Reassessing The Prescription of Levetiracetam/Keppra for Epilepsy - Dr. Ángel Aledo-Serrano, Hospital Blua Sanitas Valdebebas, Madrid, Spain
Flash-back to our most popular episode! Epileptologist & neurologist Dr. Ángel Aledo-Serrano shares his thoughts regarding the antiseizure medication Levetiracetam/Keppra, its effectiveness in controlling seizures, but also the importance of precision medicine. He also speaks of the need to improve prescribing and avoid polypharmacy for people with an epilepsy, the need for further qualitative research into treatment and care, and convincing clinicians that epilepsy is far more than seizures alone.
📺 Watch the Interview
🎧 Listen to the Podcast
👉 Listen on Spotify | Apple Podcasts | YouTube
This episode is sponsored by EASEE® by Precisis who’s had no influence over the editorial content or discussion. Learn more about EASEE® here.
Episode Highlights
Why Keppra became one of the most prescribed antiseizure medications
The clinical importance of psychiatric adverse effects
Avoiding reflex prescribing and cascade polypharmacy
Seizure control vs quality of life - the real balance
About Dr. Ángel Aledo-Serrano
Ángel is an Epileptologist & Neurologist and Co-Director at Clinical Neurosciences Institute - Blua Sanitas Valdebebas, with a focus on refractory epilepsies, developmental and epileptic encephalopathies, and functional seizures (FND).
Full profile: Angel Aledo-Serrano
Topics mentioned
keppra
levetiracetam
psychiatric adverse effects
quality of life
prescribing behaviour
polypharmacy
genetic testing
-
00:00 Ángel Aledo-Serrano
They have psychiatric problems, they have mental health problems and now we know that those problems are more important than seizures.
00:09 Torie Robinson
This is a first! I’m sharing with you our past episode with the star neurologist and epileptologist Ángel Aledo-Serrano to hear all about Keppra - or levetiracetam. It’s the almost villainised anti-seizure medication - but it’s one which provides amazing seizure control and improves quality of life for many people. Angel is also going to tell us about improving prescribing, avoiding doping people up on too many medications, and convincing other clinicians that epilepsy is way more than seizures.
This episode is presented in partnership with EASEE®, by Precisis GmbH.
Meet Ángel
00:47 Ángel Aledo-Serrano
I am an epileptologist and neurologist working in Madrid. I am seeing both children and adults. I think that's kind of not very frequent! I don't do the transition from children to adults, I am the transition. And we are starting a new project in Madrid that's very exciting.
01:10 Torie Robinson
What's the new project you're starting?
01:11 Ángel Aledo-Serrano
So I had the opportunity to start a new institution, to be the director of a new epilepsy program, it’s the Madrid Epilepsy Centre, it's the name of the new project and, it's exciting to have this opportunity because we can put our philosophy and our ideas [together[, trying to make the patient the centre of the care, and all the you know epilepsy is involving so many things and so many perspectives, and so many professionals, so we are trying to organise something with a patient with epilepsy in the centre of the care.
01:52 Torie Robinson
So that they have access not solely to an epileptologist but also to say a neuropsychiatrist, a dietician, a physical therapist and things like that?
02:03 Ángel Aledo-Serrano
Yeah, speech therapy, mental health therapy, all the work up like neurogeneticist, video EEG, MRI, so everything, social worker. So we are trying to make all this and not to make the patient go to every specialist but every specialist go to the patient, so the other way around.
02:31 Torie Robinson
Well, watch out, I think you might have a few people wanting to move to your location in Madrid because it sounds amazing what you're doing.
02:38 Ángel Aledo-Serrano
Yes, this is something we are starting. Of course, epilepsy and in the rare epilepsies or the complex epilepsies area, sometimes you get patients from all over the world, so I also do online consultations to try to reach these patients as well.
02:58 Torie Robinson
Well, one of the benefits of the internet, I think especially, you know, although of course COVID was horrific and lots of people hated, understandably, lockdown, I do think that it made more clinicians like yourself use the internet to give people treatment online, correct?
03:15 Ángel Aledo-Serrano
Absolutely, and of course you are losing something if you are not seeing the person in-person, but at the same time you have, yeah, these huge opportunities to go to a specific specialist in your gene, or in your specific epilepsy, or in your specific epilepsy issue; like the mental health problems related to epilepsy and so on.
03:44 Torie Robinson
And just so everybody knows as well Ángel, well… and did we meet on Twitter? Or was it at an event? I can't remember.
03:52 Ángel Aledo-Serrano
I think so, the first connection was on Twitter.
03:57 Torie Robinson
Anyway, so we both were working with EpiCARE and ended up seeing each other at conferences. And so, I've seen Ángel do some amazing talks, one of which you did at the SCN8A and SCN2A conference over the weekend, in Denmark. And honestly, I know I sound like I'm promoting him, but he was so good. And that will be available on one of the websites. So, make sure you check it out, everyone.
Keppra/Levetiracetam - what is it?
04:26 Torie Robinson
So, Ángel, Today you're going to be talking about levetiracetam or otherwise known brand name Keppra. Could you tell us for everybody who's not familiar, what is this drug?
04:37 Ángel Aledo-Serrano
Yeah, yeah, so this is the most commonly prescribed drug and this is a medication. So, you know, researchers and clinicians, sometimes we are focusing very, very narrow target of research, so a molecule or a gene. And sometimes we are forgetting to research or to talk about the most common things which are the most important in the end. So levetiracetam is a drug which was developed during the 90s, it was introduced in the market in 1999 (so at the end of the decade) and it was a huge revolution. Because it was a drug which could be prescribed without interactions with other drugs and it's kind of safe (regarding to cardiac problems, kidney problems, bone problems), and at the same time it's so easy to prescribe. So it was very, very different to other old medications like maybe Valproate or Phenytoin or Phenobarbital. So, in that sense it was a huge revolution and because of that it became a blockbuster.
06:04 Torie Robinson
“Blockbuster”, that's a good term for it, hehe.
06:05 Ángel Aledo-Serrano
Haha. It’s the favourite drug for all over specialists, like intensive care unit specialist, department doctors, internal medicine doctors, because it's really, really easy to use. So, at the same time we have this dark side of the story, that, of course, if you get this over prescription (so you use it too much), you are not doing it well at the same time. So, this is the, I think this is the background where our study is starting.
Reviewing evidence on Keppra
06:51 Torie Robinson
So, tell me about this specific study then, which came out I believe in April?
06:57 Ángel Aledo-Serrano
It's not an original study, it's a review study, a narrative review - which we call [a] narrative review when you go over all the references (so previous papers, previous research studies), and you try to do a summary, and also you give your opinion, your expert opinion. So, a group of epileptologists, together with my own institution, my own epilepsy programme, but also with Fabio Nassimento (he’s an epileptologist working in the US) and we tried to review all the evidence on Keppra, on levetiracetam, and tried to highlight where not to use it and where better to use it so to try to make it more specific
07:53 Torie Robinson
And by… where you say when to use it, when not to use it, you're talking about a particular situation of a person with epilepsy…
08:00 Ángel Aledo-Serrano
Yeah.
08:00 Torie Robinson
…right. So, what type of seizure they have, frequency, any other comorbidities, drugs they're taking, right, things like that.
08:08 Ángel Aledo-Serrano
Yeah, to be more precise. So, it's not Keppra for everybody. So in the last few years, we have this feeling that epilepsy is that sub-specialisation of neurology where you put Keppra and then you start to think. So it's: you just put [prescribe] Keppra! So we want to end this kind of strategy and to be more precise to help better our patients.
Negative side-effects of Keppra
08:39 Ángel Aledo-Serrano
So, for example, over the last few years we discovered that around 20 to 30% of people were treated with levetiracetam (by the way, Keppra is the commercial name but levetiracetam is the scientific name of the drug), they have psychiatric problems. They have mental health problems And now we know that those problems are more important than seizures.
09:00 Torie Robinson
For many of us, yeah!
09:11 Ángel Aledo-Serrano
A seizure is just one moment or some minutes, and mental health problems are all the time with you. So, what I can say to you, of course you know about it better than me!
09:25 Torie Robinson
What's important though, I think, is that we have people with epilepsy, and their potential carers, as well as clinicians working together, isn't it. A bit like at the conference, you know, we just had the Filadelfia conference, so none of us know everything that's the important thing to note.
09:43 Ángel Aledo-Serrano
Yeah, yeah, yeah, for sure. And you know, we were like very, very delighted to have a drug which was so easy to use, which was so safe for the heart and for the bones and for the bowels, and so on and so forth. But at the same time, who cares about the bones when you don't get any happiness from your life?
10:11 Torie Robinson
Thank you, exactly. And that didn't used to be recognised, did it? So, like you were saying, people would just, ha, “You've got uncontrolled epilepsy, just try some Keppra/levetiracetam, and good luck with that!”. But it's not solely about seizures.
Balancing and communicating side-effects
10:27 Ángel Aledo-Serrano
And I try to use this comparison: if you want to decide between your cholesterol, because of course, levetiracetam is very good for cholesterol because it has no interactions, and other drugs like carbamazepine or even eslicarbazepine, they have some effects on lipids, on cholesterol. But who cares about cholesterol if you are going to get divorced because your couple is not standing [by] you, so you have to balance that. And of course, this is only 20 to 30%. So, there is 70/80% who are not at risk of these psychiatric adverse events, but it's something you have to explain to the patient. Don't explain so much that you are causing no servo, because… you are going to have this problem.
11:24 Torie Robinson
You know what? I noticed this a lot on social media, in some special groups for people with epilepsy, they'll… somebody will be prescribed a new drug, just say for instance, levetiracetam/Keppra, and they'll say “Oh, are there any side effects? What should I do?”, and then the loudest people are always the ones who have the worst side effects and then they'll say “Well, beware, because this might make you depressed, or this might do this to…”, and then it makes people scared to even start the drug! So I think, yeah, like you're saying, we have to be careful would not, not it be honest with patients but not frighten them with potential side effects right.
12:07 Ángel Aledo-Serrano
Yeah, yeah. And you have to adapt your narrative to the personality of your patient and the family of your patient. So, you cannot tell the information the same way to everybody. So, for example, if your patient is kind of obsessive compulsive, the information has to be very, very specific but not so… I don't know…long - because they are obsessive.
12:37 Torie Robinson
And then could cause real anxiety for them as well, right? And then ironically, the anxiety in many of us can cause seizures. So, yeah, like you say, you have to be so careful. It's about being honest, complete honesty, but just how you give the information has to be tailored. Right?
12:56 Ángel Aledo-Serrano
Yeah, because of that, these kinds of prescriptions, it's better to make them when you know the patient. So, don't… because of that, it's dangerous to have these kinds of consultations where every consultation you have a different doctor. And that's quite common - at least in the health system in Spain. And you know that these kind of situations are less common when you see the same doctor always, because you have this kind of close relationship. Yeah, so this is one side, one side is to know better the safety profile, to be careful about that, and the other side is that (and of course every person with epilepsy has suffered this), is that we are putting medications in a trial and error strategy. So you are not precise, not only in the safety profile, but also in the effectiveness profile. So, sometimes you just know if it's working or not after putting it. So you can’t know it before.
Where Keppra can be more or less effective
14:14 Ángel Aledo-Serrano
So in this review, in this paper, we try to highlight the specific epilepsy syndromes or clinical scenarios or aetiologies (so genetic causes, and so on), where levetiracetam can be more effective or less effective. For example, we know, and we were talking about that in Filadelfia, in Denmark this weekend, that levetiracetam could be even harmful for some patients with SCN8A, gain of function genetics. So, for other genes, for example, PCDH19 (it's another kind of genetic epilepsy), it can be really effective, so the best drug. So, this is so important. We have to be very cautious and to try to study our patients to better to better understand which medication is going to be the best, not use levetiracetam and “see”.
15:18 Torie Robinson
Before we move on - with thanks to EASEE®, by Precisis GmbH.
Genetic testing?
15:25 Torie Robinson
Would you say it would be ideal for most or all people diagnosed with an epilepsy to have whole exome sequencing to try and identify any type of mutation, for instance?
15:36 Ángel Aledo-Serrano
So that's a really good question and it's something which is changing over time. For example, some years ago we were saying “No, so MRI, the neuroimaging, is only indicated for this kind of epilepsy and not for this kind of epilepsy.”, and now we are doing MRI for everybody. And I guess the same scenario is with genetic testing. So we are having real specific indications, the indications are growing and are expanding, but still we say that it's only indicated for people who are starting in the first years of life. So if you have a late onset epilepsy, that would be not indicated in genetic testing because you have a lower diagnostic yield.
16:34 Torie Robinson
Ah, but then, I don't know, to be sort of potentially an “annoying patient” I could say “Well just because I might be one of the people having a lower diagnostic yield, it doesn't mean that I shouldn't have it!”
16:47 Ángel Aledo-Serrano
Probably in some years we will do it for everybody. Even if you have only 2% of the ability to have a diagnosis, that's worth it because you will have more information to decide your treatment. So, of course… but of course, in general, the most important are good long video EEG, so to better understand the epilepsy syndrome. It's a generalised one, it's a focal one, which kind of discharges, you have epileptiform activity which is typical of malformation of cortical development, so then you have to look carefully to the MRI and then decide not to put levetiracetam as maybe the first disease medication. So that's very important. And what we are also understanding in the last few years is that sometimes the genetic testing could help in the safety profile.
Shorter appointments = too many medications?
17:55 Ángel Aledo-Serrano
And again, this is very important because sometimes we end up in this “cascade prescription”. I don't know if you use that in English, but it's like you put an antiseizure medication, for example, levetiracetam, you produce a mood disorder, and then you, secondarily, you produce another, uh, prescription of, antidepressant. So then the antidepressant put, uh, uh, less libido or, uh, sexual problems, and then you are using, uh, Viagra. And then you are, so it's, uh, haha.
18:35 Torie Robinson
Yeah and so it brings on basically polypharmacy, a multiple… brings on a greater diagnosis of conditions and then more drugs and you get stuck in this loop right?
18:46 Ángel Aledo-Serrano
Yeah. And this is well studied; that you are doing that if you have shorter consultations. So of course for a neurologist, if you have only 5 minutes or 10 minutes or 15 minutes of consultation, it's really difficult to go a step back, take perspective, and discontinue this medication, go down with this medication, explain a new medication, and make it in detail. So if you have less time, you put more medications in general. It's “better”, it's easier. So this is something I'm saying always in my talks to try to change and deprescribe, so stop more medications.
19:40 Torie Robinson
By reducing the number of medications, you're gonna reduce the side effects, likely, that the person experiences. Sometimes the negative side of the medications can outweigh the positive impact of a medication. I've spoken to clinicians who've told me that sometimes they'll have a patient with an epilepsy, he'll say, do you know what, “I would rather have an extra few seizures a month by through taking a lower dosage of this drug so that I can go to work and I have can improve cognitive function.”. And it's all about that balance, isn't it? And I guess a clinician learns that through getting to know their patient better through longer appointment times.
When patients lose hope
20:20 Ángel Aledo-Serrano
Yeah, yeah, yeah, and sometimes just patient’s have lost their expectations to be better and they are understanding, although they are taking for granted that it's normal to be with a mental fog. Because sometimes you don't know how are you after a long time of being depressed or being with less cognitive skills. You end up thinking that this is yourself! This is you! You don't know how intelligent you are without the medication!
21:01 Torie Robinson
So true, haha, it's like you're singing about my life, haha and the lives of so many people, and it’s exactly it. And then when somebody has felt, like you say, felt this way for a long time, been on these drugs for a long time, you can be scared to reduce those drugs or take those drugs, especially if they have had some usefulness in reducing the frequency or severity of your seizures. And yeah, it's like you're juggling all the time. And I think that that's where we really need people like yourself, Ángel, who appreciate the that juggle and how to prioritise, really, quality of life.
We need more data on Keppra
21:42 Ángel Aledo-Serrano
And we need more data on that as well, because something which we are also trying to show in our paper is that we still have grey scenarios. So, situations where we don't know what to do and we don't have information/enough information, so in the end we are just using your experience which is - of course that's really important but it's not evidence-based - and this is also maybe because, in the last few years (this is maybe changing), but in the past, we were not really interested in this kind of specific profile of the drug. So, when we study a new drug, we are just seeing the average of the effectiveness or the average of the safety profile, but we are not studying which kind of patient is improving and which kind of patient is not improving. So maybe we should change our mindset on that. I care about the average of course, but when you are in front of your patient the average is just a number. You want to know if your patient is going to respond or not; if your patient is going to have the adverse event or not. And also your patient care about that so yeah this is something we have to change in the research area.
23:24 Torie Robinson
And so if we have anybody listening right now who is interested in getting involved in research along these lines, would it be useful to get in touch with you, Ángel, or what do you think?
Symptoms other than seizures - we need qualitative research!
23:37 Ángel Aledo-Serrano
So at the time we are not doing any study of this, but it would be really nice to have the data. Of course they can reach me out. We are not studying this specific about levetiracetam, but we are doing all other kind of studies. For example trying to see if a specific gene is responding to specific medications, or, other studies are for example using qualitative methodologies. Qualitative methodologies, I think they are very important because they are not statistics they are interviews, so deep conversations
24:26 Torie Robinson
That's extremely important in the epilepsies because everybody's lives and bodies and brains are so incredibly different and how they experience the epilepsy and comorbidities (which are really not comorbidities, they're part of the epilepsy), it's all different for everybody. So yeah, that's why I appreciate what you're saying regarding qualitative research.
24:47 Ángel Aledo-Serrano
And it's crazy because we have been like, I don't know, 10 years, the last 10 years saying that epilepsy is more than seizures, but still, I don't feel the difference in... of course, we are improving in a lot of areas, but it's crazy that after so many years saying the same, it's just “makeup”!. It's just... it's not something which is truly changing. I don't know. Sometimes you just change by repetition or repetition. So maybe we should just repeat the same.
25:25 Torie Robinson
I keep saying this in every conference and people with epilepsy or mums and dads or carers listening, the epilepsy is more than seizures. I think [in] appointments bring that up. The epilepsy includes this behavioural difficulty of somebody or their cognitive function or the physical issues that come alongside seizures!
Ways to communicate to patients without inducing fear
25:50 Ángel Aledo-Serrano
And you know, now we are talking about, a lot, about how to change human behaviour and clinician behaviour (and this is coming from the climate anxiety -so I'm working a lot in the climate change area and how that's impacting people with epilepsy and clinicians caring for people with epilepsy) because we want people to change their behaviours. But telling them climate change is going to be terrible; that's not changing anything, that's only frightening, haha.
26:34 Torie Robinson
Yeah, yeah.
26:34 Ángel Aledo-Serrano
And it's causing climate anxiety. And at the same time, if we say “Epilepsy is more than seizures.”, but we only say that, you just cause anxiety maybe in the clinician because sometimes they don't have the tools to help the patients beyond the antiseizure medications. They don't have the time to have these deep conversations. So maybe it's more powerful to talk about the good examples. So, the positive ways on how people... patients and also doctors are addressing this issue. So, for example; fighting with the hospital trying to make longer consultations to talk about all the things, or having other specialists around you to talk about the other things, or having emails, or having pre-consultations. You were talking about that, how to prepare the consultation and make it more effective. So maybe we should talk about that. So not how bad we are doing that, haha, but how good we can do it!
27:57 Torie Robinson
Yeah, preparation, and we want to look at quality of time with patients, clinicians, rather than quantity of time. Sometimes we're limited with the amount of time we have together, so let's make it of higher quality for both parties. I think that's great. Thank you so much for joining us, Ángel, it’s very kind of you to donate your time to us, and no doubt we will speak soon. Thank you very much.
28:20 Ángel Aledo-Serrano
Yeah, thank you so much Torie for what you are doing in general and for having me.
Final thoughts & thanks
28:26 Torie Robinson
Thank you very much to Ángel for speaking about - with clarity - the antiseizure medication levetiracetam ( known as Keppra) and it’s pros and cons, the diversity of epilepsy symptoms, and more than anything - the importance of the quality of life of people with an epilepsy.
Again, huge thanks to EASEE®, by Precisis GmbH, for partnering with Epilepsy Sparks.
Did you find our chat with Ángel interesting? If so, please share the episode with your colleagues, friends, and family members and do give us a like and subscribe - this really helps us keep going as a channel. Let us all, together, improve understandings of the epilepsies around the world, together! See you next time.