← ADHD Experts Podcast
ADHD Experts Podcast
575- An Adult’s Guide to ADHD Treatment Considerations
01:00:48
Join John Kruse, M.D., Ph.D., to learn about stimulants vs. non-stimulants; side effects of ADHD medication; how to determine optimal dosing; combining ADHD medications; and more. Adult ADHD Treatments: Additional Resources Free Email Class: Read: ...
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- [00:04]
A
Welcome to the Attention Deficit Disorder Expert Podcast series by Attitude Magazine. My name is Annie Rogers and on behalf of the Attitude Team, I am pleased to welcome you to today's ADHD Experts presentation titled An Adult's Guide to ADHD Treatment Considerations. Leading Today's presentation is Dr. John Cruz. Dr. Cruz earned a doctorate in neuroscience and completed residency training in psychiatry. He spent three decades in San Francisco helping adults with adhd. He's the author of Recognizing Adult adhd. He's also written hundreds of popular articles on ADHD and mental health more broadly. He has more than 200 informative videos on ADHD on his free YouTube channel, and he does frequent interviews about living with ADHD. He currently lives on the Big island of Hawaii with his husband. Dr. Cruz is one of the world's foremost experts in ADHD treatment and we're so incredibly thankful to have him here today to explain the full range of treatment options available to adults with adhd, differences between stimulants and non stimulants, benefits of medication risks and side effects, dosing guidance, and more. Finally, the sponsor of today's webinar is Accentrate. Accentrate delivers personalized brain ready nutrition designed to support focus, emotional balance and overall brain health through a combination of omega 3s, vitamins and minerals. Featuring Lyso Vita LPC Ascentrate Omega products offer six times higher absorption than traditional fish oil, ensuring faster, longer lasting benefits to help you perform at your very best every day. To find more, please visit www.phoenixhealthscience.com. attitude thanks our sponsors for supporting our free webinars. Sponsorship has no influence on on speaker selection or webinar content. Okay, without any further ado, I'm so pleased to welcome Dr. John Cruz. Dr. Cruz, thank you so much for joining us today and for leading this presentation.
- [02:35]
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I'm delighted to be here today. So thank you Attitude Magazine for inviting me and I appreciate all the depth of questions and variety of questions that have already poured in. So I'll start with disclosures. So I don't have any affiliations with any drug companies, any device makers, anything connected to adhd. I do get a small amount of royalties from my book and from my YouTube channel, which is a free channel, and from writing on Medium. And the other important disclosure is that all the information presented today is for informational purposes. I'm not making specific recommendations for any of you because I don't know your individual history well enough to do so. So the points so the introduction suggested that I'd be talking broadly about everything for adhd, but we're more narrowly focusing on ADHD medications, including the major and minor side effects, the alternatives to stimulants, optimal dosing, combining medications, and each of these alone could fill an hour. So I will try to cram as much as I can in the time we have today. Part of that is to emphasize that although we're focusing on medicines today, medications are never the complete answer for treating adhd. Part of that is because everything to do with the human behavior and brain is both a combination of nature and nurture. We're always treating or working with the brain that's interacting with a specific environment, so we're not just working with a neurochemical system. Furthermore, even though so much of the interest in science on ADHD and popular attention is focused on dopamine and maybe a little bit on norepinephrine, and that levels are off or not, ADHD is at least as much a wiring issue in terms of what parts of the brain are strongly or weakly connected to each other as it is a simple neurochemical answer. So part of the treatment or working with ADHD in your life is that you need to use lifestyle approaches. And sleep, I would say, is far and away the most prominent of those. That even if you're on optimal medications and everything else is great in your life, if you're not sleeping well, you're going to have certain executive function problems. But in addition to sleep, eating is important, exercise and movement, exposure to nature is important, and some amount of relaxation, which includes meditation. Again, each of these could constitute a whole hour of talking, and I'm just breezing over them, but they're important. And in terms of talking therapies, particularly cognitive behavioral therapy, CBT has been shown to be effective in teaching people to get better at certain executive function skills. And a central aspect of any CBT program for ADHD involves how do you use the daily schedule and how do you combine that with your task list? On my own video channel, I have talks on that. So again, that could take a whole hour. And then echoing and I first heard this from Ed Hallowell, speaking more than 30 years ago. He emphasized the importance of medications and particularly stimulants. But then he'd say the most important things are finding the right fit, finding the right people in your life and the right job. And I would add, finding both the right spaces to be working in, both at home and in the workplace. So again, I'm skimming over all those and then jumping into medications, starting with what are stimulants? And unfortunately, we have two very different definitions of stimulants. We have a very broad, general definition that a stimulant is anything that's in the fancy word is a sympathomimetic. That means anything that activates or acts like the sympathetic nervous system when it's aroused. The reminder is the sympathetic nervous system is our fight or flight system. Things like Adderall or Ritalin are stimulants. Things like cocaine and methamphetamine. Street stimulants are stimulants in this broad definition. But by this broad definition, strattera is a stimulant. Wellbutrin is a stimulant. Caffeine is a stimulant. Even someone saying boo in a dark room is a stimulant. It's activating your sympathetic nervous system. So that's our broad definition. But usually within ADHD, when we're using the term stimulant, we have a narrower definition and it's actually not a really precisely defined definition. It's reserved for powerful medications that not only cause dopamine and norepinephrine reuptake, but also boost the amount of neurotransmitter release. And amphetamine is the prototypical or classical one. I'll try to use the term strong stimulant to differentiate when I'm using that term versus the more general term for stimulant. Also, all the strong stimulants, amphetamine is prototypical, the model strong stimulant, and all the other strong stimulants have at least some structural chemical similarity to it as well, as well as the mode of action similarity. And we're trying throughout pharmacology and neuropharmacology to avoid terms like antidepressant because those terms that are specifically describing a condition or something that someone is being treated don't give a lot of information and are highly misleading and lead to questions like why is my ADHD doctor giving me an antidepressant like Wellbutrin or tricyclic for my adhd? He's giving me the wrong thing. And again, if we based drugs on what they were used to treat, the very first antidepressant, isoniazid, which is a monoamine oxidase inhibitor, which was actually being used for years for tuberculosis. So if we kept calling it an anti tuberculosis agent, people would say, why are you treating my depression with anti tuberculosis agents? So we're trying to move towards describing what a drug does chemically instead of broad categorical words. And again, I highlighted why stimulant itself is a confusing, misleading term. And we'll get into that a little more with whether Ritalin is in fact a strong stimulant. One of the things that we have 40 plus years of research in kids and adults is that stimulants help more people with ADHD and help those with ADHD to a greater extent than any other treatment that's compared to any other drugs or that's compared to biofeedback or talking therapies or any other intervention. That doesn't mean they're ideal for everyone, and that doesn't mean some individuals might get better responses from other options. But overall, that describes stimulant medications. Now, when we're talking about these strong stimulants, study after study tends to lump amphetamine products, Adderall, Vyvanse, Metadate with methylphenidate products like Ritalin, Concerta, Focalin and others and call those the strong stimulants and say everything else is worse. Are not worse meaning bad, but less effective in general as an overall statement. But all the studies strongly come to the same conclusion, that amphetamine is substantially better in terms of efficacy than methylphenidate, and methylphenidate actually is closer to the non stimulants than it is to the strong stimulant amphetamine products. And that is true across all age groups.
- [10:28]
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As you probably know, October is ADHD Awareness Month. The good news is this is our time to share broadly the research, the scientific findings and the lived experiences that define ADHD today. The bad news is there's a lot of misinformation and myths to combat these days. And if you're looking for a source to help you gather up the truth about adhd, I would recommend a podcast called Hyperfocus with Ray Jacobson. In each episode, Ray speaks with a different expert, whether a scientist, doctor, researcher to dive into some of the big questions and headlines around ADHD and mental health more broadly. She talks with experts about things like how ADHD affects women's hormones, hormones, bodies and hearts, how ADHD may impact postpartum depression, and even whether ADHD is genetic. A conversation with a Harvard scientist I checked out a few episodes and I particularly liked the series that she did on reactions to the MAHA report. She had a conversation with a researcher who pointed out some of the limitations which with the data in the report as well as a discussion of the use of AI that was quite troubling. And another conversation with a psychologist who broke down what parents need to know about the MAHA report. To listen to Hyperfocus with Ray Jacobson, just search for Hyperfocus with Ray Jacobson in your podcast app. That's Hyperfocus with Ray Jacobson.
- [12:20]
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So part of the however, among children we still currently say methylphenidate products are the first choice. It's not because they are less effective than the amphetamine products. It's because they have more side effects that are more problematic for children. Whereas in adults, again the amphetamine products are stronger, better than methylfib, more effective I should say. And, and they are considered the first choice for that age group. Now I'm gonna, I know there's interest in non prescription medications or non prescription, I should say agents substances, supplements for adhd. Again, each of the subjects here could be a whole hour devoted to them. The big problem is that we don't have huge bodies of good evidence as to whether these work or, or don't work. Some of them we have some limited encouraging data, but most of them the best we can say is the animal research looks encouraging. We have a few studies that they may work, but how consistently they work or how well they work is harder to define. And there's a few exceptions. So caffeine, nicotine, we have extensive research showing they are effective and there's several older studies where, where the efficacy of caffeine, if you give a big enough dose is comparable to methylphenidate, Ritalin products. There's also some studies looking at the combination of caffeine and L theanine which may mitigate some of the arousal, activating side effects. There's, I'd say moderately good evidence that magnesium can help individuals with adhd. There's moderately good evidence that fish oil can help, although there's certainly some earlier studies that didn't show help. And I'm putting lion's mane and ketamine, there are a bunch of other products out there and maybe ketamine is the worst example where there are clinics advertising this has been shown to help with adhd. And the only thing I've been able to find in terms of research is there are one or two case examples of people on ketamine with ADHD or ADHD symptoms resolved, but there's no other clinical research on it. So lots of supplement makers. That doesn't mean it doesn't work. It just means we don't have enough good solid information. And I'd say Lion's mane is one of the rising supplements. It's a mushroom, which there's a lot of good Basic science evidence, it can help strengthen executive functions, it can preserve mitochondrial function, it suggests that it may be a good fit. But in terms of clinical data, in adhd, it's almost non existent. And that doesn't mean it's not working, it just means we haven't demonstrated it yet. So the sympathomimetics, the big stimulants in the big sense, again, they're stimulating sympathetic nervous system. So most of the side effects that they produce, and these are what we call the common and the minor ones. And minor isn't to trivialize them because these are enough to make some people stop them or be intolerable, but they're not life threatening. Again, minor isn't meant to trivialize, but sympathomimetics can cause anxiety, they can cause tremor and shaky, they can cause people to be more irritable and sometimes more aggressive. At higher doses, they can cause whole body agitation, restlessness, pacing around, they're likely to increase sweating, they can make your mouth dry, they can disrupt sleep, they can suppress appetite, and they can have mild impact on heart rate and blood pressure. Now, usually for most people, these are dose dependent. So the bigger the dose, the worse they are. Which means if you're having side effects in this category for any medication that you're taking, it usually means back down to a lower dose until it's tolerable. And again, most people develop tolerance to most of these side effects while retaining benefits of the medication. Now, in addition to the common mild side effects or minor, we have some that can kill people. And the three big ones are cardiac side effects, abuse and addiction, psychosis. And I'm sticking in brain damage because many people think that's a serious side effect of stimulants. And we'll get into the evidence is actually the opposite there. So with the severe cardiac effects, so again, this is different than the common mild effect. So the common mild effect is on average individuals taking any of these, again, either strong stimulants or even the general purpose stimulants, which many of them, again we call non stimulants, increased blood pressure about 2,5 points, increased heart rate about 2,5 points. That sort of masks that most people don't have much change at all. And maybe 15 to 20% of people have bigger impact on cardiovascular effects. There is some study, some meta analysis, one came out about a year ago suggesting after 15 years on the stimulant, strong stimulants, maybe 4% of people are getting into more serious cardiovascular effects. But that's compared to the background rate is already close to 2%. So there's a doubling. It means 96% of people aren't running into problems. And particularly, even though it was classified as serious problems, it was just described as arterial disease and not stroke. Heart attacks, the lethal, again, that's the common sympathomimetic effect. Separate from that, there are tiny groups of individuals, much less than one out of 100,000, probably closer to one out of a million in most populations who have a genetic predisposition to a fatal arrhythmia. Their wiring to their heart is not normal. When exposed to stimulants, some of these people will either have a heart attack or drop dead. That's horrible and tragic, but almost always these individuals have either personal history of fainting or other events that were suggestive that they were at risk, or they have strong family history of aunt or uncle dropped dead in their 30s with a heart attack. So again, nobody wants this to happen to them. But even the cardiologists, who would make lots of money if every single person on a strong stimulant was required to have an EKG to measure their heart rhythm beforehand. Even the cardiology organizations don't say that that's clinically necessary, as long as you take a thorough personal family history and there's no indication from there. So any alarming family history of cardiac problems is a good reason to screen with an ekg. And even someone's just worry or concern is a good reason to screen with an ekg. But most people starting even a strong stimulant do not require getting an ekg. And again, to reflect on how rare these events are, when Adderall XR was about to release in the Canadian market about probably 15, 20 years ago now, they actually held it. It was introduced then. There were concerns about cardiac death. They held it off the market for at least a year while they were studying this. And when they crunched all the pediatric numbers, there were actually a higher rate of kids not on Adderall XR who were having heart attacks than in the Adderall XR group. That doesn't mean Adderall XR prevented heart attacks. It just means pediatricians and child psychiatrists were doing a good job of screening. So again, this is extremely rare, bad event, but almost always detectable through family history and not of direct concern to most individuals.
- [20:43]
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If you've got adhd, you probably know what it's like to have racing thoughts, intense emotions, and trouble focusing. But did you know those symptoms can also be related to ocd like when you find yourself hyper focused on a fear that's consuming your mind. Or when you're spending hours checking and rechecking your work because your brain just won't let you move on until it feels just right. Or when the self criticism and shame that accompany ADHD feel especially overwhelming and persistent. ADHD and OCD can have similar symptoms and it's common for them to show up together. Both conditions can involve unwanted thoughts, but with ocd, these thoughts tend to feel especially distressing and hard to move past. This may drive you to do certain actions to try to get rid of the distress, like analyze the same thought over and over, ask for repeated reassurance, or repeat specific behaviors. Fortunately, OCD is highly treatable, but you need specialized therapy from a therapist trained to truly understand the condition and how it can interact with adhd. That's where NOCD comes in. NOCD is the world's leading provider of specialized OCD treatment. Their licensed therapists are all trained in erp, or Exposure and Response prevention therapy, the most effective treatment for for ocd. NOCD therapists understand how ADHD and OCD can interact, so they'll tailor treatment to work with your brain, not against it. Therapy with no CD is 100% virtual and it's covered by insurance for more than 155 million Americans. They also provide support between sessions so you're never alone. If you think you might be struggling with OCD along with ADHD, visit nocd.com to book a free 15 minute call and learn how they can help. That's nocd.com now a more common severe.
- [23:00]
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Side effect of a strong stimulants and this is not a risk with the non stimulants is the risk of abuse and addiction. And what's really disarming is given that millions of people are on stimulants is we still don't have lots of good hard data on how commonly individuals become addicted to either their Adderall products or their methylphenity cabinet products. Most studies that are done or most experts cite, oh, maybe somewhere between 2 to 4% of children run into addiction problems. The claim is that adults whose brains are more formed and less maybe less susceptible to peer pressure as well, the rate is even lower. But we don't have a lot of rigorous data. And again, when we're looking at millions of people on these drugs, even if 96, 98% of them don't get into addiction problems, 2% or 4% is still a huge number. Now part of what's really Confusing is when you look at studies and some studies are saying, oh, 40, 50, 60% of people on stimulants are abusing them and addicted. And what they are almost always doing is confusing different categories. So misuse is. Rates of misuse are often that high. But the definition of misuse is anyone who uses their medication in a manner that's different than explicitly prescribed. If your Prescription says take 40 milligrams of Vyvanse every day and you decide I don't need it on the weekends and don't take it, that would be classified as a misuse. Or if you get confused and some days you take two pills and sometimes you take one that by these definitions are considered misuse and add itself. ADHD contributes to people forgetting doses, to getting confused about directions or not following them clearly. So ADHD itself predisposes the high rates of misuse of medications. But that's not the same thing as abuse and addiction, which involve having deleterious. So usually they involve some amount of tolerance, they involve some amount of dependence, which means in addition to tolerance, you're having withdrawal and other and cravings for it. And abuse and addiction also imply that you are having life problems from it and you're continuing the substance even with awareness that it's causing problems for you. Now, to put the whole addiction ADHD situation in context, having ADHD itself doubles the risk of developing a substance abuse disorder in the general population. U.S. and most European studies show that about 20% of adults during their lifetime develop some sort of substance abuse problem, whether alcohol or other substances. Having ADHD doubles your risk. So you are closer to 30 or 40% of people with ADHD develop a substance abuse problem. So that's double. But if you take stimulant medications to treat your adhd, there's several studies that have shown this. Particularly if you're starting by middle school years or earlier, you lower your risk to be comparable to that of people in the general population. It's dropped from again about 35, 40% back down to 20%, doesn't eliminate it, but that's a huge decrease. And there are a few studies that haven't found those effects, but most have. Overall, Even if there's a 2, 3, 4% risk of getting addicted to this specific substance, if you're reducing your overall rate of likelihood of developing any addictive disorder by 15, 20% at a public health level, that makes it a good intervention and sort of speaking. There's also many beliefs, particularly in the substance abuse community out there, that people with substance abuse problems need to avoid all the strong prescription stimulants and we don't care whether they have ADHD or not. But there's a few well done studies showing that vyvanse among the population of people with a diagnosed substance abuse problem and ADHD increases the likelihood you're gonna stick with treatment, it increases that you're gonna complete treatment and seems to decrease rates of relapsing back to abusing a substance. So the side effect, jumping back to the strong, dangerous bad side effects of stimulants, the one that I see ignored the most in my opinion is amphetamine induced psychosis. And again, this could take a whole hour to discuss it all. So by psychosis we mean a paranoid delusional state. Usually people are worried that people are out to get them, they're spying on them, they're plotting against them. And if it's amphetamine induced, that means it's as a result of consuming stimulant medications. Some myths about this is that if you're going to get it, it's going to be happening on the first or the first day or dose or week you're taking it. And it can happen after years of taking it. There's also a myth that it's only going to happen if you're taking massively high doses. And there's a little evidence that higher doses and maybe higher lifetime exposure doses may increase the risk that some people can develop it right away. Some people also call this amphetamine induced mania because there's usually some amount of some sleep deprivation, some high energy states, sometimes talking quickly, but that's often there as a result of the person's original adhd. Unlike mania where there's usually a fair amount of grandiosity of how important wonderful I am and usually at least some amount of silliness or positive emotions mixed in with volatile negative emotions. The mood state is not pervasively anxious and paranoid. So I don't consider it a manic state. The other really important thing to emphasize about amphetamine induced psychosis is it's not an intoxication state. And by that I mean if you take enough alcohol, I mean lots of substances, focus on alcohol. If you get really, really, really drunk, you become delusional. You're saying things that are clearly not so, and maybe even seeing things that aren't there. But what happens with that alcohol delusional state, you fall asleep, you wake up the next morning with a hangover, you may be grumpy, you may be irritable, but you're not screaming the same things that were delusional as you were the day before. An alcohol delusional state. And there's a chronic condition with psychosis with alcohol. But the common delusional state with alcohol and many other substances is an intoxication. It's the effect of the drug in your brain at that moment. And what happens classically with amphetamine induced psychosis is something far more serious. And that is the symptoms tend to persist for days, weeks, months or even years after the drug has cleared your system. So to me, why this is worrisome, is it saying, at least in some people, we are changing human brains and changing them clearly for the worse. Now, again, rare events are hard to study. Again, this is a rare event, but it's rare on the order of about 1 out of 500, some studies suggest 1 out of 400 or 600 individuals who are on amphetamine products. Recent studies have not been able to detect it using the same epidemiologic methods as they do in methylphenidate. So again, this may be an additional reason not to be considering methylphenidate a full strong stimulant. Another thing that I often see in particularly some of the older researcher studies on and is this condition that's not responsive to antipsychotics. That has not been my clinical experience that the two cardinal things to do if this develops is stop taking the stimulant and start taking an antipsychotic. And again, the persistence of this, and this is limited data suggests that if you've had a single episode of this and you follow someone out 15 to 20 years, about 15 to 20% of those people are in a permanent schizophrenic, psychotic like state. So this is again, a potentially really serious condition. It is uncommon. But when it's this serious, I believe we should be spending more time explaining this to patients. And my strong recommendation for anyone who's ever had even a single event is to not retry or consider any amphetamine problem again. So the fourth potential side effect of dangerous side effect is one that I would argue we don't have evidence for. But it's one of the commonest reasons I've had where patients either were leery or reluctant to start strong stimulant treatment themselves or to have their child started. And it's the worry, oh my God, these are powerful medications. It's going to rot, destroy, damage my kid's brain or my brain. This isn't just a far fetched, ridiculous worry. Or concern. There are a few studies looking at humans who abuse street stimulants, cocaine or meth. And on autopsy, they could find damage to dopamine neurons in the brain. They could find more widespread gliosis or scarring. There's also studies on prescription stimulants, the very drugs we're giving people in animal models that also found similar damage to dopamine neurons and gliosis or scarring. So that would be really scary if I were just aware of those studies. Countering those studies, though, we have more than 30, and probably it's closer to more than 50 studies now where we looked at groups of people with ADHD who were either who had either taken stimulants for some period of time or who had never taken stimulants. Most of these are strong stimulants we're talking about. And in none of these studies have found any signs of anatomic damage to any structures or substructures within the brain. None of them have found problems with disconnection or disrupted connectivity to brain regions. And none of them have found inability to activate or functionally use the brain after stimulant use. And in fact, these studies show the opposite. And by that, I'm jumping ahead a little bit. These studies show, I guess I don't have a slide on that. So what these studies show overall is that people who took stimulants for some period of time have brains that look more like they never had ADHD than the people who avoided stimulant medication use. It almost flips it on the head. Rather than causing brain damage, the data would suggest that we may be consigning some people to more severe ADHD forever because they didn't get treated at some early point in life for adhd. That's speculative, but I think the data supports that. Why is there such a discrepancy between those few human studies with street stimulants and the broader literature on therapeutic use of prescription medications? One is there's differences in the chemicals involved. So methamphetamine, cocaine are probably causing bigger release of neurotransmitters. There's overlap between how they work and Adderall and amphetamine products work, but there are differences that are important. Second is the seismicidosis, particularly the rodent studies were using dosages 50 to 200 times bigger than the largest dose recommended for humans. Part of that is rodents have a higher metabolic rate. Some of that slightly higher dose makes sense. But when they replicated those same studies and this is getting at both speed of delivery and right of delivery. If instead of directing it in, injecting it into the abdominal cavity, they gave a similar large dose in the drinking water or injected in the syringe into the mouth of those rodents. In those studies, more closely mimicking what's happening in people, those researchers failed to find any signs of damage in the brain. So different chemicals, different size of dose. And with amphetamine stimulants, we know it's not just how big a dose, but it's how quickly the dose is delivered. So getting a same dose by iv, getting the same dose compared to orally, the IV dose is going in really quickly. It's flooding the capacity of the synaptic region to mop up extra dopamine, and extra dopamine causes all sorts of damage. But if you give that same size dose over a bigger period of time, the compensatory mechanisms of the enzymes, other parts of the system, mitochondria, can adapt or can again prevent excess damage. The pattern of usage, binge using, we see often with street stimulants is probably more likely to be damaging than taking the same dose each day. Jumping to how do we get optimal medication dosing? And this hopefully overlaps a lot. But Dr. Dodson's article, I have not read his article, but hopefully I'm not too much contradicting anything he says. My strong point is that we should be paying attention to the biological and psychological effects of the human being taking this product, not focusing and how many milligrams is it, how many milligrams is it? And when I say that the FDA, when they approve a drug including stimulants, they do make recommendations. This is the lowest recommended dose. This is the highest recommended dose. But then the FDA literature says explicitly recommendations are guideposts, guidelines that are not meant to replace an individual clinician's judgment. They are not strict limits. We are aware that a certain percentage of the population is going to require dosages bigger than the recommended high. And we know some are going to respond to dosages lower than the recommended low. So how do we assess what's going on when we're dosing one again, is trying to use measures that are as objective as possible. So this is a good use of some of the ADHD rating scales. Now, ADHD rating scales, lots of really bright people spent lots of time coming up with them. They still don't perfectly capture just what's going on with adhd. If you have ADHD and you encounter some event that makes you really anxious, that will change your answers to some of the questions and give you a different scale score. Again, that would be because anxiety intervened, not necessarily because ADHD improved or got worse as a result of the dosage and the meditation. Rating scales are useful but need to be taken with a grain of salt. And I usually encourage people to use personal measures that they can quantify as much as possible. So one example is if every day when you go into work and you see 300 emails facing you and it takes you an hour and a half to clear them out because you get distracted, you can't really prioritize, you are jumping around. But now on the medication, you can plow through those emails of fiction efficiently, effectively, and finish in 20 minutes. That's a clear subjective improvement. Or let's say before medication you can't read an article that's more than 10 or 15 minutes. So maybe a long magazine article, but certainly not a book. And now on the medication you can sit and read for two hours. That's an objective measure. So certainly most people on the medications for ADHD can subjectively say, yes, this seems to be working, but it's good to have objective measures. The. The other things that obtaining collateral information. So what your friends say, what your therapist says, what your coworkers, what your family is observing or not, and this always sounds a little pejorative, but we know that ADD ADHD itself impairs your own ability to monitor, your own attention, so your own capabilities. That doesn't mean it destroys it, it doesn't mean your own assessment is worthless, but it does mean you are likely to be missing something that might be important information. And the other general thing I say about dosing is that there's some crude correlation with body size, with gender, with severity of symptoms, but it's really crude and there's lots of individual variations. So again, focus on what's working for you in terms of benefits or side effects. So that general formula for adjusting medication dosages is to titrate. Again, this is with strong stimulants, is to titrate up quickly. These drugs have their effects immediately, within one, two, three days, or usually within one day. But since there's individual variation and whether you slept well the night before, if you're not seeing effects after three days and you have no side effects, then they go up to the next block. Two other things to remember here is that if you're starting stimulants for the very first time, about half the people have a honeymoon period where their benefits from the medication is better than they ever recapture any point later in their life. Whether that's a physiologic effect of tolerance or whether that's a psychological effect of never having anything that helped at all before now, having something, we can get into that. And there's debate as to whether tolerance is common or rare. This addiction specialists who all they're dealing with or people run into problems say everyone develops tolerance to stimulants. And the ADHD experts say that it's actually quite rare. I'm knowing we should jump to questions and answers pretty quickly. So one of the other things I highlight because some other people talking about this don't seem to be getting it accurately. I think the common claim is the strong stimulants work quickly, immediately, and everything else works slowly for adhd. But what do drugs like Strattera, Atomoxetine, tricyclic antidepressants, Wellbutrin do? They're affecting reuptake of dopamine and norepinephrine immediately. Some of them are doing other things as well. Those immediate effects you would expect would lead to immediate benefit. And if you clinically talk to people who are taking these drugs at an effective dose, they will say, yeah, I took the Wellbutrin and that day I could see I was more focused and attentive. So Guanfacine I think is a clear exception to this. And Strattera is a confusing scenario where most people can't take an effective dose immediately because I have so many side effects. But also skim over that for right now. Another topic that came up a lot in your question is when to combine medications. There's very little rigorous data on that at all. Most of it is focusing on is it safe and reasonable to combine short and long acting stimulants. So Ritalin IR with Concerta. And the answer is yes, it can make sense in terms of either extending the duration of action a few hours longer or for covering lulls in the day when you may need more medication. I would throw in here that siesta time is a biological phenomena. Many people with ADHD aren't aware that they have a lull in attention, concentration, thinking, alertness, early afternoon. It's not just dependent on having a big meal. People with ADHD tend to have less regular circadian rhythms to begin with. Some of them for the first time become aware of siesta time. My general philosophy is don't try to medicate your way out of siesta time, but just acknowledge there are times the day you're going to be less proficient at detailed work. The overarching combining non stimulants and stimulants is generally safe. But again all of these tend to be sympathomimetics so you are working on some of the same systems in the brain. Often combining a non stimulant allows someone to get away with a lower dose of a stimulant. And I would say guanfacing is a particularly useful combinatorial tool in that it tends to lower blood pressure and has some effects of reducing some of the sympathetic arousal that can occur with the others. So I know I've skimmed through a lot of things, but I am here and available for the question and answers. These are references to some of the things I've mentioned.
- [45:17]
A
Wonderful. Thank you Dr. Cruz for that incredibly informing science based presentation. I learned a great deal. Before we start the Q and A, I will quickly thank Accent Rate for sponsoring this webinar once more. I am hearing to start out from quite a few people, as we know most stimulant medications are approved by the FDA in the United States for up to ages 55 to 65. The number of people saying they hit age 65 and their doctors refuse to prescribe a stimulant whether it's new or a re prescription. Is this level of caution appropriate? A hard cap at 65 years of age?
- [46:07]
B
My simple answer is almost any hard cap is denying the individuality of certain humans. Humans vary. Cardiologist groups interestingly have not weighed in strongly on this. At least some groups have actually said what makes sense. If you're concerned if there's other cardiac issues going on and for all of us as we age we are more likely to run into develop cardiac issues. It's to get an evaluation. I mean this may be a point where you do you didn't have an EKG for 20 years on it. But if they're hitting 55 or 65 or some other again somewhat arbitrary cutoff. So we I mean I have patients who have been in their 80s one even in their 90s who continue their medications safely and with great benefit strong stimulants. So Adderall amphetamine based products are valiants. I've had some who needed to decrease their dosing because they they needed less to get a beneficial effect. But I have not seen again my sample size isn't going to be gas but none of them have run into problems of cardiac complications. So I can say there are at least some individuals who do well on stimulants into later years and are not having cardiac adverse effects. Another issue related into this regarding anyone on stimulants who's having increases in blood pressure, there are certainly some people who are sitting on the borderline between hypertensive and not and are pushed into that by these medications and often in consultation with the cardiologist. The answer is we can use a blood pressure lowering medication. Again, guanfacine can be a useful tool there or something else. So antihypertensive. So blood pressure lowering medications can be used safely with stimulants. And sometimes the cardiologist's recommendation is don't stop the stimulant but to just go up on the antihypertensive because the person's getting benefit from both medications.
- [48:34]
A
So okay, that's very helpful. There's a number of people here who say they've been told that due to a history of hypertension, stimulants are simply out of the picture for them.
- [48:49]
B
Yeah, I can say I certainly worked with people who primary care doctor. Others were, you know, said that they needed to stop. So the other thing I've had is people where it was a question whether it was having an impact or not. And again, most of the effects both physiologically and central nervous system on the brain through a stimulus are immediate direct effects. So if you your blood pressure two hours after taking your Vyvanse compared to what it was before and you do it a few days on and you do it a few days without and you're not seeing that the Vyvanse is having a direct role, then I would say clinically that that is demonstrating that this is not a part of what's contributing this individual's hypertension and therefore safe to continue to take. But I certainly have seen what your question, what the people writing in are saying is it's not uncommon for doctors to be overly cautious. Some of it I think is genuine concern about patient welfare. I think some of it is if they're seen as prescribing outside of guidelines, then if something bad happens, they're going to get in trouble. But I think we should be first and foremost focused on patient care, not on, as I will say bluntly, cover your ass medicine.
- [50:17]
A
You talked in your presentation about the fact that ADHD medication use is not linked to brain damage. But a number of people are wondering if there is any evidence indicating that long term stimulant use carries any other health risks that they should be aware of.
- [50:41]
B
So again, separate from the immediate cardiac death, again there is some sign of, I'd say more serious. But again, It's a small risk. 96% of people at 15 years weren't showing any sign. But that meant 2% above what the background placebo rate of 2% were having troubles. Yet the thing when I'm talking with individual patients that's really important to emphasize is that ADHD itself kills people. I say it that bluntly because the data is pretty darn clear. On average, if you've had ADHD since childhood, you're likely to lose seven, eight, nine years of life. That doesn't mean some people don't live a long life and some, some die tragically short. But on average it's a substantial contributor. And the two big causes seem to be suicide and accidents. So all sorts of car crashes, clumsy events and if we can prevent those for most people's bodies and brains, it seems that the cost benefit analysis is strongly in favor of on the stimulants. Is it possible? So there's one concerning study suggesting rates of Parkinsonism might be higher. What's difficult there is Parkinson S involves degradation and destruction of dopamine neurons and the substantial nigra. But we know dopamine neurons are also going to be affected in many people with adhd. So it's really the study was well done. It sounds somewhat concerning. Again, the overall rate was the vast majority of people are not developing Parkinson's. But even if it's a relative increase in risk, that would be nice to know. But it's hard to sort out confounding variables and sort out is it really the ADHD which increase the risk or maybe the more severe forms of ADHD that increase the risk rather than the medication used to treat it?
- [52:51]
A
Okay, I will mention there is a link on the attitude homepage to a write up about a new study that just came out I think last week on about 150,000 people with ADHD showing as you said, stimulant medication use significantly lowered the risk of suicidality, criminal behaviors, vehicular accidents and substance misuse. And it just is another in a long line of studies showing the same. I will move on to our next question that I see a lot of and that is is there any evidence to suggest that stimulant medication loses its efficacy with time? So in other words, should patients consider medication vacations or perhaps taking medication less than seven days a week or at a lower than optimal dosage? There's a lot of advice being given about these strategies.
- [53:56]
B
Yeah, there's a lot of advice and there has been since I started in this field in the mid-90s and extremely little evidence whatsoever. So one of the things I did three, four years ago, and this is just within my own practice in terms of sorting out how common is tolerance. So I looked at the first, I went in alphabetical order and found the first hundred patients I was working with who had been on a stable dose for years. So we're not discussing were they titrating up initially or sorting out a dose and then just looked a year later. Are they still on the same dose or did they go up or down? And again, I'm not saying my patients population is representative of all people with ADHD, but I think it's. And 80% of the individuals were on the exact same dose a year later. So one that's saying, @ least in my practice, most people aren't needing to go up. And of the little less than 20% who changed a dose, it was actually equal amounts of people going up or down on the dose. So that would suggest there's either equal likelihood and small of both sensitization or tolerance or. The other thing it emphasizes is that we're always talking about a brain interacting with its environment, not just the medications going into it, but also changes in job, changes in partner, changes in world environment. Some of that pseudo study I did or informal study was during COVID so there were stressors there, but to me it was fairly reassuring and refuting. And again, it tends to be the addiction specialists who, they are only seeing the narrow percentage of people who run into problems with these drugs. So I don't see tolerance as actually a particularly common problem. Most of the patients I've worked with, and some I've worked with for 25 years or usually continue to get benefits from the same dose unless life situations change dramatically.
- [56:06]
A
Okay, that's very helpful. We've seen over the years, as I'm sure you have, that the stimulant shortage has impacted quite a few patients. About 7% of the people here said that that was the reason why they stopped taking their medication. But a lot of people have had to, for various reasons, switch to generics, the generic version of their preferred medication. And they said, you know, it doesn't work the same. Is that possible? Is that true? What might be going on? That the generic version would not have the same effect or might carry different side effects than the name brand.
- [56:48]
B
So. So I do have colleagues who think that the differences, I mean, the FDA requires that it's the same substance and that it's release is roughly comparable, but roughly comparable means there's a 15 to 20% slop in terms of how quickly it reaches the peak level and the total amount absorbable or area under the curve. So there is some variability that's allowed by the fda. And what's really. So it's interesting, again, I have colleagues who think this is all just a psychological problem, that it's kind of like when you're doing a wine tasting and telling people this is a $200 bottle of wine versus a $20 bottle of wine. You get many more people saying, oh, the 201 is really great. It's working. You know, I like the flavor. And often in these studies, they're actually the same bottle of wine. So I'm not ruling out that there are some people in some cases where it is a psychological effect. But I believe that there are physiological reasons that there could be. Some people will detect differences. It's interesting, in my clinical practice, the two groups of medications are the stimulants and the benzodiazepines of Valium, like drugs where people fairly commonly notice brand name generic differences. And not that it doesn't happen, but it's much less common with slow indirect drugs like antidepressants, like Prozac. And I think, again, part of the reason, and we know with stimulants, strong stimulants, part of the response isn't just the concentration of dopamine or norepinephrine at that second at the synaptic junction. It's how quickly that dosage is changing from the previous minutes. And if you have a drug that goes in a little slower or faster, you aren't just getting a subjective difference, that this feels different, that can certainly be there and add into the sensation, but you are actually probably getting different physiologic output from the system because of that. So again, the first part, the subjective part, I think that does have a role. So I've had lots of people who are on Adderall immediate release, when we were titrating initially to see what they were, whether it would work or whether they'd respond. And then they'd switch over to Adderall xr, and even this is even within brand name, and they'd say, you know, the immediate release work, but this stuff doesn't do anything for me. And I'd say, it's the exact same chemical, it's the same company, how could it not? And again, daily dose is one part of the phenomenon. But how quickly that dose, how large a dose at that instant is at the receptors, and how that difference from what happened the second before is a part of physiologic action of stimulants. Okay, I'll just say that we're concerted. The FDA themselves acknowledged that several of the generic versions were not biologically equivalent even though they were chemically equivalent.
- [60:03]
A
So if this has been your experience, it is in fact not in your head. Likely. Also, there may not be a great solution on the horizon, but it's good to know.
- [60:18]
B
I mean, one thing many doctors aren't willing to do it and sometimes it doesn't work, is that you can petition your insurer to say the Sandoz brand and the Teva brand haven't worked for me. I need Abbott brand of certain drug. And the challenge there is it may be harder for them to get hold of it. Sometimes the pharmacy isn't particularly willing to cooperate, even though technically they are allowed during can and the doctor can write orders that way. But oftentimes doctors aren't willing and there can be pushback from the pharmacy and or more delays with each filler. But that's an option for people who have noted clear and consistent differences. And at least in the US on the label of your pill bottle for the generic, and it's usually in tiny, tiny print somewhere, it will specify which generic maker you have each month.
- [61:17]
A
Okay, we are almost out of time, but I did want to refer people who had asked questions about supplements and those that have science behind them. I believe, Dr. Cruz, that you have done some videos on a few of these supplements on your YouTube channel. So I was going to refer folks over there to learn more about non medication alternatives. Does that sound like a good next step for those people?
- [61:51]
B
I think the link is on the slides, but that's Dr. John Cruz, Dr. J O10K R U S E YouTube. It's a free channel and I do have talks on lion's mane and fish oil and magnesium and a host of other substances, ketamine, some of which I think we have no evidence for. And ketamine, there's at least the risk for harm, something like Lion's Mane, probably low risk for harm. But again, not a lot of data yet. But yeah, I do have more and more videos will be coming because there's clearly interest in alternatives to prescription drugs.
- [62:31]
A
Indeed there is. So as you said, we could have done a whole series on all of the topics you touched on today. So I appreciate that as a next step for folks who want to dig deeper in medication and medication alternatives. So we are out of time. But Dr. Cruz, thank you so much for joining us today, all the way from Hawaii, getting up very early to contribute your voice and your breadth of experience to our ADHD community.
- [63:03]
B
Thanks. I really enjoyed the opportunity to speak here and thanks for inviting me. And thank you for the people who submitted questions. There's a lot of thought and concern and interesting things to address here.
- [63:17]
A
Indeed there is. I think we received on the order of 338 questions today, so we clearly did not get to them all. But please know that the Attitude Team does read every single question and we do our best to answer them in our content online and in the magazine and in these webinars. So we hope that we are able to help all of you. If you would like to access the event resources for today's webinar, please visit attitudemag.com if you search for podcast 573, you will find the slides and the recording a few hours after we wrap up the live webinar. If you're listening in replay mode, you can simply click on the event description. And I hope you know that our full library of Attitude webinars is available as a podcast. It is called the ADHD Experts Podcast and it's available on most streaming platforms. To make sure you don't miss any future Attitude webinars articles or research updates, simply sign up to receive our email newsletters at Attitude. Dr. Cruz, thank you again and thanks for everyone who joined today's discussion. I hope to see you again soon. For more Attitude Podcast and information on living well with attention deficit, visit attitudemag.com that's a D D I T U D e m a g.com.
- [64:54]
D
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