Therapeutic Considerations of Antiseizure Medications-Choosing the First Anti-Seizure Medication

Video Transcription

I'm Betty Michael. I work at the Penn State Health Children's Hospital and I've been working  with children who have epilepsy for the past 14 years. I'm going to talk to you about choosing the  very first anti-seizure medication and I have no disclosures but I will at the end talk about a few  off-label uses for anti-seizure medications. At the end of this session you should have gained sufficient knowledge to choose the first anti-seizure medication for your patient with  new onset epilepsy in the outpatient setting. So you go back to work next week and you have  this adorable little kiddo in your office. You've just diagnosed him with epilepsy and now you need  to choose a medication for his condition or maybe some of you have these kinds of people in your  office. These are a little bit scary for me. How do you decide when you are looking at someone with  epilepsy what is the most appropriate medication to treat their seizures and what factors should you consider when you're making your choice? Especially when these are your choices.  We have over 30 medications that are approved for treating epilepsy.  So your patient has new onset epilepsy and the ideal anti-seizure medication should suppress  all seizures without causing any unwanted side effects. This is our gold standard and not very  many of us meet this standard. It is generally accepted that complete seizure control can be  achieved in about 50% of patients and that about 30% of these patients with epilepsy will have  inadequate control or become refractory with medication treatment. This goes back to the  studies from Kwan and Brody in the 2000s. The success rate really depends on the type of epilepsy,  the family history, and the extent of the patient's underlying neurological abnormalities.  We know that very few anti-seizure medications are effective for all seizure types and some are suboptimal because of patient-specific characteristics such as age, gender, epilepsy  syndrome, comorbidities, adverse effect profile, and drug interaction potential. So these are the factors to consider. I go through this list in my head frequently and then discuss  with the family. So the first factor is what is the type of seizure and what is the frequency?  What current medications does the patient take and what comorbid conditions do they have?  What's the age of the patient? You're going to treat children a little bit differently than you  are childbearing women and elderly. What is the time to titration? You don't want to use a long  titration medication when your patient's having hundreds of seizures per day. What is the cost of medication? There are families that have to pay for their medication out of pocket.  What is the dosing frequency and what kind of medication adherence can you expect?  So these are the epilepsy types. It's not an ILAE approved list but it doesn't make it easier to  discuss the different types of epilepsies and medications. So the first epilepsy is absence.  The next is focal. Then we have generalized, then undetermined as to focal or generalized. This is the one that gives us the biggest headaches. And then epilepsy syndromes.  The next factor are comorbid conditions. Does your patient have any of these conditions that you know about? And these are not an exhaustive list but you can look at the list  and these are not an exhaustive list but some of the neurologic conditions that we see  for patients with epilepsy are headaches, brain tumors, and cognitive difficulties.  Some of the cardiac issues are arrhythmias. There are lots of mental health difficulties or comorbid conditions including depression, irritability, and bipolar disorder. There are  patients with renal issues including renal failure or renal stones. Infectious comorbid conditions such as neutropenia. Does the patient have HIV or any bleeding disorders?  Are they overweight or are they obese? Do they have diabetes? Are they taking oral contraceptives?  Are they greater than 65? Are they of childbearing years or are they less than three years of age?  Oops. So talking about the age of the patient, in the pediatric world we pay very close attention  to the form of the medication that we use. Whether it's liquid, chewable, swallow tabs, or sprinkle caps. Usually the liquid forms are pretty awful tasting so sometimes you  need to think about the form that the medication comes in. Is it a sprinkle? Can you use it as a  sprinkle cap or can you do a chewable? Many children, even teenagers, aren't able to swallow  pills. Under age three we definitely want to avoid sodium valproate unless you absolutely  feel it necessary and then you need to monitor very closely. We avoid using phenobarbital as  Michelle just talked about back when Lily was placed on medication. Phenobarbital was the best  medication out there but we know now that it can cause cognitive side effects and phenytoin can be  irregularly absorbed and can cause some blood disgraces. In the childbearing years you want to  avoid using valproate and topiramate due to the possible teratogenic effects and the effect of  the anti-seizure medication treatment on hormonal functioning, sexuality, and pregnancy is also a  factor to be considered in terms of your choice of medications. Carbamazepine, phenytoin, phenobarbital,  primidone, topiramate, and oxcarbazepine all can induce hepatic pathways that are responsible for catabolism of female sex hormones, can lead to alterations in the menstrual cycle,  and has a higher turnover of the components of the oral contraceptive pills and depo forms of steroids. So this increases the rate of breakthrough pregnancy  which may not be a good thing for that particular patient.  In the older adults you want to avoid medications that can cause somnolence  so enzyme-inducing drugs should be avoided due to the high risk of drug-drug interaction  and metabolic derangements. Some of the newer anti-seizure medications with low drug interaction  potential have advantages in the elderly such as leucosamide, breviracetam, and ezlocarbazepine  acetate. The dose adjustment in this population and the advice that we would give would be to slowly titrate at up to a low target dose to minimize the risk of adverse effects.  So we also want to look at the potential for medication side effects and again this is not an exhaustive list but some of the more common side effects that we see from medications.  In the neurological realm topiramate has been known to be causative of cognitive side effects.  Levotiracetam can cause irritability or mood changes and many of the other ASMs can create  ataxia or sedation. Sometimes it takes several weeks for children to or for people to adjust  to starting new medication. In the gastrointestinal realm nausea and vomiting are very common with  ethosuxamide, diarrhea, poor taste, decreased or increased appetite such as decreased appetite  or weight loss with topiramate or weight gain with valproate. In the mental health realm alterations in mood behavior and suicidal thoughts should factor into your decision.  These are more commonly seen with levotiracetam and then ASMs can also cause sleep difficulties.  Cardiovascular we see prolonged QT and prolonged PR intervals so for the patients who have  arrhythmias you may want to rethink your choice. In the infectious realm pancytopenia has been  seen with phenytoin. Musculoskeletal we can see tremors and we can see an exacerbation in tics with lamotrigine. In the metabolic realm hyponatremia is often seen with oxcarbazepine  and elevated transaminases are often seen with epidiolex and valproate.  In the allergy realm we can see difficulties with allergies using carbamazepine and lamotrigine  and everyone's heard of Stevens-Johnson syndrome related to especially to lamotrigine.  The next factor we consider are the drug titration rates and this is not an exhaustive list either  but the article by Kim has a much broader list of medications. So briviracetam can be increased  weekly or bi-weekly and given as a twice a day dosing. Carbamazepine can be increased at weekly  Carbamazepine can be increased at weekly intervals and can be used as a twice or three  time a day dosing. Ethosuxamide can be increased on weekly intervals and is typically given as a  twice a day dosing. Lamotrigine takes a much longer period of time so the weekly changes  occur over 10 to 12 weeks and the medication is given twice a day. There is an extended release  dosing for patients over the age of 13. Levotiracetam can also be increased in weekly intervals and given as a twice a day dosing also has an extended release form for daily dosing.  Oxcarbazepine is increased in weekly intervals twice a day dosing also an extended release form and tapiramate is typically increased in bi-weekly dosing and  given twice a day an extended release is also available for this medication.  Valproate is increased in weekly intervals. Some like to give it twice a day, others three times  a day and zanisamide is increased bi-weekly and this is a medication that is dosed once a day.  So we'll talk about the types of epilepsy and the first type of epilepsy is absence epilepsy.  The mainstays of treatment for absence epilepsy are ethosuxamide, valproate or lamotrigine.  Adjunctively you can add on ethosuxamide, lamotrigine or valproate and other options include clobizam, clonazepam, levotiracetam, tapiramate and zanisamide.  Some of the drugs that will worsen seizures in absence epilepsy are carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin and vigabatrin.  For focal epilepsy the mainstays of treatment are carbamazepine, lamotrigine, levotiracetam, oxcarbazepine and sodium valproate. At our institution our  providers prefer to start with oxcarbazepine but carbamazepine is a great medication if you have  a patient who has autosomal dominant nocturnal frontal lobe seizures. Some of the adjunctives that you can add on are clobizam or tapiramate and other choices include  azlicarbazepine acetate, leucosamide and zanisamide.  For generalized epilepsy valproate and levotiracetam are generally considered first line treatments. Adjunctive treatment can include lamotrigine, tapiramate and zanisamide  and other choices include parampanol. Some of the drugs that can worsen seizures are carbamazepine, oxcarbazepine, gabapentin, phenytoin and vigabatrin.  Epilepsies of undetermined origin are often difficult. The first line includes the more broader spectrum anti-seizure medications levotiracetam, valproate or lamotrigine and  depending on how frequent they are occurring you may not want to start with lamotrigine.  Some of the adjunctive medications that you can add on are valproate, clobizam, briviracetam,  tapiramate and zanisamide. Other choices are parampanol, leucosamide and azlicarbazepine acetate. This is a busy slide and I apologize for that but these are some of the more common  epilepsy syndromes that we see. The first being benign epilepsy with central temporal spikes which when I put this talk together was that title but now has a new title.  So the mainstays of treatment are levotiracetam, carbamazepine and oxcarbazepine.  We also don't always need to treat these seizures. Everyone has feelings about how frequently the seizures are going and so sometimes we will not treat this.  Children with Lennox-Gastaut syndrome, the first line is typically sodium valproate  followed by lamotrigine, tapiramate, rifinamide, clobizam and cannabidiol.  For those with Dravet syndrome, sodium valproate is generally considered first line  and you can pick and choose from all the rest. Fenfluramine, sturopentol, clobizam, cannabidiol, tapiramate, ketogenic diet, VNS and so forth. You can often use ethosuxamide for the  patients who are having absences. For juvenile myoclonic epilepsy,  valproate and levotiracetam are typically considered first line. You want to avoid valproate in someone who is female and of childbearing years. And in juvenile absence  epilepsy, the same thing. You would want to avoid using valproate in someone who is female and of childbearing years. So some of the off-label uses of anti-seizure medications.  So anxiolytics, you can think about if your patient's super anxious, you could think about these medications such as pregabalin, clonazepam and clobizam. Those with migraines,  think about tapiramate, zanisamide or valproate. I also have some patients who I have tried  levotiracetam with and have had some limited success. Patients who might need a mood stabilizer  because they have either bipolar disorder or mood disorder, think about valproate, lamotrigine or carbamazepine. Those with neuropathic pain, consider pregabalin,  gabapentin or carbamazepine. Anyone who's overweight or you think that they might need  some help with weight loss, consider tapiramate or zanisamide. And for anti-Parkinsonian agent,  you could consider starting with zanisamide. So what is the impact on our clinical care and practice? You always want to use a targeted approach, get your seizure type,  know what the seizure type is and select the most appropriate medication for that particular seizure type. If you don't have a focus or the focus is unknown, you would want to use  an anti-seizure medication with more broad spectrum mechanism of action, such as levotiracetam. Then as you gather more information, you may move to a more targeted approach.  You want to monitor for side effects and medication adherence in the pediatric population,  especially in teenagers. This is definitely a challenge for us. Considering their comorbidities,  if they have headaches, consider tapiramate. If they have mental health issues, consider  carbamazepine or lamotrigine. You really want to try to get the most coverage for epilepsy type  and comorbidity out of your medication choice. And I want to thank you for your attention.

Video Summary

In a presentation about selecting initial anti-seizure medications for children with epilepsy, Betty Michael highlights key factors in making informed decisions. Emphasizing the importance of seizure type, frequency, patient age, and comorbid conditions, she explains that achieving complete seizure control is challenging, with success rates around 50%. Michael advises considering medication side effects, dosing, cost, and patient lifestyle when choosing treatment. Options vary across epilepsy types, with specific recommendations for absence, focal, and generalized seizures, among others. Additionally, certain medications may require careful adjustment for special populations, such as those of childbearing age or the elderly. Michael further discusses off-label uses for anxiety, migraines, mood stabilization, and neuropathic pain, stressing the need for a targeted yet flexible approach in epilepsy management to maximize treatment efficacy and patient well-being.

Asset Subtitle

Presenter:

Elizabeth “Betty” Michael, MS, CPNP-PC, CSN, is a Certified Pediatric Nurse Practitioner and Certified School Nurse working in the Pediatric Epilepsy Program at the Penn State Children's Hospital for the past 13 years. She has been a Certified Pediatric Nurse Practitioner since 1992 and has worked in Primary Care Pediatrics, Acute Pediatrics and in the Cleft Palate Craniofacial Center at the Children's Hospital in Pittsburgh. In her current position, she has worked to expand the Ketogenic Diet Program and established a "First Seizure" clinic. She focuses on patient and family education in the Epilepsy Clinic and has developed educational materials currently used in the Epilepsy Clinic.

Keywords

anti-seizure medications

epilepsy treatment

seizure control

medication side effects

off-label uses