Episode 3: Deep Dive into ADHD Medication Part 2 with Henry Shelford and Dr. Shyamal Mashru

Henry and Dr. Shyamal talking about the various aspects of ADHD Medication. Dr. Shyamal is a consultant psychiatrist practicing both in the NHS in Adult ADHD service and in his private clinic, ADHDHealthClinic. You can contact him through his website: adhdhealthclinic.co.uk. The clinic also has its own page on ADHD and Medication.

You can watch the video interview on YouTube here. 

TRANSCRIPT:

Henry Shelford: Hi, it’s Henry Shelford. I’m CEO and Co-founder of ADHD UK. I have ADHD. This is the second, in our series on ADHD and medication, and it’s a part of our Deep Dive series. So the aim of Deep Dive is to go as deep as needed to answer the questions. So we never know how long these are going to be.

So this is the second in the series on ADHD medication because we overran on the first, there was too much to answer. And in conversation, we think we’re going to have three. But who knows? So the aim is to answer the question. I’m delighted, as ever, to have, Dr, Shyamal Mashru, join us.He’s fantastic, extraordinarily knowledgeable. Welcome. 

Dr. Shyamal Mashru:Hi Henry, hello everyone who’s watching thanks for having me again. 

Henry Shelford: A wonderful part, thank you for doing this. We left off slightly in a rush because both of us were like, whoa, is that the time? We’ve got a meeting. And the main thing we’d covered is why people take ADHD medication and that had dropped us into some of the feet, like how the reasons what that impact from a, personal perspective.So from a lived experience perspective, what we’re going to do in this session is really talk about the chemistry of it. And so what are the medications, what do they do? And we need to start with what is going on in the brain for someone with ADHD to understand how the medications interact with that. So over to you, like what’s going on in my brain. Good luck with that. What’s going on in my brain right now. 

Dr. Shyamal Mashru:The current thinking so I have to caveat, this is obviously a baby in terms of a research topic. There’s still lots of discoveries going on in a few years time. There might be more developments, but the current thinking is that there is a lack of two chemicals in the brain in the frontal part of the brain, which is a lack of dopamine and noradrenaline. So I will give an example of how those relate to real-life symptoms to make this a bit more real life for people that are watching.

Noradrenaline breaks down to become adrenaline in your blood and that’s released during fight, fright and flight situations when there’s a perceived threat or an emergency. That is why people with ADHD will often do better when there’s a hard deadline right in front of them or because that’s a perceived threat. So that their noradrenaline levels that have been low start kicking in and then they get the task done. And that would also explain things like procrastination from a chemical perspective. Obviously there’s a lot more to that than that. Just the chemical perspective with procrastination, but that’s one of the ways it relates in terms of.

Henry Shelford: So I get so I think what you’re saying is when there’s a, some kind of crisis or something that pushes your, adrenaline buttons, then this neuroadrenaline chemical is there. So we get focused. Essentially we get our focus chemical in those situations, but  like day to day, why is neuroadrenaline important?

Like what cause I’m not fight or flight when I’m trying to. Maybe we, the kids read a bit excited or reading like, and that’s not the same for other people. So they’re not in fight or flight when they’re doing that. But I can’t focus them. So what’s happening? 

Dr. Shyamal Mashru: There’s noradrenaline, but then there’s also a dopamine that’s involved in this.

Which plays a very big role, right? So dopamine is as part of the reward, it’s involved in the reward circuitry of the brain. Okay. So if you have low levels of dopamine, you’re going to get bored of things quickly, and then you’re going to look for a new reward. The brain, like any part of the body, tries to heal itself, right?

It’s a natural human response, evolutionary response. You’ll look for the next new interesting thing. Now, if we look at that on an obvious level, that’s why people are constantly taking up new hobbies, new interests, blah, blah, blah. But if you pull that back to a more subtle level That could, in theory, explain why people are It’s not necessarily a deficit of their attention while they’re jumping attention across different things.

Because, it’s the classic one, when I ask patients, when you go on the internet, do you open lots of tabs? And, inevitably, most of them do, right? It’s because, but this is with everyone, most people that are listening to this, who may have ADHD, or think they may have ADHD, look at your computer screen right now.

Henry Shelford: And I think a lot of people also talk about like when they’re trying to tell people, explain to people their brains, they’re like, it looks like I’ve got lots and lots of tabs open in my brain all the time. 

Dr. Shyamal Mashru: Absolutely. Because what’s happening chemically is The brain’s realizing, oh, my dopamine levels are low, I need to push them up.

That’s a new shiny thing. Activate the reward circuit in my brain. Rush of dopamine, it falls off again. Brain thinks, I need to activate this again because my dopamine levels are low. Pushes up again, next new interesting thing.

Henry Shelford: So the brain’s creating, so it’s looking for ways to get dopamine. These are ways that work for other people, so that’s why social media is successful because of the dopamine that it gives people in that feedback loop that people get.

And what you’re saying for someone with ADHD, those dopamine hits are much more important because it’s basically the only way we’re getting. 

Dr. Shyamal Mashru: But when we talk about that feedback loop, one thing with the noradrenaline, so noradrenaline works on your nervous system. Now, in theory, therefore, if you keep having to activate your nervous system under this pressured way, you can also then, over time, have an, a hypersensitive nervous system.

And that could, if you, I’m just talking theoretically now, could explain why people get into anxiety loops as well, right? Because their nervous system is very quick to trigger. because it’s been doing that constantly throughout their life. 

Henry Shelford: I think I, when I’m talking about, I use the phrase, when if you exercise a part of your brain, it gets stronger.

And if you use anxiety as your way to get stuff done, you’ll, you use it more and it becomes you like, and it takes over and say, yeah, mental muscles got stronger. 

Dr. Shyamal Mashru: And then also you have, so this is what’s called endogenous increases, meaning you’re doing it internally.

And then obviously people look for things exogenously. which means external things to get their dopamine and noradrenaline. So some people might really enjoy quite, high adrenaline activities for other people. They might, get that, that they might even get their dopamine from, substances or from that’s a tricky one because some people are using substances to manage their symptoms as well.

So what I’m trying to say is it’s quite a normal human response and something internally is not quite correct. Internally, you will try and correct it. And then also externally from the environment, you will try and correct it. So it makes sense why this is happening from a chemical perspective.

Henry Shelford: Neurodermaline, I understand, increases in the morning, and so if it’s the chemical that helps you wake up and start your day. And so people with ADHD with less of that, are they going to, are they more likely to have Trouble in the morning because that chemical’s not there. 

Dr. Shyamal Mashru: I think the biggest trouble that they’re going to have in the morning is because they didn’t sleep that, straight away the night before.

That’s more the bigger the problem. Because that’s what I normally hear from patients. They, time blindness, they got, they lost track of time. They couldn’t switch off their thoughts. What do they do? What do people do nowadays? Pick up the phone. They watch ADHD UK interviews late into the night Or whatever or not or whatever else right and they’re probably feeling groggy in the morning videos and podcasts 

Dr. Shyamal Mashru: Yeah And that’s probably one of the bigger reasons why so so they get this sort of social jet lag because they still have to wake Up, you know at whatever time in the morning, but they’ve lost the passage of time at night What’s interesting about this and I don’t really know.

We don’t really know what the link is many people will say Okay, even though they felt tired in the morning But then again, at night, they could still end up doing the same thing until they do it for three, four nights, then they’re absolutely shattered. They might have an early night. Now, that’s probably linked to a different thing to do with melatonin and sleep cycles, but that’s going probably a bit off topic there.

Henry Shelford: Yeah. Also, isn’t it just pretty simple the challenge of sleep remains, and in that cycle, your level of tiredness is having to match up to the challenge of the sleep, and if, until it gets that, for that example, you go three days. That’s where tiredness is now a bigger issue than the challenge of sleep.

Dr. Shyamal Mashru: But, so say for someone like myself, if I’ve had a poor night’s sleep, the next night I won’t be able to do that again, even if I really tried. But generally, for people with ADHD, the interesting thing is they’ll be really tired that morning, but then a night again, they couldn’t, the second night, they could still do the same thing, which is something quite interesting, which I see in most people.

Henry Shelford: Yeah, and one of the things I think why sleep is such a, if you look at anyone who has issues with sleep, and it’s fatigued, they’ve got a problem with focus, they’ve got a problem with memory, they’ve got a, problem with energy. So you’ve got to be someone with it. ADHD who has those already. Like tiredness is a real problem because it’s knocking you even further Makes things even harder. 

Dr. Shyamal Mashru: Yeah, and it’s gonna make procrastination worse because you’ve absolutely knackered You’re not going to feel motivated to do those, especially those either mundane or complex tasks. You’re going to struggle.

Henry Shelford: We will do a deep dive on sleep at some point without question. Come on. Back to talk. Let’s stay on track. And how much they know about these, the dopamine and the neuro adrenaline for ADHD, like what evidence they have. If they, they stuck a probe in someone’s brain, like how do they know?

Dr. Shyamal Mashru: So there’s something very interesting about. medication and the link to this. So medications look primarily, so stimulant medication, which is the first line of treatment looks to increase your dopamine and noradrenaline, pathways, neurons in your brain. Now there have been studies called functional, I think they’re called functional MRI scans where they’re basically radioactively label, dopamine and noradrenaline molecules.

And what they show is, Not only does the medication increase those chemicals in certain parts of the brain, but interestingly, and this was a very interesting finding, medication actually only really works well when you’re actually doing tasks. So this is an interesting one from when I meet clients, for example, like University students, because what they will tell me is my medication was working great during term time.

I eat, they would have had assignments, exams, whatever they would have had. Then it’s summer holidays and that doctor, I don’t know if it’s working anymore. So then what we know about medication is that yes, it increases dopamine and noradrenaline, but it seems to really propagate those pathways when they have to be activated By a task.

It doesn’t seem it does it to a much more benign level if you were not doing so you for example, let’s say you’re doing your working week You might be able to see that during that working week when I’m taking my medications Yes, I can really focus and you know much more productive whatever but then on the weekends for some reason It almost feels, it might feel slightly less effective unless you’re very busy with household things that you have to get done, then that’s different because you’re still doing, you’re still activating that part of it. But if you’re not. It might almost feel like, I don’t know if this is working for me. 

Henry Shelford: That was an important point. So tasks don’t need to be work or project. It can be cleaning, talking to someone, engaging. But it’s it’s having something to do with.

Dr. Shyamal Mashru: That’s when they work the best. That’s what the studies are showing. Which I think is a very interesting thing, which might not be talked about actually that much. And it explains a lot. 

Henry Shelford: It does, like certainly I find I get, but I don’t put it a lot towards my ADHD in that I’m really at peace when I’ve got something to do. Yeah. And I don’t, if you’re trying to sit me down and say, relax, like that’s a form of torture, whereas if you give me something to do, then I’m super happy. So I now structure my life, making sure I have things to do. 

Dr. Shyamal Mashru: And also there’s a paradoxical effects between the attentive side and the hyperactive impulsive side, which is, many people will tell me, Actually, if I’m fidgeting with something in my hand, I can focus better on what the person is saying. If I’m not doing that, then actually I’m struggling then a bit more with focus.

So there is some link there. We’re not exactly sure what that is, but I hear this all the time.

Henry Shelford: The way I think about it is like, when I’m talking about hyperactivity, I say to you, people often think of hyperactivity much like a cat, it goes, run, and then see run, see.

And for me, a hyperactivity is an energy that must be used. And I must vent it at all times. And if I don’t, it literally boils in me like it’s painful. No, and I really can’t take very long. Like I’ve got to move and if you want to torch me, you put me in the front of some kind of big lecture or or a big hole on a squeaky chair, moly.

Dr. Shyamal Mashru: That is awful. The yeah, but which is why then if I’m fidgeting, got something to move, so I’m playing with a pen at the moment, I had been the whole time, and I realized I might have been clicking, and I was like, oh, I should take that away from the microphone. Yeah.

Henry Shelford: But it’s vented. So it’s not, just that’s suggesting a different mechanism. So instead of the energy, needing to move. It’s needing to vent. And I, otherwise, I’ve got this thing boiling in me and I definitely can’t concentrate. To do with that venting has to do with it enabling concentration. It’s more to do with it, not stopping me concentrate. 

Dr. Shyamal Mashru: And for some people, they’ll actually say, that energy starts feeling inwards. And then mentally. That ceaseless mental activity also can happen. 

Henry Shelford: I think a lot of people like to call it, hyperactivity in the brain. I like that’s certainly some way I talk to it to sometimes help people help people understand, and I always think it’s quite interesting when we’re talking about ADHD, how many people want to be referred to as ADD, Attention Deficit Disorder, which was only a name for the condition in America between 1980 and 1987.

It’s really interesting to reflect on why do people and why people hung on to that and it’s because there’s a stereotype of hyperactivity, which is a small kid running around and as an adult, you’re like, I’m not a small kid running around. I’m not running around. And I don’t want that association.

So I prefer to people to ADD. But when we talk about the hyperactivity, what normally is happening is people have worked out socially acceptable ways to vent the energy. So that means when you’re talking, it means moving your arms, it means doing that, it means touching your hair, touching your face, means your glasses going on and off, it’s all It’s those kind of things, but it’s that venting.

I think we’ve talked a bit about so the main, issues are, a, lack of neuroadrenaline. I think there’s a place for us to do a deep dive on just the pure chemistry of of the brain, and ADHD, but let’s talk about the main medications. What are they doing?

Dr. Shyamal Mashru: Yeah, so the national guidelines, in the UK, the NICE guidance says that the first line of treatment is stimulant medication. So as I said, so stimulants will increase your dopamine and noradrenaline in the brain. In my experience, the first thing that patients will see clinically is an improvement in their quote unquote inattentive symptoms.

And I think the reason why that is, is because those are easier to measure. If you are getting your tasks done and being more productive. That’s much easier to measure. But the other big improvement that we see, which many patients will say was the most disabling symptom, which we. spoke about in the last talk is a sense of emotional well being.

People feel internally calmer, and I think that probably talks to that energy that you’re talking about, which can be quite uncomfortable at times. 

Henry Shelford: So how does it link though through to dopamine and neurodermaline?  

Dr. Shyamal Mashru: We aren’t entirely clear on that one, because those chemicals also link to things like serotonin. But for people listening, by the way, if you’ve never deep dived into anything medical, I’m telling you the answer of, we’re not really sure is very common. And it’s if you have this idea that everyone has a really clear idea how lots of things, you’re in for a deep disappointment.

I think we are just touching the iceberg here, the tip of the iceberg in terms of what we know about this condition, especially in adulthood. Or throughout the lifespan. Bearing in mind that up until 2008, this wasn’t even mentioned in the nice guidance in adults as A DHD, as it, as it is.

So we are very, we are, this is a baby in terms of what we know in research terms. So there are certain things that are going on here that are not clear. There are links. I don, I know this is gonna deviate off, off topic a little bit, but there are links to the immune deviations will be.

There are links to the immune system, some sort of link with a hyperactive immune system, because we see a lot of autoimmune conditions with ADHD as well.

Henry Shelford: There’ll be people what there’s a significant link to autoimmune conditions and allergies. And, LS, Dan loss, all of those things, thyroid condition. So it’s so acid reflux. 

Dr. Shyamal Mashru: Yeah. That where it’s linking, We don’t have a clear answer as to why that’s happening. But what we do know is that many of these people Will have said, will say to me, I’ve tried all the different sort of serotonergic antidepressants under the sun and it never had this kind of impact for me.

And for many people in the end they’ll say I don’t even now care about the attention and concentration ’cause this is the biggest impact for me. 

Henry Shelford: And for those that, to bring that tangent back, it was because, Shai was talking about the potential of involvement of the serotonin pathway. And I think what you’re saying there is because people have taken.

Medications that we know impact the serotonin pathway. That’s the reason why we don’t think it’s that. And it’s, so some of our understanding is derived from that kind of knowledge. 

Dr. Shyamal Mashru: So we are not sure why it’s helping so much with emotion improvement, but there’s something in that, many people that were labeled with treatment resistant depression and stuff like that. That’s big impact. 

Henry Shelford: So the first sort of major medication for. A DHD was Ritalin, which is, methylphenidate. 

Dr. Shyamal Mashru: So I’ll just break it down. So in terms of the stimulants, broad brush speaking, you’ve got amphetamine based stimulants, and then you’ve got the methylphenidate family of stimulants.

They work in slightly different ways. So amphetamines work by increasing production of dopamine and noradrenaline as well as, decreasing reuptake, or, breakdown of it. Whereas methylphenidate primarily works by decreasing reuptake as opposed to also increasing production. And then within those two chemical families, you have long acting or extended release and short acting or immediate release.

So if you think about it as four different options, really long acting, amphetamine based stimulant, short acting amphetamine based stimulant. Long acting methylphenidate, short acting methylphenidate. Now, long acting means you take your medication in the morning. Typically, it takes an hour to an hour and a half for the medication levels to rise and for it to kick in, that’s what people say.

And then it can last between 6 to 12 hours. Now, why I put a big range on there is because everyone has different sensitivities to medication. Some people will say, at a fairly low dose, it lasted 9 10 hours. Another person might say I don’t think it barely lasted three, four hours. And that’s why we have this process called titration.

Because as you build up the dose, it should last longer. But also, as you build up the dose, you increase the risk of side effects. And that’s why it’s quite important to get that right with a professional. Because it’s not a one size fits all. With short acting medications, they work much faster. They kick in within 30 minutes.

And that’s why But then they’re out of the system within two to four hours. And again it’s the same principle. Different people have different sensitivities. As you build up the dose, it will increase the duration within that time frame, but it will also increase the risk of side effects as well. 

Henry Shelford: What do you feel like the differences between the people for whom long release is more likely to work and the people for whom short release?

Dr. Shyamal Mashru: The national guidance sensibly says that we should always start adults with long acting stimulant medications. For more information, visit www. FEMA. gov I tend to use short acting stimulants for different reasons. So why do we start with the long acting is because it’s a pain to take multiple medications a day.

And it’s more of a pain when you have ADHD. There are some situations where I will use short acting meds. The first one being, if someone gets to high doses of long acting medication, so say someone who’s not very as sensitive to medication and tells me, look, it’s not lasting longer than the afternoon, then I might add in a short acting, equivalent to try and prolong the duration. So give that in the afternoon. The second reason is, and we’ll talk about side effects, I’m sure, but there are certain side effects that can happen with long acting meds where you have to switch to short acting meds. The third reason is patient preference. Some people will say, look, I don’t necessarily want my meds to last all day long.

I just, I have a really busy morning, and not such a busy afternoon. And I just want it really for the morning period. The fourth reason would be when people are doing shift work. So if they’re doing, a few nights where they have to work, followed by, a few days. So they can’t consistently just take the medication every morning. And this gives short acting regime will give some more flexibility. Okay. In dosing because it doesn’t last as long. 

Henry Shelford: How does it work, in terms of trying to do stuff in the day, doesn’t it peak and drop? Like, how? 

Dr. Shyamal Mashru: Yeah so what I do is, tell patients, what are the signs that your medication levels are coming down?

So those signs are, you will start to feel a lot more tired. Some people feel really quite exhausted suddenly, that’s called a crash, when the medication levels drop too fast. They’ll find that they are, A lot, a lot more distracted. Some people have described it as brain fog. They just can’t think as clearly.

There will be a shift, a change. That’s when I know, that dose is lasting this long for this person. And that’s when I know what to do next in terms of dosing.

Henry Shelford: That’s interesting. So that essentially you want to be quite a good student of self and understand and and be sensitive to that, obviously being very quite difficult if you’re, if you’ve got lost in something or you don’t recognize it.

Dr. Shyamal Mashru: I was just going to say, just to finish up on that, thing about what are the different classes of medication. So that’s the first line of treatment. Now not everyone can have stimulant medications. People, for example, with certain physical health, sort of complications, especially around their heart, you might be a bit more concerned with stimulant medications because like I said, we’ll probably talk about this in the side effects section, but it can increase blood pressure and heart rate, which is something that we would monitor obviously during your titration.

And thereafter if someone has a high sort of already a history of high blood pressure, and lots of cardiovascular complications, you might not want to start with stimulant medication, in which case. You might want to go for non stimulant medication. Non stimulant medications typically work by increasing noradrenaline alone, not just, not dopamine as much.

But the way that they work is quite different to stimulants in that they load slowly into your system, a bit like an antidepressant does. So they take longer to work. They’ll take six to eight weeks to work, and they’re a bit more gentle. Stimulants come in and out of the system quite hard, which is a good thing in terms of, yes, you, people will say, Oh, it was miraculous.

And I felt effects really quickly, but they also come out of the system very quickly, whereas a non stimulants a bit more gentler on your body in some ways. And it has less effects in terms of increasing blood pressure and heart rate. It still does to an extent, and we have to monitor it. But for people that are at more high risk, you might not go for the stimulant first.

Henry Shelford: And what do they do, like how do they work on the brain? 

Dr. Shyamal Mashru: Essentially, they’re increasing noradrenergic pathways. But I think the reason so you could say, therefore they should do the same thing as a stimulant in terms of side effects. But if they’re doing it in a much more gentle way, stimulants a bit more aggressive in the way that they’re doing that.

And those kind of surges are making you more prone to higher blood pressure because if you have surges of noradrenaline, you, your blood vessels constrict. And that leads to higher blood pressure within the vessels. And also increased noradrenaline will make your heart pump faster. And so if that’s happening a bit more aggressively, let me just caveat this, in someone who doesn’t have a history of cardiac problems, it’s not, it sounds very scary, you won’t really see these problems in titrations.

It’s only when people have already got a baseline history of the blood vessels are already tight, the heart’s already pumping very hard, etc. Those are the ones that you wouldn’t want to. necessarily go down this route. Welcome to the reason why everyone, it’s part of the guidance, you have an ECG prior to medication.

On that note, not ECG. There are certain, so the NICE guidance changed in 2018 around this. So if you’re gonna go on any medication, you would need to monitor your blood pressure, heart rate, and weight. You would need a doctor to listen to your heart sounds to make sure you don’t have any sort of added or irregular heart sounds, which would indicate your heart is not beating correctly.

You don’t need an ECG. unless there are certain parameters, mainly around, essentially, if you have cardiac history or cardiac complications or a very close relation to yours, first degree relatives, so sibling or mother or father have a very strong history of cardiac problem, then you would need an ECG. So ECGs are not routinely done anymore. 

Henry Shelford: I think some, because I wanted to be people watching this, definitely, I think for some organizations, They do it as a routine, part of their care. And I know certainly a lot of, yeah, a lot of times people are having to go and do that if they’re being seen privately with a private organisation.

Dr. Shyamal Mashru: Yeah, I’m aware of that as well, but the national guidance is not that. In the NHS we don’t do it routinely. Because it’s not part of the guidance. And actually, just to put these medications a little bit in context here, there are other medications that are being routinely prescribed that could have much more harmful effects, actually.

I’m not saying that they don’t come without their risks. Nine times out of ten, let’s put it this way. When I’ve asked a cardiologist, I’m not sure if I should start this person on a stimulant. Most times they’ve said, actually, it’s completely fine. Most cases. The main ones where it’s not very fine is when people have already got difficulty controlling their blood pressure.

That one can be a bit tricky, but most times, or if they’ve got very strange, arrhythmias, where they’re needing pacemakers to correct their heart rhythms, et cetera. But most times the cardiologist comes back and says, actually, it’s fine.

Henry Shelford: Thank you. So I think you’ve gone through the sort of main the main medications and their impact on that.

And how often do you find yourself changing someone from the sort of methylphenidate to the amphetamine or vice versa?

Dr. Shyamal Mashru: Before I answer this, I’m not affiliated to any drug companies or I’m not pushing any, products or anything like that. In my experience I tend to start with the, unless there’s reasons why I can’t, I tend to start with a long acting amphetamine.

Two reasons for that. In adults, the data, and certainly my clinical experience shows, They can be slightly more effective than methylphenidate, not a big difference, slightly more effective. The main reason why I like to do it though is because I’m finding that more patients are tolerating side effects better with the long acting amphetamine versus methylphenidate.

Now there is a small group of patients which do better the other way around and we’re not really sure why that happens. But in the majority of cases, I typically would start with the long acting amphetamine. Also, sort of family genetics plays a role. So they might tell me, look, my sibling tried a long acting amphetamine and they had all these horrendous side effects, but they did amazingly well with methylphenidate.

I have found that there is some sort of pharmacogenetics there, because that other sibling that I’m seeing will often have the same outcome as well. Yeah, and obviously ADHD has a large genetic component, so it’s quite, it’s not uncommon to be seeing siblings.  

Henry Shelford: Yeah, absolutely. Now our next the next one we’re going to be doing, Is on, we are going to look at optimizing medication and minimizing side effects.

So we’re going to go into side effects as our next video, which will be the third video of what was intended to be a one series video. We’re getting to be like the Hitchhiker’s Guide to the trilogy that became fearful of being corrected, but I believe it got to five. And they called it the increasingly inaccurately named trilogy.

Yeah, which I’m looking forward to because I think it’s obviously, it’s very big topic. This has been. Yeah, very important. How do they make them long, long lasting? Like, how does that work? 

Dr. Shyamal Mashru: I can speak about Lisdexamphetamine, which is the long acting amphetamine.

The way that works is Lisdexamphetamine is actually a pro drug. The dexamphetamine part of Lisdexamphetamine is the active molecule. The lysine layer around that is the sort of the protective capsule around it. So it’s the lysine slowly degrades in your system and then you get the active molecule dexamphetamine and that explains why it takes that hour and a half for you to see the effects or feel the effects of the medication. So it’s not instant. 

Henry Shelford: How’s the lysine removed?

Dr. Shyamal Mashru: It metabolizes with the long acting amphetamines, it’s related to your red blood cells pathways, with the methylphenidates. It just slowly degrades as part in the gut. And so then you get the feeling of the active molecule.

But that’s the key thing is that’s why you get the difference between. The long acting where people will say, yeah, it takes about an hour and a half. Whereas the short acting is much quicker. And those two medications can feel different when you take them. Because one of them, the long acting, can sometimes feel a bit smoother in its effect.

Because it goes up slowly and it tails off slowly. Whereas the short acting one, some people can feel a bit, what they say, rushy from it. They feel that surge and then they feel it go down. Not everyone likes that feeling of the short acting meds. But when you combine the two, you lose the impact of that rushy feeling, because you’ve already got medication in your system, and then what you’re trying to do is just prolong the effects of medication.

And I think that’s when short acting meds work really well. 

Henry Shelford: Interesting. How and the lysine Is that mechanism used for any other medications? Is that sort of lysine breakdown system used? 

Dr. Shyamal Mashru: I was getting put on the spot on the pharmaceutical questions. Not entirely sure because I think I’ve become so ADHD eyes now. I’m not entirely sure. I don’t want to, I don’t want to, I look 

Henry Shelford: Curious to see what are the, what in those other medications, what’s happening is there anything we can learn from how. their use with regards to idiot that particularly this one’s obviously this deck was Chazelle Vance.

And how is it broken down? So you said it’s red blood cells. So does that mean that if I eat a huge steak the night before, and I don’t know if that has an impact on my red blood cells, I’m showing a fearsome lack of knowledge. But are there things that can impact the lysine? 

Dr. Shyamal Mashru: I don’t know about impacting the lysine.

In all honesty, but there are, I have, so this is more anecdotal information now, which I get from patients. Some patients will say certain things help. So having high protein diets. Seems to help prolong medication and make it feel smoother being very hydrated helps Some people said things like magnesium citrate supplements help We’re not entirely sure how these things are really helping to be honest But when you hear it so many times you there has to be something going on with that like I say, this is still, there are so many question marks here as to why this is happening.

And what I was also going to say is, the manufacturers say that you should always, have food with your medication, generally. And there’s two reasons for that. One is because if you don’t, you can get a lot stronger side effects. And, but then food can have two different effects for people.

Some people have said, when I have food with the medication, I feel like it lasts longer, but then other people have said, when I don’t have food with the medication, it lasts longer, so it’s not entirely clear. What, what’s exactly going on there, 

Henry Shelford: Which does go back to that whole be a student of self like it’s really important.

I’ve interviewed the CEO of a startup in Israel, who’s using smartwatches to monitor the impact of the effectiveness of effective time of medication. So they can look at, various things, notably beats per minute of your heart, and, you can see that change, use that to, and so I think that, that can also be, and that came out of the fact that their own son has ADHD, tried a medication and it impacted only, Their inattentive sorry, their hyperactive aspects and it didn’t impact their inattentive aspects.

So they then sought medication and felt that, that need to help particularly children be able to understand the impact of medication to help them optimize it. But it does also, and that’s where it goes to the point you said earlier, if the different, like you will find a medication might work for one person, but not for another.

And there can be that, there can be that need. I had a question recently, which said. We have people say on ADHD, people are taking these products long term. We don’t know what they’re like long term and essentially inferring that they shouldn’t take them. What’s your answer to that?

Dr. Shyamal Mashru: So scientifically there’s only one real long term effect that we do know about medication, which I think people should be aware of, which is over time, there can be a risk in some individuals That, that it can slightly increase your baseline blood pressure and heart rate, particularly blood pressure. And that’s to do with noradrenaline causing a constriction of your blood vessels.

And that increases the, it’s like watering your garden hose. If you squeeze it tight, you’re going to, the water pressure is going to go up. Same principle, right? In some people, you do see that. And that’s why as part of the national guidelines. Even once you’re stable on medication, at least once every six months, you should be checking your blood pressure and heart rate.

At least once every six months. I tell patients to do it a bit more frequently than that. Because by the time they’ve gone through a titration process, they’re quite in the habit of checking it, I’m not saying to get obsessed about it, but at least once every two, three months, I just tell patients to keep an eye on it.

The kind of magic numbers, if your blood pressure is consistently going above 140 over 90, or your pulse rate or heart rate is consistently going above 120, those are high. Now, the key thing that I would say is, you must check your readings at rest when you’ve been sat down for 10 15 minutes, not when you’ve gone up and down the stairs looking for the blood pressure machine.

Even if you’re very quite physically fit. Those readings are very dynamic and it can look quite different. In terms of when you should check it, you’re going to find the highest readings about two hours after you take your medication, because that’s when your medication levels are at their peak. So I sometimes tell people check it two hours after and also check it towards the end of the day.

And if there’s a huge difference, you can see how much impact your medication is having on blood pressure. Those are the key numbers. If you’re consistently getting resting blood pressures over 140, over 90, or consistently getting heart rates above 120, which is, way above your baseline before you started meds, You need to tell your sort of clinician about that.

Henry Shelford: Great, thank you. And to that question on, people saying people haven’t taken these drugs for a long time, so we shouldn’t be giving people, we don’t have any evidence, so it’s dangerous, so we shouldn’t do it. What do you say to those people? 

Dr. Shyamal Mashru: I would say that the longer term impact and risk of having untreated ADHD can be a lot worse.

So if you’re looking at burden on the community, you Henry, you’ll know probably a lot about this, but essentially, the financial burden, the risk to yourself, the damages that it causes over time in relationships with work with education, you will Probably cause yourself a lot more damage in your life by not treating now.

I’m not saying not I’m not saying everyone has to have medication Just you know I think i’ve probably mentioned this when we’ve spoken before not saying everyone needs to have medication some people will do very well with just coaching but Okay, it’s like i’ll explain like this in some ways It’s telling anyone with any chronic condition, right?

Okay, let’s take rheumatoid arthritis, right? It’s like telling them don’t take your methotrexate or your, your steroids because they have risks. Yeah, but if you don’t take them, you’re at risk of breaking your joints and your bones, et cetera. Everything has to be weighed up.

Henry Shelford: Yeah. Yeah. Every pill has its price. Like it’s, they’ve all got a side effect. That’s and you have to weigh out the benefits to that cost and be naive to not expect that. I think to the people who are worried on the long term aspects, one, they need to know there, there is within the medical and pharmaceutical profession, a very clear process for monitoring of medications.

And if you see an adverse effect, or something unexpected. Then as a medic, you report it to the pharmaceutical company. There’s an obligation to, to keep those records and and analyze them and see what’s happening. So there is a catch. So that’s after a lot of research has happened, there is in this sort of secondary catch.

Dr. Shyamal Mashru: But simpler than that, Henry, if you’ve got problems, if you’re having problems with your meds, tell your clinician that prescribed your meds. 

Henry Shelford: Yes, no, absolutely. I think the point of things like emerging late, the other thing to say is because I’ve had that argument presented to me a few times.

It’s just what are you what are you going to do, mate? The only way to understand if something is going to work long term is it be taken long term. And you’re essentially taking a view that we can have no new medications for chronic conditions. Because we can never take it long term without you, someone like you, popping up and going they don’t know.

We’ve done a lot of research. We’ve done a lot of understanding, of core understanding of that is based on, as much as is possible. There’s usually quite close related medications that have been taken long term. We don’t get a choice in this. And one, one other thing I want to add so Ritalin has been on the market since the, I think mid fifties, 1950s, if I think I’m looking it up, actually 1954 is when it came out, right?

That’s quite a long time now. What are we looking at? 70 years? Yeah, that’s what we’re looking at. FDA in America is very hard on these kind of things, right? And looking at drug safety, that’s a long time, and it’s been good news for a long time. So you could argue that well, you’d see the long term effects now in some generation, right?

Look, I think for some of these people, they’re just looking for reasons to, to hate and they’re often not believers in ADHD and they’re just trying to find different levers to attack on. Obviously like the pharmaceutical industry we’ve had, medications have had problems, like it is, like it’s not unknown, that’s why there’s the sort of red flag process. But I think at that point, a number of these medications have been used for a long time, but let’s say, Ritalin with amphetamine based, no sorry, methamphetamine based, we’ve had others with amphetamine based, and yeah, so something like L Vance with the lysine is different, but The core is not I think the fundamental is you can’t have new medications for chronic conditions without paying this risk aspect, it’s lots of work is underministicated, but you can’t just say we’re not using this because it’s not been used for a long time because you’ll never have a new medication for a long term condition ever again because you’ve just gone, we’re stopping this.

Dr. Shyamal Mashru: And to another point on this note, so I do get patients, obviously, now I’m talking about private practice, people must, probably may know about shared care agreements, where you have to, part of the guidance is that you need to be reviewed annually by a specialist, and patients will complain, or say, why do I have to keep coming back to see you? It’s because you, these things need to be monitored properly. 

So while, generally you don’t see huge risks, but at the same time, we do know that this is there. So it has to be monitored properly. But what I would say is if it is being monitored properly, then you’re really minimizing that as much as you possibly can.

Henry Shelford: Yeah. Now look, last time we ran and I realized in a panic, I was supposed to be somewhere else. And so this time we’re going to finish on time. So this is part of a series where we’re doing ADHD medication, purposely trying To deep dive into it, to answer as many questions as possible. Number three is going to be on the, side effects.

So optimize medication and side effects and minimizing them. And then we are going to be doing which almost certainly, let’s see where it goes, but we’re gonna be doing at least one video, if not a series, on non-pharmaceutical interventions. That is going to be. accompanied by actually then similar deep dives, but with coaches and we’ve obviously got medical expertise here, but on the non medical interventions, coaches have a deep depth of going to run in parallel to support that, coaches on individual aspects.

So that actually, that area is actually going to become very deep, but we need to know from the medical perspective on those interventions. Non pharmaceutical interventions, and then we’ll go deeper with the people who are doing those on day to day. Shai, you’re amazing, thank you. I’ve always loved these sessions, and learn something, and we’ll learn a lot.

Yeah, you’re absolutely fantastic. Dr. Shamal Mashru, if you’re watching the video, you’ll, there’ll be links through to his to his private practice, links through to to him. So if you want to let me know more, do go there. Time to say goodbye. Thank you very much. so much. And time for me to sign out on on this.

Thank you very much for watching. Obviously, we’re a charity. Thank you very much. We get no money from government, Everything we do is funded by people by individuals. We can do nothing without you, so do consider, donating or fundraising. Honestly, this is hard Charities, what you may be watching at a different time, but it hasn’t changed for a long time.

We’ve been on a financial knife’s edge. I’m sure we are when you’re watching this. It is tough as, and, anything can do to support gratefully received. Dr. Marshu donates his time, at no cost, into supporting people with ADHD through doing this with this charity, obviously through his own work.

We’re very grateful for that. Thank you for watching. We’ll be back for the third in this series, who knows, could be a fourth and look forward to, yeah, you joining then. Thank you.