Transcription
Hello, good evening. Welcome back to Eye Care for Your Brain with Dr. Sullivan, board-certified neuropsychologist, licensed psychologist, previous caregiver in an earlier lifetime. Here I am, coming to you as often as I can with free brain health lectures. My job is to come to you with high-quality scientific evidence so you can become the most informed consumer of brain health information and make your way in the world with your brain health challenge to the best of your ability.
I want to welcome any of you who are new to our channel. To me, tonight, we've had so many new subscribers to our YouTube channel, probably going to hit 20,000 by the weekend, which is just so exciting. We've been at this for five years now, and it's so rewarding to see our community grow and grow.
Tonight, we're going to talk about Topamax and the brain. You might actually know me from my video on another medication called Gabapentin, and that one, I think we're up to almost 180,000 views on that one. So, what that taught me is you all want to know more about medications from an objective source, and my job is to give you all the information that I think you need to know to work with your doctor in your life to come up with a decision for you. Education is empowerment here at Eye Care for the Brain. So let's get started with our free brain health lecture for today.
Today, you're going to learn about the history of Topamax, how they make it, it's actually very interesting, what it is derived from, how it works, the populations that it's FDA approved in, and what are the experiences of people taking it, with a focus, of course, as your neuropsychologist, on the cognitive side effects. Possible cognitive side effects. Topamax has a higher dropout rate than other drugs that are very similar, about 25% of people can't tolerate the medication, mostly due to cognitive side effects, earning it the nickname "Dopamax," if you've heard heard that before, let me know.
It also goes by a generic name, Topiramate. It was discovered in 1979, only got approved for medical use in the U.S. in in 1996, and the first indication for Topamax was for seizure control in adults and children. It then got repackaged in 2004 and is on the market for migraine prevention in adults and also for a a little-known childhood disorder named Lennox-Gastaut syndrome, so for kids over the age of two. But like Gabapentin, it actually has taken on a huge life of its own in terms of the off-label uses, and that's how many of you actually come to Topamax. If you are comfortable saying in the comments why you take it, would be helpful to see what people are on here for. In 2019, it was the 68th most commonly prescribed medication in America, over 10 million prescriptions per year. So it is widely described beyond seizure and migraine control.
And just a few of the indications that people take it for are diabetes with nerve damage, bipolar disorder, depression, impulsivity, weight gain, alcohol addiction, fibromyalgia, PTSD, binge eating disorder, borderline personality disorder, treatment-resistant schizophrenia, Tourette Syndrome, cocaine addiction, neuropathic pain, and most commonly, it's gotten a new life in treating obesity. So, very similar to Gabapentin, it's kind of all over the map.
Topamax has a unique biochemical profile. It is actually a sugar, which I thought was very interesting, a sulfamate substitute monosaccharide made from fructose. Fructose, of course, is a naturally occurring sugar in many fruits and vegetables. Topamax has many, what we call, mechanisms of action. So it actually does quite a few things, and you can kind of put them into two different camps. One is that it excites neurons, and in another camp, it actually inhibits neurons. So on one, you have a very activating effect, and on the other hand, you actually have kind of a quieting effect.
It works as an anti-convulsant by obviously inhibiting neurons. Neurons that are firing, uh, in in kind of a haphazard way, all of a sudden, group networks of neurons start to fire together more excitedly than they should, and then we get a seizure. It can inhibit voltage-dependent sodium channels. It can increase GABA, a neurotransmitter that we talk about in other issues, and part of it is it can actually inhibit glutamate receptors. Now, glutamate is a very important neurotransmitter to know about, and typically we don't think of it very positively because it does cause trouble in brain cells and and really it can cause hyperstimulation. And we often see it after a brain injury, specifically after TBIs. If you actually look at glutamate in the brain after TBI, it goes off the charts because it's really an indicator that there's been damage. But it can also do things like modulate calcium channels, chloride channels, uh, it it can increase the transmission of potassium. So it's got multiple, multiple ways that it works in the brain, which is probably why it's kind of a a catch-all and it has all of these different uses.
It is very quickly absorbed. After the first use, it takes about 21 hours to actually get into a steady state in the human body, and it takes about four days in both directions. So four days to really come to your regulated stable level, and it takes about four days, maybe even a little longer, maybe five days, to completely clear out of your system.
The big thing I want you to know about Topamax is the side effects are very dose-dependent. So what I mean by that is the higher you go, it's very clear the more cognitive side effects there are. And the tipping point is in different studies anywhere from 100 to 300 milligrams. So especially once you get up to 300, what you see in the research is a lot of people actually drop out of the studies. So it's hard to follow them over time because we're not really getting a representative sample. After about two hours after taking a tablet is when the Topamax is going to be at its maximum concentration, and this is why if you actually track people when they report their side effects, they tend to be about two hours after you take the pill, which makes sense because it's at its highest concentration.
It is mostly metabolized in the liver. There's some kidney processing involved as well, and interestingly, about 70% of Topamax leaves us through our urine completely unchanged. So we're really only absorbing about 30%, which is on par with a lot of other medications.
There are side effects that are kind of well-established. If you go to the doctor, they're going to talk to you about them. And then there's other ones that are just kind of well-known in patient circles that I hear a lot from my patients, but I don't necessarily hear them getting talked about it with their neurologist, which is a huge part of why we're here today.
So in 2001, the FDA came out warning people about something called myopia with Topamax, and basically, that's when far away objects look blurry. You also are at risk in the beginning of getting a very specific type of glaucoma that can happen. The experience is kind of pain in the eyes and again, kind of a blurring. These symptoms typically begin within the first month, including the blurry vision and the eye pain. And stopping the medicine might cause the damage, but there's some concern that maybe it isn't able to be reversed once the damage has happened.
In 2011, we had the second FDA kind of warning about it for pregnant women, increasing the risk of cleft lip or cleft palate. So it's now in the pregnancy category D, which basically says there's positive evidence that the fetus is at risk. However, there are potential benefits that may warrant use of the drug in pregnant women despite the potential risk. So a lot of these medications are very personal choices between you and your doctor. And again, I I'm not a physician, I'm a psychologist, I'm not licensed to prescribe medication. You shouldn't take medication advice from me. I'm here to tell you how it affects your neuropsychology, but I do really believe in people being informed. And it's not to cast a negative shadow on this medication because it does a lot of good things, but we also do want to talk honestly about what the risks are.
So let's just put the cleft palate risk in perspective. So if you take Topamax in the first trimester, you have a 1.4% chance of having a baby that has a cleft palate. Now, this is compared if you have to take Topamax, let's just say you have seizures and you have to take it for other reasons, your risks are only 0.33 to 0.55. So it basically doubles the very small risks that you're going to have a baby that has that problem. Those are kind of the two biggies, and those are in a very small set of patients.
Then we have the whole list. This is what I typically hear from my people who are coming to see me for cognitive concerns. People discontinue Topamax to the rate of about one in four. So that's again, it gets back to the 25% of people who find it to be intolerable. So the big things are sleepiness, tingling, loss of appetite, nausea, a sour taste in the mouth, or carbonated drinks tasting flat. Now, those are two kind of unusual side effects that can happen as people are increasing their dose. Typically tends to happen on the front end when you first start to take it. But we also do see that people struggle to get off this medication, that there are withdrawal issues. And on that side, what we can see is a lot of emotional instability, so depression, anxiety, suicidal thoughts, apathy. There's one case report in the literature about depersonalization, which is a feeling of being very disconnected or detached from your body, even though you are in reality, you know, you're not psychotic, but you just have this feeling like maybe you're not real. It's a very, uh, disturbing feeling.
So let's review how well it works in those two populations of seizures and migraines. So in seizures, it's actually considered a broad-spectrum agent, which means it actually gives people seizure control over multiple types of seizures. So we think about partial onset, generalized onset. People either use it alone in what they call monotherapy, or they use it as an adjunct. The thing about seizures and Topamax is that you typically need a high dose for it to be effective. So what they think is about 400 is the starting point in the person with seizures' brain to get seizure control. If you remember what I just said a few moments ago, a 300 milligram seems to be the tipping point for cognitive symptoms. So we're already kind of in that land where when it's working, we're probably going to see some of the the bigger problems with the cognitive symptoms. So about 50% of people get good seizure control when it's at the 400 milligram level. Uh, again, in this population, we do see once again, it comes back to one in four, 25% of people.
The cognitive symptoms that people complain about with Topamax are word-finding. Knowing, you know, that word, but you just can't find the file. It's like the bridge connecting the two towns was burned down, and there's just not a way to get from point A to point B. Probably one of the most, uh, frustrating cognitive symptoms. You know, anybody who's got that tip-of-the-tongue syndrome, we know how annoying that is. Imagine if that happened to you all the time. It gets very frustrating. We also see complaints about verbal memory. Okay. So as you go up in Topamax, these cognitive symptoms actually get worse. What we find is if we go up slower on Topamax, people complain of the cognitive symptoms longer. And once they actually get up to their therapeutic dose, it looks like cognitive symptoms actually taper off. So it looks like it's at the worst in the beginning.
You also have to remember a very important point with Topamax is that the the issue you are using it to treat also has its own cognitive risk profile, right? So having seizures is a risk factor for cognitive dysfunction. And in fact, the most common place that seizures set up is in the temporal lobes, and for some reason, the left, it has a greater likelihood of being in the left temporal lobe, where that's where word-finding happens, that's where a lot of verbal memory happens. So what we think is that people who take Topamax for seizures are going to have the biggest cognitive complaints because they've actually got two layers of reason to have the cognitive symptoms. I hope that that makes sense.
So in this group of people with seizures, if there are the biggest cognitive symptoms in these people, how is it going to reveal itself? And I love research like this because it looks at the practical, looking at how do these cognitive symptoms, maybe some of those visual symptoms, how do they manifest in everyday life? Well, at least two study studies have looked at driving ability in people with seizures. Now, in North Carolina, where I am, you can't drive a car unless you've been seizure-free for six months. So let's assume that that's going on. So there was one high-quality randomized placebo-controlled double-blind study that looked at the impact of Topamax versus Lamictal, which is another anti-seizure medication. And what they tried to recreate on a computer was all of the cognitive skills you would need in order to drive. So they looked at divided attention, visual scanning, field of view, basically tried to recreate what it's like to be behind the wheel. And what they found is that the Topamax group had a restricted field of view after eight weeks, and they were still having this problem after 16 weeks. So it never got better. So what the restricted field of view is, is basically these people aren't seeing all of visual space. There's a little bit of blinders that are on, and this was not thought to be due to the glaucoma or the myopia that I had mentioned to you before.
We also see that simple target identification, so let's say like being able to see a ball, you know, passing across your car, and your ability to do two things at one time was worse in the Topamax group driving than it was in the Lamictal group. And doing two things at one time, multitasking, is actually a huge part of driving, right? You're, I mean, so many things. You're you're potentially talking to someone on the radio, looking in your rear view mirror, gas, brake, uh, pedal decisions. Me, it's basically a huge giant piece of multitasking. So what they made the equivalent of driving on Topamax was basically being on a low dose of alcohol or a 0.5 milligram tablet of Xanax. So that is pretty significant, I think it's important to know.
Now, migraine and epilepsy actually share a lot of biological features. So it's not kooky to think that these two things, that's why they're FDA approved. They're actually very similar in terms of hyper excitability of of neurons. So in people with migraine, Topamax seems to work by basically calming overactive pain signal firing in neurons, right? So you've got brain cells that are kind of overactive and, uh, probably excreting a lot of glutamate, and the Topamax is able to come in and kind of calm these things down. So when you take Topamax for migraine, it's actually for prevention. That's key. You don't get a migraine, experience pain, and then take Topamax. It's meant to be preventative. Takes about 8 to 12 weeks to get that benefit. Some people see it in four to six, but typically we think eight to twelve. And it actually works pretty good. And the best thing is it works at much lower doses. So that's key. People with headaches in the literature are supposed to be on about 100 milligrams a day, but I can tell you clinically, I see way more than that. It's not uncommon for me to see people who are on 200 to 500. The most common reported side effects in migraine are pins and needles feelings in about 50% of people, fatigue, not wanting to eat, those memory complaints, and weight loss.
If you look at people with migraine and ask them about their cognitive function, once again, you see about 25% of people who take it for migraine saying, look, I think I'm having trouble finding my words. But again, what we see is the complaints are the worst in the first month. Now, that might be a little bit skewed because what I found in many of the research studies I reviewed for you was that the people that complain the most at the beginning of the trial drop out of the study. So the question is, are we actually tracking real the same people over time, or what is the dropout rate? That's something that we're interested in when we review the the validity, the credibility of research findings. But what we do see is when we do objective testing on people with migraine who take Topamax, is that we do see that their ability to pay attention is worse. So, very, very important to know that if you're starting to take Topamax, you want to make sure you're kind of double-checking behind yourself.
We definitely use it in mental health challenges now. I've seen it in plenty of people with bipolar. With bipolar, it's kind of thought of as like a second-line or an add-on. It does seem to reduce depression and anger, seems to help with reactivity. Again, because you now know the way Topamax works, as it calms down brain cells, they've used it in aggressive behaviors in people with dementia, people who have Down syndrome who also have aggression or agitation. It seems to work in them. And, uh, again, if you follow these people too, what you what you see is that about one in four people complain that they can't think the same way.
So, you know, we've made a lot of progress with medications, but the truth is, we also have a lot to learn in terms of people's unique genetic ability to process substances. And hopefully, that's the wave of the future is that we're going to do genetic testing on people before we make decisions about medication, just like they do now for some antidepressants. You can get your cheek swabbed, and your doctor can get a list back of the ones that are going to be more likely to be successful. Hopefully, we're going to personalize medicine in the next decade to where we can do that for everything. Because very similar to statins, there's definitely a group of people who just do not tolerate statins well. So there's something about the genetics of some of us that just just make it so we're not able to tolerate it.
Now, when you get normal, I say normal in quotes, volunteers to be kind of the control subjects, and you look at their EEG patterns at 100 milligrams, we are seeing changes in their brain waves. So they have an increase in Delta and Theta and reductions in Alpha. And basically, what that state feels like is sedation, that feels like reduced processing speed. So I think that gives us a good insight into the experience of someone taking Topamax.
Now, are you ready for me to totally flip this around and and make you realize how open-minded you need to be when we're having these brain health conversations? Topamax, in some people, may also be what we call neuroprotective. So it could actually, instead of causing cognitive side effects, there's, uh, in animal models, Topamax has been shown to be neuroprotective under certain circumstances. For example, when they give an animal, like a mouse, a what they call a sham brain injury or a stroke, it actually is showing us that Topamax crosses the blood-brain barrier, as we know in humans, and it decreases that elevated glutamate, which then goes on to show a more rapid recovery and higher functioning of the animal. That's pretty significant. And in fact, they're considering after spinal cord injury or maybe after even stroke, could giving Topamax to people in those early days actually reduce the impact of the brain injury? They have. Now, this is not unique to Topamax because we actually see it in Gabapentin, we see it in benzodiazepines like Xanax and Klonopin. We know in experimental models of stroke, seizure, TBI, if you give people a little dose of these medications early on, we actually see that these people do better. Now, that's not the case after a very short window, and it's not to the point where we can recommend it for humans yet. But it's just to say, a lot of people are always looking for the negative side of big pharma, and there's oftentimes two two sides of the story.
So I do want you to understand what are the potential risks. I don't want you to expect that the bad side effects are going to happen to you. But if they do, I want you to be validated that they are real. But at the same time, I think we just have to keep up with the scientific literature, make sure we're reading good quality studies to understand that many of these drugs wind up being FDA approved for one thing, but then take a left turn with some research, and then next thing you know, we maybe have our big breakthrough in some other area.
The goal of these lectures is to create an audience that is more informed. One of my biggest concerns is that we're not getting enough time with our brain health providers, and that's what really motivated me five years ago to want to put these free lectures out on the internet. If if you don't know what's going on with you, I think human beings very naturally go to anxiety and worry that it's something much more dire.
Okay, so very important to me that you understand there's three final things I need to tell you about Topamax before we go. The first one is, do not drink while you take it. Alcohol definitely causes increased sedation or drowsiness, much more than you realize. So that's important. Can increase your risk of having seizures while you take Topamax. Topamax also interferes by about 30% with the effectiveness of the birth control pill. So if something that's, you know, happening in your life, you need to understand. Do not cold turkey stop this medication. You absolutely need to titrate, especially if you take it for seizures. You can easily have a rebound seizure. Um, very, very important to not just stop it on your own, and you might need a longer tapering period than you even realize. Don't ignore a blurry vision or eye pain. It's always key to walk through the risk-benefit ratio with your medical provider, okay? Oftentimes, these cognitive side effects that we see in Topamax are at higher doses and in the earlier phase. So if your doctor really feels strongly that this is a medication, know that that hopefully it will get a little bit better over time. Your job is to be the best communicator that you can be with your prescriber. So I always encourage my patients to keep a journal with dates, times, what are their specific side effects, and share it with your doctor. If your doctor is not interested, time to get a new doctor if if you can.
Okay, to date, there's no data to suggest any long-term negative side effects from Topamax, like a risk of dementia or brain tumor, anything like that. There's no apparent structure to the brain. The best rules of thumb are to like all medications, start low and go slow. Always advocate for yourself to be on the lowest dose that is effective for you. Okay, so many medications have side effects. It's all about that delicate balance of what is good for you versus what you might have to learn to adapt to or what's intolerable too. There might come a a fine line where you just don't feel like it is worth it to you.
I would love to know your experience with Topamax. I think our brain health community would like to know your experience. As you are comfortable, share in the comments. If you're watching us on YouTube, please do hit that subscribe button. We would love to create the biggest community that we possibly can because this is how you're going to find your power. You're gonna be a consumer, someone who who takes in high-quality information so you can go into those neurology appointments and know what you're talking about and be able to advocate for you to have the very best life experience with your brain health challenge. Thank you so much for watching me. I look forward to seeing you next time, and I hope you take care. Bye-bye.