increase the concentration in the synapse.

    And then for amphetamine class, in addition to the inhibition of the reuptake, you also enhance the release of the dopaminergic neurotransmitters from the presynaptic neuron to the synapse. And so based on this, you know, you can kind of guess that amphetamine is a little bit more potent and stronger than the methylphenidate class, and obviously, with being more potent, it has a higher chance of causing a side effect as well.

    So, in terms of choosing which class to start, it's really a personal preference and everybody has their own experience and their own, like, comfort level with prescribing either class. So, it's never wrong to pick one. I generally prefer methylphenidate. It has, at least for now, has way more dosing options and way more formulations. You can really adjust them and really give the patient a very, like, individualized regimen.

    And it is sometimes considered lighter, so it does not really cause as many side effects as the amphetamine class. However, sometimes for kids with more severe combined types, especially with a lot of hyperactivity and emotional dysregulation, so sometimes being aggressive, with their ADHD symptoms, they, sometimes, they do better with stronger medication, and so Adderall class.

    One of the thing discovered more recently, several years ago, it was published on "The New England Journal of Medicine" is the absolute risk of psychosis. Basically, it was a study done in the New England area, don't quote me, but I think it was a very large study, is they looked at, I think, around, like, 20,000 adolescents and young adults who are on stimulants.

    And the absolute risk of psychosis was higher with the amphetamine class than with the methylphenidate class. So, it's about 2.8 versus 1.7 episodes per 1000 person-years. And it was statistically significant. And so this study basically showed us correlation but this is not a causation study. So, one of the thought after this study came out in the community, some of us think that it's not really that the amphetamine is more likely to cause psychosis compared to methylphenidate.

    It could be due to that people who are on amphetamine class, they typically have a more severe ADHD because the majority of providers, we all basically think methylphenidate is more better tolerated, however, is not as strong as amphetamine. So, it could be just due to people with more...harder to treat ADHD, they have a higher chance of getting psychosis or higher chance of getting comorbid psychiatric conditions.

    So, this is not a causation but it is association. So, I always just tell parents about this as well. And obviously, if psychosis happen and, for example, like auditory hallucination happens when they're being treated with stimulants, especially after starting a new stimulant or after dose increase, please obviously hold the medication. Sometimes change to a different medication, either from Adderall class or methylphenidate class, or try a non-stimulant and things like that. You can definitely do that.

    And lastly, just as I said before, prescribing stimulants sometimes, especially for people with true ADHD that is debilitating, like treating them with stimulants, manage them with stimulants, can be quite rewarding because actually the vast majority of people will respond. So, for example, 6% to 75% of the patients will show response to one stimulant and this number increased to almost 90% if they tried both.

    Currently, we still don't have the exact way to predict how they will respond and who will respond to which one. You know, sometimes parents will come to you with, like, some genetic testing or some lab work they get from like, third party telling them that what kind of stimulants will work better. We really don't have robust data to suggest that. Okay. So, this is just the paper, like, stating the association between stimulants.

    So, now we are gonna go into the each individual stimulants, so let's start with the methylphenidate class. So, this is the table that if you're interested of getting them, you can. You can just email me and I will send you the PowerPoint. So, basically, it's the way for you to convert each stimulant. So, the R here stands for Ritalin and it is the half-life of the stimulants. So, for example, the shortest action Ritalin, the old Ritalin or methylphenidate immediate-release. So, we'll get into like the single hump, the flat, ascending later.

    So, for example, for the immediate-release Ritalin, it lasts for about 2 or 3 hours, and then if you go to sustained-release, you times the 2 to 3 hours to times 1.5, and then times 1.75 to 2 with Concerta, and then you can go up from there. So, it's just a way for you to kind of know, like, which stimulants to choose when you hear the story, like, how long the kids really need the stimulants for their school or for other, like, activities.

    And so this is for the Adderall class. So, the shortest action Adderall class is the dextroamphetamine. And they only last for about like two to four hours. And then generally speaking, Adderall class, amphetamine class, they all last longer than the methylphenidate class, especially to their counterpoint.

    And so let's start with the methylphenidate class. So the most classic methylphenidate class is the Ritalin. So, basically, it's just immediate-release. So, give you a single hump. So, give you a peak and a trough. And so it lasts for about two to four hours and it peaks around like one and a half hours. And Ritalin class has a low bioavailability. So it's only the D-isomer is effective in the methylphenidate.

    And so the L-isomer is really not as effective as the D-isomer. And so at moderate doses, it will give you a linear of pharmacokinetics. So, the more you give, the more effect you will get. The good things about Ritalin is really know that there aren't many drug [inaudible 00:16:18] interactions and the absorption is not really affected with food, unlike the Adderall class.

    And the Ritalin class, for the immediate-release Ritalin, you can crush the tablets into, like, powder and it also comes in liquid formulation as well. And so it's definitely much easier to use in younger kids, especially if they cannot swallow a pill. And so this is the Ritalin sustained-release. I'm sorry, for all those acronyms. And they're all named in different ways, it's sometimes can be confusing as well.

    This one is not relevant anymore. So, it's kind of like an older class of sustained-release drug. So, it lasts just slightly longer than the immediate-release Ritalin. So it lasts for about like about five hours. And this a wax-based delivery system, so they embedded the medication into a wax, and then it'll give you a very flat line plasma concentration, but the release and absorption is not very reliable and you cannot chew them. You have to swallow the wax-based medication as a whole, so we don't really use this anymore.

    And then the next one is called Metadate, Metadate CD. So, it is also methylphenidate and so basically it is a capsule with two different kind of beads. It has about 30% of immediate-release. Once you take it, you will release the methylphenidate immediately. And then 70% of the extended-release beads will release later. So, you will give your ascending level.

    So, usually, later on, the late morning or early afternoon, the dose will be higher. It is beads, so you can sprinkle them on food and ideally not to chew on the beads. This one, we will get into this. So, this one, it will be appropriate for kids who tolerate the immediate-release Ritalin, and then you think they're ready for an extended-release medication, especially they need the immediate-release in the afternoon, so the Metadate might be the one to go.

    And then the Ritalin ER. ER stands for extended-release, or Ritalin LA, so long-acting. So, this one lasts for about 6 to 10 hours. It has a 50:50 ratio. So, 50% of the beads are short or immediate-release or release immediately, and the 50%, they're delayed-release. So, basically give you two peaks. The hope of all those 50:50 ratio medication, when they created, is to kind of leave out the lunch period so kids can eat.

    And so that's the theory and in my opinion, it actually works for some kids, like, especially they...some start to lose weight or not have adequate weight gain and they don't eat lunch, and then sometimes it's good to change them into a 50:50 ratio long-acting stimulants. And so they basically give you two humps. Okay. So, this one is also a capsule with beads in them, so you can sprinkle them on food as well.

    And the next one is Concerta. Concerta, so it is one of the Ritalin long-acting. It's covered by insurance and it's very, like, widely used, and actually, patients tolerate Concerta pretty well usually without that many headaches or appetite suppression. And so methylphenidate, unlike the 50:50 ratio beads-based capsule, methylphenidate actually use an automatic controlled-release.

    So, you can see the graph here is basically the one end of the capsule has, like, an opening or an exit. And then another end has kind of like sponge kind of structure. And when it absorb water, it will push the medication from compartment number one into the body. So, you know, it sounds very fancy and it's all good, and it turned out this mechanism is not that efficient.

    And so that's the reason why Concerta...a part of the reason why Concerta comes in kind of weird dosing, it's not a wrong number. Like all other stimulants, they come in like 10, 15, 20, 35, things like that. However, Concerta comes in like 18, 36, or 54, it's because typically speaking, Concerta usually will require a slightly higher dose given this less efficient release mechanism.

    For example, Ritalin 15 milligram probably should be translated into...convert into Concerta 18. And Ritalin 30 should go to Concerta 36, and Ritalin 45 should go to Concerta 54. And the last one is Focalin XR. So, Focalin XR is only the D-isomer of the Ritalin. As we said before, the L-isomer in methylphenidate is not that effective. So, Focalin is only the D-isomer. So, it is more potent than Ritalin or the traditional methylphenidate.

    And so the Focalin XR, extended-release. So, it lasts for about 10 to 12 hours. And it also is a beads-based capsule. So, it has 50% immediate release and 50% delay release. So, it's also 50:50 ratio and give you a double hump and the hope is to leave out the lunchtime so kids can eat.

    One other thing is please remember, if you convert people from Ritalin to any kind of other Ritalin class like Concerta, Metadate, or Ritalin immediate-release when you convert to Focalin, please half the dose. At least, in the beginning, you half the dose. If they need more, you can always give them more. And so the last one is Daytrana Patch. This is one of the longest-acting Ritalin class or methylphenidate class.

    So, it's basically a patch and when you put it on the body, it will give you a flat, sometimes ascending release of the methylphenidate. Important things to remember with the patch is it has a delay. It takes about one and a half hours to like two hours to start working. And so you have to really time your day right. So, if you wanna use the patch...because sometimes when you use patch, it's usually younger kids, they, they don't wanna take anything by mouth, and then you might wanna use the patch.

    And then although 12 hours might be too long for younger kids, the beauty of the patch is you can remove them. And, yeah, usually, we remove like after nine hours, and then they will still last for another like three hours, but you can always remove it even earlier than that if you want a shorter period of time. And another thing is [inaudible 00:23:12] can do, but it's not should not be written on the prescription, the patch can, actually, can be cut.

    But that's something that you might have to talk to people who have more experience with using it, but you can actually cut the patch to give them, like, a lower dose or, like, short period for release. And because of the patch, it does not go through the first pass clearance in the GI system. So the dose of the patch is also lower. The weight-based dosing is also lower than typically or a methylphenidate.

    So, if you wanna use the patch, usually start everybody on 10-milligram and go up from there. And after you use a patch or put on the patch, please wash your hand. And sometimes the patch will leave some, like, redness around there, or sometimes the glue will be on the skin. That's totally fine. You can just use some olive oil, you can wipe them off.

    And then another thing about patch is sometimes when people are on patch, stable for a while, and then they suddenly stop responding to it, the first thing to do is you should rotate the placement and don't place it always at the same place. And the last one is Quillivant. So, it is probably, to my understanding, maybe the only one or one of the few, the longer-acting that is liquid.

    So that comes in handy for kids who cannot swallow pills and they need a longer-acting. The issue we run into is Quillivant extended-release, they actually last very long. It lasts for like 10 to 12 hours. And so kids who cannot swallow pills tend to be younger kids so most of the time they don't really need 12 hours. So that might be the issue, that we run into it.

    And Quillivant sometimes can be too strong for them to the point that they don't really eat dinner and they cannot fall asleep. But if you have to use that, for example, for kids on the autism spectrum, they really have sensory issue, cannot swallow anything, like, solid, then obviously you can try. It gives you ascending level. So then it will go up, go up.

    It doesn't give you, like, the value between the two humps to leave out the lunchtime. And when you give Quillivant, before you give it, just make sure you shake the bottle. And so here is something I just want everybody to kind of do a mental exercise because, you know, we just talk about all those different kind of methylphenidate.

    They're basically all methylphenidate, they're just packed in a different way and they have different doses, different mechanisms. So, sometimes it's a little bit hard to remember. And so here, I just wanna go through this graph with you, so you can kind of do the mental exercise with me and together, so kind of to help you to absorb the things we just talked about.

    So, here there are four medications, there are the level after they or people take the medication, after taking the medication and they're all the serum level of the methylphenidate. So, the four medications, they are the Metadate CD, Focalin XR, Concerta, and the Ritalin long-acting. And that's the dose there.

    So, the yellow line is the dose of 18-milligram and the purple line is 20-milligram every day. And the green, the blueish green one is 40-milligram every day. And the orange one is 20-milligram every day. So, first, you can see there are... If you compare the yellow and the purple line, so obviously the yellow line, the doses are lower, is 18-milligram, and the purple line is 20-milligram. However, the serum level is much, much lower.

    Almost half in the yellow line compared to the 20-milligram of the purple line. And one thing you probably will remember, that the Concerta comes in weird dosing, it is not really like the 10, 15, or things like that. And also Concerta has a less efficient, like, delivery mechanism. So, at similar dose, the serum level achieved by Concerta is much lower.

    So, in this case, so the yellow line, it is Concerta. And then if you look at...and also you can see that Concerta does not really give you a double hump. Basically, it give you ascending level, and then it goes down. So give you pretty much one peak. And so it does not really give you like a lunch dip in terms of the serum level. And then you can kind of see there, the purple one give you a dip.

    And obviously, the orange and the blueish, like, green one also give you a dip, about like four hours after you give the medication. So, the purple one here, it is Metadate. And then if you compare the green and the orange one, they give you double humps and give you... So, they're basically, 50:50 ratio. So, 50% of the beads, they're released immediately, and 50% of the beads, they are delayed.

    So, they are released, like, in the afternoons after lunch. So, they basically reach similar level. However, the orange line, the dose is half the green line. So, if you remember, Focalin only has the bioavailable isomer of the methylphenidate so that the the orange line, it is Focalin XR. So, at half dose, compared to the Ritalin long-acting, you will achieve the same level.

    And then... Oh, sorry. One other thing I said around over there is the purple line, it is Metadate. So Metadate, actually, the ratio is not 50:50. It is about, like, 30:70. So they really don't give you the double peak, as you can see here with Ritalin and the Focalin. So, the Metadate gives you a peak similar to Concerta by reaching a higher level because the delivery mechanism is better than the automatic delivery mechanism in Concerta.

    So, yeah, we've seen that before. So, yellow is Concerta, purple is Metadate, and green is Ritalin long-acting, and orange is... Okay. So, that's about Ritalin. And then let's talk about the Adderall class. So, Adderall class, the shortest acting Adderall or actually the first stimulant ever like generally used in practice is Dexedrine.

    So, Dexedrine is dextroamphetamine and it is super short-acting. It's basically very similar to immediate-release Ritalin. It lasts about two hours. And the dosing equivalent is similar to Adderall. So, Dexedrine 10-milligram equals to Adderall 10-milligram, but Adderall obviously lasts much longer than Dexedrine. So, Dexedrine is usually useful only for evening dosing.

    So, if there's a kid that has a lot of difficulties in the evening with homework and sometimes with behavior as well, and then you don't really wanna affect their sleep, then Dexedrine can be the one to use. You can use Dexedrine for that because it should wear off after two to three hours. And then for Adderall immediate-release, so even this is immediate-release, so there's really no extended-release mechanism in Adderall IR.

    However, it still lasts almost twice as long as the Ritalin immediate-release. And so basically, in practice, it's also the same. The Adderall is usually more effective and more [inaudible 00:31:00]. And since this is immediate release, so it will give you like a single hump and there's no, like, complicated liver mechanism, so you can just crush them, crush the pill.

    And then Adderall XR. So, Adderall XR has a 50:50 ratio in the beads. And so it's very similar to Adderall IR given BID. So, one in the morning, one after lunch and they give you a double hump. And they last much longer, up towards like 12 hours. So, it is even longer than most of the long-acting Ritalin, so it's longer than Ritalin long-acting, it is longer than Metadate, it is longer than Concerta. So, one of the thing is Adderall class generally is dosing at half dose of methylphenidate class.

    We are gonna get into this, but if you wanna convert methylphenidate class to amphetamine class, and it is always right just to start at the lowest dose of Adderall and go upwards, or if you don't wanna do that, just half the dose and go from there. And the last one we are gonna cover for the Adderall class is the Lisdexamfetamine or another name is Vyvanse.

    So, Vyvanse, it is a newer version, a newer Adderall class stimulant. So, it lasts pretty long. It lasts about 8 to 14 hours and it is a pro-drug, so they have to go through the first pass, the GI system to be bioavailable. I think that's part of the reason why a lot of insurance, they actually cover it despite of it being extremely expensive, is due to that the fact that it's very hard to abuse Vyvanse by, you know, sniffing or using IV.

    So, I think there's a push to use Vyvanse instead of other potentially, like, abusable stimulants least in the Adderall class. So, the downside of Vyvanse is you have to swallow whole. And the dosing right now, given it is relatively a newer drug, so we don't really have a reliable conversion, even from the Adderall class to Vyvanse. And the weight-based max dosing, yet to be determined.

    So, usually how we dose Vyvanse is it comes in 10, 20 dosing and 30, 40 dosing. So, you usually can start with 20 and go up by 10 depending on their, like, tolerability and clinical response. And another thing I find, like one of the advantage of Vyvanse, is compared to like other XR, like people tend to have less headache or know, like, less severe side effects with Vyvanse. People tolerate it just fine.

    So, some of the pros about using stimulants, so for the methylphenidate class, they're usually not affected by food, and the duration does not usually increase with a higher dose. And often since it's a little bit milder, so often, you will need to increase dose in the first 6 to 12 months, even without, like, weight gain. And sometimes the bioavailability is not as good as the amphetamine class.

    And as for amphetamine class, really it sometimes interacts with over-the-counter medication like antacid, or even like orange juice, like vitamin C will change the absorption. And if you eat a lot of fatty foods, sometimes it can slow the absorption that makes the stimulant last very long. And sometimes with Adderall, even with Adderall immediate-release formulation, if you give them a higher dose, you can just last longer.

    And the amphetamine has a higher bioavailability, and it's more consistently absorbed. And the Vyvanse has a longer half-life. Okay. So, as I said before, we don't really dose stimulants based on their weight. We start at a lower dose and work our way up. However, there is a recommended maximum dose based on weight. For example, for the methylphenidate class, with exception of the patch and the Focalin, usually, you should be maxed out at 2-milligram per kilogram per day.

    And as I said before, the Focalin class is only the D-isomer, so it's twice as effective as the Ritalin class. And other Ritalin, and so the Daytrana, so the methylphenidate patch, it is more potent as well. So, most of the time those two medication is generally maxed out at 1-milligram per kilogram per day.

    And amphetamine is generally around 1 to 1.5-milligram per kilogram per day with Vyvanse being 1-milligram per kilogram per day. So, just for me to remember, typically when I do it in clinic is I just do like a mental math. If it's less than 1-milligram per kilogram per day, for any kind of stimulants, I know that I'm generally in a safe range. And after, if I do the calculation, it's more than 1-milligram per kilogram per day, I will go to that particular medication to look at the particular max weight dosing based on the clinical trial.

    But generally speaking, if it's under 1-milligram per kilogram per day, you're safe. Okay. So, last, I just wanna give you a little bit more, like, practical clinical, like, a dosing plan for different age. So, for example, most of the time, you know, typically speaking, like FDA actually approves stimulants after age of 6, and sometimes a lot of insurance will give you age limits.

    So, most of the time, we start using stimulants after age of 6, but there is exception, especially sometimes when the behavior is out of control and the behaviors, if they pose a safety issue for the patient or the people around them, we do consider starting stimulants at a younger age. However, I recommend to use the lowest dose possible and try immediate-release dose formulation first before you jump into an extended-release.

    For example, for a preschooler or kindergartener, usually start with methylphenidate with the lowest dose. You can start with 2.5-milligram. You can start with once a day just in the morning, but typically because it really only lasts for about like about three hours, so oftentimes you will need another dose after lunch sometimes. If you reach 5-milligram BID, so basically 10-milligram of methylphenidate, that's where the extended-release formulation starts.

    So, in that situation, I would recommend to go to Metadate 10-milligram or higher. And you just give it once-a-day in the morning. And obviously, you can use other extended-release methylphenidate class as well, just knowing that if you change to Focalin, please half the dose. And you can also use Quillivant if they cannot do the capsules or tablets, but knowing that Quillivant lasts pretty long, up towards 12 hours. So you have to really time your day right and sometimes even start with a lower dose.

    And for kids who are in elementary school or middle school, you can just start with Metadate and then titrate in 10-milligram increments. If they need, like, a homework dosing, so, like, evening dosing, you can either use immediate-release Ritalin, so it lasts about two or three hours, or you can use Dexedrine. I usually, just to make things easier, I don't mix methylphenidate and the Adderall class together.

    I don't know if that's the, absolutely, the right way to do, but I usually don't mix those two class together. And if the Metadate does not last through the school day, you can change to Quillivant, Focalin XR or Adderall XR. If they can swallow pills like whole, not chewing them and they can swallow it, they can go to Concerta.

    And just knowing if you do the Concerta dose conversion, you should add a little bit more dose to the Concerta. For middle schooler or high schooler, you can just start with Concerta 18-milligram in the morning and increase by 18-milligram increments. So most of the time Concerta is actually very well tolerated. People usually don't get headache and the appetite suppression is not very high either. Okay.

    So, then one of the thing I wanna just touch upon is insurance coverage. So, obviously, every insurance cover different things. And just this is an example for Nebraska Medicaid. So, for example, Healthy Blue, all those stimulants, they are covered for...but it does have age limit. I'm pretty sure it's either 5 or 6 but please double-check with them.

    And so for example, for the long-acting amphetamine class, the Adderall XR, and the Vyvanse, they're covered, and the long-acting methylphenidate. Vyvanse is actually very interesting. Medicaid actually cover it and sometimes private insurance do not cover it because Vyvanse is actually surprisingly expensive.

    As I said before, I think one of the reason might be, I'm just guessing, why Medicaid cover Vyvanse is because the less abuse risk with Vyvanse. And then for the long-acting methylphenidate class, the Focalin XR, the Concerta, and QuilliChew, they're all covered. And for the short-acting class Ritalin, like Methylin, the liquid form of the Ritalin, and the Adderall, they're all covered. Okay.

    So then we're gonna go through some quick questions, and then we're just gonna go through together and then we'll leave about 10 minutes for questions. So, let's start with question one. So, this is a 5-year-old girl. Her weight is about 18 kilo, who was recently diagnosed with ADHD. The school tried behavior modifications for younger kids under 6. That's definitely the first thing to do, do behavior modifications, but she continued to have inattentiveness.

    Of note, she could not swallow pills yet. I try not to give stimulants for kids younger than 6, especially if they haven't tried behavior modifications. And another thing people sometimes can try is, you know, non-stimulants, although we did not touch upon like Clonidine, Guanfacine or other non-stimulants here. However, one of the thing is non-stimulants, they're usually better for hyperactivity. For example, Clonidine and Guanfacine, they're not super helpful for inattentiveness.

    For severe inattentiveness to the point that their academic performance is affected, sometimes we'll have to give them stimulants. And so here, so we can go through the options. So, she's young and her weight is not very high. And so, you know, the thing we can do... The good thing about stimulants is I can say that all options are reasonable. You can try any one of them.

    I just wanna just share my thought to see...and share my reasoning, the why I would do it this way. So, I think in her case, I will either do option A or option B depending on how bad her behavior is and how long her day is, and does she really need the afternoon dose. So, it's either A or B. I will usually just start with A. So start with immediate-release Ritalin 2.5-milligram in the morning, and it comes in liquid and you can even crush the pills to see how she does.

    So, okay. So, she was started on Ritalin immediate-release 2.5-milligram in the morning and was eventually up-titrated to Ritalin immediate-release 5-milligram twice a day. So, one in the morning and one after lunch, not in the evening. And her ADHD symptoms have improved greatly. I would then do what? So, if she can tolerate pills, so the next step I would do is to give her Metadate.

    So change to Metadate 10-milligram in the morning because it's just once a day and better, like, compliance and better side effect profile as well. And then question two. So, this is a 12-year-old boy. He weighs about 40 kilo, has been diagnosed with ADHD for years. He has been taking Concerta 36-milligram in the morning. He had initial good response. However, more recently he could not focus at school, particularly in the morning and the afternoons were fine and he has no appetite for lunch.

    So, first of all, so I will have done the same thing. I will start him on Concerta. It is usually better tolerated. They don't usually get that much headache with it. But again with methylphenidate class, often you will need those increase after several months and people really get used to it. So, just to remind, just refresh your memory, so we talked about, so Concerta has an automatic delivery system, so it has a ratio of 22 to 78.

    So, you give a tiny bit, like in the morning, immediate-release and more later, and give your ascending level instead of giving you two peaks. So, that probably might explain why the morning is worse because he's not really getting as much of the stimulant, the methylphenidate in the morning, compared to the afternoon. And he's not eating lunch. So, one thing to think about is to change him to a Ritalin class longer-acting, like 50:50 ratio stimulants.

    So, you will give him two peaks and deliver the same amount of stimulants in the morning compared to the afternoon and leave out the lunchtime. And so for 50:50 ratio methylphenidate class, you have Ritalin long-acting and the Focalin XR as well. So, in this case, I think option C and option E, they're both correct.

    So, one of the thing to think is why is the Focalin dose much lower than the Ritalin long-acting. It's because first of all, Concerta 36 is probably equals to about 30-milligram of Ritalin long-acting. And then when you convert to Focalin, you have to dose, so go to 15, but feel free to increase. If they tolerate it and they need more, you can always give them more.

    So, question three. So, this is an 11-year-old girl. She weighs about 34 kilo and she has been taking Focalin 35-milligram in the morning for several weeks after multiple medication trials and those adjustment for her ADHD. However, her symptoms are still not controlled, with worsening school performance. She denies any side effect from the stimulants and then what I would then do what?

    And so first of all, if you look at it, so definitely she probably has a hard-to-treat ADHD. So she weighs about 34 kilo and her Focalin is almost like is over 1 milligram per kilo per day. So that's a good dose for Focalin for her weight. So, at this point, I think we can say that she has failed the methylphenidate class. Sometimes for kids with more severe ADHD, they might benefit more from the Adderall class.

    So, when we change class, for people who are already on the long-acting medication, especially for they are over like 10 years of age, you don't have to start with the immediate-release. You can just go to another long-acting medication. And so here, we have 2 options here, Adderall XR 30-milligram in the morning, or Adderall XR 10-milligram in the morning.

    So, you know, if her symptom is really, really bad, you really want her to get to a good dose, it is reasonable to go to 30 because Focalin and the Adderall class, although we said that if you convert from methylphenidate class to Adderall class, you should half the dose, but Focalin, it is twice as potent as other methylphenidate, so you can do a pretty much one-to-one conversion. So, you can just give her, like, Adderall XR 30-milligram in the morning.

    If you wanna be careful, you can always just start with Adderall XR 10-milligram and go up every 3 days, every week to see her response. Okay. So, she was started on Adderall 10-milligram in the morning and she had initial partial response. Her dose was later increased to Adderall XR 30-milligram in the morning. Her ADHD symptoms are much improved now, however, she's having some headache and which has not improved with hydration. I would then?

    So, first of all, oftentimes in case they have headaches with stimulants, it's near dehydrated. We just have them drink more water. A lot of them actually will improve. And also try to limit some screen time, especially before bedtime. That will help as well. And so in her case, she's benefiting from the Adderall class, which it is good to see after she failed the methylphenidate class, but she's having some side effect on it.

    And so in this case, one other thing is Vyvanse, as I said before, this is a relatively newer version of Adderall class stimulants, and generally speaking has a better side effect profile than Adderall XR. So, in this case, I will change her to Vyvanse 20-milligram. And usually, I don't really do conversion. I just start with the lower dose of the Vyvanse and go up there because the weight-based dosing with Vyvanse is not really well established yet and...okay.

    So, our last question. So, this is a 7-year-old boy. He's about 25 kilo, was diagnosed with ADHD by questionnaire age of 5. And he was initially treated with Dexedrine regular release of 5-milligram at 7:00 a.m. and had initial response. Recently he started to have really difficult afternoons. And so what I would do. So, let's see. That he is on Dexedrine 5-milligram in the morning.

    So, Dexedrine lasts for about like three hours. It's very short, so it's not surprising that his afternoon is a little bit out of control. So first of all, is I don't usually change class in the very beginning. I usually would like to exhaust all the options in one class before I shift class because if you shift back and forth Ritalin class, Adderall class, sometimes it makes things a little bit more complicated.

    So, in this case, I would not do Ritalin because he responded to Dexedrine. However...and he probably nee​d a different formulation of the Adderall class, the amphetamine class. And so here, we can see, so change to Adderall immediate-release 5-milligram in the morning and Adderall extended-release 10-milligram at 7:00 a.m. or add a second dose of regular-release of the Dexedrine 5-milligram after lunch.

    And so I think you can add a second dose in the afternoon, or you can just give Adderall immediate-release 5-milligram in the morning because the Adderall immediate-release is already almost twice as long as the Dexedrine. And so the PCP added a second dose of 5-milligram of Dexedrine at 2:00 p.m. and his afternoon improved. However, he now would not eat lunch or dinner and he become very hungry and ate a lot around 7:00 p.m.

    So, most of the time when their ADHD is controlled and then you have more side effect either like headache or their appetite is really, like, all over the place, one of the things you do is to try to change the longer-acting. So, here the options is change to Ritalin. As I said before, I don't really switch class that prematurely. And then the options are change to Adderall IR 5-milligram at 7:00 a.m. and Adderall 5-milligram at 2:00 p.m. or change to Adderall XR 10-milligram at 7:00 a.m. or change to Dexedrine, a slightly longer-acting, 10-milligram at 7:00 a.m.

    And so here, I would say if we do option C, it probably will make his symptoms worse in terms of side effects because it's the same dose as the Dexedrine but the Adderall IR lasts longer than the Dexedrine. So, he probably will have more issues with appetite. And then the Dexedrine dispersals and the one...the slightly longer-acting Dexedrine doesn't really last that long, will not be able to cover him for the whole day.

    So, here I would do is the Adderall extended-release, XR, 10-milligram in the morning. So, Adderall extended-release, just to refresh your memory, is also 50:50 ratio. So, it'd give you two humps and leave the lunchtime. So, hopefully, it will give him a more controlled release of stimulants and he can still eat lunch. Okay. All right. So, that's all I wanna go through. So, thank you so much for your attention and please let me know if you have any questions. And if you want the presentation, just email me, I'm happy to share.

    Woman: Thank you, Dr. Luo, for your time and expertise today. Again, we encourage you all to stay connected with us and take advantage of our free monthly CME opportunities. Watch for follow-up email communications announcing our upcoming presentations with the "Boys Town Physician Education Series," or visit our website at Thank you for joining us today.

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